Whole Body Irradiation Induces Diabetes and Adipose Insulin Resistance in Nonhuman Primates.

PURPOSE: Diabetes mellitus is a delayed effect of radiation exposure in human and nonhuman primates. Diabetes mellitus is characterized by peripheral tissue insulin resistance, and as a result, irradiation exposure may cause important changes in insulin-sensitive tissues such as muscle and adipose. METHODS AND MATERIALS: We prospectively investigated changes in response to irradiation (4 Gy whole body exposure) in 16 male rhesus macaques. We evaluated changes in body composition and glycemic control for 2 years. Insulin responsiveness, lipolysis, inflammation, and fibrosis were evaluated at study end. RESULTS: Irradiated animals accumulate less fat and significantly increased percent glycation of hemoglobin A1c over time, such that 40% of irradiated monkeys had values that define them as diabetic at 2 years. Subcutaneous (SQ) adipose tissue was insulin resistant, as evidenced by reduced phosphorylation of the insulin receptor substrate-1 in response to insulin challenge and had increased basal lipolysis despite comparable insulin exposures to control animals. Irradiated SQ adipose tissue had more macrophage infiltration and adipocytes were larger. The observed hypertrophy was associated with decreased glycemic control and macrophage infiltration correlated with decreased adiponectin, signifying that inflammation is associated with worsening health. No evidence of SQ adipose fibrosis was detected. CONCLUSIONS: Our study is the first to prospectively illustrate that sublethal irradiation exposures directly propagate metabolic disease in the absence of obesity in nonhuman primates and implicate SQ adipose dysfunction as a target tissue.

Opportunistic body composition evaluation in patients with esophageal adenocarcinoma: association of survival with 18F-FDG PET/CT muscle metrics.

OBJECTIVE: 18F-FDG PET is widely used to accurately stage numerous types of cancers. Although 18F-FDG PET/CT features of tumors aid in predicting patient prognosis, there is increasing interest in mining additional quantitative body composition data that could improve the prognostic power of 18F-FDG PET/CT, without additional examination costs or radiation exposure. The aim of this study was to determine the association between overall survival and body composition metrics derived from routine clinical 18F-FDG PET/CT examinations. METHODS: Patients who received baseline 18F-FDG PET/CT imaging during workup for newly diagnosed esophageal adenocarcinoma (EAC) were included. From these studies, psoas cross-sectional area (CSA), muscle attenuation (MA), SUVmean, and SUVmax were obtained. Correlation with overall survival was assessed using a Cox Proportional Hazards model, controlling for age, body mass index, 18F-FDG dose, glucose level, diabetes status, in-hospital status, and tumor stage. RESULTS: Among the 59 patients studied, psoas MA and SUVmax were found to be significant predictors of survival (HR 0.94, 95% CI 0.88-0.99, p = 0.04, and HR 0.37, 95% CI 0.14-0.97, p = 0.04, respectively) and remained independent predictors. Psoas CSA and SUVmean did not significantly influence survival outcomes. CONCLUSIONS: Characterization of psoas muscles as a surrogate marker for sarcopenia on baseline 18F-FDG PET/CT imaging is relatively easily obtained and may offer additional prognostic value in patients with EAC.

Effects of Melatonin on the Body Composition, Physical Performance, and Blood Erythrocyte Indexes of C57Bl/6J Mice Exposed to Continuous Illumination.

Male C57Bl/6J mice were exposed to daily 24-h illumination over 14 days and daily intragastrically received melatonin (1 mg/kg) or water (placebo). Controls were kept under standard day/night (14/10 h) conditions. Melatonin prevented the development of anemia in mice exposed to continuous illumination, which was proven by higher blood hemoglobin levels by the end of the experiment in melatonin-treated animals in comparison with the placebo group. Studies by the low-field NMR spectrometry detected lower lean body mass, total body water, and especially, fat content (by ~13%) in animals receiving placebo. Melatonin treatment led to an increase in the lean body mass and total body water on day 7 (in comparison with the placebo group) without affecting fat mass. On day 14 of continuous illumination, lean body mass increased in comparison with the corresponding parameter in the control and placebo groups. Melatonin had no effect on the physical endurance of mice exposed to continuous illumination (assessed by the grid hanging test).

Phase Angle as an Objective and Predictive Factor of Radiotherapy-induced Changes in Body Composition of Male Patients With Head and Neck Cancer.

BACKGROUND: Unfavorable changes in body composition are frequent among patients with head and neck cancer (HNC). Unfortunately, in daily clinical practice, there is a lack of reliable diagnostic tools for predicting changes in body composition in individuals following radiotherapy (RT). Among non-invasive tools, bioelectrical impedance analysis (BIA) seems to be most promising. One BIA parameter, the phase angle (PA), reflects condition of various body cells and their mass in detail. MATERIALS AND METHODS: Using BIA, the body composition was measured prior to and after RT in 52 male patients with HNC. PA derived from BIA prior to RT was tested as a predictor of body composition changes developing during RT. RESULTS: Patients with low PA had a greater than 9.3-fold higher chance of body mass index (BMI) reduction below 18.5 kg/m2 and over 5.9-fold and 4.2-fold higher chance of lean mass and fat mass reduction after therapy end compared with patients with a high PA value. PA values demonstrated significant diagnostic accuracy for detection of fat-free mass, lean mass and BMI reduction in the study group [area under the curve (AUC)=0.781, 0.774 and 0.786, respectively]. CONCLUSION: PA prior to RT is a useful marker for selection of individuals with HNC who are at a high risk of unfavorable changes in body composition.

