Ideal BW Research Articles

Chicken meal is not an appropriate reference protein for estimating protein quality of ingredients used in extruded diets intended for dogs.

The indicator amino acid oxidation (IAAO) method has been used to determine metabolic availability (MA) of amino acids in feedstuffs for pigs, humans, and preliminarily for cats. Peas are a commonly used protein source in grain-free extruded dog diets. However, peas have a poor sulfur amino acid (AA) ratio (methionine [Met]:cysteine) with Met being the first limiting AA. Furthermore, little is known about the MA of Met in peas fed to dogs. Therefore, our objective was to compare the MA of Met in peas to chicken meal (CM), as a gold-standard reference protein. The study was done as a replicated 5 × 5 complete Latin square design. Ten neutered male mixed-breed dogs (1.5 years old; 26.0 kg ± 2.4kg body weight; BW) fed to maintain ideal BW received all dietary treatments: BAS: lamb-based diet (deboned lamb and lamb meal) providing Met at 50% of its requirement (0.27g/100g dry matter [DM]), CHK: CM and lamb-based diet, and PEA: ground dried pea and lamb-based diet both providing Met at 68% of its requirement (0.35 and 0.37g/100g DM, respectively). Two other treatments were created by blending BAS with PEA (BAP) and the BAS with CHK (BAC) to create diets with Met at 59% of requirement (0.32 and 0.31g/100g DM, respectively). This resulted in three graded levels of Met for both CM and peas to allow for a slope-ratio assay approach to quantify MA with the BAS diet as the common first point. All other AAs were provided to meet at least 120% of the AAFCO recommendations for adult dogs. The BAS diet, with supplemental DL-Met, was fed for a 2-wk wash-in period. After 2 d of diet adaptation IAAO was performed. Dogs were fed 13 small meals where meal 6 contained a priming dose (9.4mg/kg BW) of L-[1-13C]-phenylalanine (Phe; 99%) as well as a constant dose (2.4mg/kg BW) in meals 6-13. Breath samples were collected and enrichment of 13CO2 was measured using isotope-ratio mass spectrometry to calculate the rate of Phe oxidation (F13CO2 umol/kg BW/h). Oxidation was analyzed via SAS using PROC GLIMMIX with dog and period as random effects, and diet, %Met, and their interaction as fixed effects. Unexpectedly, the slope of Phe oxidation, in response to increasing Met intake, from CM was 31% of that of peas, indicating a lower MA for Met in CM as compared to peas. This finding may be due to damage of AAs during rendering. At this time, CM in extruded diets is not an acceptable reference protein to determine MA of AAs in dogs, and the MA of Met from peas cannot be confidently assessed.

PSIX-13 Intake Differences in Small Dogs Suggest a Need for Size-Specific Energy Considerations

Abstract The domestic dog is one of the most diverse mammalian species in the world. However, knowledge regarding potential differences in metabolism and disparities in nutritional considerations due to body size is limited. The primary focus of this study was to investigate differences in energy needs of small dogs compared with medium and large dogs by analyzing longitudinal intake for individuals of varying body sizes. A secondary aim was to assess age-associated differences in the energy needs of small dogs by comparing longitudinal intake between young and old small dogs. Caloric intake (kcal/d), metabolic body weight (MBW)-adjusted caloric intake (kcal/kg0.75/d; MBW-Kcal), and BW were assessed in a population of mature adult dogs dogs (10.8 ± 1.9 yr; n = 58) categorized into three size groups based on ideal body weight; small (≤11 kg; n = 19), medium (11 < x < 22 kg; n = 29), nd large (≥ 22 kg; n = 10). The second study population was made up of small dogs less than seven years old (1.2 ± 0.8 yr; ≤11 kg; n = 46). All dogs were fed to maintain ideal BW. Intake was measured daily; BW was recorded monthly. The activity factor (AF) of each dog was calculated by dividing daily caloric intake by their resting energy requirement. ANOVA was used to assess effects of size and age on all data. Nonparametric test of medians was conducted to evaluate the distribution of MBW-Kcal. As expected, caloric intake increased as size increased (P < 0.001); however, this effect was not attenuated by adjusting for MBW (P < 0.001). Mean MBW-Kcal was greater in small dogs than medium (P < 0.001) and large dogs (P = 0.031). The variance of MBW-Kcal in small dogs was greater than in large (P < 0.001) and medium dogs (P < 0.001), indicating that small dogs had a larger range in the distribution of caloric intake even when adjusted for MBW (Figure 1). Mean AF of small dogs (1.7) was also greater than large (1.5; P = 0.030) and medium dogs (1.5; P < 0.001), but the AF of medium and large dogs were similar (P = 0.650). MBW-kcal and AF were similar between small old and young dogs (P > 0.05). These data demonstrate that even when adjusted for MBW, small dogs may require more calories to maintain BW than their medium- and large-breed counterparts, and this increased caloric need appears to be sustained in both dmall young and old dogs. These results suggest that small breed dogs have different metabolic factors driving caloric needs compared with larger dogs and further emphasize that nutritional guidelines should be updated to better reflect the energy needs of small dogs across life stages.

