The Effect of Wheel Exercise on Functional Indices of Cachexia in Tumor-bearing Mice.

INTRODUCTION: Cancer-related fatigue and muscle wasting have received significant attention over the last few decades with the goal of establishing interventions that can improve cancer patient life quality and survival. Increased physical activity has shown to reduce cancer-associated fatigue and has been proposed as a promising therapeutic to attenuate cancer-induced wasting. However, significant gaps remain in our understanding of how physical activity affects the compositional and functional changes that initiate muscle wasting. The purpose of the current study was to determine the effect of wheel exercise on body composition and functional indices of cancer cachexia before the development of significant wasting. METHODS: Thirteen-week-old male Apc (MIN) and C57BL/6 (B6) mice were given free wheel access (W) or a locked wheel (Sed) for 5 wk. RESULTS: Wheel activity was reduced in the MIN compared with B6; however, wheel access increased complex II expression in isolated skeletal muscle mitochondria regardless of genotype. Wheel access had no effect on tumor burden or plasma interleukin-6 in the MIN. MIN-W increased body weight and lean mass compared with MIN-Sed, and there was a direct correlation between wheel distance and lean mass change. MIN-W increased grip strength and treadmill time to fatigue compared with MIN-Sed. Within MIN-W mice, skeletal muscle fatigability was only improved in high runners (>60 min·d). CONCLUSIONS: Our results suggest that there were therapeutic benefits of increased activity related to body composition, behavior, and whole-body function that were not dependent on exercise duration; however, there was an exercise threshold needed to improve skeletal muscle fatigability in tumor-bearing mice. Interestingly, wheel access was able to improve compositional and functional outcomes without mitigating tumor number or size.

Resistance Training Impact on Mobility, Muscle Strength and Lean Mass in Pancreatic Cancer Cachexia: A Randomized Controlled Trial.

OBJECTIVE: To determine the efficacy of a three-month resistance training programme on the mobility, muscle strength and lean body mass of patients with pancreatic cancer-induced cachexia. DESIGN: Randomized controlled trial. SETTING: Elsahel Teaching Hospital, outpatient clinic of the Faculty of Physical Therapy, Cairo, Egypt. PARTICIPANTS: Patients with pancreatic cancer-induced cachexia. INTERVENTIONS: Participants were randomized to the resistance training group (n = 20) and control group (n = 20). MAIN MEASURES: Outcomes including mobility, muscle strength and lean body mass were measured at baseline, three months after surgical resection and 12 weeks after intervention. RESULTS: The mean (SD) age was 51.9 (5.03) years and body mass index was 21.1 (1.13) kg/m²; 65% of patients were male. Compared to the control group, the resistance training group showed significant improvement in mobility: 400-m walk performance (270.3-256.9 seconds vs 266.4-264.2 seconds, respectively) and chair rise (13.82-12.53 seconds vs 13.77-13.46 seconds, respectively). Similarly, muscle strength was also significantly improved in the resistance training group than in the control group; we observed increase in peak torque of knee extensors (P = 0.004), elbow flexors (P = 0.001) and elbow extensors, improvement in lean mass of the upper limb (6.28-6.46 kg vs 6.31-6.23 kg, respectively) and lower limb (16.31-16.58 kg vs 16.4-16.31 kg, respectively). CONCLUSION: A three-month resistance training improved the mobility of patients with pancreatic cancer-induced cachexia. Muscle strength and lean body mass also improved.

Treatment opinion of rehabilitation in sarcopenia and cachexia for oncological patients.