Combined analysis of miRNA-181a with phase angle derived from bioelectrical impedance predicts radiotherapy-induced changes in body composition and survival of male patients with head and neck cancer.

BACKGROUND: Nutritional deficits developing as an effect of applied radiotherapy (RTH) negatively affect patients' quality of life, survival, and therapy outcomes. We demonstrated novel approach to prediction of RTH-induced changes in body composition of patients with head and neck cancer using phase angle (PA) derived from bioelectrical impedance in combination with miRNA-181a expression. RESULTS: Patients with simultaneous presence of low PA and high miRNA expression were at a significantly higher risk of decreasing the fat-free mass index (FFMI) <14.9 kg/m2 (odds ratio [OR] = 5.14; P = .02), FFM < 44.7 kg (OR = 6.20; P = .04), and lean mass (OR = 10.0; P = .04) during the therapy period. Receiver operating curve analysis allowed to predict changes in FFMI, lean mass, and FFM with area under the curve calculation over 0.700. The simultaneous presence of high miRNA and low PA negatively affected patients' survival (OR = 5.12; P = .02). CONCLUSION: Evaluation of PA in combination with miRNA demonstrates higher diagnostic accuracy and predictive value for detecting RTH-induced changes in body composition of patients with cancer.

Murine vs human tissue compositions: implications of using human tissue compositions for photon energy absorption in mice.

METHODS:: Dual energy CT (DECT) images of 9 female mice were used to extract the effective atomic number Zeff and the relative electron density ρe for each voxel in the images. To investigate the influence of the tissue compositions on the absorbed radiation dose for a typical kilovoltage photon beam, mass energy-absorption coefficients µen/ρ were calculated for 10 different tissues in each mouse. RESULTS: Differences between human and murine tissue compositions can lead to errors around 7.5 % for soft tissues and 20.1 % for bone tissues in µen/ρ values for kilovoltage photon beams. When considering the spread within tissues, these errors can increase up to 17.5 % for soft tissues and 53.9 % for bone tissues within only a single standard deviation away from the mean tissue value. CONCLUSION:: This study illustrates the need for murine reference tissue data. However, assigning only a single mean reference value to an entire tissue can still lead to large errors in dose calculations given the large spread within tissues of µen/ρ values found in this study. Therefore, new methods such as DECT and spectral CT imaging need to be explored, which can be important next steps in improving tissue assignment for dose calculations in small animal radiotherapy. ADVANCES IN KNOWLEDGE:: This is the first study that investigates the implications of using human tissue compositions for dose calculations in mice for kilovoltage photon beams.

Artificial light at night and captivity induces differential effects on leukocyte profile, body condition, and erythrocyte size of a diurnal toad.

Light pollution or artificial lighting at night (ALAN) is an emerging threat to biodiversity that can disrupt physiological processes and behaviors. Because ALAN stressful effects are little studied in diurnal amphibian species, we investigated if chronic ALAN exposure affects the leukocyte profile, body condition, and blood cell sizes of a diurnal toad. We hand-captured male toads of Melanophryniscus rubriventris in Angosto de Jaire (Jujuy, Argentina). We prepared blood smears from three groups of toads: "field" (toads processed in the field immediately after capture), "natural light" (toads kept in the laboratory under captivity with natural photoperiod), and "constant light" (toads kept in the laboratory under captivity with constant photoperiod/ALAN). We significantly observed higher neutrophil proportions and neutrophils to lymphocytes ratio in toads under constant light treatment. In addition, we observed significantly better body condition and higher erythrocyte size in field toads compared with captive toads. In summary, ALAN can trigger a leukocyte response to stress in males of the diurnal toad M. rubriventris. In addition, captivity can affect the body condition and erythrocyte size of these toads.

Feasibility and Preliminary Efficacy of a 10-Week Resistance and Aerobic Exercise Intervention During Neoadjuvant Chemoradiation Treatment in Rectal Cancer Patients.

