Increased mitochondrial surface area and cristae density in the skeletal muscle of strength athletes.

Mitochondria are the cellular organelles responsible for resynthesising the majority of ATP. In skeletal muscle, there is an increased ATP turnover during resistance exercise to sustain the energetic demands of muscle contraction. Despite this, little is known regarding the mitochondrial characteristics of chronically strength-trained individuals and any potential pathways regulating the strength-specific mitochondrial remodelling. Here, we investigated the mitochondrial structural characteristics in skeletal muscle of strength athletes and age-matched untrained controls. The mitochondrial pool in strength athletes was characterised by increased mitochondrial cristae density, decreased mitochondrial size, and increased surface-to-volume ratio, despite similar mitochondrial volume density. We also provide a fibre-type and compartment-specific assessment of mitochondria morphology in human skeletal muscle, which reveals across groups a compartment-specific influence on mitochondrial morphology that is largely independent of fibre type. Furthermore, we show that resistance exercise leads to signs of mild mitochondrial stress, without an increase in the number of damaged mitochondria. Using publicly available transcriptomic data we show that acute resistance exercise increases the expression of markers of mitochondrial biogenesis, fission and mitochondrial unfolded protein responses (UPRmt ). Further, we observed an enrichment of the UPRmt in the basal transcriptome of strength-trained individuals. Together, these findings show that strength athletes possess a unique mitochondrial remodelling, which minimises the space required for mitochondria. We propose that the concurrent activation of markers of mitochondrial biogenesis and mitochondrial remodelling pathways (fission and UPRmt ) with resistance exercise may be partially responsible for the observed mitochondrial phenotype of strength athletes. KEY POINTS: Untrained individuals and strength athletes possess comparable skeletal muscle mitochondrial volume density. In contrast, strength athletes' mitochondria are characterised by increased cristae density, decreased size and increased surface-to-volume ratio. Type I fibres have an increased number of mitochondrial profiles with minor differences in the mitochondrial morphological characteristics compared with type II fibres. The mitochondrial morphology is distinct across the subcellular compartments in both groups, with subsarcolemmal mitochondria being bigger in size when compared with intermyofibrillar. Acute resistance exercise leads to signs of mild morphological mitochondrial stress accompanied by increased gene expression of markers of mitochondrial biogenesis, fission and mitochondrial unfolded protein response (UPRmt ).

Sarcopenia and loss of muscle mass in patients with lung cancer undergoing chemotherapy treatment: a systematic review and meta-analysis.

BACKGROUND: In patients with cancer, sarcopenia is associated with treatment related complications, treatment cessation, poor quality of life and reduced overall survival. Despite this, there is limited knowledge about changes in skeletal muscle mass during chemotherapy. The aim of this systematic review and meta-analysis was to investigate the change of skeletal muscle mass and sarcopenia during chemotherapy treatment among patients with lung cancer. METHODS: A systematic literature search was conducted in three databases, PubMed, EMBASE and Web of Science. Observational studies with patients with lung cancer were eligible for inclusion if skeletal muscle mass was measured before and after receiving chemotherapy treatment. RESULTS: Ten cohort studies with a total of 867 participants met the inclusion criteria. During 5.2 ± 2.9 months of chemotherapy treatment, patients with lung cancer experienced a significant loss of skeletal muscle mass with a standardized mean difference (SMD) of: -0.25 (95% CI -0.47 to -0.03). The pretreatment prevalence of sarcopenia varied across studies from 35% to 74%. Only one study reported prevalence of sarcopenia both before and after chemotherapy treatment with an increase from 35% to 59%. CONCLUSION: The present data demonstrate a marked loss of skeletal muscle mass in patients with lung cancer undergoing chemotherapy treatment, as well as a high prevalence of sarcopenia. As sarcopenia is associated with poor clinical outcomes, it seems important to include and use assessments of skeletal muscle mass in clinical practice to identify patients in need for interventions. Moreover, interventional studies to hinder development of sarcopenia are needed.

Reasons for lack of treatment in patients with locally advanced, unresectable or metastatic urothelial carcinoma.