INTRODUCTION: Cachexia is defined as a syndrome of multifactorial etiology characterized by severe weight loss, loss of muscle and fat mass and increase in protein catabolism. Cachexia in cancer is a predominant and debilitating syndrome. Sarcopenia is a primary disease of older age characterized by loss of muscle mass due to the aging process. Sarcopenia can be defined as a combination of low muscle strength and muscle mass. Sarcopenia often occurs in the geriatric population. METHOD: This is a review article, search for articles in Pubmed database, JCR and Cochrane database was made with the following keywords: “sarcopenia”, “cachexia”, “rehabilitation” and “exercise”. RESULT: The main therapy of rehabilitation is exercise. Exercise can reduce the inflammatory response induced by cachexia or sarcopenia. Exercise can support autophagy. Physical activity can slow down weight loss and improve skeletal muscle function. Adequate strength exercise and aerobic exercise are important benefits for patients. Strength and aerobic exercise increase muscle strength and function and represent an important treatment strategy for cachexia and sarcopenia. CONCLUSION: Rehabilitation treatment is an important part of treatment for patients with cachexia and sarcopenia.

Adaptation of Fatigue Affected Changes in Muscle EMG Frequency Characteristics for the Determination of Training Load in Physical Therapy for Cancer Patients.

Cancer patients often experience loss in body weight and also a decrease in muscle mass, which results in the reduction of physical activity and mobilization of the patient. To decelerate the loss of muscle mass, as part of the cancer treatment patients frequently undergo physical therapy and considering the physical capabilities of the patients, with moderate loads. Moreover, frequent studies also observed for cancer patients, together with the decrease in muscle mass a shift into fast-twitch muscle fibers from slow-twitch fibers. The aim of our study therefore was to determine how motor fibers behave under moderate isometric load executed until total exhaustion. 11 university students (G1), and 14 elite athletes (G2) participated in the study. 65% of the maximal voluntary contraction (MVC) was determined for the biceps brachii muscle, and with this load holding a weight, participants had to sustain a 90 deg. isometric elbow flexion in a standing posture until complete fatigue occurred. EMG activity for the biceps brachii muscle was measured and frequency analysis was performed. 3 windows were determined in the fatiguing protocol: the first (W1), middle (W2), and last (W3) 5 s, and also frequency analysis for MVC was performed (MAX) between 0 and 260 Hz with 20 Hz wide frequency bands. The results indicate, that as the protocol progressed in time and the effect of fatigue increased (from W1 to W3) the activity of low frequency muscle fibers significantly increased (0-40 Hz) while activity of high frequency muscle fibers (60-260 Hz) significantly decreased for G1 and G2 groups identically. We can conclude, that training applied with constant moderate tension as fatigue increases will result in the increased activation of the lower frequency slow-twitch muscle fibers, but the increase of fatigue in the lower frequency fibers will not result in the increase in the activation level of the higher frequency fast-twitch fibers. Consequently, because as slow-twitch fibers are being used at moderate loads and even when fatigue occurs in these fibers the fast-twitch fibers will not work, higher muscle loads are needed if the aim is to activate fast-twitch fibers. Considering the shift into fast-twitch muscle fibers from slow-twitch fibers for cancer patients, in some cases if the patient's age and physical status allows during the physical treatment, higher loads and consequently higher levels of activation might be beneficial for the retardment of loss concerning the fast-twitch fiber mass.

Progressive resistance training in cachectic head and neck cancer patients undergoing radiotherapy: a randomized controlled pilot feasibility trial.

BACKGROUND: Cancer cachexia is a prevalent symptom of head and neck neoplasms. The reduction in skeletal muscle mass is one of the main characteristics which can lead to poor physical functioning. The purposes of this pilot randomized controlled trial were to determine the feasibility of progressive resistance training in cachectic head and neck cancer patients during radiotherapy and to explore possible risks and benefits. METHODS: Twenty cachectic participants with head and neck cancer receiving radiation were randomized to obtain either a machine supported progressive resistance training (n = 10) or usual care (n = 10). The training took place 3 times weekly for 30 min. Intervention included 3 exercises for major muscle groups with 8-12 repetition maximum for 3 sets each. Bioelectrical impedance analysis, hand-held dynamometry, Six-Minute Walk Test and standardized questionnaires for fatigue and quality of life were used for evaluating outcomes at baseline before radiotherapy (t1), after 7 weeks of radiotherapy (t2) and 8 weeks after the end of radiotherapy (t3). RESULTS: All participants (n = 20) completed the trial. No serious adverse events occurred. At the initial assessment the cachectic patients had already lost 7.1 ± 5.2% of their body weight. General fatigue (score 10.7 ± 3.3) and reduced quality of life (score 71.3 ± 20.6) were prevalent in cachectic head and neck cancer patients even before radiotherapy. An average improvement of weight loading for leg press (+ 19.0%), chest press (+ 29.8%) and latissimus pull-down (+ 22.8%) was possible in the intervention group. Participants had at least 13 training sessions. The outcome measures showed nonsignificant changes at t2 and t3, but a trend for a better course of general fatigue and quality of life at t2 in the intervention group. CONCLUSIONS: Despite advanced tumor stage and burdensome treatment the intervention adherence is excellent. Progressive resistance training in cachectic head and neck cancer patients during radiotherapy seems to be safe and feasible and may have beneficial effects of general fatigue and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03524755 . Registered 15 May 2018 - Retrospectively registered.

