Exercise and cancer-related lymphedema in the lower limbs-a randomized cross-over trial on high-intensity interval training (HIIT) with and without compression garments

Purpose: The aim was to evaluate the safety and possibility of performing high-intensity interval training (HIIT) on a stationary bike for participants with cancer-related lower limb lymphedema (LLL) with and without compression garments in a cross-over design. Methods: Twenty-one participants with LLL were randomized to two sessions of HIIT on a stationary bike, one with and one without compression garments. The sessions were separated by a seven-day washout period. The trial was carried out in a hospital setting from September to November 2018. The acceptability and safety of the intervention were assessed. The safety was evaluated as adverse events and immediate and 24-h changes in self-reported symptoms (pain, heaviness, and tension). Additionally, recruitment, completion rate, and post-exercise changes in LLL were assessed by circumferential measurements of the legs, dual energy X-ray absorptiometry (DXA), and bioimpedance spectroscopy (BIS), respectively. Results: Twenty-one out of 35 (60%) eligible patients were included, and 19 (90%) patients completed both exercise sessions. Acceptability was high, and there were no adverse events. There was no clinically relevant difference between performing exercise with and without compression in self-reported symptoms or in limb volume. Small statistically significant differences in soft tissue mass (164.2 g corresponding to 1.4%) and extracellular fluid (L-Dex range &lt; 5 units) were observed with and without compression, respectively, both favoring exercise with compression. Conclusion: HIIT on a stationary bike was acceptable for patients with LLL and seemed safe regardless of the use of compression garments. Trial registration: Clinicaltrials.gov registration (NCT03653819).</p

Osteoporosis among Fallers without Concomitant Fracture Identified in an Emergency Department: Frequencies and Risk Factors

We aimed to determine whether the Emergency Department (ED) is a suitable entrance point for osteoporosis screening among fallers without concomitant fracture compared to referral from general practice. Furthermore, to identify factors associated with osteoporosis among fallers. Methods. Patients aged 50–80 years sustaining a low-energy fall without fracture were identified from an ED (n = 199). Patients answered a questionnaire on risk factors and underwent osteodensitometry. Data was compared to a group of patients routinely referred to osteodensitometry from general practice (n = 201). Results. Among the 199 included fallers, 41 (21%) had osteoporosis. Among these, 35 (85%) reported either previous fracture or reduced body height (>3 cm). These two risk factors were more frequent among fallers with osteoporosis compared to fallers with normal bone mineral density or osteopenia (previous fracture P = .044, height reduction P = .0016). The osteoporosis frequency among fallers from ED did not differ from a similarly aged patient-group referred from general practice (P = .34). Conclusion. Osteodensitometry should be considered among fallers without fracture presenting in the ED, especially if the patient has a prior fracture or declined body height. Since fallers generally have higher fracture risk, the ED might serve as an additional entrance to osteodensitometry compared to referral from primary care

Similar clinical outcome after unicompartmental knee arthroplasty using a conventional or accelerated care program: A randomized, controlled study of 40 patients

Background and purpose Over the last 5 years, there has been increasing interest in reducing length of hospitalization (LOS) through accelerated programs. We examined the clinical outcome of patients undergoing a unicompartmental knee replacement (UKR) in an accelerated care program (A group) compared to a conventional care program (C group)

Exercise-Mediated Lowering of Glutamine Availability Suppresses Tumor Growth and Attenuates Muscle Wasting

Glutamine is a central nutrient for many cancers, contributing to the generation of building blocks and energy-promoting signaling necessary for neoplastic proliferation. In this study, we hypothesized that lowering systemic glutamine levels by exercise may starve tumors, thereby contributing to the inhibitory effect of exercise on tumor growth. We demonstrate that limiting glutamine availability, either pharmacologically or physiologically by voluntary wheel running, significantly attenuated the growth of two syngeneic murine tumor models of breast cancer and lung cancer, respectively, and decreased markers of atrophic signaling in muscles from tumor-bearing mice. In continuation, wheel running completely abolished tumor-induced loss of weight and lean body mass, independently of the effect of wheel running on tumor growth. Moreover, wheel running abolished tumor-induced upregulation of muscular glutamine transporters and myostatin signaling. In conclusion, our data suggest that voluntary wheel running preserves muscle mass by counteracting muscular glutamine release and tumor-induced atrophic signaling

