Adjusted Body Weight Research Articles

Evaluation of carboplatin toxicities and efficacy using different body weight descriptors in the Calvert formula.

e14017 Background: Carboplatin dosing is calculated using the Calvert formula that includes glomerular filtration rate (GFR). In practice, GFR is often substituted by creatinine clearance (CrCl) with the Cockcroft-Gault (CG) equation. However, there is no standardization of which body weight descriptors should be utilized. Data suggest use of total body weight (TBW) may overestimate CrCl in overweight patients, while adjusted body weight may better estimate CrCl. The primary objective is to determine the impact of using different weight descriptors (DWD) in place of TBW for carboplatin dosing. Methods: This was a single-center, retrospective cohort study. Patients over 18 who were intended to receive at least 6 cycles of carboplatin with target area under the curve (AUC) of 5 or 6 and paclitaxel 175 to 225 mg/m2 were included. DWD included: adjusted body weight for overweight and obese patients, ideal body weight for normal weight patients and TBW for underweight patients. Primary endpoint was the composite of grade 3 or 4 anemia, thrombocytopenia and neutropenia (hematologic toxicity). Secondary endpoints included individual parameters of the primary endpoint, dose delays, dose reductions, progression-free survival, overall survival and objective response rate. Results: A total of 117 patients were included (DWD: n = 39; TBW: n = 78). Results on survival analysis, anemia and dose reductions are pending. Conclusions: To our knowledge, this is the first evaluation of patient outcomes specifically comparing carboplatin dosing calculations. Although there is a trend toward decreased grade 3 and 4 hematologic toxicities in the DWD group, there is no statistically significant difference in this under powered cohort. However, there was a significant decrease in treatment delays and days of treatment delay (p < 0.001) in the DWD group. Further studies are needed to evaluate the impact of DWD on carboplatin dosing. [Table: see text]

Changes of renal sinus fat and renal parenchymal fat during an 18-month randomized weight loss trial

Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma. We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging. Participants (age=48 years; 89% men; body-mass-index=31kg/m2) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend<0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus-fat (-9%; p<0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p=0.13 vs. baseline) significantly decreased, and similarly across the intervention groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with weight-loss per-se (p<0.05). In a model adjusted for age, sex, and visceral-adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with decreased pancreatic, hepatic and cardiac fats (p<0.05 for all) and with decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (β=0.13; p=0.05), triglycerides/HDL-c (β=0.13; p=0.05), insulin (β=0.12; p=0.05) and gamma glutamyl transpeptidase (β=0.24; p=0.001), but not with improved renal function parameters or blood pressure. Decreased intake of sodium was associated with a reduction in %renal-parenchymal-fat, after adjustment for 18 months weight-loss (β=0.15; p=0.026) and hypertension (β=0.14; p=0.04). Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic parameters, independent of changes in weight or hepatic fat, rather than with improved renal function or blood pressure parameters. CLINICALTRIALS. NCT01530724.

Multiple-transportable Carbohydrate Has Minimal Impact On Long-distance Triathlon Race Performance

PURPOSE: In the laboratory, the ingestion of multiple-transportable carbohydrates (fructose, glucose) in beverages at high rates (>1.3 g·min-1) enhances exogenous carbohydrate oxidation, fluid absorption, gut comfort, and performance, relative to single carbohydrate equivalents. In competition, however, endurance athletes prefer to ingest carbohydrate in a solid-gel-drink format but whether multiple-transportable carbohydrates in the mixed format also enhance competition performance is unknown. The objective of the study was to determine the effect of multiple- vs. single-transportable carbohydrate on triathlon race performance when ingested in the common format of bars, gels and drinks. METHODS: A double-blind randomized controlled trial was conducted within two sanctioned half-ironman triathlon races held 3 weeks apart in 74 well-trained male triathletes (18-60 y; >2 y competition experience). Carbohydrate was ingested before (94 g) an during the race from bars (25%), gels (35%) and drink (40%) comprising a 2:1 glucose/maltodextrin:fructose ratio vs isocaloric placebo glucose/maltodextrin only. Ingestion was apportioned by unit-distance covered during the cycle (2.5 g·km-1) and run (7.8 g·km-1) averaging 78.6 g·h-1 (SD 6.6). Post-race 0-10 unit Likert-type scales were completed to assess gut comfort and energy. RESULTS: The trial returned low dropout rate (9%), high compliance and sensitivity (typical error 2.2%), but the effect of the multiple-transportable carbohydrate on overall performance time (-0.6%, 95%CI -1.8%, 0.7%), swim, bike, and run times, and on nausea, gut comfort and perceived energy was of trivial-small magnitude without statistical significance. Within-subject covariate adjustment for pre-exercise body weight, heat stress, and within-race change in body weight had negligible impact on outcomes. CONCLUSION: Multiple-transportable carbohydrate ingested in the common bar-gel-drink format provided negligible benefit to long-distance triathlon performance. The experience of the large sample intervention study showed that in-competition clinical trials offer ecological validity, and high throughput rate, compliance, and sensitivity for evaluation of health and performance interventions in athletes. Funding: Nestec Ltd, Switzerland.