MO580HYPOPROTEIC DIET SUPPLEMENTED WITH KETOANALOGUES IN PATIENTS WITH ADVANCED DIABETIC KIDNEY DISEASE – EFFECTS ON MINERAL BONE DISORDERS

Abstract Background and Aims Dietary protein restriction is rediscussed as mainstay approach in advanced Chronic Kidney Disease (CKD), both in diabetics and non-diabetics to defer renal replacement therapy (RRT), mainly by better metabolic control; improvements in mineral bone disorders (MBD) were also suggested, but less studied in Diabetic Kidney Disease (DKD). An unicentric prospective interventional trial aimed to assess the effects of ketoanalogue-supplemented low protein diet (sLPD) on proteinuria and CKD progression (data already presented). The parameters of MBD were also evaluated. Method Adult diabetic patients (452) with stable CKD stage 4+, proteinuria>3g/g creatininuria and SGA A were enrolled in a run-in phase (3 mo), with LPD (0.6g/kg dry ideal bw). Those who proved adherent (92, 64% males, median age 55.7 yrs, 65% on insulin) received sLPD (Ketosteril®, 1 tablet/10kg) for 12mo. Monitoring and treatment followed the Best Practice Guidelines. The primary endpoint was proteinuria during intervention as compared to pre-enrolment. Serum levels of calcium, phosphates and iPTH were considered to assess MBD. Nutrition, inflammation (SGA, BMI, serum albumin, CRP) and compliance were safety parameters. Results In patients with advanced DKD and severe proteinuria, sLPD was associated with a 69 (63; 82) % reduction in proteinuria (data presented). Significant amelioration in MBD was noted: serum levels of calcium and phosphates were significantly ameliorated at the end of the study as compared to enrolment - 4.3 (4.2-4.9) vs 3.2 (3.1-3.5) mg/dL and 5.4 (4.9-6.1) vs 8.2 (7.8-8.9) mg/dL, respectively. Serum iPTH significantly decreased: 185 (168-212) vs 375 (354-585) pg/mL. The need for calcium supplementation decreased: 6.5 (6.0-6.7) vs 7.0 (6.8-7.3) g/day. Vitamin D was required by only 35% vs 65% of patients. Nutritional status was preserved and dietary compliance was very good throughout the study. Conclusion In patients with advanced DKD ketoanalogue supplemented low protein diet seems to be effective and safe as part of MBD management.

Protein Intake and Human Health: Implications of Units of Protein Intake

ABSTRACTUnderstanding the health effects of protein intake is bedeviled by a number of factors, including protein quality and source. In addition, different units, including grams, grams per kilogram body weight (g/kg BW), and percent energy, may contribute to confusion about protein's effects on health, especially BW-based units in increasingly obese populations. We aimed to review the literature and to conduct a modeling demonstration of various units of protein intake in relation to markers of cardiometabolic health. Data from the Framingham Heart Study Offspring (n = 1847; 60.3 y; 62.5% women) and Third Generation (n = 2548; 46.2 y; 55.3% women) cohorts and the NHANES 2003–04 (n = 1625; 46.2 y; 49.7% women) and 2005–06 (n = 1347; 43.7 y; 49.5% women) cycles were used to model cross-sectional associations between 7 protein units (grams, percent energy, g/kg ideal BW, g/kg actual BW, BW-adjusted g/kg actual BW, g/kg lean BW, and g/kg fat-free BW) and 9 cardiometabolic outcomes (fasting glucose, systolic and diastolic blood pressure, total and HDL cholesterol, triglycerides, BMI, waist circumference, and estimated glomerular filtration rate). The literature review indicated the use of myriad units of protein intake, with differential results on cardiometabolic outcomes. The modeling demonstration showed units expressed in BW were confounded by BW, irrespective of outcome. Units expressed in grams, percent energy, and ideal BW showed similar results, with or without adjustment for body size. After adjusting for BW, results of units expressed in BW aligned with results of grams, percent energy, and ideal BW. In conclusion, protein intake in cardiometabolic health appears to depend on protein's unit of expression. Authors should be specific about the use of WHO (g/kg ideal BW) compared with US (g/kg actual BW) units, and ideally use gram or percent energy in observational studies. In populations where overweight/obesity are prevalent, intake based on actual BW should be reevaluated.

PSIII-25 Adipose gene expression of mature neutered male cats during the transition from a lean to an obese phenotype

Abstract Obesity is the most prevalent disease in companion animals. Feline pets have access to palatable and nutrient dense foods and often live a sedentary lifestyle leading to a positive energetic balance. Obese companion cats are more predisposed to suffer from insulin resistance and diabetes. This study examined changes in abdominal subcutaneous adipose tissue over a 36-wk course of ad libitum feeding to provide insights into early gene regulation in metabolic pathways associated with weight gain and metabolic dysfunction. Nine neutered male cats (mean age 8 ± 0.3 yr) were fed to maintain ideal BW at baseline (wk 0), and then fed ad libitum for 36 wk. At wk 0, 12, 24, and 36, biopsies were collected from subcutaneous adipose deposits of the abdomen. RNA was isolated using a commercially available extraction kit specific for lipids (RNeasy lipid tissue mini kit, Qiagen). mRNA expression of over 40 genes encoding adipokines, transcription factors, glucose transporters, inflammatory processes, and metabolic enzymes was measured by Fluidigm multiplex qPCR. This generated a gene expression profile portraying the upregulation of genes associated with energy storage but not energy mobilization. Leptin expression was increased 20-fold as adipose mass increased. Interestingly, gene transcription for the receptors of insulin signaling (IR, IRS1, ISR2) were downregulated, even when genes leading to glucose transport (GLUT4, GPR120/FFR4) were upregulated. This relationship could show a disconnect between the quenching of insulin signaling (insulin resistance), while also fueling glucose transport early in weight gain, providing a potential focus of interest for future investigation. The gene expression of transcription factors PPARG1, PPARG2 and SREBP1c were higher in ad libitum fed cats as was lipoprotein lipase, but not hormone sensitive lipase. These findings indicate an orchestrated metabolic response to accommodate for adipogenesis and maintain lipid homeostasis due to increased calories during ad libitum feeding.