BACKGROUND: The proportion of patients with locally advanced, unresectable or metastatic urothelial carcinoma that do not receive systemic anticancer treatment and the reasons for lack of treatment are largely unknown. The aim of this study was to investigate the prevalence and overall survival of this patient group and reasons for omission of treatment. MATERIAL AND METHODS: This retrospective, single-center cohort study from Rigshospitalet, Denmark included patients diagnosed with locally advanced, unresectable or metastatic urothelial carcinoma during the study period from 1 January 2010 to 31 March 2016 who did not receive systemic anticancer treatment. Patients were identified through the Danish Pathology Register and the electronic medical records. RESULTS: 100 patients were included, representing 34% of all patients diagnosed with locally advanced, unresectable or metastatic urothelial carcinoma at Rigshospitalet during the study period. Lack of treatment was most often due to poor physical condition (59%), decreased renal function (15%), or patient preferences (14%). Median overall survival was 1.9 months (95% CI: 1.6-2.8 months). CONCLUSION: One in three patients diagnosed with locally advanced, unresectable or metastatic urothelial carcinoma in the pre-immunotherapy era did not receive systemic anticancer treatment. Prompt identification of advanced disease and interventions to optimize these patients for treatment are essential. Our findings underscore the compelling need for novel, better tolerated treatment regimens in this frail patient group.

Effects of age on muscle power, postural control and functional capacity after short-term immobilization and retraining.

OBJECTIVES: This study investigated the effect of lower limb immobilization and retraining on postural control and muscle power in healthy old and young men. METHODS: Twenty men, nine old (OM:67.3±4.4 years) and eleven young (YM:24.4±1.6 years) underwent 2 weeks of unilateral whole-leg casting, followed by 4 weeks of retraining. Measures included center of pressure (CoP) sway length and area during single- and double-leg stance, maximal leg extensor muscle power, habitual and maximal 10-m gait speed, sit-to-stand performance, and 2-min step test. RESULTS: After immobilization, leg extension muscle power decreased by 15% in OM (from 2.68±0.60 to 2.29±0.63 W/kg, p<0.05) and 17% in YM (4.37±0.76 to 3.63±0.69 W/kg, p<0.05). Double-leg CoP sway area increased by 45% in OM (218±82 to 317±145 mm2; p<0.05), with no change in YM (p=0.43). Physical function did not change after immobilization but sit-to-stand performance (+20%, p<0.05) and 2-min step test (+28%, p<0.05) increased in OM following retraining. In both groups, all parameters returned to baseline levels after retraining. CONCLUSION: Two weeks of lower limb immobilization led to decreases in maximal muscle power in both young and old, whereas postural control was impaired selectively in old men. All parameters were restored in both groups after 4 weeks of resistance-based retraining.

Arm lean mass determined by dual-energy X-ray absorptiometry is superior to characterize skeletal muscle and predict sarcopenia-related mortality in cirrhosis.

Sarcopenia worsens survival in patients with advanced liver disease including cirrhosis. In this study, we aimed to characterize skeletal muscle status by dual-energy X-ray absorptiometry (DXA) in patients with cirrhosis and examine the association between different skeletal muscle compartments and mortality. We included 231 men and 84 women (Child A, B, and C) with cirrhosis and 315 healthy matched controls (231 men and 84 women). Body composition was assessed with DXA. Appendicular skeletal muscle index (ASMI), arms index (AI), and legs index (LI) were calculated by normalizing lean mass to height squared. Low ASMI was defined as ASMI < 7.0 kg/m2 in men and <5.5 kg/m2 in women. Biochemical and hemodynamic data were recorded for cirrhotic patients and mortality data retrieved from registers. Low ASMI was more prevalent in both men (49%) and women (43%) with cirrhosis compared with healthy men (8%) and women (5%) (P < 0.001). ASMI and LI were lowest in Child B, whereas AI decreased gradually with advancing Child class. ASMI was inversely associated with mortality in men [HR = 0.74 (0.59-0.93), P < 0.01], and this was mainly driven by AI [HR = 0.37 (0.18-0.71), P < 0.01]. AI showed closer association than ASMI or LI to both the severity of liver disease and to mortality, which may be due to increasing prevalence of leg edema with disease progression in this population. Determination of arm lean mass may add information on survival in patients with cirrhosis.NEW & NOTEWORTHY Sarcopenia increases mortality in patients with end-stage liver disease. We show that arm lean mass determined by dual-energy X-ray absorptiometry is a better marker than the traditional appendicular skeletal muscle mass when predicting sarcopenia-related mortality in patients with cirrhosis of different severity. The findings add to the dispute about the optimal method for repeated assessments of skeletal muscle status in patients with cirrhosis and may have implications for clinical decision making.

Mortality of older acutely admitted medical patients after early discharge from emergency departments: a nationwide cohort study.

