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Obesity is an important contributing factor to the pathophysiology of atrial fibrillation (AF) and its complications by causing systemic changes, such as altered haemodynamic, increased sympathetic tone, and low-grade chronic inflammatory state. In addition, adipose tissue is a metabolically active organ that comprises various types of fat deposits with discrete composition and localization that show distinct functions. Fatty tissue differentially affects the evolution of AF, with highly secretory active visceral fat surrounding the heart generally having a more potent influence than the rather inert subcutaneous fat. A variety of proinflammatory, profibrotic, and vasoconstrictive mediators are secreted by adipose tissue, particularly originating from cardiac fat, that promote atrial remodelling and increase the susceptibility to AF. In this review, we address the role of obesity-related factors and in particular specific adipose tissue depots in driving AF risk. We discuss the distinct effects of key secreted adipokines from different adipose tissue depots and their participation in cardiac remodelling. The possible mechanistic basis and molecular determinants of adiposity-related AF are discussed, and finally, we highlight important gaps in current knowledge, areas requiring future investigation, and implications for clinical management.

Introduction: The association between obesity and outcome in critical illness is unclear. Since the amount of visceral adipose tissue(VAT) rather than BMI mediates the health effects of obesity we aimed to investigate the association between visceral obesity, BMI and 90-day mortality in critically ill patients. Method: In 555 critically ill patients (68% male), the VAT Index(VATI) was measured using Computed Tomography scans on the level of vertebra L3. The association between visceral obesity, BMI and 90-day mortality was investigated using univariable and multivariable analyses, correcting for age, sex, APACHE II score, sarcopenia and muscle quality. Results: Visceral obesity was present in 48.1% of the patients and its prevalence was similar in males and females. Mortality was similar amongst patients with and without visceral obesity (27.7% vs 24.0%, p = 0.31). The corrected odds ratio of 90-day mortality for visceral obesity was 0.667 (95%CI 0.424–1.049, p = 0.080). Using normal BMI as reference, the corrected odds ratio for overweight was 0.721 (95%CI 0.447–1.164 p = 0.181) and for obesity 0.462 (95%CI 0.208–1.027, p = 0.058). Conclusion: No significant association of visceral obesity and BMI with 90-day mortality was observed in critically ill patients, although obesity and visceral obesity tended to be associated with improved 90-day mortality.

Cystic fibrosis (CF) has been linked to altered drug disposition in various studies. However, the magnitude of these changes, influencing factors, and underlying mechanisms remain a matter of debate. The primary aim of this work was therefore to quantify changes in drug disposition (top-down) and the pathophysiological parameters known to affect pharmacokinetics (PKs; bottom-up). This was done through meta-analyses and meta-regressions in addition to theoretical PK simulations. Volumes of distribution and clearances were found to be elevated in people living with CF. These increases were larger in studies which included patients with pulmonary exacerbations. Differences in clearance were smaller in more recent studies and when results were normalized to body surface area or lean body mass instead of body weight. For the physiological parameters investigated, measured glomerular filtration rate and serum cytokine concentrations were found to be elevated in people living with CF, whereas serum albumin and creatinine levels were decreased. Possible pathophysiological mechanisms for these alterations relate to renal hyperfiltration, increases in free fraction, and inflammation. No differences were detected for cardiac output, body fat, fat free mass, hematocrit, creatinine clearance, and the activity of drug metabolizing enzymes. These findings imply that, in general, lower total plasma concentrations of drugs can be expected in people living with CF, especially when pulmonary exacerbations are present. Given the potential effect of CF on plasma protein binding and the variability in outcome observed between studies, the clinical relevance of adapting existing dosage regimens should be evaluated on a case-by-case basis.

Consumers are increasingly encouraged to consume more plant-based foods and lower their consumption of foods from animal origin. Concurrently, older adults are recommended to consume an adequate amount of high-quality dietary protein for the prevention of age-related muscle loss. In the current Perspective article, we discuss why it may not be preferred to consume a vegan diet at an older age. Our perspective is based on the proposed lower bioavailability and functionality of proteins in a vegan diet due to the matrix of the whole-food protein sources, the lower essential amino acid (EAA) content, and specific EAA deficiencies in proteins derived from plant-based foods. We propose that a vegan diet increases the risk of an inadequate protein intake at an older age and that current strategies to improve the anabolic properties of plant-based foods are not feasible for many older adults. We provide recommendations for further research to substantiate the remaining knowledge gaps regarding the consequences of a vegan diet on skeletal muscle mass and strength at an older age.Statement of Significance: To our knowledge, this is the first article that provides an evidence-based perspective regarding the potential impact of a vegan diet on muscle mass and strength in older adults. The current perspective is highly relevant considering the envisaged shifts towards sustainable dietary guidelines.