Associations of Dietary Protein and Energy Intakes With Protein-Energy Wasting Syndrome in Hemodialysis Patients

IntroductionThe associations of dietary protein and/or energy intakes with protein or energy wasting in patients on maintenance hemodialysis are controversial. We examined these in the Hemodialysis (HEMO) Study.MethodsIn 1487 participants in the HEMO Study, baseline dietary protein intake (grams per kilogram per day) and dietary energy intake (kilocalories per kilograms per day) were related to the presence of the protein-energy wasting (PEW) syndrome at month 12 (defined as the presence of at least 1 criteria in 2 of the 3 categories of low serum chemistry, low body mass, and low muscle mass) in logistic regression models. In additional separate models, protein intake estimated from equilibrated normalized protein catabolic rate (enPCR) was also related to the PEW syndrome.ResultsCompared with the lowest quartile, the highest quartile of baseline dietary protein intake was paradoxically associated with increased risk of the PEW syndrome at month 12 (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 2.79–6.05). This relationship was completely attenuated (OR: 1.35; 95% CI: 0.88–2.06) with adjustment for baseline body weight, which suggested mathematical coupling. Results were similar for dietary energy intake. Compared with the lowest quartile of baseline enPCR, the highest quartile was not associated with the PEW syndrome at 12 months (OR: 0.78; 95% CI: 0.54–1.12).DiscussionThese data do not support the use of dietary protein intake or dietary energy intake criteria in the definition of the PEW syndrome in patients on maintenance hemodialysis.

Energy expenditure in people with motor-complete paraplegia.

The present descriptive clinical and laboratory study is cross-sectional in design. The primary aim is to describe and compare resting energy expenditure (REE) and energy expenditure (EE) during different standardized sedentary, non-exercise and exercise activities in people with motor-complete paraplegia (Th7 to Th12.). A secondary aim was to compare men and women. Thirty-eight adults (10 women) with SCI, T7-T12 AIS A-B, were recruited. All the data were collected through indirect calorimetry. REE was measured in supine for 30 min after 8 h of overnight fasting. Activity energy expenditure (AEE) for activities was measured for seven minutes during sedentary, non-exercise physical activity (NEPA) and exercise activities. AEE increased four to eight times when engaging in NEPA compared to that in sedentary activities. Men had significantly higher resting oxygen uptake compared to women, 0.19 vs 0.15 l min-1 (P=0.005), REE per 24 h, 1286 vs 1030 kcal (P=0.003) and EE during weight-bearing activities. However, these became nonsignificant after adjustment for body weight and speed of movement, with a mean resting oxygen uptake of 2.47 ml O2 per kg min-1 for the whole group (women 2.43 and men 2.57 ml O2 kg-1 min-1, P=0.49). NEPA increases AEE up to eight times compared to sedentary activities. Gender differences in oxygen uptake during both rest and weight-bearing activities were diminished after adjustment for body weight. The mean resting oxygen uptake for the whole group was 2.47 ml O2 kg-1 min-1. These results highlight the importance, especially of NEPA, for increasing total daily EE in the target population.