2304-PUB: Liraglutide also Has Favorable Effects on Body Composition without Decrease in Lean Body

Background/Objective: It has been known that liraglutide GLP-1 therapy produces a decrease in body weight with a concurrent decrease in appetite. However, we felt it was important to investigate this phenomenon more deeply in order to ascertain whether there were effects an leanness or body fat, especially visceral fat which may induce atherosclerosis. Method: We conducted an observation study to investigate the effect of liraglutide therapy (n=53), a GLP-1RAg, on body composition in patients during hospitalization. These results were compared with those obtained from insulin therapy (n=130). Diet therapy (ideal BW x 27 kcal/day including <25% fat and >55% carbohydrate) and exercise therapy after every meal were provided. Body weight changes, body composition (i.e., lean body mass and % body fat) and were analyzed. Result: We found the body weights of subjects receiving liraglutide decreased by 2.4 ± 2.0. However, for insulin therapy, subjects body weight only decreased by 1.6 ± 2.1 kg (p < 0.05). In addition, lean body mass in the liraglutide and insulin groups showed no significant changes from the first day of therapy. However, regarding visceral fat area (VFA), we found that patients undergoing liraglutide and insulin therapy tended to experience a decrease (101±152.4 vs. 113±171.7 cm2). Conclusion: Our study showed the administration of liraglutide reduced visceral fat, but not lean body mass. In addition, we found that diet and exercise therapy mostly contribute to decrease in visceral fat regardless of the medication. Disclosure S. Kaneko: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd. Y. Ueda: None. Y. Tahara: None.

Fecal microbiota composition changes after a BW loss diet in Beagle dogs.

In developed countries, dogs and cats frequently suffer from obesity. Recently, gut microbiota composition in humans has been related to obesity and metabolic diseases. This study aimed to evaluate changes in body composition, and gut microbiota composition in obese Beagle dogs after a 17-wk BW loss program. A total of six neutered adult Beagle dogs with an average initial BW of 16.34 ± 1.52 kg and BCS of 7.8 ± 0.1 points (9-point scale) were restrictedly fed with a hypocaloric, low-fat and high-fiber dry-type diet. Body composition was assessed with dual-energy X-ray absorptiometry scan, before (T0) and after (T1) BW loss program. Individual stool samples were collected at T0 and T1 for the 16S rRNA analyses of gut microbiota. Taxonomic analysis was done with amplicon-based metagenomic results, and functional analysis of the metabolic potential of the microbial community was done with shotgun metagenomic results. All dogs reached their ideal BW at T1, with an average weekly proportion of BW loss of -1.07 ± 0.03% of starting BW. Body fat (T0, 7.02 ± 0.76 kg) was reduced by half (P < 0.001), while bone (T0, 0.56 ± 0.06 kg) and muscle mass (T0, 8.89 ± 0.80 kg) remained stable (P > 0.05). The most abundant identified phylum was Firmicutes (T0, 74.27 ± 0.08%; T1, 69.38 ± 0.07%), followed by Bacteroidetes (T0, 12.68 ± 0.08%; T1, 16.68 ± 0.05%), Fusobacteria (T0, 7.45 ± 0.02%; T1, 10.18 ± 0.03%), Actinobacteria (T0, 4.53 ± 0.02%; T1, 3.34 ± 0.01%), and Proteobacteria (T0, 1.06 ± 0.01%; T1, 1.40 ± 0.00%). At genus level, the presence of Clostridium, Lactobacillus, and Dorea, at T1 decreased (P = 0.028), while Allobaculum increased (P = 0.046). Although the microbiota communities at T0 and T1 showed a low separation level when compared (Anosim's R value = 0.39), they were significantly biodiverse (P = 0.01). Those differences on microbiota composition could be explained by 13 genus (α = 0.05, linear discriminant analysis (LDA) score > 2.0). Additionally, differences between both communities could also be explained by the expression of 18 enzymes and 27 pathways (α = 0.05, LDA score > 2.0). In conclusion, restricted feeding of a low-fat and high-fiber dry-type diet successfully modifies gut microbiota in obese dogs, increasing biodiversity with a different representation of microbial genus and metabolic pathways.

Prognostic significance of nutritional risk index in patients with metastatic esophageal squamous cell cancer.