BACKGROUND: Neoadjuvant chemoradiation treatment (CRT) in rectal cancer patients is associated with a reduction in physical capacity, lean mass and increased fatigue. As a countermeasure to these treatment-related adverse effects, we examined the feasibility and preliminary efficacy of a 10-week exercise program during CRT. METHODS: Ten rectal cancer patients (7 men, aged 27-70 years, body mass index = 26.4 ± 3.8 kg/m2) receiving CRT undertook supervised resistance and aerobic exercise twice weekly. Assessments were undertaken pre- and post-intervention for upper and lower body muscle strength by 1-RM, muscle endurance, physical performance tests, body composition by dual X-ray absorptiometry, quality of life, and fatigue. RESULTS: There was a significant loss in appendicular skeletal muscle (-1.1 kg, P = .012), and fat mass (-0.8 kg, P = .029) following CRT. Despite the loss in skeletal muscle, leg press ( P = .030) and leg extension ( P = .046) strength improved by 27.2% and 22.7%, respectively, and leg press endurance by 76.7% ( P = .007). Changes in strength were accompanied by improved performance ( P < .05) in 6-m fast walking speed (6.9%) and dynamic balance as determined by the 6-m backwards walk (15.5%). There was minimal change in quality of life and fatigue, and no adverse events related to training. CONCLUSIONS: Exercise during neoadjuvant CRT appears to be feasible and well tolerated in rectal cancer patients and may enhance physical function while minimizing adverse changes in body composition and cancer-related fatigue. These initial findings need to be confirmed in randomized controlled trials.

Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy.

Body composition, defined as the proportions and distribution of lean and fat tissues in the human body, is an emergent theme in clinical oncology. Severe muscle depletion (sarcopenia) is most easily overlooked in obese patients; the advent of secondary analysis of oncologic images provides a precise and specific assessment of sarcopenia. Here, we review the definitions, prevalence and clinical implications of sarcopenic obesity (SO) in medical and surgical oncology. Reported prevalence of SO varies due to the heterogeneity in the definitions and the variability in the cut points used to define low muscle mass and high fat mass. Prevalence of SO in advanced solid tumor patient populations average 9% (range 2.3%-14.6%) overall, and one in four (24.7%, range 5.9%-39.2%) patients with body mass index ≥ 30 kg/m2 are sarcopenic. SO is independently associated with higher mortality and higher rate of complications in systemic and surgical cancer treatment, across multiple cancer sites and treatment plans. These associations remain unexplained, however, it has been hypothesized that patients with sarcopenia are generally unfit and unable to tolerate stress. Another proposed mechanism relates to increased exposure to antineoplastic therapy, i.e. a large fat mass would be expected to inflate drug dose in BSA-based treatments, causing an increased rate of dose-limiting toxicity. Pharmacokinetic data are needed to confirm or refute this hypothesis. Old age, deconditioning, cancer progression, acute or chronic nonmalignant disease and drug side-effects are suggested causes of muscle loss, and it is unknown the degree to which this can be reversed. Sarcopenia can be readily detected before start of cancer treatment, however, clinical management protocols for SO patients require development. Studies of cancer treatment dose-modulation are in progress.

ASSESSMENT OF THE LATE EFFECTS ON BONES AND ON BODY COMPOSITION OF CHILDREN AND ADOLESCENTS TREATED FOR ACUTE LYMPHOCYTIC LEUKEMIA ACCORDING TO BRAZILIAN PROTOCOLS. / AVALIAÇÃO DOS EFEITOS ÓSSEOS TARDIOS E COMPOSIÇÃO CORPORAL DE CRIANÇAS E ADOLESCENTES TRATADOS DE LEUCEMIA LINFOIDE AGUDA SEGUNDO PROTOCOLOS BRASILEIROS.

OBJECTIVE: To evaluate the impact of therapy on bone mineral density (BMD) and body composition in survivors of acute lymphoblastic leukemia (ALL) treated in accordance with Brazilian protocols by the Brazilian Cooperative Group of Treatment of Lymphoblastic Leukemia in Childhood (GBTLI) LLA-93 and LLA-99. METHODS: A cross-sectional study with 101 patients was performed. BMD and body composition were evaluated using bone densitometry and were interpreted according to the age group and the reference population. Values between -1.1 and -1.9 in the group of children under 20 years were considered as risk group for low BMD z-scores. BMD values were compared to clinical characteristics, treatment received and body composition. A chi-square test, Fisher's exact test, likelihood ratio and Student's t-test were applied, with a 5% significance level. RESULTS: The patients presented a frequency of fractures of 2%, of osteonecrosis, 2%, and of low BMD, 2.9%. In the group of 79 patients under 20 years of age, three had low BMD. The 16 that presented risk for low BMD, demonstrated lower valutes in lumbar vertebrae L1-L4 (p=0.01) and whole body (p=0.005), and smaller values of lean body mass (p=0.03). In the group of 22 patients over 20 years of age, ten had osteopenia. CONCLUSIONS: The low impact of treatment on BMD of this study confirms the concept that the bone mass gain occurs with increasing age and that the treatment does not influence the process. The population at risk for low BMD values presented lower bone mass values and could benefit from a long-term monitoring for possible bone toxicity.