Daily cumulative hip load is associated with radiographic progression of secondary hip osteoarthritis

Purpose: Hip osteoarthritis (OA) is a chronic disease; however, the mechanical risk factor during gait for hip OA progression has not been identified. The purpose of this study was to evaluate the association between mechanical load during gait at baseline and subsequent radiographic progression of hip OA over 12 months. Methods: Fifty patients with secondary hip OA except for end-stage hip OA participated in this prospective cohort study. To assess the change in joint space width (JSW), films at baseline and approximately 12 months later were paired by patients but blinded as to patient and sequence to the reader to avoid bias. Radiographic progression of hip OA was defined as reduction of more than 0.5 mm per year in JSW. Intrarater reliability [ICC (1,1)] of the JSW measurement was 0.99, and minimum detectable change of the JSW was 0.39. With radiographic progression of hip OA as dependent variable (yes/no), univariate and multivariate logistic regression analyses were performed. Independent variables were age, body weight, hip pain (visual analog scale), radiographic variables (CE angle, Sharp angle, acetabular head index, and acetabular roof obliquity), hip impairments (range of motion and muscle strength), and gait-related variables. Gait-related variables were recorded using an 8-camera Vicon motion system at a sampling rate of 200 Hz, and using force plates at a sampling rate of 1,000 Hz. A total of 20 reflective markers were placed by a single experienced examiner. At least 3 successful trials for each patient were recorded for analysis. Gait-related variables included steps per day, gait speed, peak hip joint moment, hip joint moment impulse, and daily cumulative hip load in 3 planes. The number of steps was recorded by a pedometer for 7 consecutive typical days within a month from the day of gait analysis. Daily cumulative hip load was calculated as a product of the non-normalized hip moment impulse in each of 3 planes and the mean number of steps per day for the affected limb (number of steps/day divided by 2). The criterion for inclusion in multivariate analysis was P < 0.1 in univariate logistic regression analysis. Since age and body weight at baseline can be potential confounders, those 2 variables were included in the multivariate model. A P value < 0.05 was considered statistical significant. Results: Of the 50 patients, 21 (42.0%) were classified into the progression group. Change in JSW in the progression group was 1.3 ± 0.8 mm. In univariate logistic regression analysis, increased daily cumulative hip load in the frontal plane at baseline was significantly associated with progression of hip OA (p = 0.038). On average, the cumulative hip load in the frontal plane in the progression group was approximately 1.4 times higher than that in the no progression group (Fig. 1). Minimum JSW (p = 0.066) and steps per day (p = 0.062) were also potential variables for multivariate logistic regression analysis (Fig. 1). The correlation coefficient (ρ = 0.74) between steps per day and daily cumulative hip load in the frontal plane was over the threshold for multicollinearity. Therefore, minimum JSW and daily cumulative hip load in the frontal plane were entered into multivariate logistic regression analysis. In multivariate analysis, reduced minimum JSW and increased daily cumulative hip load in the frontal plane at baseline were associated with radiographic hip OA progression independently. Even after adjustment for age and body weight, minimum JSW and daily cumulative hip load in the frontal plane were remained in the model (Table 1). Conclusions: This study provides evidence that higher daily cumulative hip load at baseline, particularly in the frontal plane, is associated with radiographic progression of hip OA defined by a > 0.5-mm cartilage thickness loss in 12 months. Our findings will help identify patients with higher risk of hip OA progression and clarify the target of intervention to slow hip OA progression.Table 1Multivariate logistic regression predicting the progression of hip osteoarthritisOR (95% CI)P-valueOR (95% CI) adjusted for age and body weightP-valueMinimum JSW at baseline (mm)0.63 (0.40–0.99)0.0460.49 (0.25–0.94)0.031Daily cumulative hip load in frontal plane (kNm seconds)1.02 (1.00–1.04)0.0301.03 (1.01–1.05)0.013 Open table in a new tab

Exploring some intersections between pharmacokinetics, factor VIII measurement and human morphometrics – impact of recent advances in haemophilia study design on our understanding of optimal haemophilia treatment

Exploring some intersections between pharmacokinetics, factor <scp>VIII</scp> measurement and human morphometrics – impact of recent advances in haemophilia study design on our understanding of optimal haemophilia treatment

Impact of carbohydrate restriction in the context of obesity on prostate tumor growth in the Hi-Myc transgenic mouse model.

