Body Composition, Symptoms, and Survival in Advanced Cancer Patients Referred to a Phase I Service

Background: Body weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown. Methods: We reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI); body composition was evaluated utilizing computerized tomography(CT) images. A body mass index (BMI)$25 kg/m 2 was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria. Results: Most patients were overweight (n = 65, 63$25 kg/m 2. Sarcopenic patients were older and less frequently African-American. Symptom burden did not differ among patients classified according to BMI and presence of sarcopenia. Median (95% confidence interval) survival (days) varied according to body composition: 215 (71–358) (BMI,25 kg/m 2; sarcopenic), 271 (99–443) (BMI,25 kg/m 2; non-sarcopenic), 484 (286–681) (BMI$25 kg/m 2; sarcopenic); 501 d (309–693) (BMI$25 kg/m 2; non-sarcopenic). Higher muscle index and gastrointestinal cancer diagnosis predicted longer survival in multivariate analysis after controlling for age, gender, performance status, and fat index. Conclusions: Patients referred to a Phase I clinic had a high frequency of sarcopenia and a BMI$25 kg/m 2, independent o

Locomotion and muscle mass measures in a murine model of collagen-induced arthritis

Background: Rheumatoid arthritis (RA) is characterized by chronic poly-arthritis, synovial hyperplasia, erosive synovitis, progressive cartilage and bone destruction accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in the skeletal muscle and can in part be explained by a decreased physical activity. The murine collagen induced arthritis (CIA) model has been proven to be a useful model in RA research since it shares many immunological and pathological features with human RA. The present study explored the interactions between arthritis development, locomotion and muscle mass in the CIA model. Methods: CIA was induced in male DBA/1 mice. Locomotion was registered at different time points by a camera and evaluated by a computerized tracing system. Arthritis severity was detected by the traditionally used semi-quantitative clinical scores. The muscle mass of the hind-legs was detected at the end of the study by weighing. A methotrexate (MTX) intervention group was included to study the applicability of the locomotion and muscle mass for testing effectiveness of interventions in more detail. Results: There is a strong correlation between clinical arthritis and locomotion. The correlations between muscle mass and locomotion or clinical arthritis were less pronounced. MTX intervention resulted in an improvement of disease severity accompanied by an increase in locomotion and muscle mass. Conclusion: The present data demonstrate that registration of locomotion followed by a computerized evaluation of the movements is a simple non invasive quantitative method to define disease severity and evaluate effectiveness of therapeutic agents in the CIA model.

Reference values for body composition and associations with blood pressure in Kenyan adults aged ≥50 years old

Objectives: To develop age and sex-specific centile reference curves for fat free mass (FFM) and fat mass (FM) adjusted for height in an adult Kenyan population and to investigate the association between FM, FFM and blood pressure (BP). Methods: Measures of body composition from bioimpedance analyses and BP were collected in 1,995 participants aged ≥50y in Nakuru County, Kenya. Reference curves were produced using the LMS method. Multivariable linear regression models were used to test the cross-sectional association between body composition indexes and BP. Results: The age and sex-specific reference curves for body composition (FMI and FFMI) confirm that FFMI is lower in both men and women with increasing age. FMI declines with age in women while among men the decline starts after 70 years. FFM was higher in men (47.4 ± 7.2 kg) than in women (38.8 ± 5.5 kg), while FM was lower in men (17.3 ± 8.1 kg) than in women (24.4 ± 10.2 kg). FMI, FFMI and BMI were all positively associated with systolic and diastolic BP, and after adjusting for body weight, FFMI remained positively associated with systolic BP and the FMI remained positively associated with diastolic BP. There was no evidence to suggest that FMI and FFMI were superior to measurement of BMI alone. Conclusion: These body composition reference curves provide normative data on body composition for older adults in Kenya. Further research should consider the prospective associations with health, including frailty-related outcomes

Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project)

Objective: To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. Design: Evaluator blinded, randomised controlled trial. Setting: 16 clinical sites across 11 European countries, January 2016 to 31 October 2019. Participants: 1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls). Interventions: The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months. Main outcome measures: The primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes. Results: Mean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; P<0.001) and 1.0 point (95% confidence interval 0.5 to 1.6 points; P<0.001) in favour of the multicomponent intervention at 24 and 36 months, respectively. The decline in handgrip strength at 24 months was smaller in women assigned to the multicomponent intervention than to control (0.9 kg, 95% confidence interval 0.1 to 1.6 kg; P=0.028). Women in the multicomponent intervention arm lost 0.24 kg and 0.49 kg less appendicular lean mass than controls at 24 months (95% confidence interval 0.10 to 0.39 kg; P<0.001) and 36 months (0.26 to 0.73 kg; P<0.001), respectively. Serious adverse events occurred in 237/605 (39.2%) participants assigned to the multicomponent intervention and 216/600 (36.0%) controls (risk ratio 1.09, 95% confidence interval 0.94 to 1.26). In participants with SPPB scores of 8 or 9, mobility disability occurred in 46/155 (29.7%) in the multicomponent intervention and 38/159 (23.9%) controls (hazard ratio 1.25, 95% confidence interval 0.79 to 1.95; P=0.34). Conclusions: A multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people

Metabolic syndrome and risk factors for cardiovascular disease: are nonagenarians protected?

This study assessed cardiovascular disease risk factors in three groups of human subjects aged 20–34 [young, 20 male (M)/33 female (F)], 60–74 (aged, 29M/29F), and > 90 years (nonagenarian, 47M/50F). Components of the metabolic syndrome, cardiovascular disease, and markers of inflammation and oxidative stress were assessed. Nonagenarians weighed less than the two other groups (P < 0.001); however, there was no difference in percent fat among the three groups. Aged individuals had the highest prevalence of the metabolic syndrome (P < 0.001) according to the Adult Treatment Panel III classification. Both fibrinogen and homocysteine concentrations were significantly higher in the nonagenarians compared to younger groups. However, there were no significant differences between groups in fasting insulin, high sensitive C-reactive protein, and plasminogen activator inhibitor 1 concentrations. There were also no relationships between inflammation/ oxidative stress and the metabolic syndrome or cardiovascular disease although nonagenarians appear to be protected from oxidative damage to DNA

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Beneficial effects of physical activity in an HIV-infected woman with lipodystrophy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lipodystrophy is common in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy, and presents with morphologic changes and metabolic alterations that are associated with depressive behavior and reduced quality of life. We examined the effects of exercise training on morphological changes, lipid profile and quality of life in a woman with human immunodeficiency virus presenting with lipodystrophy.</p> <p>Case presentation</p> <p>A 31-year-old Latin-American Caucasian woman infected with human immunodeficiency virus participated in a 12-week progressive resistance exercise training program with an aerobic component. Her weight, height, skinfold thickness, body circumferences, femur and humerus diameter, blood lipid profile, maximal oxygen uptake volume, exercise duration, strength and quality of life were assessed pre-exercise and post-exercise training. After 12 weeks, she exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC) (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high-density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%), exercise duration (37.5%) and strength (65.5%). Quality of life measures improved mainly for psychological and physical measures, independence and social relationships.</p> <p>Conclusions</p> <p>These findings suggest that supervised progressive resistance exercise training is a safe and effective treatment for evolving morphologic and metabolic disorders in adults infected with HIV receiving highly active antiretroviral therapy, and improves their quality of life.</p