OBJETIVO: Avaliar o impacto da terapia sobre a densidade mineral óssea (DMO) e composição corporal em sobreviventes da leucemia linfoide aguda (LLA), tratados de acordo com os protocolos brasileiros do Grupo Cooperativo Brasileiro de Tratamento de Leucemia Linfoide Aguda na Infância (GBTLI), LLA-93 e LLA-99. MÉTODOS: Em estudo transversal com 101 pacientes, avaliaram-se a composição corporal e a DMO por meio da densitometria óssea, interpretando-a conforme a faixa etária e a população de referência. Foi considerado grupo de risco para baixa DMO valores de z-escore entre -1,1 e -1,9 no grupo dos menores de 20 anos. Compararam-se os valores da DMO com características clínicas, tratamento recebido e composição corporal. Foram utilizados os testes qui-quadrado, exato de Fisher, razão de verossimilhança e t de Student, com nível de significância de 5%. RESULTADOS: Foram encontradas 2% de fraturas, 2% de osteonecrose e 2,9% de baixa DMO. No grupo de pacientes com menos de 20 anos, três apresentaram baixa DMO. Os 16 pacientes com risco para baixa DMO exibiram menores valores em vértebras lombares L1-L4 (p=0,01), corpo total (p=0,005) e valores mais baixos de massa magra (p=0,03). No grupo de 22 pacientes com mais de 20 anos, dez demonstraram osteopenia. CONCLUSÕES: O baixo impacto do tratamento sobre a DMO neste estudo ratifica o conceito de que o ganho de massa óssea ocorre com o aumento da idade e que o tratamento não influencia tal processo. A população de risco para baixa DMO demonstrou valores menores de massa óssea, podendo beneficiar-se de um acompanhamento em longo prazo para uma possível toxicidade óssea.

AVALIAÇÃO DOS EFEITOS ÓSSEOS TARDIOS E COMPOSIÇÃO CORPORAL DE CRIANÇAS E ADOLESCENTES TRATADOS DE LEUCEMIA LINFOIDE AGUDA SEGUNDO PROTOCOLOS BRASILEIROS / ASSESSMENT OF THE LATE EFFECTS ON BONES AND ON BODY COMPOSITION OF CHILDREN AND ADOLESCENTS TREATED FOR ACUTE LYMPHOCYTIC LEUKEMIA ACCORDING TO BRAZILIAN PROTOCOLS

RESUMO Objetivo: Avaliar o impacto da terapia sobre a densidade mineral óssea (DMO) e composição corporal em sobreviventes da leucemia linfoide aguda (LLA), tratados de acordo com os protocolos brasileiros do Grupo Cooperativo Brasileiro de Tratamento de Leucemia Linfoide Aguda na Infância (GBTLI), LLA-93 e LLA-99. Métodos: Em estudo transversal com 101 pacientes, avaliaram-se a composição corporal e a DMO por meio da densitometria óssea, interpretando-a conforme a faixa etária e a população de referência. Foi considerado grupo de risco para baixa DMO valores de z-escore entre -1,1 e -1,9 no grupo dos menores de 20 anos. Compararam-se os valores da DMO com características clínicas, tratamento recebido e composição corporal. Foram utilizados os testes qui-quadrado, exato de Fisher, razão de verossimilhança e t de Student, com nível de significância de 5%. Resultados: Foram encontradas 2% de fraturas, 2% de osteonecrose e 2,9% de baixa DMO. No grupo de pacientes com menos de 20 anos, três apresentaram baixa DMO. Os 16 pacientes com risco para baixa DMO exibiram menores valores em vértebras lombares L1-L4 (p=0,01), corpo total (p=0,005) e valores mais baixos de massa magra (p=0,03). No grupo de 22 pacientes com mais de 20 anos, dez demonstraram osteopenia. Conclusões: O baixo impacto do tratamento sobre a DMO neste estudo ratifica o conceito de que o ganho de massa óssea ocorre com o aumento da idade e que o tratamento não influencia tal processo. A população de risco para baixa DMO demonstrou valores menores de massa óssea, podendo beneficiar-se de um acompanhamento em longo prazo para uma possível toxicidade óssea.

ABSTRACT Objective: To evaluate the impact of therapy on bone mineral density (BMD) and body composition in survivors of acute lymphoblastic leukemia (ALL) treated in accordance with Brazilian protocols by the Brazilian Cooperative Group of Treatment of Lymphoblastic Leukemia in Childhood (GBTLI) LLA-93 and LLA-99. Methods: A cross-sectional study with 101 patients was performed. BMD and body composition were evaluated using bone densitometry and were interpreted according to the age group and the reference population. Values between -1.1 and -1.9 in the group of children under 20 years were considered as risk group for low BMD z-scores. BMD values were compared to clinical characteristics, treatment received and body composition. A chi-square test, Fisher’s exact test, likelihood ratio and Student’s t-test were applied, with a 5% significance level. Results: The patients presented a frequency of fractures of 2%, of osteonecrosis, 2%, and of low BMD, 2.9%. In the group of 79 patients under 20 years of age, three had low BMD. The 16 that presented risk for low BMD, demonstrated lower valutes in lumbar vertebrae L1-L4 (p=0.01) and whole body (p=0.005), and smaller values of lean body mass (p=0.03). In the group of 22 patients over 20 years of age, ten had osteopenia. Conclusions: The low impact of treatment on BMD of this study confirms the concept that the bone mass gain occurs with increasing age and that the treatment does not influence the process. The population at risk for low BMD values presented lower bone mass values and could benefit from a long-term monitoring for possible bone toxicity.