IntroductionPreviously, we showed that carbohydrate restriction with calorie restriction slowed tumor growth in xenograft mouse prostate cancer models. Herein, we examined the impact of carbohydrate restriction without calorie restriction on tumor development within the context of diet-induced obesity in the Hi-Myc transgenic mouse model of prostate cancer.MethodsMice were randomized at 5 weeks of age to ad libitum Western diet (WD; 40% fat, 42% carbohydrate; n=39) or ad libitum no carbohydrate ketogenic diet (NCKD; 82% fat, 1% carbohydrate; n=44). At age 3 or 6 months, mice were sacrificed, prostates weighed and prostate histology, proliferation, apoptosis, and macrophage infiltration evaluated by H&E, Ki67, TUNEL and F4/80 staining, respectively. Body composition was assessed by DEXA, serum cytokines measured using multiplex, and Akt/mTOR signaling assessed by Western.ResultsCaloric intake was higher in the NCKD group, resulting in elevated body weights at 6 months of age, relative to the WD group (45g vs. 38g; p=0.008). Despite elevated body weights, serum MCP-1 and IL-1α levels were lower in NCKD versus WD mice (p=0.046 and p=0.118, respectively), and macrophage infiltration was reduced in prostates of NCKD versus WD mice (p=0.028). Relative Akt phosphorylation and phospho-S6 ribosomal protein levels were reduced in prostates of NCKD versus WD mice. However, while mice randomized to NCKD had smaller prostates after adjustment for body weight at 3 and 6 months (p=0.004 and p=0.002, respectively), NCKD mice had higher rates of adenocarcinoma at 6 months compared to WD mice (100% vs. 80%, p=0.04).ConclusionsDespite higher caloric intake and elevated body weights, carbohydrate restriction lowered serum MCP-1 levels, reduced prostate macrophage infiltration, reduced prostate weight, but failed to slow adenocarcinoma development. Together, these data suggest that although carbohydrate restriction within the context of obesity may reduce obesity-associated systemic inflammation, it is not sufficient to counteract obesity-associated tumor growth.

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing.

Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966-July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs' properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients.

Daily cumulative hip moment is associated with radiographic progression of secondary hip osteoarthritis.

To investigate whether higher daily cumulative hip moment at baseline is associated with subsequent radiographic progression of hip osteoarthritis (OA) over 12 months. Fifty patients with secondary hip OA, excluding patients with end-stage hip OA, participated in this prospective cohort study. Joint space width (JSW) of the hip was measured at baseline and 12 months later. With radiographic progression of hip OA (>0.5mm/year in JSW) as dependent variable (yes/no), univariable and multivariable logistic regression analyses were performed to assess the association between load-related parameters during gait (i.e., peak hip moment, hip moment impulse, and daily cumulative hip moment [product of hip moment impulse and mean steps/day]) and hip OA progression with and without adjustment for age, body weight, and minimum JSW. Of the 50 patients (47.4±10.7 years old), 21 (42.0%) were classified into the progression group. The higher daily cumulative hip moment in the frontal plane at baseline was statistically significantly associated with radiographic progression of hip OA (adjusted odds ratio (OR) [95% confidence interval (CI)], 1.34 [1.06-1.70]; P=0.013). The higher daily cumulative hip moment in the sagittal plane was also approaching significance in its association with hip OA progression (adjusted OR, 1.80 [0.99-3.26]; P=0.052). In the female patients with secondary hip OA, higher daily cumulative hip moment, particularly in the frontal plane, was a predictor of radiographic progression of hip OA over 12 months. Reduction in daily cumulative hip moment by modification in gait and physical activity may potentially slow hip OA progression.

Therapeutic drug monitoring and use of an adjusted body weight strategy for high-dose voriconazole therapy.