156 Background: It has been suggested that nutritional indicators predict the prognosis of esophageal cancer. Nutritional risk (NR) as prognostic factor evaluated by NR index (NRI) in metastatic esophageal squamous cell cancer (ESCC) has not been clarified. Methods: We retrospectively reviewed the data of consecutive patients (pts) with metastatic ESCC who received chemotherapy (CTx) as initial treatment at Shizuoka Cancer Center between April 2008 and December 2015. The selection criteria were as follows: histologically confirmed squamous cell carcinoma; no indication for curative resection or definitive chemoradiotherapy (dCRT); adequate organ function; no prior CTx, radiotherapy (RT) or chemoradiotherapy; no other advanced malignancies. NR was calculated by following formula: NRI = (1.489*serum albumin) + (41.7*present body weight [BW] / ideal BW). NR was classified into 4 groups according to NRI: major (NRI &lt; 83.5), moderate (NRI = 83.5-97.5), mild (NRI = 97.5-100), none (NRI &gt; 100). Multivariate analysis was carried out using cox proportional hazard to estimate the hazard ratio for overall survival (OS). Results: The patients’ characteristics of 138 pts who met the selection criteria were as follows: median age (range), 67 (33-86) years; male/female, 123/15; performance status (PS) 0/1/2, 62/68/8; number of metastatic sites 1/2/3/4, 55/56/23/4; smoking history -/+, 19/119; previous esophagectomy -/+, 118/20; median skeletal muscle index (range), 44.5 (27.8-63.2); median body mass index (range), 20.3 (14.3-27.4); NR major/moderate/mild/none 22/37/26/53; median serum C-reactive protein (CRP) level (range), 0.75 (0.01-20.48) mg/dL. The most common chemotherapy regimen used was fluoropyrimidine plus cisplatin (93%), and 70 patients (50%) received concomitant RT. Median OS was 4.6 months in pts with major NR and 11.8 months in others (p &lt; 0.001). Multivariate analysis for OS identified PS 2, female sex, metastatic sites &gt; 2, CRP ≥ 1mg/dL, and major NR independently associated with poor survival. Conclusions: Major NR calculated by NRI formula associated with poor survival in pts with metastatic ESCC.

Reexamining the ideal depth of endotracheal tube in neonates

The appropriate endotracheal tube (ET) depth for the newborn with respiratory failure is important. Inappropriate ET depth increases the risk of uneven lung expansion and collapse. This retrospective study aimed to compare the final ideal ET depth with Tochen's formula in Taiwanese intubated neonates, and to determine the correlation between neonatal factors and final ideal ET depth, and to devise an accurate predictive formula for use in Taiwan. Data were collected from neonates who required endotracheal intubation and who were admitted to the Neonatal Intensive Care Unit from 2011 to 2015. Correlations between the final ideal ET depth, GA, and BW were assessed using the Pearson correlation test. Multiple regression analysis was used to produce a formula to predict appropriate ET depth from mouth angle to midtracheal position of neonates. A total of 139 neonates were enrolled in this study. The final ideal ET depth was in concordance with Tochen's formula only in 19 neonates (13.7%); relatively deeper in 30 (21.6%) neonates; and shallower than the values from Tochen's formula in 90 (64.7%) neonates. Multiple regression analysis showed that the BW and GA together produced best prediction for final ideal ET depth in our study population. SGA and gender were shown to be insignificantly related to final ideal ET depth. Our study showed the final ideal ET depth was shallower than Tochen's formula in 64.7% of neonates. Tochen's formula might not be suitable to predict ET depth for neonates in Taiwan. In our study, the new formula: 4.0+1.0 BW (kg)+0.05 GA (weeks) provides a more accurate value and alternative method for evaluating the final ideal ET depth in Taiwan. A practical guideline for Asian neonates should be validated by prospective studies with large sample sizes.

Prediction of porcine carcass iodine value based on diet composition and fatty acid intake.

The pig industry uses a variety of fat sources (FS) and fat levels (FL) in diets to increase energy content. The objective was to investigate the impact of FS and FL on rate and efficiency of gain, apparent total tract digestibility of dietary fat, and pork fat composition and test dietary predictors of carcass iodine value (IV). A total of 1,213 pigs (PIC 280 × PIC Camborough 42; PIC, Inc., Hendersonville, TN) with an initial BW of 32.0 ± 0.4 kg were randomly allotted to 1 of 6 dietary treatments on d 0. Treatments were arranged as a 2 × 3 factorial, with 2 FS, choice white grease (CWG; IV = 66.8) and corn oil (COIL; IV = 123.2), and 3 FL, 2, 4, or 6%. Ten pens of approximately 20 pigs each (0.70 m/pig) were randomly assigned to each of the 6 treatments. All pigs were on trial for 105 d. Pigs were harvested in 1 of 3 marketing pulls, to achieve an ideal market BW across differing rates of gain, at which time belly fat samples were collected (d 105 [457 pigs], 117 [309 pigs], or 134 [432 pigs]). Diet and belly fat samples were analyzed for fatty acid profile. Daily rate of gain was not impacted by FS or FL ( ≤ 0.325). Increasing FL and dietary energy concentration increased G:F ( < 0.001). No difference was evident for G:F between FS ( = 0.107). Increasing FL of CWG resulted in greater daily intake of SFA and MUFA than increasing FL of COIL ( < 0.001). Increasing levels of COIL resulted in greater daily intake of PUFA than increasing levels of CWG ( ≤ 0.012). Feeding CWG tended to result in great caloric efficiency adjusted for carcass yield than feeding COIL ( = 0.074). The inclusion of COIL instead of CWG tended to increase true total tract digestion of acid hydrolyzed ether extract on d 39 ( = 0.066) but not on d 104 ( = 0.402). Increasing COIL increased carcass IV at a greater magnitude than increasing CWG, resulting in a FS × FL interaction on d 105, 117, and 134 ( < 0.001). Dietary linoleic acid concentration and daily intake had a stronger linear relationship than IV product (IVP; = 0.95 vs. = 0.94 vs. = 0.85, respectively). In conclusion, limiting linoleic acid dietary concentration and intake is key to lowering carcass IV. To meet a carcass IV standard of 74 g/100 g, linoleic acid concentration had to be <3.4% and intake had to be <88 g/d. Dietary linoleic acid is a superior predictor of carcass IV compared with IVP, especially when high-fat diets are used.