Triagem nutricional por meio do MUST no paciente oncológico em radioterapia / Nutrition screening by MUST on the oncological patient in radiotherapy / Triage nutricional por médio de MUST para pacientes oncológicos en radioterapia

Introdução: a radioterapia contribui para a redução da ingestão alimentar e maior perda de peso, devido ao aparecimento de sintomas gastrointestinais, o que consequentemente leva à desnutrição. Objetivo: i dentificar o risco nutricional, por meio do Malnutrition Universal Screening Tool (Must ), em pacientes com câncer submetidos à radioterapia. Método: estudo transversal, realizado com pacientes ambulatoriais do s erviço de radioterapia do Hospital de câncer de Pernambuco, durante outubro/2014 a maio/2015. Foram avaliadas as características socioeconômicas, demográficas, estilo de vida (fumo, álcool e atividade física), variáveis antropométricas (peso habitual, atual e iMc), comorbidades (hipertensão e diabetes), tipos de neoplasias, tempo de diagnóstico e tratamento. o risco nutricional foi identificado utilizando-se o Must , que classifica o paciente com risco ou sem risco, e em baixo, médio e alto risco nutricional. Resultados: Foram estudados 150 pacientes com média de idade de 47,3 anos, a maioria mulheres (72%) e proporções semelhantes de adultos e idosos. observou-se que a maioria do grupo era procedente do interior do estado, inativos/aposentados e recebiam 1-3 salários mínimos. o risco nutricional foi significantemente maior nos idosos (62,9%), em que predominou o alto risco (45,7%), enquanto nos adultos a maioria evidenciou sem risco (61,2%). as neoplasias mais frequentes foram as ginecológicas (59,4%) com ganho de peso de 33,3%; em seguida, os tumores de cabeça e pescoço com elevada perda ponderal (p=0,007). Conclusão: o Must detectou risco nutricional em 50% dos pacientes estudados, com predominância nos idosos, a maioria com alto risco. n a neoplasia de cabeça e pescoço, predominou a perda ponderal; enquanto, no ginecológico, o ganho de peso. r essalta-se a importância da realização de triagem ambulatorial para instituir precocemente uma terapia nutricional especializada.

Introduction: radiotherapy contributes to the reduction of food intake and increased weight loss due to the appearance of gastrointestinal symptoms, which consequently leads to malnutrition. Objective: i dentify nutritional risk through the Malnutrition universal screening tool (Must ), in patients submitted to radiotherapy for the treatment of cancer. Method: c ross-sectional study with outpatients at the radiotherapy service of the cancer Hospital of Pernambuco, during o ctober 2014 until May 2015. s ocio-demographic characteristics, lifestyle (smoking, alcohol use and physical activity), anthropometric variables (habitual weight, current weight and body mass index), comorbidities (hypertension and diabetes), tumor type, time since diagnosis and duration of treatment were evaluated. n utritional risk was assessed using the Must , which classifies patients as being at low, medium or high nutritional risk. Results: 150 patients were studied with an average age of 47.3 years, with a predominance of women (72%) and similar proportions of adults and elderly individuals. The sample mainly comprised individuals from in-state regions and inactive/retired individuals who received one to three times the minimum salary. nutritional risk was significantly higher among elderly individuals (62.9%), among whom high risk predominated (45.7%), whereas most adults had no risk (61.2%). The most frequent tumors were gynecological (59.4%) with weight gain (33.3%), followed by tumors of the head and neck region with a high degree of weight loss (p = 0.007). Conclusion: The use of Must led to the detection of nutritional risk in 50% of the studied patients, with a predominance of elderly individuals, the majority of whom were at high risk. tumors of the head and neck led to weight loss, whereas gynecological tumors led to weight gain. out-patient nutritional screening is important for the early establishment of specialized nutritional counselin

Introducción: la radioterapia contribuye a la reducción de la ingesta de alimentos y el aumento de la pérdida de peso debido a la aparición de los síntomas gastrointestinales, que en consecuencia lleva a la desnutrición. Objetivo: identificar el riesgo nutricional, a través del Malnutrition Universal Screening Tool (Must ), en pacientes con cáncer sometidos a radioterapia. Método: estudio transversal con pacientes ambulatorios en el servicio de radioterapia del Hospital de cáncer de Pernambuco, realizado desde octubre/2014 hasta mayo/2015. s e evaluaron características sociodemográficas, estilo de vida (tabaco, alcohol y actividad física), variables antropométricas (peso habitual, actual e icM), comorbideces (hipertensión y diabetes), tipos de neoplasias, tiempo de diagnóstico y tratamiento. el riesgo nutricional se evaluó utilizándose el Must que clasifica al paciente en bajo, medio y alto riesgo nutricional. Resultados: se estudiaron 150 pacientes con promedio de edad de 47,3 años, en su mayoría mujeres (el 72%) y proporciones semejantes de adultos y ancianos. s e observó que la mayoría del grupo era procedente del interior del estado, inactivos/jubilados y recibían 1-3 sueldos mínimos. e l riesgo nutricional significante fue mayor en los ancianos (el 62,9%) en el que predominó el alto riesgo (el 45,7%), mientras en los ancianos la mayoría evidenció sin riesgo (el 61,2%). las neoplasias más frecuentes fueron las ginecológicas (el 59,4%) con aumento de peso del 33,3%; en seguida, los tumores de cabeza y cuello con elevada pérdida ponderal (p=0,007). Conclusión: e l Must detectó riesgo nutricional en el 50% de los pacientes estudiados, con predominancia en los ancianos, la mayoría con alto riesgo. e n la neoplasia de cabeza y cuello predominó la pérdida ponderal, mientras que en el ginecológico el aumento de peso. s e resalta la importancia de la realización de selección ambulatorio para instituir precozmente una terapia nutricional especializad