BACKGROUND: The mortality of older patients after early discharge from hospitals is sparsely described. Information on factors associated with mortality can help identify high-risk patients who may benefit from preventive interventions. The aim of this study was to examine whether demographic factors, comorbidity and admission diagnoses are predictors of 30-day mortality among acutely admitted older patients discharged within 24 h after admission. METHODS: All medical patients aged ≥65 years admitted acutely to Danish hospitals between 1 January 2013 and 30 June 2014 surviving a hospital stay of ≤24 h were included. Demographic factors, comorbidity, discharge diagnoses and mortality within 30 days were described using data from the Danish National Patient Registry and the Civil Registration System. Cox regression was used to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for all-cause mortality. RESULTS: A total of 93,295 patients (49.4% men) with a median age of 75 years (interquartile range: 69-82 years), were included. Out of these, 2775 patients (3.0%; 95% CI 2.9-3.1%) died within 30 days after discharge. The 30-day mortality was increased in patients with age 76-85 years (aHR 1.59; 1.45-1.75) and 86+ years (aHR 3.35; 3.04-3.70), male gender (aHR 1.22; 1.11-1.33), a Charlson Comorbidity Index of 1-2 (aHR 2.15; 1.92-2.40) and 3+ (aHR 4.07; 3.65-4.54), and unmarried status (aHR 1.17; 1.08-1.27). Discharge diagnoses associated with 30-day mortality were heart failure (aHR 1.52; 1.17-1.95), respiratory failure (aHR 3.18; 2.46-4.11), dehydration (aHR 2.87; 2.51-3.29), constipation (aHR 1.31; 1.02-1.67), anemia (aHR 1.45; 1.27-1.66), pneumonia (aHR 2.24; 1.94-2.59), urinary tract infection (aHR 1.33; 1.14-1.55), dyspnea (aHR 1.57; 1.32-1.87) and suspicion of malignancy (aHR 2.06; 1.64-2.59). CONCLUSIONS: Three percent had died within 30 days. High age, male gender, the comorbidity burden, unmarried status and several primary discharge diagnoses were identified as independent prognostic factors of 30-day all-cause mortality.

Geriatric assessment and intervention in older vulnerable patients undergoing surgery for colorectal cancer: a protocol for a randomised controlled trial (GEPOC trial).

BACKGROUND: The incidence of colorectal cancer (CRC) increases with age. Older patients are a heterogeneous group ranging from fit to frail with various comorbidities. Frail older patients with CRC are at increased risk of negative outcomes and functional decline after cancer surgery compared to younger and fit older patients. Maintenance of independence after treatment is rarely investigated in clinical trials despite older patients value it as high as survival. Comprehensive geriatric assessment (CGA) is an evaluation of an older persons' medical, psychosocial, and functional capabilities to develop an overall plan for treatment and follow-up. The beneficial effect of CGA is well documented in the fields of medicine and orthopaedic surgery, but evidence is lacking in cancer surgery. We aim to investigate the effect of CGA on physical performance in older frail patients undergoing surgery for CRC. METHODS: GEPOC is a single centre randomised controlled trial including older patients (≥65 years) undergoing surgical resection for primary CRC. Frail patients (≤14/17 points using the G8 screening tool) will be randomised 1:1 to geriatric intervention and exercise (n = 50) or standard of care along (n = 50) with their standard surgical procedure. Intervention includes preoperative CGA, perioperative geriatric in-ward review and postoperative follow-up. All patients in the intervention group will participate in a pre- and postoperative resistance exercise programme (twice/week, 2 + 12 weeks). Primary endpoint is change in 30-s chair stand test. Assessment of primary endpoint will be performed by physiotherapists blinded to patient allocation. Secondary endpoints: changes in health related quality of life, physical strength and capacity (handgrip strength, gait speed and 6 min walking test), patient perceived quality of recovery, complications to surgery, body composition (Dual-energy X-ray absorptiometry and bioelectric impedance), serum biomarkers, readmission, length of stay and survival. DISCUSSION: This ongoing trial will provide valuable knowledge on whether preoperative CGA and postoperative geriatric follow-up and intervention including an exercise program can counteract physical decline and improve quality of life in frail CRC patients undergoing surgery. TRIAL REGISTRATION: Prospectively registered at Clinicaltrials.gov NCT03719573 (October 2018).

Assessment of acute bone loading in humans using [18F]NaF PET/MRI.