A Phase I Trial of Total Marrow and Lymphoid Irradiation (TMLI)-Based Transplant Conditioning in Patients (Pts) with Relapsed/Refractory Acute Leukemia

Background: Current hematopoietic cell transplant (HCT) regimens for patients with relapsed refractory acute leukemia have 3-year overall survival (OS) rates for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) of 19% and 16% respectively. Previous studies demonstrated that intensification of total body irradiation (TBI) is not possible due to excessive regimen-related toxicity. Because image-guided targeted radiation therapy (e.g., total marrow and lymphoid irradiation (TMLI)) allows for the precise delivery of radiation through the sculpting of radiation to areas of high risk and disease burden, intensification of radiation dose to target structures as part of a HCT preparative may be possible without increased radiation-related toxicities or non-relapse mortality. Herein we report the results of a phase I trial that combines TMLI (1200-2000 cGy) with fixed doses of etoposide (VP16) and cyclophosphamide (CY); the primary objective is to determine the maximum tolerated dose/recommended phase II dose of TMLI.Methods: TMLI together with VP16 and CY before allogeneic HCT was assessed for patients with relapsed/refractory AML and ALL. TMLI was administered on days -10 to -6, VP16 60 mg/kg (adj bw) on day -5, and CY 100 mg/kg (ideal bw) on day -3. The initial radiation dose was 1200 cGy, delivered in 150 cGy fractions twice daily. The radiation dose was escalated in increments of 150 cGy, up to 1500 cGy, by use of a standard 3x3 design. At this point, the dose was raised in 100 cGy increments to a 2000 cGy maximum with a rolling 6 design. Bone marrow (n=3) or peripheral blood stem cells (n=48) were given on day 0. Tacrolimus and sirolimus were administered for graft versus host disease (GVHD) prophylaxis. Dose limiting toxicity (DLT) was defined according to the Bearman and CTCAE 3.0 scales, the latter for hematologic toxicity. The radiation dose delivered to the liver and brain was kept at 1200 cGy. Median normal organs received 16-60% of the dose (oral cavity 28%, lung 44%, esophagus 33%).Results: From 3/14/2008 to 1/30/2014, 51 patients underwent transplantation on this trial. (See table.)Our phase I trial/safety studies found the TMLI/CY/VP16 conditioning regimen to be well tolerated at TMLI doses up to 2000 cGy; 1-year estimates of non-relapse mortality and overall survival were 8.3% (95% CI: 2.6-18.4) and 54.4% (95% CI: 39.3-67.3) respectively (median follow-up: 23.5 months).Relapsed, progressed, or persistent disease after transplant occurred in 33 patients (bone marrow, 26; extramedullary disease, 6; concurrent bone marrow/extramedullary, 1). Of the 18 patients who were treated with a dose of 1700 cGy or higher, 17 achieved a complete remission at the day +30 evaluation. No radiological-based maximum tolerated dose (MTD) was defined. We determined that the median organ dose at 2000 cGy would be lower than that seen for total body irradiation (TBI), but a higher dose may result in reaching or exceeding TBI organ dose levels. We therefore stopped at 2000 cGy, above which non-targeted organs may no longer be protected.Acute GVHD (aGVHD) developed in 28 (55%) of patients; of those 7 (14%) developed grades 3-4. The most common toxicities across the tested dose levels were grade 1 GI toxicity and grade 2 stomatitis. One patient (treated at 1500cGy) developed grade 3 stomatitis. No additional DLTs were experienced across all dose levels.Conclusion: A dose of 2000 cGy targeted to lymph nodes and marrow in combination with CY and VP16 can be safely administered in the context of related and unrelated HCT, using tacrolimus and sirolimus for GVHD prophylaxis. We did not see increased incidence of aGVHD, and the day +100 NRM rate was <5%. A phase II trial is currently being conducted.TablePatient characteristicsVariableMedian (range) or NAge at transplant (yrs)34 (16-57)Disease diagnosis AML ALL Ph- ALL Ph+ biphenotypic undifferentiated3313221Disease status at HSCT 1 RL 2 RL IF14334Cytogenetic risk (SWOG criteria) favorable intermediate unfavorable unknown significance122199KPS at HSCT80 (60-100)Donor source sibling HLA matched unrelated mismatched (1 allele) unrelated25521WBC at HSCT1.4 (0.1-14.9)% Blasts in blood at transplant*4 (0-93)% Blasts in marrow at transplant*52 (8-98)Extramedullary disease at time of HSCT11*Excludes patients with solely extramedullary disease, n=4 DisclosuresStein:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Research Funding. Snyder:Incyte: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Forman:Mustang: Research Funding; Amgen: Consultancy.