Impact of a ketogenic diet intervention during radiotherapy on body composition: II. Protocol of a randomised phase I study (KETOCOMP).

BACKGROUND: We have found that a ketogenic diet (KD) during the course of radiotherapy (RT) was feasible and led to a preservation or favorable changes of body composition. Based on these observations and theoretical considerations, we initiated a study to investigate the impact of a KD or a ketogenic breakfast intervention in patients undergoing RT. METHODS: All patients presenting for curative RT with age between 18 and 75, body mass index between 18 and 34 kg/m2 and a histologically confirmed cancer of the breast, colorectum or head and neck region are considered for inclusion. Exclusion criteria are Karnofsky index <70, pregnancy, metallic body parts that interfere with bioimpedance analysis (BIA), type I diabetes, known enzyme defects that contradict a KD and renal insufficiency. Randomization is achieved by all consecutive patients first entering the control group and then an intervention group 1 until both groups contain 15 breast, 15 colorectal and 5 head and neck cancer patients. Intervention group 1 will receive each radiotherapy fraction after an overnight fast and subsequently ingest a ketogenic breakfast consisting of (i) 50-250 ml of a medium-chain triglyceride drink (betaquick®, vitaflo, Bad Homburg, Germany) plus (ii) 5-15 g amino acids (MAP, dr. reinwald healthcare gmbh+co kg, Schwarzenbruck, Germany). If willing to undertake a complete KD for the duration of RT, patients are entered into intervention group 2. Intervention group 2 does not have to fast prior to RT fractions but will be supplemented with MAP analogous to intervention group 1. The control group will not receive dietary advice to follow a KD or reduce carbohydrate intake. The objective is twofold: (i) to test whether the ketogenic interventions are feasibly, as measured by the number of dropouts; (ii) to see whether intervention groups 1 and 2 attain a better preservation of BIA phase angle than the control group. ENDPOINTS: Primary endpoints are the feasibility of the interventions (measured through dropout rates), and changes in body weight and composition (measured through BIA). Secondary endpoints are changes in quality of life (EORTC questionnaires) and blood parameters as well as the occurrence and grade of toxicities and grade of regression after surgery in case of colorectal carcinomas.

Type 2 Diabetes is a Delayed Late Effect of Whole-Body Irradiation in Nonhuman Primates.

One newly recognized consequence of radiation exposure may be the delayed development of diabetes and metabolic disease. We document the development of type 2 diabetes in a unique nonhuman primate cohort of monkeys that were whole-body irradiated with high doses (6.5-8.4 Gy) 5-9 years earlier. We report here a higher prevalence of type 2 diabetes in irradiated monkeys compared to age-matched nonirradiated monkeys. These irradiated diabetic primates demonstrate insulin resistance and hypertriglyceridemia, however, they lack the typical obese presentation of primate midlife diabetogenesis. Surprisingly, body composition analyses by computed tomography indicated that prior irradiation led to a specific loss of visceral fat mass. Prior irradiation led to reductions in insulin signaling effectiveness in skeletal muscle and higher monocyte chemoattractant protein 1 levels, indicative of increased inflammation. However, there was an absence of large defects in pancreatic function with radiation exposure, which has been documented previously in animal and human studies. Monkeys that remained healthy and did not become diabetic in the years after irradiation were significantly leaner and smaller, and were generally smaller and younger at the time of exposure. Irradiation also resulted in smaller stature in both diabetic and nondiabetic monkeys, compared to nonirradiated age-matched controls. Our study demonstrates that diabetogenesis postirradiation is not a consequence of disrupted adipose accumulation (generalized or in ectopic depots), nor generalized pancreatic failure, but suggests that peripheral tissues such as the musculature are impaired in their response to insulin exposure. Ongoing inflammation in these animals appears to be a consequence of radiation exposure and can interfere with insulin signaling. The reasons that some animals remain protected from diabetes as a late effect of irradiation are not clear, but may be related to body size. The translational relevance for these results suggest that muscle may be an important and underappreciated target organ for the delayed late effect of whole-body irradiation, leading to increased risk of insulin resistance and diabetes development.

Testosterone and body composition in men after treatment for rectal cancer.

