The potential therapeutic effects of creatine supplementation on body composition and muscle function in cancer

Low muscle mass in individuals with cancer has a profound impact on quality of life and independence and is associated with greater treatment toxicity and poorer prognosis. Exercise interventions are regularly being investigated as a means to ameliorate treatment-related adverse effects, and nutritional/supplementation strategies to augment adaptations to exercise are highly valuable. Creatine (Cr) is a naturally-occurring substance in the human body that plays a critical role in energy provision during muscle contraction. Given the beneficial effects of Cr supplementation on lean body mass, strength, and physical function in a variety of clinical populations, there is therapeutic potential in individuals with cancer at heightened risk for muscle loss. Here, we provide an overview of Cr physiology, summarize the evidence on the use of Cr supplementation in various aging/clinical populations, explore mechanisms of action, and provide perspectives on the potential therapeutic role of Cr in the exercise oncology setting

Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: A randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine

Background: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods: This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion: Exercise medicine may positively alter tumour biology through numerous mechanical and nonmechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration: anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016

Priorities, policies and (time)scales : the delivery of emissions reductions in the UK transport sector

Peer reviewedPreprin

Exercise effects on muscle quality in older adults: A systematic review and meta-analysis

To systematically review and analyse the effects of exercise on morphological and neuromuscular muscle quality (MQ) outcomes in older adults and assess a range of possible moderators that may affect the impact of exercise on MQ outcomes. Using PRISMA guidelines, randomised controlled trials were searched in CINAHL, EMBASE, LILACS, PubMed, SciELO, Web of Science, MedNar, OpenGrey and OpenThesis databases. Eligible trials examined the effects of exercise interventions on morphological and neuromuscular MQ in older adults ( ≥ 60 years). Twenty-one trials (n = 973 participants) were included. Exercise significantly improved morphological MQ (effect size (ES) = 0.32, 95% CI 0.13–0.51, P \u3c 0.001) with significant results maintained for studies assessing muscle density and intermuscular adipose tissue (ES = 0.45–0.52, P \u3c 0.05). For neuromuscular MQ, exercise provided significant positive effects (ES = 0.49, 95% CI 0.29–0.69, P \u3c 0.001) but only maintained for physically healthy participants (ES = 0.43, P \u3c 0.001), resistance exercise interventions (ES = 0.64, P \u3c 0.001), or studies assessing 1-RM or knee extensor isokinetic muscle strength relative to leg lean mass (ES = 0.48–0.62, P = 0.001). Associations between exercise duration and changes in MQ measures were not observed (P \u3e 0.05). Supervised exercise interventions significantly improved different measures of MQ regardless of exercise duration, although these effects were small-to-moderate and not supported across all population-, exercise-, and methods-related features

Effects of short- and long-term exercise training on cancer cells in vitro: Insights into the mechanistic associations

Exercise is a therapeutic approach in cancer treatment, providing several benefits. Moreover, exercise is associated with a reduced risk for developing a range of cancers and for their recurrence, as well as with improving survival, even though the underlying mechanisms remain unclear. Preclinical and clinical evidence shows that the acute effects of a single exercise session can suppress the growth of various cancer cell lines in vitro. This suppression is potentially due to altered concentrations of hormones (e.g., insulin) and cytokines (e.g., tumor necrosis factor alpha and interleukin 6) after exercise. These factors, known to be involved in tumorigenesis, may explain why exercise is associated with reduced cancer incidence, recurrence, and mortality. However, the effects of short- (\u3c8 weeks) and long-term (≥8 weeks) exercise programs on cancer cells have been reported with mixed results. Although more research is needed, it appears that interventions incorporating both exercise and diet seem to have greater inhibitory effects on cancer cell growth in both apparently healthy subjects as well as in cancer patients. Although speculative, these suppressive effects on cancer cells may be driven by changes in body weight and composition as well as by a reduction in low-grade inflammation often associated with sedentary behavior, low muscle mass, and excess fat mass in cancer patients. Taken together, such interventions could alter the systemic levels of suppressive circulating factors, leading to a less favorable environment for tumorigenesis. While regular exercise and a healthy diet may establish a more cancer-suppressive environment, each acute bout of exercise provides a further “dose” of anticancer medicine. Therefore, integrating regular exercise could potentially play a significant role in cancer management, highlighting the need for future investigations in this promising area of research

Resistance exercise dosage in men with prostate cancer: Systematic review, meta-analysis and meta-regression