SUN-PP070: Postoperative Glucose Variability: Association with Clinical Outcome After Cardiac Surgery

Rationale: ESPEN guidelines recommend using equations based on the BW before acute illness because of fluid retention, with questionable accuracy of this BW. The aim of this study is to ascertain the accuracy of the ESPEN equation using different BW vs. EE measured by IC, in ventilated patients and to determine the most suitable BW Methods: All mechanically ventilated patients staying >72 h in ICU, with FiO2 < 60%, PEEP< 9 cmH2O, no pulmonary fistula or lung multi-resistant bacteria were included and had IC measurement. We calculated EE with the ESPEN equation (20 25 kcal/kg acute phase and 25 30 kcal/kg post-acute phase), using several BW: anamnestic (BWAN), measured (BWMES), adjusted for water balance (BWADJ) and ideal BW calculated for a body mass index of 22.5 and 25 kg/m2. Results are presented as mean±SD. Calculated EE was compared to EE measured by IC, with ANOVA repeated measure and Bonferroni post-hoc test, as well as Bland Altman analysis Results: We included 85 patients (57±19 y, 61 men, SAPS II 50±14), including 47 in acute phase. EE calculated with BWAN, BWADJ and BWMES significantly overestimated measured EE by IC (1910±458 kcal/d; p < 0.0001). Differences of calculated EE were statistically significant between the various BW used (p < 0.0001).

Correlation of weight-based i.v. immune globulin doses with changes in serum immunoglobulin G levels.

Correlations between the i.v. immune globulin (IVIG) dose and the change in serum immunoglobulin G (IgG) concentration with three methods of weight-based dosing were investigated. A retrospective medical records review was conducted to identify patients in a multicenter healthcare system who received IVIG over a 10-year period and had serum IgG measurements within two days before and two days after the date of IVIG administration. For each of the 11 adults and 7 adolescents identified, the relationship between the weight-based dose of IVIG (determined using actual body weight [BW], adjusted BW, or ideal BW [IBW]) and the resulting change in serum IgG was evaluated. Correlation coefficients and corresponding p values for the three dosing methods were calculated and compared. Among adult patients, the correlation of IVIG dose and postdose change in serum IgG was strongest with dosing by IBW (correlation coefficient [r], 0.83 [p < 0.05] versus r values of 0.73 and 0.70 for dosing by adjusted BW or actual BW, respectively [p = 0.05 for both]); the corresponding r values in adolescent patients were 0.99, 0.99, and 0.95, respectively (p < 0.005 for all). There were no statistically significant differences between the r values calculated for the three weight-based dosing methods in either adults or adolescents. In adult patients, the correlation between the dose of IVIG and the change in IgG level was strongest when doses were calculated using IBW; comparable degrees of correlation were observed with the three evaluated methods of weight-based dosing in the adolescent population.

Estimation of body weight and development of a body weight score for adult equids using morphometric measurements1

Excessive BW has become a major health issue in the equine (Equus caballus) industry. The objectives were to determine if the addition of neck circumference and height improved existing BW estimation equations, to develop an equation for estimation of ideal BW, and to develop a method for assessing the likelihood of being overweight in adult equids. Six hundred and twenty-nine adult horses and ponies who met the following criteria were measured and weighed at 2 horse shows in September 2011 in Minnesota: age ≥ 3 yr, height ≥ 112 cm, and nonpregnant. Personnel assessed BCS on a scale of 1 to 9 and measured wither height at the third thoracic vertebra, body length from the point of shoulder to the point of the buttock, neck and girth circumference, and weight using a portable livestock scale. Individuals were grouped into breed types on the basis of existing knowledge and were confirmed with multivariate ANOVA analysis of morphometric measurements. Equations for estimated and ideal BW were developed using linear regression modeling. For estimated BW, the model was fit using all individuals and all morphometric measurements. For ideal BW, the model was fit using individuals with a BCS of 5; breed type, height, and body length were considered as these measurements are not affected by adiposity. A BW score to assess the likelihood of being overweight was developed by fitting a proportional odds logistic regression model on BCS using the difference between ideal and estimated BW, the neck to height ratio, and the girth to height ratio as predictors; this score was then standardized using the data from individuals with a BCS of 5. Breed types included Arabian, stock, and pony. Mean (± SD) BCS was 5.6 ± 0.9. BW (kg) was estimated by taking [girth (cm)(1.48)6 × length (cm)(0.554) × height (cm)(0.599) × neck (cm)(0.173)]/3,596, 3,606, and 3,441 for Arabians, ponies, and stock horses, respectively (R(2) = 0.92; mean-squared error (MSE) = 22 kg). Ideal BW (kg) was estimated by taking [length (cm) × 2.8] + [height (cm) × 4.2] - 611, 606, and 577 for Arabians, ponies, and stock horses, respectively (R(2) = 0.86; MSE = 24). Equids with a BCS of ≥ 7 had a greater likelihood of being overweight, and the model suggested cutoffs at the 48th and 83rd percentiles for underweight and overweight individuals, respectively. Morphometric measurements were successfully used to develop equid BW-related equations.