PURPOSE: The acute effect of loading on bone tissue and physiology can offer important information with regard to joint function in diseases such as osteoarthritis. Imaging studies using [18F]-sodium fluoride ([18F]NaF) have found changes in tracer kinetics in animals after subjecting bones to strain, indicating an acute physiological response. The aim of this study is to measure acute changes in NaF uptake in human bone due to exercise-induced loading. METHODS: Twelve healthy subjects underwent two consecutive 50-min [18F]NaF PET/MRI examinations of the knees, one baseline followed by one post-exercise scan. Quantification of tracer kinetics was performed using an image-derived input function from the popliteal artery. For both scans, kinetic parameters of KiNLR, K1, k2, k3, and blood volume were mapped parametrically using nonlinear regression with the Hawkins model. The kinetic parameters along with mean SUV and SUVmax were compared between the pre- and post-exercise examinations. Differences in response to exercise were analysed between bone tissue types (subchondral, cortical, and trabecular bone) and between regional subsections of knee subchondral bone. RESULTS: Exercise induced a significant (p < <0.001) increase in [18F]NaF uptake in all bone tissues in both knees, with mean SUV increases ranging from 47% in trabecular bone tissue to 131% in subchondral bone tissue. Kinetic parameters involving vascularization (K1 and blood volume) increased, whereas the NaF extraction fraction [k3/(k2 + k3)] was reduced. CONCLUSIONS: Bone loading induces an acute response in bone physiology as quantified by [18F]NaF PET kinetics. Dynamic imaging after bone loading using [18F]NaF PET is a promising diagnostic tool in bone physiology and imaging of biomechanics.

Sarcopenia and Postoperative Complication Risk in Gastrointestinal Surgical Oncology: A Meta-analysis.

OBJECTIVE: The aim of the study was to evaluate sarcopenia as a predictor of postoperative risk of major and total complications after surgery for gastrointestinal cancer. BACKGROUND: Sarcopenia is associated with poor survival in gastrointestinal cancer patients, but the role of sarcopenia as prognostic tool in surgical oncology has not been established, and no consensus exists regarding assessment and management of sarcopenic patients. METHODS: We performed a systematic search for citations in EMBASE, Web of Science, and PubMed from 2004 to January 31, 2017. Random effects meta-analyses were used to estimate the pooled risk ratio for postoperative complications by Clavien-Dindo grade (total complications: grade ≥2; major complications: grade ≥3) in patients with sarcopenia versus patients without sarcopenia. Stratified analyses were performed by sarcopenia criteria, cutoff level, assessment methods, study quality, cancer diagnosis, and "Enhanced Recovery After Surgery" care. RESULTS: Twenty-nine studies (n = 7176) were included with sarcopenia prevalence ranging between 12% and 78%. Preoperative incidence of sarcopenia was associated with increased risk of major complications (risk ratio 1.40; 95% confidence interval, 1.20-1.64; P < 0.001; I = 52%) and total complications (risk ratio 1.35; 95% confidence interval, 1.12-1.61; P = 0.001; I = 60%). Moderate heterogeneity was found for both meta-analyses. Subgroup analyses showed that sarcopenia remained a consistent risk factor across stratification by sarcopenia criteria, assessment methods, study quality, and diagnoses. CONCLUSIONS: Sarcopenia was associated with an increased risk of complications after gastrointestinal tumor resection, but lack of methodological consensus hampers the interpretation and clinical utilization of these findings. Combining assessment of muscle mass with measures of physical function may increase the prognostic value and accuracy in preoperative risk stratification.

Blood flow restricted training leads to myocellular macrophage infiltration and upregulation of heat shock proteins, but no apparent muscle damage.

KEY POINTS: Muscular contractions performed using a combination of low external loads and partial restriction of limb blood flow appear to induce substantial gains in muscle strength and muscle mass. This exercise regime may initially induce muscular stress and damage; however, the effects of a period of blood flow restricted training on these parameters remain largely unknown. The present study shows that short-term, high-frequency, low-load muscle training performed with partial blood flow restriction does not induce significant muscular damage. However, signs of myocellular stress and inflammation that were observed in the early phase of training and after the training intervention, respectively, may be facilitating the previously reported gains in myogenic satellite cell content and muscle hypertrophy. The present results improve our current knowledge about the physiological effects of low-load muscular contractions performed under blood flow restriction and may provide important information of relevance for future therapeutic treatment of muscular atrophy. ABSTRACT: Previous studies indicate that low-load muscle contractions performed under local blood flow restriction (BFR) may initially induce muscle damage and stress. However, whether these factors are evoked with longitudinal BFR training remains unexplored at the myocellular level. Two distinct study protocols were conducted, covering 3 weeks (3 wk) or one week (1 wk). Subjects performed BFR exercise (100 mmHg, 20% 1RM) to concentric failure (BFRE) (3 wk/1 wk), while controls performed work-matched (LLE) (3 wk) or high-load (HLE; 70% 1RM) (1 wk) free-flow exercise. Muscle biopsies (3 wk) were obtained at baseline (Pre), 8 days into the intervention (Mid8), and 3 and 10 days after training cessation (Post3, Post10) to examine macrophage (M1/M2) content as well as heat shock protein (HSP27/70) and tenascin-C expression. Blood samples (1 wk) were collected before and after (0.1-24 h) the first and last training session to examine markers of muscle damage (creatine kinase), oxidative stress (total antibody capacity, glutathione) and inflammation (monocyte chemotactic protein-1, interleukin-6, tumour necrosis factor α). M1-macrophage content increased 108-165% with BFRE and LLE at Post3 (P < 0.05), while M2-macrophages increased (163%) with BFRE only (P < 0.01). Membrane and intracellular HSP27 expression increased 60-132% at Mid8 with BFRE (P < 0.05-0.01). No or only minor changes were observed in circulating markers of muscle damage, oxidative stress and inflammation. The amplitude, timing and localization of the above changes indicate that only limited muscle damage was evoked with BFRE. This study is the first to show that a period of high-frequency, low-load BFR training does not appear to induce general myocellular damage. However, signs of tissue inflammation and focal myocellular membrane stress and/or reorganization were observed that may be involved in the adaptation processes evoked by BFR muscle exercise.

Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle.

KEY POINTS: In human skeletal muscles, the current view is that the capacity for mitochondrial energy production, and thus endurance capacity, is set by the mitochondria volume. However, increasing the mitochondrial inner membrane surface comprises an alternative mechanism for increasing the energy production capacity. In the present study, we show that mitochondrial inner membranes in leg muscles of endurance-trained athletes have an increased ratio of surface per mitochondrial volume. We show a positive correlation between this ratio and whole body oxygen uptake and muscle fibre mitochondrial content. The results obtained in the present study help us to understand modulation of mitochondrial function, as well as how mitochondria can increase their oxidative capacity with increased demand. ABSTRACT: Mitochondrial energy production involves the movement of protons down a large electrochemical gradient via ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is assumed to be constant. However, recent experimental studies have shown that respiration per mitochondria varies. Modelling studies have hypothesized that this variation in respiration per mitochondria depends on plasticity in cristae density, although current evidence for such a mechanism is lacking. In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long-term endurance training. Furthermore, we show that frequently recruited mitochondria-enriched fibres have significantly increased cristae density and that, at the whole-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish an elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents, as well as improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements.

Assessment of muscle function using hybrid PET/MRI: comparison of 18F-FDG PET and T2-weighted MRI for quantifying muscle activation in human subjects.

PURPOSE: The aim of this study was to determine the relationship between relative glucose uptake and MRI T 2 changes in skeletal muscles following resistance exercise using simultaneous PET/MRI scans. METHODS: Ten young healthy recreationally active men (age 21 - 28 years) were injected with 18F-FDG while activating the quadriceps of one leg with repeated knee extension exercises followed by hand-grip exercises for one arm. Immediately following the exercises, the subjects were scanned simultaneously with 18F-FDG PET/MRI and muscle groups were evaluated for increases in 18F-FDG uptake and MRI T 2 values. RESULTS: A significant linear correlation between 18F-FDG uptake and changes in muscle T 2 (R 2 = 0.71) was found. for both small and large muscles and in voxel to voxel comparisons. Despite large intersubject differences in muscle recruitment, the linear correlation between 18F-FDG uptake and changes in muscle T 2 did not vary among subjects. CONCLUSION: This is the first assessment of skeletal muscle activation using hybrid PET/MRI and the first study to demonstrate a high correlation between 18F-FDG uptake and changes in muscle T 2 with physical exercise. Accordingly, it seems that changes in muscle T 2 may be used as a surrogate marker for glucose uptake and lead to an improved insight into the metabolic changes that occur with muscle activation. Such knowledge may lead to improved treatment strategies in patients with neuromuscular pathologies such as stroke, spinal cord injuries and muscular dystrophies.

Effects of high-intensity training on cardiovascular risk factors in premenopausal and postmenopausal women.