INTRODUCTION: Preoperative radiotherapy for rectal cancer may affect Leydig cell function. However, the diagnosis of posttreatment hypogonadism is complicated as sexual symptoms associated to hypogonadism can rely on adverse events of pelvic radiation and surgery. AIM: The objective of this study was to investigate the association of testosterone levels and body composition. The clinical value of such an association is tested subsequently in the study population. METHODS: This was a longitudinal study with prospective registration during 2010-2012 and 1-year follow up. Men with rectal cancer stage I-III, treated with radiotherapy and surgery, were eligible, and 40 of 53 men were available for analysis. MAIN OUTCOME MEASURES: The areas of skeletal muscle and adipose tissue were assessed on a defined section of a computed tomography at baseline and after 1 year. Androgen levels were recorded from morning blood samples. RESULTS: The area of skeletal muscle was related to the level of bioavailable testosterone (P = 0.01) but not to the level of serum testosterone (P = 0.36). The subcutaneous adipose tissue was not related to testosterone levels. Men with posttreatment serum testosterone levels of 8-12 nmol/L and longitudinal loss of psoas muscle area had a significantly increased luteinizing hormone-testosterone ratio compared with those with longitudinal gain of psoas muscle. CONCLUSIONS: The area of psoas muscle is related to the unbound fraction of circulating testosterone in men treated for rectal cancer. The longitudinal loss of psoas muscle in men with borderline levels of serum testosterone seems to be an androgen-related symptom associated with compensatory activation of the pituitary-gonadal axis indicating a testicular failure in this group of patients.

Redistribution of body composition in patients with Graves' disease after iodine-131 treatment.

OBJECTIVE: The objective of this study was to investigate body composition redistribution at 3 months after radioactive iodine therapy (RAI). METHODS: Eighty patients with Graves' disease (GD) for RAI and 18 volunteers were recruited. All patients underwent thyroid status test and dual-energy x-ray absorptiometry at baseline and 3 months after RAI. According to the second thyroid status test, patients were divided into the following groups: A, with aggravated hyperthyroidism; B-1, with improved hyperthyroidism; B-2, with euthyroidism; and B-3, with hypothyroidism. RESULTS: Total lean mass (LM) but fat mass (FM) and bone mineral content (BMC) of whole GD patients after RAI recovered to be not different with controls. Compared with baseline, in group A, FM in the left leg increased, and LM in left arm, right arm, trunk and total LM decreased (P<0.05). In B-2, FM in the head increased, and LM in the head, right arm, trunk and total LM increased (P<0.05). In B-3, FM in the right leg and total body fat percentage decreased, but FM in the head, android-to-gynoid fat ratio and body mass index increased (P<0.05); LM of all sites, weight and total mass increased (P<0.05); BMC in lumbar spine and left leg, and total BMC decreased (P<0.05). Body composition of unmentioned sites was retained after RAI in each group (P>0.05). CONCLUSIONS: Replenishment of LM gets priority rather than FM and BMC during the first 3 months after RAI, and the increase in LM starts from the upper body; head is the regional site in which FM recovery occurs first.

Reflexiones sobre la memoria del agua y los espectros infrarrojos en el area de salud: a propósito de determinar la composición corporal con isótopos estables / Reflections on water memory and infrared spectra in the health area: a purpose of determining body composition with stable isotopes

Se presenta conceptos sobre la determinación de la composición corporal a través del uso de la técnica de isótopos estables, como el deuterio, mediante el uso de muestras de saliva en escolares de gran altitud. Dichas muestras se encuentran enriquecidas por el óxido de deuterio en todo el cuerpo del escolar y son analizadas con la espectrometría infrarroja con transformada de Fourier. En la actualidad, en el campo de la electromagnética, se hace hincapié sobre una nueva propiedad de las secuencias de ADN bacteriano que inducen a la producción de ondas electromagnéticas, resaltando la memoria que tiene el agua al poder mantener los fragmentos de ADN por largo tiempo, que son generadores de señales, definidos como Biomarcadores, que permitirían la detección de infecciones bacterianas crónicas en el organismo humano a través del uso de la electromagnética. La reflexión a la que se llega, es que muestras de saliva contaminadas con microorganismos, como las bacterias, interfieren con la medición del enriquecimiento de deuterio identificada por el equipo FTIR. Se deja como lección aprendida, el insistir sobre la higiene oral previa a la hora de tomar muestras de saliva, que minimice la contaminación con microorganismos, para lograr determinar el enriquecimiento alcanzado con el deuterio, y así no incurrir en el error de medición que daría resultados no reales del agua corporal total de los sujetos estudiados.

This workpresents concepts about determining body composition byusing the stable isotope technique, as deuterium, using saliva samples in school children at high altitude. These samples are achieved by the enrichment of deuterium oxide in the whole body of the school children and then are analyzed with Fourier transform infrared spectrometer. Currently there is an emphasis on a new property of the bacterial DNA sequences that induce the production of electromagnetic waves, that highlights the water memory to be able to maintain the DNA fragments, signal generators that are defined as Biomarkers, which allow the detection of chronicle bacterial infections in the body. A reflection is that saliva samples contaminated with microorganisms such as bacterias interfere with the measurement of the deuterium enrichment identified by FTIR equipment. The learnt lesson is about oral hygiene, which minimizes contamination with microorganisms from the saliva samples to determine the enrichment achieved with deuterium, and not to make the mistake of measuring actual results would total body water of the subjects studied.