Effect of Body Weight Loss on Cardiopulmonary Function Assessed by 6‐Minute Walk Test and Arterial Blood Gas Analysis in Obese Dogs

BackgroundFew studies show the detrimental effect of canine obesity on cardiopulmonary function (CPF). The 6‐Minute Walk Test (6MWT) is a noninvasive exercise test easy to perform in clinical settings.ObjectiveThe aim of this study was to investigate the effect of obesity and body weight loss (BWL) on CPF assessed by the 6MWT and arterial blood gas analysis.AnimalsSix experimental Beagles and 9 privately owned obese dogs were enrolled in a diet‐induced BWL program.MethodsArterial blood gas analysis and 6MWT were repeated in obese subjects (BCS 8‐9/9), in the middle of BWL (overweight, BCS 6‐7/9), and in lean dogs (BCS 5/9). Heart rate (HRp) and oxygen saturation (SpO2) were measured by pulse oximetry before the 6MWT, at midtest, and during a 5‐minute recovery period.ResultsTwelve dogs completed the BWL program (initial BW, 27.3 ± 2.9 kg; final BW, 20.85 ± 2.9, lsmeans ± SE, P ≤ .001). BWL caused a significant increase in 6MWT walked distance (WD; obese: 509 ± 35 m; overweight: 575 ± 36 m; lean: 589 ± 36 m; P ≤ .05). Resting arterial blood gas results were not influenced by BWL. Including all time points, obese dogs showed higher HRp and lower SpO2 compared to overweight and lean dogs. SpO2 at the end of the walk was significantly lower in obese dogs.Conclusion and Clinical ImportanceObesity negatively affects 6MWT performances in dogs. The 6MWT may be used to demonstrate the efficacy of BWL to improve CPF and quality of life in obese dogs. Although BWL induced significant improvement of cardiopulmonary parameters before ideal BW, WD improved until the end of the BWL program.

Phase I Trial of Escalated Doses of Targeted Marrow Radiation Delivered by Tomotherapy Combined with Etoposide and Cyclophosphamide; An Allogeneic HCT Preparative Regimen for Patients with Advanced Leukemia

AbstractAbstract 218 Background:Overall survival (OS) for acute leukemia in relapse (RL) or induction failure (IF) treated with HCT is 16–19% (Duval et al., JCO 2010). While randomized studies have shown a dose response relationship, with higher doses of radiation resulting in decreased relapse, this benefit is offset by increased treatment related mortality. Patients and Methods:To explore the safety and tolerability of targeted radiation treatment in the context of HCT, a phase I trial is being conducted in which escalated doses of targeted whole body radiation is delivered to marrow bearing and lymphoid areas, while sparing non hematopoietic (vital) organs. The transplant preparative regimen is as follows: tomotherapy on days −10 to −6; etoposide 60mg/kg [adj bw] on day −5 with cyclophosphamide 100mg/kg [ideal bw] on day −3. The radiation dose was started at 1200cGy delivered in 150 cGy fractions twice a day. As part of the design, the dose of radiation was escalated in increments of 150 cGy until 1500 cGy and then 100 cGy incrementally using cohorts of three until ultimately dose limiting toxicity is reached according to the Bearman and CTCAE 3.0 (for hematologic toxicity) scales. Liver and brain dose was kept at 1200 cGy. Normal organs received 17–62% of the marrow dose (lung 47%, esophagus 35% and oral cavity 28%). All patients received peripheral blood stem cells on day 0. GVHD prophylaxis consisted of tacrolimus and sirolimus. Results:To date, a total of 26 patients have been transplanted; from 3/14/2008 to 2/9/2012. Additional patient characteristics are as follows:Age median 33y (20–54y)AML n=12, ALL Ph- n=10, ALL Ph+ n=2, Biphenotypic n=2Disease status at HCT, 1RL n=9, 2RL n=2, IF n=15Cytogenetic risk: intermediate n=13, unfavorable n=8 and information not available n=5KPS at HCT median 80 (70–100)Donor source sibling n=13, HLA matched related n=6, mismatched (1 allele) unrelated n=7WBC at HCT median 1.9 (0.1–14.9)blasts (blood) at HCT median 0.5% (0–85%)blasts (marrow) at HCT median 46% (10–85%)Two patients presented with extramedullary disease at time of HCT.With a median follow-up for alive patients of 16.1 months (5.3–47.7), the OS and cumulative incidence of relapse/progression at 1 year are 55% (95%CI: 44–65) and 34.6% (95%CI: 17.1–52.9) respectively. Five patients have been treated at 1600 cGy, the current dose level being tested, without reaching DLT. Twenty-two patients (85%) achieved CR at their day 30 post transplant evaluation. Twelve (46%) of patients developed acute GvHD; 5(42%) of these developed grades 3–4. The day 30 and day 100 NRM was 0% and 8% respectively. The most common toxicity across the dose levels tested is grade 2 stomatitis (Bearman Scale). Causes of death were disease progression/persistent disease n=10, GvHD n=2 and infection n=1. Conclusion:These results are encouraging and suggest that 1) doses of targeted whole body, marrow and lymphoid radiation delivered by Tomotherapy can be safely escalated to 1600 cGy in combination with etoposide and cyclophosphamide (DLT not reached and dose escalation continues); and that 2) a reduction in relapse/progression compared to published reports can be achieved without increasing NRM in this high risk population. Disclosures:No relevant conflicts of interest to declare.