A high-dose 12 mg/kg/day (6 mg/kg twice daily) voriconazole regimen was recommended by the CDC to treat patients injected with contaminated methylprednisolone acetate that caused a multi-state fungal outbreak in 2012-13. Therapeutic drug monitoring results of this unique regimen are unknown, as is the most appropriate dosing weight for obese patients. We evaluated voriconazole trough measurements for this dosing scheme, as well as the use of adjusted body weight dosing for obese patients. Voriconazole trough levels were analysed in obese (BMI ≥35 kg/m 2 ) and non-obese (BMI <35 kg/m 2 ) patients who were given initial therapy with 12 mg/kg/day. Of 138 patients, the first steady-state voriconazole troughs were supratherapeutic (>5 mg/L) in 65 (47%) patients, therapeutic (2-5 mg/L) in 57 (41%) patients and subtherapeutic (<2 mg/L) in 16 (12%) patients. Twenty-three patients had pre-steady-state dose decreases due to supratherapeutic levels, with subsequent first steady-state troughs in the therapeutic ( n = 17) and subtherapeutic ( n = 6) categories. Voriconazole doses >11 and >8 mg/kg/day produced mainly first steady-state supratherapeutic troughs in 44 obese and 94 non-obese patients, respectively. An initial 12 mg/kg/day was progressively lowered to a median maintenance dose of 8.5 mg/kg/day in the obese and 8.6 mg/kg/day in the non-obese. A high-dose voriconazole regimen produced initial supratherapeutic troughs that required dose adjustment downward by nearly 30%. Adjusted body weight dosing in obese patients resulted in a similar maintenance dose to total body weight dosing in the non-obese, and appears to be a sensible dosing strategy for these patients.

Fatness vs Fitness with Cardio-Metabolic Risk Factors in Adolescents from the Western Australian Pregnancy (Raine) Cohort Study

The aim of this study was compare the concurrent influences of cardiorespiratory fitness and fatness with a range of cardio-metabolic risk factors in adolescents aged 17 years from the Western Australian Pregnancy (Raine) Cohort Study. Fatness was determined from waist circumference. Cardiorespiratory fitness was estimated from heart rate recordings during sub-maximal cycle ergometry with adjustment for body weight. Fatness and fitness were assessed as continuous measures to avoid the use of arbitrary cut points. Linear regression analysis methods were employed. Fatness was positively associated with systolic blood pressure (p < 0.001), triglycerides (p < 0.001), LDL-C (p = 0.007) and hs-CRP (p < 0.001). Fatness also increased the risk of being pre-hypertensive or hypertensive (p = 0.001). There were no significant associations of fitness on any of these outcomes. A positive association between HOMA-IR and fatness (p < 0.001) was attenuated by fitness (p < 0.001). Fatness was inversely associated with HDL-C in both sexes (p < 0.001), while fitness was positively associated with HDL-C only in females (p = 0.03). Fitness was inversely associated with diastolic blood pressure (p < 0.001) whereas there was no association with fatness. This study has shown that fitness attenuated the adverse effects of fatness on selected cardio-metabolic risk factors; however, fatness had generally stronger associations with an adverse cardio-metabolic profile in this population of adolescents. Strategies to avoid excessive weight gain will need to focus on both eating patterns and physical activity in earlier childhood to minimise the risk of cardiovascular and metabolic disease in later life.

Changes in body weight and food security of adult North Korean refugees living in South Korea.

BACKGROUND/OBJECTIVESRelocation to new environments can have a negative impact on health by altering body weight and dietary patterns. This study attempted to elucidate changes in body weight, food security, and their current food and nutrient consumption in adult North Korean refugees (NKR) living in South Korea (SK).SUBJECTS/METHODSThis study analyzed data on 149 adult NKR from a North Korean refugee health in SK cohort at four time points (leaving North Korea, entering SK, first examination, and second examination). Body weight was self-reported at the two earlier time points and directly measured at the two later time points. Food security, diet-related behaviors (dietary habits and food consumption), and sociodemographic information were obtained using a self-administered questionnaire. Nutrient intake information was obtained by one-day 24-hour recall. Statistical analyses were performed with SPSS ver 23.0.RESULTSBody weight increased during relocation by an average of 4 kg, although diversified patterns were observed during the settlement period in SK. Approximately 39.6% of subjects maintained their body weight between the first and second examinations, whereas 38.6% gained and 22.1% lost at least 3% of their body weight at the first examination by the second examination. Food security status improved from 12.1% food secure proportion to 61.7%. NKR showed generally good food and nutrient consumption (index of nutrient quality: 0.77–1.93). The body weight loss group showed the most irregular meal consumption pattern (P < 0.05), and eating-out was infrequent in all three groups. Consumption frequencies of food groups did not differ by group, except in the fish group (P = 0.036).CONCLUSIONThis study observed considerable body weight adjustment during the settlement period in SK after initial weight gain, whereas food security consistently improved. More detailed understanding of this process is needed to assist healthy settlement for NKR in SK.