Objective: This study was carried out to evaluate the relationship between the nutritional status, anthropometric measurements and dietary inflammatory index (DII) of professional football players exposed to long-term intense exercise. Method: Twenty-one professional male football players with a mean age of 26.00±5.69 years playing in the same club participated in the study. The nutritional status of the football players was evaluated with 3-day food consumption record (2 days of training and 1 match day). DII scores were calculated using data on 34 nutrient/nutritional ingredients obtained from the food consumption records. Body fat percentage in the anthropometric evaluations were determined by caliper and skinfold thicknesses. Results: The median DII scores of the football players were found as – 3.42 (-9.95 – 0.95), and their nutritional intake were found to be antiinflammatory. When the relationship between the DII scores of the football players and their anthropometric measurements was examined, a positive and significant correlation (R: .476; p: .029) was found between their DII score and their abdominal adiposity. However, there was no significant correlation (p> .05) between the DII scores and the other anthropometric measurements. In addition, there was a significant negative correlation (R: – .468; p: .032) between fiber consumption and abdominal adiposity, and a significant positive correlation between carbohydrate and fat consumption and body weight (respectively R= .730 p= .000; R= .526 p= .014). Conclusion: It has been revealed that the football players participating in our study generally have an anti-inflammatory diet. It was also found that abdominal adiposity was higher in the football players with high DII scores.

Addressing skeletal muscle mass loss is an important focus in oncology research to improve clinical outcomes, including cancer treatment tolerability and survival. Exercise is likely a necessary component of muscle-mass-preserving interventions for people with cancer. However, randomized controlled trials with exercise that include people with cancer with increased susceptibility to more rapid and severe muscle mass loss are limited. The aim of the current review is to highlight features of cancer-related skeletal muscle mass loss, discuss the impact in patients most at risk, and describe the possible role of exercise as a management strategy. We present current gaps within the exercise oncology literature and offer several recommendations for future studies to support research translation, including (1) utilizing accurate and reliable body composition techniques to assess changes in skeletal muscle mass, (2) incorporating comprehensive assessments of patient health status to allow personalized exercise prescription, (3) coupling exercise with robust nutritional recommendations to maximize the impact on skeletal muscle outcomes, and (4) considering key exercise intervention features that may improve exercise efficacy and adherence. Ultimately, the driving forces behind skeletal muscle mass loss are complex and may impede exercise tolerability and efficacy. Our recommendations are intended to foster the design of high-quality patient-centred research studies to determine whether exercise can counteract muscle mass loss in people with cancer and, as such, improve knowledge on this topic.

Background & aims: Sarcopenia is a muscle disorder associated with loss of muscle mass, strength and function. Early screening, diagnosis and treatment may improve outcome in different disease conditions. A wide variety of tools for estimation of muscle mass is available and each tool has specific technical requirements. However, different investigational settings and lack of homogeneity of populations influence the definition of gold standards, proving it difficult to systematically adopt these tools. Recently, the European Working Group on Sarcopenia in Older People (EWGSOP) published a revised recommendation (EWGSOP-2) and algorithm for using tools for screening and diagnosing sarcopenia. However, agreement of the EWGSOP2 criteria with other classifications is poor and although an overview of available tools is valuable, for the purpose of clinical decision-making the reverse is useful; a given scenario asks for the most suitable tools.Results: Tools were identified for screening, diagnostics and longitudinal monitoring of muscle mass. For each of these clinical scenarios the most appropriate tools were listed and for each technique their usability is specified based on sensitivity and specificity. Based on this information a specific recommendation is made for each clinical scenario.Conclusion: This narrative review provides an overview of currently available tools and future developments for different clinical scenarios such as screening, diagnosis and longitudinal monitoring of alterations in muscle status. It supports clinical decision-making in choosing the right tools for muscle mass quantification depending on the need within a given clinical scenario as well as the local availability and expertise. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.