BACKGROUND: Menopause is associated with increased risk of cardiovascular disease and the causal factors have been proposed to be the loss of estrogen and the subsequent alterations of the hormonal milieu. However, which factors contribute to the deterioration of cardiometabolic health in postmenopausal women is debated as the menopausal transition is also associated with increased age and fat mass. Furthermore, indications of reduced cardiometabolic adaptations to exercise in postmenopausal women add to the adverse health profile. OBJECTIVE: We sought to evaluate risk factors for type 2 diabetes and cardiovascular disease in late premenopausal and early postmenopausal women, matched by age and body composition, and investigate the effect of high-intensity training. STUDY DESIGN: A 3-month high-intensity aerobic training intervention, involving healthy, nonobese, late premenopausal (n = 40) and early postmenopausal (n = 39) women was conducted and anthropometrics, body composition, blood pressure, lipid profile, glucose tolerance, and maximal oxygen consumption were determined at baseline and after the intervention. RESULTS: At baseline, the groups matched in anthropometrics and body composition, and only differed by 4.2 years in age (mean [95% confidence limits] 49.2 [48.5-49.9] vs 53.4 [52.4-54.4] years). Time since last menstrual period for the postmenopausal women was (mean [95% confidence limits] 3.1 [2.6-3.7] years). Hormonal levels (estrogen, follicle stimulation hormone, luteinizing hormone) confirmed menopausal status. At baseline the postmenopausal women had higher total cholesterol (P < .001), low-density lipoprotein-cholesterol (P < .05), and high-density lipoprotein-cholesterol (P < .001) than the premenopausal women. The training intervention reduced body weight (P < .01), waist circumference (P < .01), and improved body composition by increasing lean body mass (P < .001) and decreasing fat mass (P < .001) similarly in both groups. Moreover, training resulted in lower diastolic blood pressure (P < .05), resting heart rate (P < .001), total cholesterol (P < .01), low-density lipoprotein-cholesterol (P < .01), total cholesterol/high-density lipoprotein-cholesterol index (P < .01), and improved plasma insulin concentration during the oral glucose tolerance test (P < .05) in both groups. CONCLUSION: Cardiovascular risk factors are similar in late premenopausal and early postmenopausal women, matched by age and body composition, with the exception that postmenopausal women have higher high- and low-density lipoprotein-cholesterol levels. A 3-month intervention of high-intensity aerobic training reduces risk factors for type 2 diabetes and cardiovascular disease to a similar extent in late premenopausal and early postmenopausal women.

Positive effects of 1-year football and strength training on mechanical muscle function and functional capacity in elderly men.

PURPOSE: A decline in physical capacity takes place with increasing age that negatively affects overall physical function including work ability and the ability to perform typical activities of daily living (ADL). The overall aim of the present study was to determine the neuromuscular adaptations to long-term (1 year) football and strength training in older untrained adults, and to assess the concurrent effect on functional ADL capacity. METHODS: Twenty-seven healthy elderly males (68.2 ± 3.2 years) were randomly assigned to 12 months of either recreational football training (FT: n = 10), strength training (ST: n = 9) or served as inactive controls (CON: n = 8). Recreational football training consisted of small-sided training sessions whereas strength training consisted of high intensity exercises targeting the lower extremity and upper body. Maximal thigh muscle strength and rate of force development (RFD) were assessed with isokinetic dynamometry, while postural balance and vertical jumping performance were evaluated using force plate analysis. Furthermore, functional ability was evaluated by stair-ascent and chair-rising testing. RESULTS: A total of nine, nine and seven participants from FT, ST and CON, respectively, were included in the analysis. Both exercise regimens led to substantial gains in functional ability, evidenced by 24 and 18 % reduced stair-ascent time, and 32 and 21 % increased chair-rising performance in FT and ST, respectively (all P < 0.05). Long-term strength training led to increased concentric (14 %; P < 0.01) and isometric (23 %; P < 0.001) quadriceps and isometric hamstring strength (44 %; P < 0.0001), whereas football training mainly resulted in enhanced hamstring strength (18 %, P < 0.05) and RFD (89 %, P < 0.0001). CONCLUSIONS: Long-term (1 year) strength training led to increased quadriceps and hamstring strength, whereas the adaptations to football training mainly included enhanced strength and rapid force capacity of the hamstring muscles. Gains in functional ability were observed in response to both training regimens, evidenced by reduced stair-ascent time and increased chair-rising performance. Long-term football exercise and strength training both appear to be effective interventional strategies to improve factors of importance for ADL by counteracting the age-related decline in lower limb strength and functional capacity among old male adults. This could potentially be a way to improve work ability of senior workers.

Prevalence and population characteristics associated with frailty in a rural low socioeconomic area in Denmark: the Lolland-Falster Health Study.