Impact of Obesity in Patients with Multiple Myeloma Receiving High-Dose Melphalan Followed By Autologous Hematopoietic Cell Transplantation

▪Background: Chemotherapy administration to obese patients poses significant challenges due to the potential for augmented toxicities. There are limited guidelines and literature available on the dosing of high-dose therapy followed by autologous hematopoietic cell transplantation (HCT) in obese patients and dosing practices vary widely. We conducted a single-center, retrospective cohort study to compare outcomes and toxicities after high-dose melphalan followed by autologous HCT among non-obese (body mass index [BMI] < 30 kg/m2), obese (BMI 30-34.9 kg/m2), and severely obese (BMI ≥ 35 kg/m2) multiple myeloma patients.Patients and Methods: A total of 462 consecutive patients transplanted between January 2004 and December 2011 were included. Patients who had received a tandem transplant and those with the diagnosis of amyloidosis were excluded. The primary endpoint of the study was to compare the incidence of non-relapse mortality (NRM) and overall survival (OS) rates across all three cohorts. Secondary endpoints included progression-free survival (PFS), incidence of relapse, hospital length of stay, hospital readmission rates, engraftment and grade 3 and 4 non-hematologic toxicities.Results: All three cohorts had similar baseline characteristics except for age ≤ 65 years (yrs) (severely obese 85.3%, obese 66.7%, non-obese 63%; p = 0.001), and the use of adjusted body weight for melphalan dosing (severely obese 41.2%, obese 25.7%, non-obese 4.5%; p < 0.0001). Across all three cohorts, there were no significant differences in NRM, relapse/progression, OS, PFS, engraftment, response to transplant, hospital length of stay, 30-day readmission rates, grade 3 to 4 nausea, vomiting, enteritis, or renal toxicity. In univariate analyses, Durie-Salmon Stage (DSS) 3 was the only independent predictor of inferior OS. DSS 3 and ≥ 2 lines of therapy were significant predictors of inferior PFS. In a multivariate analysis, DSS 3 (hazard ratio [HR] 2.28, 95% confidence interval [CI]: 1.01-5.13, p = 0.05), age > 65 yrs (HR 2.13, 95%CI: 1.19-3.82, p = 0.01), serum creatinine (Cr) ≥ 1 mg/dL were associated with higher NRM, whereas actual weight (AW) dosing was associated with decreased risk of NRM (HR 0.38, 95%CI: 0.19-0.72, p = 0.003). Additionally, age ≤ 65 yrs (HR 1.32, 95%CI: 1.03-1.71, p = 0.03), baseline serum Cr ≤ 1.5 mg/dL were associated with increased risk of relapse/progression, whereas disease status ≥ partial response prior to HCT (HR 0.71, 95%CI: 0.54-0.94, p = 0.02) and BMI ≥ 35 kg/m2 (HR 0.62, 95%CI: 0.44-0.87, p = 0.01) were associated with decreased risk of relapse/progression. In a subgroup analysis evaluating only patients with AW dosing of melphalan, febrile neutropenia was more common in non-obese patients compared to obese and severely obese patients (71.4% versus 56.4% and 62.5%, respectively; p = 0.03).Conclusions: High-dose melphalan and autologous HCT can be performed safely in obese myeloma patients and BMI of ≥ 30 kg/m2 does not appear to be associated with adverse transplant outcomes. Further analysis is needed to evaluate the effect of dose adjustments on outcomes. DisclosuresAlsina:Onyx: Speakers Bureau; Millenium Pharmaceuticals: Research Funding; Novartis: Research Funding; Signal Genetics: Consultancy; Onyx: Consultancy. Nishihori:Signal Genetics: Research Funding; Novartis: Research Funding.