Progressive resistance training in head and neck cancer patients during concomitant chemoradiotherapy:design of the DAHANCA 31 randomized trial

Abstract Background Head and neck cancer patients undergoing concomitant chemoradiotherapy (CCRT) frequently experience loss of muscle mass and reduced functional performance. Positive effects of exercise training are reported for many cancer types but biological mechanisms need further elucidation. This randomized study investigates whether progressive resistance training (PRT) may attenuate loss of muscle mass and functional performance. Furthermore, biochemical markers and muscle biopsies will be investigated trying to link biological mechanisms to training effects. Methods At the Departments of Oncology at Herlev and Aarhus University Hospitals, patients with stage III/IV squamous cell carcinoma of the head and neck, scheduled for CCRT are randomized 1:1 to either a 12-week PRT program or control group, both with 1 year follow-up. Planned enrollment is 72 patients, and stratification variables are study site, sex, p16-status, and body mass index. Primary endpoint is difference in change in lean body mass (LBM) after 12 weeks of PRT, assessed by dual-energy X-ray absorptiometry (DXA). The hypothesis is that 12 weeks of PRT can attenuate the loss of LBM by at least 25%. Secondary endpoints include training adherence, changes in body composition, muscle strength, functional performance, weight, adverse events, dietary intake, self-reported physical activity, quality of life, labor market affiliation, blood biochemistry, plasma cytokine concentrations, NK-cell frequency in blood, sarcomeric protein content in muscles, as well as muscle fiber type and fiber size in muscle biopsies. Muscle biopsies are optional. Discussion This randomized study investigates the impact of a 12-week progressive resistance training program on lean body mass and several other physiological endpoints, as well as impact on adverse events and quality of life. Furthermore, a translational approach is integrated with extensive biological sampling and exploration into cytokines and mechanisms involved. The current paper discusses decisions and methods behind exercise in head and neck cancer patients undergoing concomitant chemoradiotherapy. Trial registration Approved by the Regional Ethics Committee for the Capital Region of Denmark (protocol id: H-15003725) and registered retrospectively at ClinicalTrials.gov ( NCT02557529 ) September 11th 2015

Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles

Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo

High-intensity resistance and impact training for patients with hormone-sensitive prostate cancer and bone metastases—study protocol of a randomized clinical trial

Background: Men with metastatic prostate cancer are at an increased risk of metabolic syndrome, cardiovascular disease, and pathological fracture. The latter is both attributed to the cancer itself, bones are the most common site of metastases in prostate cancer, as well as the treatment with androgen deprivation therapy. Exercise therapy has been shown to be beneficial, but with uncertainty about its safety, applicability, and suitability for patients with prostate cancer and bone metastases. In these patients, we aim to investigate the safety and efficacy of exercise therapy that specifically targets bone in terms of bone density in the legs. Methods/design: This blinded, randomized, controlled trial will include 102 patients with prostate cancer and bone metastases. Participants will be assigned to a supervised 32-week high-intensity progressive resistance and impact training program (intervention group) or standard treatment including a municipal 12-week standard training program, if desired (control group). Primary outcomes are changes in physical capacity and lower extremity strength measured by the 30-s Chair Stand Test. Secondary outcomes include bone mineral density and body composition, physical function, quality of life, safety (i.e., adverse events and pain), hospitalizations, physical activity, falls, feasibility, and patient experiences. Data will be collected at baseline, midway intervention (16 weeks), post-intervention (32 weeks), and follow-up (44 weeks). Discussion: This study is the first to examine a long-term high-intensity progressive resistance and impact training in patients with prostate cancer and bone metastases. While exercise recommendations for these patients have typically been cautious, high-intensity progressive resistance and impact training has demonstrated safety and benefit in patients with osteoporosis. This research will shed light on the efficacy and safety of progressive resistance and impact training in patients with prostate cancer and bone metastases, potentially improving treatment-related side effects and quality of life. Trial registration: This trial is approved by the Regional Ethics Committee for the Capital Region of Denmark (J.nr.:H-23015286) and by the Danish Data Protection Agency (j.nr.: P-2023–2018). The study was prospectively registered at ClinicalTrials.gov on February 24, 2024 (ID: NCT06259279).</p