The Long-Term Impact of Severe Burn Trauma on Musculoskeletal Health.

Severe burn injury causes a profound stress response that leads to muscle and bone cachexia. Evidence suggests that these deficits persist for several months or even years after injury and are associated with growth delay, increased incidence of fractures, and increased hospital admissions for musculoskeletal disorders. Thus, there is an overwhelming need to determine the optimal acute and rehabilitative strategies to mitigate these deficits and improve quality of life for burn survivors. To date, there is limited research on the long-term impact of cachexia on functional performance and overall health, as well as on the lasting impact of pharmacological, nutritional, and exercise interventions. The aim of this review is to emphasize the long-term consequences of musculoskeletal cachexia and determine the best evidence-based strategies to attenuate it. We also underline important knowledge gaps that need to be addressed in order to improve care of burn survivors.

A multidisciplinary rehabilitation programme for cancer cachexia improves quality of life.

OBJECTIVES: Patients with cancer cachexia have severely impaired quality of life (QoL). Multidisciplinary, multimodal treatment approaches have potential for stabilising weight and correcting other features of this syndrome, but the impact on QoL is unknown. METHODS: A retrospective analysis of QoL in patients with advanced cancer, referred for the management of cachexia by a specialised multidisciplinary clinic (The McGill Cancer Nutrition Rehabilitation Program clinic at the Jewish General Hospital (CNR-JGH)). QoL was assessed at visits 1-3 using a dedicated QoL tool for cachexia, and the change in QoL was calculated for each patient. The correlation between clinical features and QoL at baseline and subsequent change in QoL was analysed, to determine what factors predict improvements in QoL during the CNR-JGH intervention. RESULTS: 374 patients assessed at visit 1 with mean weight loss of 10.2% over the preceding 6 months. Baseline QoL scores were severely impaired but clinically important improvements were observed over visits 1-3 to the CNR-JGH clinic. Improvements in QoL were not determined by baseline characteristics and were similar in all patient subgroups. However, those patients who gained weight and increased their 6 min walk test (6MWT) had the greatest improvements in QoL. CONCLUSIONS: Improving management of all facets of the cancer cachexia syndrome, including poor QoL, remains a priority. The multimodal approach to management of cancer cachexia offered by the CNR-JGH results in clinically important improvements in QoL. All patients who are able to receive this type of intervention have similar potential to improve their QoL, but the greatest benefits are seen in those who gain weight and improve their 6MWT.

Impact of a multidisciplinary rehabilitation nutrition team on evaluating sarcopenia, cachexia and practice of rehabilitation nutrition.