The limited screening value of insulin-like growth factor-I as a marker for alterations in body composition in very long-term adult survivors of childhood cancer.

BACKGROUND: The clinical relevance of low IGF-I levels, caused by cranial radiotherapy, in adult childhood cancer survivors has not been studied extensively. We evaluated whether IGF-I is a useful marker for altered body composition and growth hormone deficiency (GHD) in this group. PROCEDURE: We analyzed retrospective data from 610 adult childhood cancer survivors, retrieved from the late effects clinic. Median age at diagnosis was 6 years (interquartile range 3-11) and follow-up time was 18 years (13-24). We assessed IGF-I standard deviation scores (SDS), anthropometrical measures, growth hormone stimulation tests in patients with clinical signs of GHD, and measures of body composition (assessed by dual X-ray absorptiometry, Lunar Prodigy). RESULTS: In 58 cranially irradiated acute leukemia survivors (25 Gy (24-25)) and 56 locally irradiated brain tumor survivors (42 Gy (35-54)) we found significantly lower IGF-I SDS (P < 0.001), lower height SDS (P < 0.001), higher body mass index (P = 0.01), higher waist-hip ratio (WHR; P = 0.001), higher total fat percentage SDS (P < 0.001), and lower lean body mass SDS (P < 0.001), as compared to 452 not cranially irradiated survivors. IGF-I showed a weak inverse correlation with BMI (r = -0.12, P = 0.04), WHR (r = -0.15, P = 0.01), total fat percentage (r = - 0.14, P = 0.02), and a positive correlation with lean body mass (r = 0.15, P = 0.01). In patients with low IGF-I levels, IGF-I did not significantly differ between subjects with and without GHD as determined by GH-stimulation testing (P = 0.39). CONCLUSION: This study shows that IGF-I has limited value as a marker for alterations in body composition in adult childhood cancer survivors.

New treatment of cellulite with infrared-LED illumination applied during high-intensity treadmill training.

Phototherapy improves cellular activation which is an important factor for the treatment of cellulite. The objective of this research was to develop and evaluate the effects of a new (noninvasive and nonpharmacological) clinical procedure to improve body aesthetics: infrared-LED (850 nm) plus treadmill training. Twenty women (25-55 years old) participated in this study. They were separated in two groups: the control group, which carried out only the treadmill training (n = 10), and the LED group, with phototherapy during the treadmill training (n = 10). The training was performed for 45 minutes twice a week over 3 months at intensities between 85% and 90% maximal heart rate (HR(max)). The irradiation parameters were 39 mW/cm(2) and a fluence of 106 J/cm(2). The treatment was evaluated by interpreting body composition parameters, photographs and thermography. This was primarily a treatment for cellulite with a reduction of saddlebag and thigh circumference. At the same time, the treadmill training prevented an increase of body fat, as well as the loss of lean mass. Moreover, thermal images of the temperature modification of the thighs are presented. These positive effects can result in a further improvement of body aesthetics using infrared-LED together with treadmill training.

Ionising radiation triggers fat accumulation in white adipose tissue.

PURPOSE: To investigate changes in gonadal white adipose tissue and lipogenesis-related gene expression induced by radiation exposure. MATERIALS AND METHODS: Groups of two-month-old C57BL/6 mice were exposed whole-body to ¹³7Cs γ-rays at a single dose (5 gray [Gy]) or fractionated doses (1 Gy x 5 times, 0.5 Gy x 10 times, or 0.2 Gy x 25 times). Six months after irradiation, gonadal white adipose tissue was isolated from mice. Two and 25-month-old mice were used as young and old study references. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure messenger RNA (mRNA) expression of genes related to: (i) Primary lipid metabolism (ATP-citrate lyase [ACL], malic enzyme1 [ME1] and glucose-6-phosphate dehydrogenase 2 [G6PD2]), (ii) glucose uptake (glucose transporter 4 [GLUT4]), (iii) fatty acid synthesis (sterol regulatory element binding transcription factor 1 [SREBP-1c], fatty acid synthetase [FAS] and acetyl-coenzyme A carboxylase beta [ACC]), (iv) triglyceride synthesis (diacylglycerol O-acyltransferase 1 [DGAT1] and diacylglycerol O-acyltransferase 2 [DGAT2]), and (v) adipose-derived hormones (leptin [LEP]). RESULTS: The weight of gonadal white adipose tissue in the irradiated groups tended to increase compared to the non-irradiated group though the radiation-induced increase in white adipose tissue was only significant for the 5 x 1 Gy group. The mRNA levels of SREBP-1c, ACC, FAS, ACL, GLUT4, ME1 and G6PD2 were relatively lower in γ-irradiated groups than in non-irradiated groups. The mRNA levels of leptin and DGAT were relatively higher than non-irradiated groups. The changes in expression of these lipogenesis-related genes caused by γ-irradiation showed a very similar pattern to changes caused by ageing. CONCLUSIONS: A physical agent such as γ-rays can trigger biological responses resulting in fat accumulation of gonadal white adipose tissue in mice.