Effects of tumor type, degree of obesity, and chemotherapy regimen on chemotherapy dose intensity in obese cancer patients

The American Society of Clinical Oncology recently published a Clinical Practice Guideline entitled "Appropriate Chemotherapy Dosing for Obesity Adult Patients with Cancer." The panel recommended that full weight (actual weight)-based cytotoxic chemotherapy doses are used to treat obese patients with cancer, particularly when the goal of treatment is cure. However, no study has examined dosage calculation methods used for obese cancer patients in Japan. Here, we retrospectively studied the relationships between chemotherapy dose intensity, the occurrence of adverse events, and treatment outcomes in obese patients undergoing chemotherapy. Patients were divided into two groups: the actual BW group (BWg) was composed of patients receiving dosage amounts calculated using their actual BW (n = 64), and the ideal BWg was composed of patients receiving dosage amounts calculated using their ideal BW (n = 41). There were significant differences in the incidence of Grade 3/4 hematological toxicity in the actual and ideal BWg in solid tumor patients, but not in patients with hematological malignancies. In solid tumor patients with ≥30 body mass index (BMI), the incidence of Grade 3/4 hematological toxicity was significantly lower in the ideal BWg than in the actual BWg. Particularly, in patients with complications, incidence of Grade 4 hematological toxicity was significantly higher in the actual BWg than in the ideal BWg. These results suggest that the tumor type, degree of obesity, complications, and choice of chemotherapy regimen should be considered when determining chemotherapy dosage for obese patients.

EVALUATION OF NUTRITIONAL STATUS IN PERITONEAL DIALYSIS (PD) PATIENTS

In 2009, analysis of the French Language Peritoneal Dialysis Registry (RDPLF) data revealed that 6 patients out of 355 (1,7%) were transferred to HD because of malnutrition after a median period of 31 months. Furthermore, malnutrition was responsible for the death of 5.1 % patients after a median period of 14 months. So, as nutritional status has been shown to impact morbidity and mortality of dialysis patients, we set out to measure this status in incident PD patients of 2 European centers using various validated methods. The techniques used were: anthropometric,BMI and biochemical measurements, SGA, Brandes score, total (renal and peritoneal) creatinine excretion, dietician records, handgrip strength, DEXA, multifrequency electrical bioimpedance (TBIA). Daily dietary protein intake was less than 1g/kg ideal BW in 35 % of pts while 38% ate more than 1.2 g/kg; daily total (oral and peritoneal) caloric intake was 28±8 kcal/kg. Fifteen % of patients (median age 71) had a very low serum albumin level ( 50 g/l (median age 64 years). Very significant correlations were found between: 1) estimation of fat mass by skinfold thickness and that modelised from the water volume determined by TBIA (r²: 0.56, p

COMPANION ANIMALS SYMPOSIUM: Obesity in dogs and cats: What is wrong with being fat?1

Few diseases in modern pets are diet induced. One possible exception to this is obesity, which is ultimately caused by consuming more calories than needed by the dog or cat. Although fat is the most concentrated and efficiently stored source of calories, and protein least so, an excess of calories from any source will contribute to adiposity. Obesity is an excess of body fat sufficient to result in impairment of health or body function. In people, this is generally recognized as 20 to 25% above ideal BW. This degree of excess is important in dogs as well. A lifelong study in dogs showed that even moderately overweight dogs were at greater risk for earlier morbidity; these dogs required medication for chronic health problems sooner than their lean-fed siblings. The average difference in BW between groups was approximately 25%. Obese cats also face increased health risks, including an increased risk of arthritis, diabetes mellitus, hepatic lipidosis, and early mortality. The risk for development of diabetes increases about 2-fold in overweight cats and about 4-fold [corrected] in obese cats. Altered adipokine secretion appears to be an important mechanism for the link between excess BW and many diseases. Once considered to be physiologically inert, adipose tissue is an active producer of hormones, such as leptin and resistin, and cytokines, including many inflammatory cytokines such as tumor necrosis factor-α, IL-1β and IL-6, and C-reactive protein. The persistent, low-grade inflammation secondary to obesity is thought to play a causal role in chronic diseases such as osteoarthritis, cardiovascular disease, diabetes mellitus, and others. For example, tumor necrosis factor-α alters insulin sensitivity by blocking activation of insulin receptors. In addition, obesity is associated with increased oxidative stress, which also may contribute to obesity-related diseases. Management of obesity involves nutritional modification as well as behavioral modification. Increased protein intake combined with reduced calorie intake facilitates loss of body fat while minimizing loss of lean body mass. Limiting treats to 10% of calorie intake and increasing exercise both aid in successful BW management.

Phase I Trial of Escalated Doses of Targeted Marrow Radiation Delivered By Tomotherapy Combined With Etoposide and Cyclophosphamide; an Allogeneic HCT Preparative Regimen for Patients With Advanced Leukemia

Overall survival (OS) for acute leukemia in relapse (RL) or induction failure (IF) treated with HSCT is 16-19% [Duval et al JCO.2010]. While randomized studies have shown a dose response relationship, with higher doses of radiation resulting in decreased relapse, this benefit is offset by increased mortality. We report the initial results of a Phase I trial of 12 patients transplanted between 3/2008 and 7/2010 in which escalated doses of targeted whole body radiation to marrow bearing areas delivered by Tomotherapy on days -10 to -6 was added to etoposide 60mg/kg [adj bw] day -5 and cyclophosphamide 100mg/kg [ideal bw] day -3.