BACKGROUND/AIMS: To determine whether the presence of a multidisciplinary rehabilitation nutrition team affects sarcopenia and cachexia evaluation and practice of rehabilitation nutrition. METHODS: A cross-sectional study using online questionnaire among members of the Japanese Association of Rehabilitation Nutrition (JARN) was conducted. Questions were related to sarcopenia and cachexia evaluation and practice of rehabilitation nutrition. RESULTS: 677 (14.7%) questionnaires were analysed. 44.5% reported that their institution employed a rehabilitation nutrition team, 20.2% conducted rehabilitation nutrition rounds and 26.1% conducted rehabilitation nutrition meetings. A total of 51.7%, 69.7%, 69.0% and 17.8% measured muscle mass, muscle strength, physical function and cachexia, respectively. For those with a rehabilitation nutrition team, 63.5%, 80.7%, 82.4% and 22.9% measured muscle mass, muscle strength, physical function and cachexia, respectively, whereas 46.7%, 78.0% and 78.1% of the respondents reported implementation of nutrition planning strategies in consideration of energy accumulation, rehabilitation training in consideration of nutritional status and use of dietary supplements, respectively. Multivariate logistic regression analysis showed that the use of a rehabilitation nutrition team independently affected sarcopenia evaluation and practice of rehabilitation nutrition but not cachexia evaluation. CONCLUSIONS: The presence of a multidisciplinary rehabilitation nutrition team increased the frequency of sarcopenia evaluation and practice of rehabilitation nutrition. J. Med. Invest. 64: 140-145, February, 2017.

Exercise capacity, physical activity, and morbidity.

Muscle weakness and atrophy are key characteristics of the aging adult but can also be found in chronically ill patients with heart failure, cancer, renal failure, and chronic infectious diseases all associated with an accelerated level of muscle dysfunction. Reduced physical activity levels and exercise intolerance increase muscle loss and decrease quality of life in both the aging and heart failure populations. The purpose of this review is to provide an overview of the effects of aging and heart failure on skeletal muscle function and how exercise training can improve long-term outcomes associated with skeletal muscle dysfunction.

Neuromuscular electrical stimulation of the thighs in cardiac patients with implantable cardioverter defibrillators.

BACKGROUND: The aim of this systematic review was to update scientific knowledge concerning the safety of neuromuscular electrical stimulation (NMES) to increase exercise capacity and prevent cardiac cachexia in patients with implantable cardioverter defibrillators (ICDs). METHODS: A systematic review including the electronic databases PubMed, MEDLINE, and SCOPUS was conducted for the time period from 1966 to March 31, 2016. RESULTS: Only four articles fulfilled the inclusion criteria (three original articles/safety studies and one case report). The three (safety) studies used NMES to increase muscle strength and/or endurance capacity of the thighs. NMES did not show electromagnetic interference (EMI) with ICD function. EMI was described in a case report of 2 patients with subpectoral ICDs and application of NMES on abdominal muscles. CONCLUSION: This review indicates that NMES may be applied in cardiac ICD patients if 1) individual risks (e. g., pacing dependency, acute heart failure, unstable angina, ventricular arrhythmic episode in the last 3 months) are excluded by performing a safety check before starting NMES treatment and 2) "passive" exercise using NMES is performed only for thighs and gluteal muscles in 3) compliant ICD patients (especially for home-based NMES) and 4) the treatment is regularly supervised by a physician and the device is examined after the first use of NMES to exclude EMI. Nevertheless, further studies including larger sample sizes are necessary to exclude any risk when NMES is used in this patient group.

Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated. METHODOLOGY/PRINCIPAL FINDINGS: In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated. CONCLUSIONS/SIGNIFICANCE: In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD. TRIAL REGISTRATION: UMIN Clinical Trial Registry C000000061.

Establishing a cancer nutrition rehabilitation program (CNRP) for ambulatory patients attending an Australian cancer center.