BACKGROUND: Frailty is a major geriatric syndrome that predicts increased vulnerability to minor stressor events and adverse outcomes such as falls, fractures, disability and death. The prevalence of frailty among individuals above the age of 65 varies widely with an overall weighted prevalence of 10.7%. OBJECTIVES: The purpose of this study was to examine the prevalence of prefrailty and frailty in community-dwelling older adults from the regions of Lolland-Falster, which is one of the most socioeconomically disadvantaged areas of Denmark with lower income and lower life expectancy compared with the general Danish population. Moreover, the objective was to find selected individual characteristics associated with frailty. DESIGN: An observational, cross-sectional registry-based population study with data from the regions of Lolland-Falster collected between February 2016 and February 2020. RESULTS: The study included 19 000 individuals. There were 10 154 above the age of 50 included for analysis. Prevalence of frailty in the age group of 50-64 years was 4.7% and 8.7% in the age group of 65 years and above.The study demonstrates associations between frailty and high age, female gender, low education level, low income, smoking, living alone, frequency of seeing one's children and getting help when needed. These associations are comparable with findings from other studies. CONCLUSION: The syndrome of frailty consists of not only physiological and medical issues but also education, life conditions such as living alone and living in poverty and how you evaluate your own health.

ROBot-assisted physical training of older patients during acUte hospitaliSaTion-study protocol for a randomised controlled trial (ROBUST).

BACKGROUND: During hospitalisation, older patients spend most of their time passive in bed, which increases the risk of functional decline and negative adverse outcomes. Our aim is to examine the impact of robot-assisted physical training on functional status in older geriatric patients during acute hospitalisation. METHODS: This is a single-centre investigator-blinded placebo-controlled randomised controlled trial including geriatric patients aged ≥ 65 years, able to ambulate before hospitalisation, and with expected length of stay ≥ 2 days. In addition to standard physiotherapy treatment, the intervention group receive active robot-assisted resistance training and the control group passive robot-assisted sham training. Exclusion criteria are as follows: ambulation without assistance at the time of inclusion, known severe dementia, delirium, patients who have received less than three training sessions at discharge, terminal illness, recent major surgery/lower extremity fracture, conditions contradicting the use of training robot, lower extremity metastases, deemed unsuitable for robot-assisted training by a healthcare professional, or weight > 165 kg. The primary outcome is functional status assessed by change in Barthel Index-100 and 30-s chair stand test between inclusion and day of discharge. Secondary outcomes include functional status at 1- and 3-month follow-up, quality of life, depression, concern about falling, falls, cognition, qualitative interviews, need of homecare, discharge destination, readmissions, healthcare costs, sarcopenia, muscle quantity (bioimpedance), and mortality. Clinical meaningful change of the Barthel Index is 5 points. A recent study in geriatric patients reported a 6.9-point change following exercise. With a significance level of 5%, 80% power, and a drop-out rate of 20%, 244 participants per group (n = 488) are needed to detect the same mean difference. With a significance level of 5%, 80% power, and a drop-out rate of 20%, 74 participants per group (n = 148) are needed to detect a minimum clinical change of 2.6 repetitions for 30-s chair stand test. Recruitment started in January 2023 and is expected to continue for 19 months including follow-up. DISCUSSION: If our study shows that in-hospital robot-assisted training prevents functional decline in older patients, this may have a major impact on the individual patient due to increased wellbeing and a higher level of independency. In addition, society will benefit due to potential decrease in the need of municipality-delivered homecare following discharge. TRIAL REGISTRATION: ClinicalTrials.gov NCT05782855. Registration date: March 24, 2023.

The SaVe project - Sarcopenia and Vertigo in aging patients with colorectal cancer: A study protocol for three randomized controlled trials.

INTRODUCTION: Older patients with cancer range from fit to frail with various comorbidities and resilience to chemotherapy. Besides nausea and fatigue, a significant number of patients experience dizziness and impaired walking balance after chemotherapy, which can have great impact on their functional ability and health related quality of life. Symptoms are easily overlooked and therefore often underreported and managed, which is why symptoms could end up as long-lasting side effects. The aim of this study is to investigate the development of dizziness, decline in walking balance, and sarcopenia and the effect of a comprehensive geriatric assessment and 12 weeks of group-based exercise on these symptoms. The exercise intervention includes vestibular and balance exercises, and progressive resistance training, to counteract the symptoms in older patients with colorectal cancer treated with chemotherapy. MATERIALS AND METHODS: This is a randomized controlled trial including patients ≥65 years initiating (neo)adjuvant or first-line palliative chemotherapy for colorectal cancer. Patients will undergo a comprehensive assessment program including measures of vestibular function, balance, muscle strength, mass, and endurance, peripheral and autonomic nerve function, and subjective measures of dizziness, concern of falling, and health related quality of life. Tests will be performed at baseline, 12, and 24 weeks. Patients will be placed in three different randomized controlled trials depending on chemotherapy regimen and randomized 1:1 to comprehensive geriatric assessment and exercise three times/week or control. Participants in both groups will continue with usual care, including standardized oncological treatment. In total, 150 patients are needed to assess the two primary outcomes of (1) maintenance of walking balance assessed with Dynamic Gait Index and (2) lower limb strength and endurance assessed with 30 Second Sit-to-Stand Test at 12 weeks. The primary outcomes will be analyzed using a mixed linear regression model investigating the between-group differences. DISCUSSION: Trial enrollment began in April 2023 and is the first trial to evaluate reasons for dizziness, decline in walking balance, and sarcopenia in older patients receiving chemotherapy. The trial will provide new and valuable knowledge in how to assess, manage, and prevent dizziness, decline in walking balance, and sarcopenia in older patients with colorectal cancer. TRIAL REGISTRATION: The Regional Ethics Committee (j.nr. H-22064206). Danish Data Protection Agency (P-2023-86) and ClinicalTrials.gov (NCT05710809).