Oxygen conserving mitochondrial adaptations in the skeletal muscles of breath hold divers

BackgroundThe performance of elite breath hold divers (BHD) includes static breath hold for more than 11 minutes, swimming as far as 300 m, or going below 250 m in depth, all on a single breath of air. Diving mammals are adapted to sustain oxidative metabolism in hypoxic conditions through several metabolic adaptations, including improved capacity for oxygen transport and mitochondrial oxidative phosphorylation in skeletal muscle. It was hypothesized that similar adaptations characterized human BHD. Hence, the purpose of this study was to examine the capacity for oxidative metabolism in skeletal muscle of BHD compared to matched controls.MethodsBiopsies were obtained from the lateral vastus of the femoral muscle from 8 Danish BHD and 8 non-diving controls (Judo athletes) matched for morphometry and whole body VO2max. High resolution respirometry was used to determine mitochondrial respiratory capacity and leak respiration with simultaneous measurement of mitochondrial H2O2 emission. Maximal citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HAD) activity were measured in muscle tissue homogenates. Western Blotting was used to determine protein contents of respiratory complex I-V subunits and myoglobin in muscle tissue lysates.ResultsMuscle biopsies of BHD revealed lower mitochondrial leak respiration and electron transfer system (ETS) capacity and higher H2O2 emission during leak respiration than controls, with no differences in enzyme activities (CS and HAD) or protein content of mitochondrial complex subunits myoglobin, myosin heavy chain isoforms, markers of glucose metabolism and antioxidant enzymes.ConclusionWe demonstrated for the first time in humans, that the skeletal muscles of BHD are characterized by lower mitochondrial oxygen consumption both during low leak and high (ETS) respiration than matched controls. This supports previous observations of diving mammals demonstrating a lower aerobic mitochondrial capacity of the skeletal muscles as an oxygen conserving adaptation during prolonged dives.</div

The effects of empagliflozin on measured glomerular filtration rate and estimated extracellular and plasma volumes in patients with type 2 diabetes

Aims: To investigate the effects of empagliflozin on measured glomerular filtration rate (mGFR), estimated plasma volume (PV) and estimated extracellular volume (ECV) in a cohort of patients with type 2 diabetes (T2D) and high risk of cardiovascular events. Materials and Methods: In this prespecified substudy of the randomized, placebo-controlled SIMPLE trial, patients with T2D at high risk of cardiovascular events were allocated to either empagliflozin 25 mg or placebo once daily for 13 weeks. The prespecified outcome was between-group change in mGFR, measured by the 51Cr-EDTA method after 13 weeks; changes in estimated PV and estimated ECV were included. Results: From April 4, 2017 to May 11, 2020, 91 participants were randomized. Of these, 45 patients from the empagliflozin group and 45 patients from the placebo group were included in the intention-to-treat analysis. Treatment with empagliflozin reduced mGFR by −7.9 mL/min (95% confidence interval [CI] −11.1 to −4.7; P &lt; 0.001), estimated ECV by −192.5 mL (95% CI −318.0 to −66.9; P = 0.003) and estimated PV by −128.9 mL (95% CI −218.0 to 39.8; P = 0.005) at Week 13. Conclusions: Treatment with empagliflozin for 13 weeks reduced mGFR, estimated ECV and estimated PV in patients with T2D and high risk of cardiovascular events.</p