PURPOSE: To establish a multidisciplinary Cancer Nutrition Rehabilitation Program (CNRP) for the management of the anorexia-cachexia syndrome (ACS) in an Australian cancer center and to evaluate outcomes of 2 months participation in the CNRP METHOD: Patients were eligible if they had significant anorexia/weight loss, identified by their oncologist or the Malnutrition Screening Tool. In the 9 months that funding was available, 54 participants (37 males, 17 females; median age, 62 years) enrolled. They had mainly lung or gastrointestinal cancers, with 67% receiving chemotherapy concomitantly. Baseline assessments of nutrition and physical status were: median weight 62.7 kg, median weight loss 10.2%, median BMI 21.2 kg/m(2), and 78% malnourished according to PG-SGA. Median baseline Karnofsky performance score (KPS) was 70%, with reduced right-hand grip strength (RGHS; median, 27 kg) and endurance (median, 6 min walk test 6MWT 442 m). Patients received individualized nutritional interventions, exercise programs, and symptom management and were followed prospectively for up to 6 months. RESULTS: Twenty-five (58%) of 41 evaluable CNRP participants attended the 2-month follow-up. Median weight (63.4 kg), KPS (80%), endurance (6MWT 570 m), and strength (RGHS 28 kg) were all improved. Edmonton symptom assessment scores (36 vs 27) and C-reactive protein levels (39 vs 22) fell. Participants were significantly more likely to return for re-evaluation if at baseline they were having anticancer therapy (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.3-16.2) or could walk >420 m in 6 min (OR 21, 95% CI 1.9-227). CONCLUSION: A CNRP may be beneficial for patients with advanced cancer and the ACS, but identification of patients who are likely to stay on the program is needed.

Evolución de la capacidad aeróbica del paciente EPOC tras entrenamiento de la musculatura periférica / Evolution of the aerobic capacity of the copd patient after training of the peripheral musculature

Objetivo: Evaluar el efecto de un programa de entrenamiento de alta intensidad a intervalos sobre la musculatura periférica de un grupo pacientes EPOC. Material y métodos: Se incluyeron 18 enfermos (10 hombres y 8 mujeres) con una media de edad de 57,5 años. Todos ellos realizaron entrenamiento de alta intensidad a intervalos en cicloergómetro durante 10 semanas, con 3 sesiones por semana. La duración de cada sesión fue de 45min. Antes del inicio del entrenamiento y una vez finalizado este, se practicaron ergometrías a todos los pacientes. Resultados: Se hallaron mejorías significativas en el trabajo físico total o potencia máxima tolerada (PMT) (p<0,001), consumo máximo de oxígeno (VO2 máx) (p<0,003), unidades metabólicas (MET) (p<0,003) y sensación de disnea (p<0,001). La frecuencia cardíaca no se modificó de forma significativa (p<0,44) al comparar los datos pre y postentrenamiento para esta variable. Conclusiones: El entrenamiento de alta intensidad a intervalos mejoró la condición física y la tolerancia al ejercicio en enfermos EPOC (AU)

Objective: Evaluate the effect of a high-intensity training program at intervals on the peripheral musculature of a group of COPD patients. Material and methods: The group of subjects consisted of 18 ill patients (10 men and 8 women) averaging 57.5 years of age. During 10 weeks, all of them underwent high-intensity training at intervals in cycloergometry, on a weekly basis of three sessions. Each session lasted 45min. Before starting and after finishing each session, ergometries were performed on every patient. Results: There were considerable improvements in the total physical activity or Maximum Tolerated Potency (MTP) (p<0.001), in the Maximum Oxygen Consumption (VO2 max) (p<0.003), in the metabolic units (MU) (p<0.003), and in the feeling of dyspnea (p<0.001). The comparison of pre-training and post-training information for the cardiac frecuency reveals that this variable was not significantly altered (p<0.44) Conclusions: The high-intensity training program at intervals improved the physical condition of the COPD patients and their tolerance to physical exercise (AU)

Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease.

BACKGROUND: Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD. METHODS: Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25). RESULTS: No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean -23.1 m (95% CI -71.7 to 25.5) post loading and -21.5 m (95% CI -90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score -7.7 (95% CI -14.9 to -0.5)). CONCLUSIONS: Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD.

Modafinil augmentation of mirtazapine in a failure-to-thrive geriatric inpatient.

The failure-to-thrive syndrome in geriatric patients is marked by social withdrawal, apathy, depression, anorexia, and cognitive impairment. For therapy to be effective, the treatment plan must target several of theseareas. This case report describes one such course of treatment for a patient with multiple myeloma with failure-to-thrive who was successfully treated with modafinil and mirtazapine. By using combination pharmacotherapy, we were able to achieve immediate results in a gravely ill patient.