Quality of life in patients with myositis is associated with functional capacity, body composition, and disease activity-Baseline data from a randomized controlled trial.

OBJECTIVE: To investigate the potential associations between functional capacity, muscle strength, body composition, and disease-related measures and quality of life in patients with myositis. METHODS: Baseline measures of functional capacity (functional index 3 (FI3), 2-minute walk test (2MWT), timed up and go (TUG) and 30-s sit-to-stand (30-STS)), muscle strength (incl. leg and handgrip strength), maximal leg extensor power, body composition (appendicular lean mass, fat percentage/mass) and disease-related measures (disease activity & damage core sets) were examined for their associations with quality of life (physical- and mental component summary scores, Short Form 36 questionnaire (SF-36)) by means of Spearman's correlation analysis. RESULTS: A total of 32 patients with myositis were included. Positive correlations between SF-36 physical component summary score (PCS) and FI3, 30-STS, TUG, 2MWT, leg extensor power, leg strength, bench press strength, and handgrip strength were observed. In contrast, fat percentage and fat mass correlated negatively with PCS. In disease-related measures, Extramuscular global assessment, health assessment questionnaire, physician global damage, and patient global damage scores were negatively associated with SF-36 PCS. No correlations to the mental component summary score of SF-36 were observed. CONCLUSION: All measures of functional capacity were positively related to the SF-36 physical component summary score, indicating higher functional capacity positively affects quality of life in patients with myositis. Health assessment questionnaire and patient global damage scores demonstrated the strongest correlations with SF-36 physical component summary scores, further supporting these patient-reported outcomes as viable monitoring tools in patients with myositis.

GDF-15 is associated with sarcopenia and frailty in acutely admitted older medical patients.

BACKGROUND: Growth differentiation factor-15 (GDF-15) has been associated with senescence, lower muscle strength, and physical performance in healthy older people. Still, it is not clear whether GDF-15 can be utilized as a biomarker of sarcopenia and frailty in the early stages of hospitalization. We investigated the association of plasma GDF-15 with sarcopenia and frailty in older, acutely admitted medical patients. METHODS: The present study is based on secondary analyses of cross-sectional data from the Copenhagen PROTECT study, a prospective cohort study including 1071 patients ≥65 years of age admitted to the acute medical ward at Copenhagen University Hospital, Bispebjerg, Denmark. Muscle strength was assessed using handgrip strength, and lean mass was assessed using direct segmental multifrequency bioelectrical impedance analyses and used to clarify the potential presence of sarcopenia defined according to guidelines from the European Working Group on Sarcopenia in Older People. Frailty was evaluated using the Clinical Frailty Scale. Plasma GDF-15 was measured using electrochemiluminescence assays from Meso Scale Discovery (MSD, Rockville, MD, USA). RESULTS: We included 1036 patients with completed blood samples (mean age 78.9 ± 7.8 years, 53% female). The median concentration of GDF-15 was 2669.3 pg/mL. Systemic GDF-15 was significantly higher in patients with either sarcopenia (P < 0.01) or frailty (P < 0.001) compared with patients without the conditions. Optimum cut-off points of GDF-15 relating to sarcopenia and frailty were 1541 and 2166 pg/mL, respectively. CONCLUSIONS: Systemic GDF-15 was higher in acutely admitted older medical patients with sarcopenia and frailty compared with patients without. The present study defined the optimum cut-off for GDF-15, related to the presence of sarcopenia and frailty, respectively. When elevated above the derived cutoffs, GDF-15 was strongly associated with frailty and sarcopenia in both crude and fully adjusted models.