Purpose Resistance training (RT) improves an array of treatment-related adverse effects in men with prostate cancer, however, the minimal dosage required is unknown. We systematically reviewed the RT effects in prostate cancer patients to determine the minimal dosage regarding the exercise components (type, duration, volume, and intensity) on body composition, physical function, muscle strength, cardiorespiratory fitness, body mass index (BMI), and prostate-specific antigen (PSA). Methods Using PRISMA guidelines, MEDLINE, CINAHL, EMBASE, SPORTDiscus, and Web of Science databases were searched. Eligible randomised controlled trials examined prostate cancer patients undertaking resistance-based exercise programs during or following treatment. Meta-analysis was undertaken when more than 3 studies were included. Associations between mean differences and the exercise components were tested by univariate and multivariate meta-regression analysis. Results Twenty-four papers describing 22 trials and involving 1,888 prostate cancer patients were included. Exercise improved fat mass (-1% in body fat and -0.5 kg in fat mass), lean mass (+0.5 kg in lean and appendicular lean mass), functional capacity (i.e., chair rise, 400-m test, 6-m fast walk and stair climb tests) and fitness outcomes (i.e., VO2 peak and muscle strength) (P=0.040 - \u3c 0.001) with no change in BMI or PSA (P= .440 - .735). Meta-regression indicated no association between exercise type, RT duration, weekly volume and intensity and primary outcomes (P= .075 - .965). There was a significant association between RT intensity and chest press muscle strength (favouring moderate-intensity, P= .012), but not in other secondary outcomes. Conclusion In untrained older men with prostate cancer initiating an exercise program, lower volume at moderate-to-high intensity is as effective as higher volume RT for enhancing body composition, functional capacity and muscle strength in the short-term

The project did not come to us with a solution : Perspectives of research teams on implementing a study about electronic health record-embedded individualized pain plans for emergency department treatment of vaso-occlusive episodes in adults with sickle cell disease

BACKGROUND: This study aimed to capture the implementation process of the ALIGN Study, (An individualized Pain Plan with Patient and Provider Access for Emergency Department care of Sickle Cell Disease). ALIGN aimed to embed Individualized Pain Plans in the electronic health record (E-IPP) and provide access to the plan for both adult patients with sickle cell disease (SCD) and emergency department providers when a person with SCD comes to the emergency department in vaso-occlusive crises. METHODS: Semi-structured interviews were conducted with research teams from the 8 participating sites from the ALIGN study. Seventeen participants (principal investigators and study coordinators) shared their perspectives about the implementation of ALIGN in their sites. Data were analyzed in three phases using open coding steps adapted from grounded theory and qualitative content analysis. RESULTS: A total of seven overarching themes were identified: (1) the E-IPP structure (location and upkeep) and collaboration with the informatics team, (2) the role of ED champion, (3) the role of research coordinators, (4) research team communication, and communication between research team and clinical team, (5) challenges with the study protocol, (6) provider feedback: addressing over-utilizers, patient mistrust, and the positive feedback about the intervention, and (7) COVID-19 and its effects on study implementation. CONCLUSIONS: Findings from this study contribute to learning how to implement E-IPPs for adult patients with SCD in ED. The study findings highlight the importance of early engagement with different team members, a champion from the emergency department, study coordinators with different skills and enhancement of communication and trust among team members. Further recommendations are outlined for hospitals aiming to implement E-IPP for patients with SCD in ED

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

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\u3c .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

Recreational soccer as sport medicine for middle-aged and older adults: A systematic review

Background Strategies to prevent or attenuate the age-related decline in physical and physiological function and reduce chronic disease risk factors are of clinical importance. Objective To examine the health benefits of recreational soccer in middle-aged and older adults. Design Systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources All available records up until 9 June 2017 in PubMed, Web of Science, SPORTDiscus, MEDLINE, Embase, CINAHL Plus, PsycINFO and Cochrane Library databases. Eligibility criteria for selecting studies All randomised trials with or without a control group (randomised controlled trials or randomised uncontrolled trials) and non-randomised controlled trials that used recreational soccer, which includes small-sided soccer games, as the sole or principal intervention, and reported relevant effects in untrained/sedentary, healthy or unhealthy adults aged 40 years and above were included. Results Five trials described in 13 articles were included, which scored 6–9 out of 12 points on the modified Delphi quality rating scale. The duration was from 12 to 52 weeks, with various frequencies, volumes and game formats performed both outdoors and indoors with men and women. The trials indicate that recreational soccer may result in improvement in cardiovascular function, body composition and functional ability, although no significant changes were observed in postural balance. Conclusion Recreational soccer should be considered an alternative exercise modality for untrained, healthy or unhealthy middle-aged and older adults of both sexes to maintain an active lifestyle and mitigate a wide array of physical and physiological age-related changes