Left Ventricular Function Assessed by One-Point Carotid Wave Intensity in Newly Diagnosed Untreated Hypertensive Patients.

To investigate whether newly diagnosed untreated hypertensive patients show higher left ventricular (LV) contractility, as assessed by traditional echocardiographic indices and carotid wave intensity (WI) parameters, including amplitude of the peak during early (W1 ) and late systole (W2 ). A total of 145 untreated hypertensive patients were compared with 145 age- and sex-matched normotensive subjects. They underwent comprehensive echocardiography and WI analysis. WI analysis was performed at the level of the common carotid artery. The diameter changes were the difference between the displacement of the anterior and posterior walls, with the cursors set to track the media-adventitia boundaries 2 cm proximal to the carotid bulb and calibrated by systolic and diastolic BP. Peak acceleration was derived from blood flow velocity measured by Doppler sonography with the range-gate positioned at the center of the vessel diameter. WI was based on the calculation of (dP/dt)×(dU/dt), where dP/dt and dU/dt were the derivatives of BP (P) and velocity (U) with respect to time. One-point pulse wave velocity (PWVβ) and the interval between the R wave on ECG and the first peak of WI (R-W1 ), using a high definition echo-tracking system implemented in the ultrasound machine (Aloka), were also derived. After adjustment for body weight, heart rate, and physical activity, the two groups had similar general characteristics and diastolic function. However, hypertensives showed significantly higher LV mass, LV ejection fraction (LVEF), circumferential and LV end-systolic stress, and one-point PWV as well as W1 (13.646 ± 7.368 vs 9.308 ± 4.675 mmHg m/s3 , P =.001) and W2 (4.289 ± 2.017 vs 2.995 ± 1.868 mmHg m/s3 , P =.001). Hypertensives were divided into tertiles according to LVEF: W1 (11.934 ± 5.836 vs 11.576 ± 5.857 vs 17.227 ± 8.889 mmHg m/s3 , P <.0001) was higher in the highest LVEF tertile along with relative wall thickness, midwall fractional shortening, endocardial fractional shortening, and R-W1 . Newly diagnosed hypertensives show increased LVM and LV contractility, including carotid WI parameters and R-W1 values, as compared with normotensive subjects, but no differences in LV diastolic function.

The Association between Renal Hyperfiltration and the Sources of Habitual Protein Intake and Dietary Acid Load in a General Population with Preserved Renal Function: The KoGES Study.

Although the differential response of the kidney to the acute load of various sources of dietary protein in subjects with normal renal function is well known, the influence of habitual dietary protein intake and dietary acid load on renal function has not been tested well. The association between renal hyperfiltration (RHF), the earlier and possibly reversible stage of chronic kidney disease, and the sources of habitual dietary protein and dietary acid load was analyzed with the baseline data of 123,169 middle-aged healthy Koreans of a large prospective cohort study, who had a baseline estimated glomerular filtration rate (eGFR) >60 mL/min/m2 and no known history of diabetes and/or hypertension. eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation using serum creatinine and RHF was defined as eGFR >95th percentile after adjustment for age, sex, height, and body weight. Dietary acid load was calculated with estimated net endogenous acid production (eNEAP). Although the level of habitual intake of animal protein was positively and vegetable protein was negatively associated with RHF, this association was significant only in women and younger participants (younger than sex-specific median age). The odds for RHF increased as the percentile rank of eNEAP increased until about the 50th percentile and then leveled off. The positive association between eNEAP and RHF was significant in both sexes and age groups. Dietary acid load was associated with RHF regardless of sex and age and rather than the amount of the total or the individual sources of habitual dietary protein, may be a better target for the dietary intervention of chronic kidney disease.

Association between renal function and chemotherapy-related toxicity in older adults with cancer.

To evaluate the association between renal function (RF) and chemotherapy-related toxicity (CRT) in older adults with cancer and to compare the effect of different RF formulas and body weight measurements on this association. This is a secondary analysis of data from a prospective multicenter study of patients ≥ age 65 who were starting a new chemotherapy regimen. RF was estimated with 4 formulas (modified Jelliffe [Jelliffe], Cockcroft-Gault [CG], Wright, and Modification of Diet in Renal Disease [MDRD]), using actual, ideal and adjusted body weights for 492 patients. The association between baseline RF and grade 3-5 CRT was evaluated by unconditional logistic regression. As a continuous variable, decreased creatinine clearance (CrCl) calculated by CG with actual body weight was associated with increased odds of CRT (OR 1.12, P<0.01; 95% CI 1.04-1.20) indicating that on average for every 10mL/min decrease in CrCl the odds of CRT increased by 12%. Very low RF (in the lowest 10%) with all formulas (CG, Jelliffe, Wright and MDRD) was associated with increased odds for CRT. This association is independent of the type of chemotherapy received (those requiring dose adjustment for renal function vs not). Neither primary dose reduction nor chemotherapy duration was associated with CRT. Serum creatinine alone was not associated with increased odds of CRT (OR 0.67, P=0.15). Decreased RF is associated with increased odds of CRT and should be considered when assessing risk of CRT in older adults with cancer. Serum creatinine alone is not adequate for risk assessment.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

Evaluation of heparin dosing based on adjusted body weight in obese patients

Results of a study to determine whether heparin dosing based on adjusted body weight (BWAdj) instead of actual body weight (ABW) can lead to faster achievement of therapeutic activated partial thromboplastin time (aPTT) values in obese patients are presented. A single-center retrospective cohort study was conducted to assess aPTT outcomes before and after implementation of a revised heparin protocol specifying BWAdj-based dosing for obese patients. The primary outcome was the percentage of first aPTT values within the target range after heparin initiation. Secondary outcomes included the median time to the first on-target aPTT and the rate of clinically significant bleeding. After protocol implementation, there was no significant difference between obese and nonobese patients in the primary outcome (17% and 21%, respectively, had first aPTT values in the target range) or in the median time to achieve the first on-target aPTT value. Among obese patients, on-target aPTT values were achieved significantly faster with BWAdj-versus ABW-based dosing (14 hours versus 24 hours, p = 0.002). Prior to implementation of BWAdj-based heparin dosing, obese patients had a higher rate of clinically significant bleeding than nonobese patients (11% versus 1%, p = 0.01); postimplementation bleeding rates did not differ significantly. The percentages of first aPTT values in the targeted range did not differ significantly in obese and nonobese patients before and after protocol implementation. The use of BWAdj for dose calculation in obese patients was associated with faster achievement of an aPTT value in the target range.

Repeated Water Avoidance Stress Alters Mucosal Mast Cell Counts, Interleukin-1β Levels with Sex Differences in the Distal Colon of Wistar Rats.

Background/AimsThis study was aimed at evaluating differences in the effects of repeated water avoidance stress (rWAS) on colonic movement, mucosal mast cell counts, cytokine levels, and visceromotor response (VMR) to colorectal distension (CRD) in rats of both sexes.MethodsWistar rats were divided into stress and no-stress groups. Rats in the stress group were exposed to rWAS (1 hr/day) for 10 days. Mucosal mast cells were immunohistochemically stained with anti-mast cell tryptase antibody and counted. The colonic mucosal cytokine levels were measured with enzyme-linked immunosorbent assay. The VMR to CRD (visceral analgesia) was assessed by using a barostat and noninvasive manometry.ResultsThe mean number of fecal pellets in the rWAS group increased significantly as compared with that in the no-stress group in both sexes. After adjustment for body weight, the female rats had a significantly higher pellet output than the male rats. The mucosal mast cell count of the female rWAS group was higher than that of the male rWAS group (13.0 ± 0.9 vs 8.8 ± 0.6; P < 0.001). The colonic mucosal interleukin-1β level was also higher only in the female rats of the rWAS group than in those of the no-stress group. On days 10 and 11, a decrease in VMR to CRD was observed at 40 and 60 mmHg in both sexes of the rWAS group, without a sex-based difference.ConclusionsThe colonic response to stress appeared to be more sensitive in the female rats than in the male rats. However, stress-induced visceral analgesia had no sex-related difference and the underlying mechanism needs to be further evaluated.