The effect of physical activity on breast cancer risk may be partly mediated by sex steroid hormones. This review synthesized and appraised the evidence for an effect of physical activity on sex steroid hormones. Systematic searches were performed using MEDLINE (Ovid), EMBASE (Ovid), and SPORTDiscus to identify experimental studies and prospective cohort studies that examined physical activity and estrogens, progestins, and/or androgens, as well as sex hormone binding globulin (SHBG) and glucocorti-coids in pre- and postmenopausal women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to appraise quality of the evidence. Twenty-eight randomized controlled trials (RCT), 81 nonrandomized interventions, and six observational studies were included. Estrogens, progesterone, and androgens mostly decreased, and SHBG increased, in response to physical activity. Effect sizes were small, and evidence quality was graded moderate or high for each outcome. Reductions in select sex steroid hormones following exercise supports the biological plausibility of the first part of the physical activity-sex hormone-breast cancer pathway. The con-firmed effect of physical activity on decreasing circulating sex steroid hormones supports its causal role in preventing breast cancer.

ObjectivesTo quantify energy expenditure and intake in professional female footballers playing on a national and/or international level. Second, to determine the prevalence of low energy availability among these players, defined as MethodsFifty-one players completed a 14-day prospective observational study during the 2021/2022 football season. Energy expenditure was determined using the doubly labelled water method. Energy intake was assessed using dietary recalls, while global positioning system determined the external physiological load. Descriptive statistics, stratification and the correlation between explainable variables and outcomes were conducted to quantify the energetic demands.ResultsThe mean energy expenditure for all players (22±4 years) was 2918±322 kcal. Mean energy intake was 2274±450 kcal, resulting in a discrepancy of ~22%. Carbohydrate intake was below the recommended guidelines on match day at 4.5±1.9 g/kg. The mean energy availability was 36.7±17.7 kcal/kg FFM/day on matchday and 37.9±11.7 kcal/kg FFM/day on training days, resulting in a prevalence of 36% and 23% for low energy availability during the observational period, respectively.ConclusionThese elite female football players displayed moderate energy expenditure levels and failed to meet the recommended levels of carbohydrate intake. In conjunction with inadequate nutritional periodisation, this will likely hamper performance through inadequate muscle glycogen resynthesis. In addition, we found a considerable prevalence of low energy availability on match and training days.

Background: Patients with locally advanced rectal cancer are often considered for neoadjuvant chemoradiotherapy before resection. This presurgical treatment can have negative effects on physical fitness, muscle mass, and treatment compliance, which can negatively influence clinical outcomes. Objective: The aim of this study was to evaluate physical fitness and skeletal muscle mass before and after neoadjuvant chemoradiotherapy in single subjects with locally advanced rectal cancer. Design: An observational longitudinal study of single subjects. Methods: Routine care data were retrospectively analyzed. Data consisted of tumor characteristics, clinical data (eg, side effects and toxicity of the neoadjuvant chemoradiotherapy, loss of body mass), data on performance-based physical fitness, and computed tomography-derived skeletal muscle mass. An independent-samples t test or its nonparametric equivalent was performed on outcome measures to test for significant differences between T-0 and T-1. For comparing several subgroups in this cohort, the Mann-Whitney U test was performed and correlations were studied using the Pearson or Spearman correlation coefficient, as appropriate. Results: Data from 25 single subjects were available. Aerobic capacity (n = 25, P = .033) and skeletal muscle mass (n = 16, P = .005) were significantly reduced after neoadjuvant chemoradiotherapy. Although not statistically significant, a large number of patients demonstrated a decrease in muscle strength and functional mobility after completing neoadjuvant chemoradiotherapy. In 14 patients (56%), adverse events, dose-limiting toxicity, or early termination of treatment occurred. Conclusions: Aerobic capacity and skeletal muscle mass decreased following neoadjuvant chemoradiotherapy, with large interindividual differences concerning the changes in physical fitness and muscle mass. This between-subject variability indicates the importance of a personalized treatment approach.

Purpose: The aim of the study was to observe the relationship between age, body mass index (BMI), physical activity, and kyphosis angle parameters with respiratory function capacity in community-dwelling older adults and to determine the main predictor. Methods: A prospective cross-sectional study was carried out with 70 older adults. Physical activity level was questioned with the Physical Activity Scale for Elderly (PASE). Thoracic kyphosis degrees were measured with a digital inclinometer. Pulmonary Function Test (PFT) was used to measure pulmonary function capacity. The correlation between age, BMI, PASE, thoracic kyphosis angle with parameters of PFT measurement was analyzed. In addition, a linear multivariate regression model was built to determine the main predictor. Results: The mean age of the participants was 69.88 +/- 4.52 years. There was a low degree but a statistically significant positive correlation between BMI and FEV1 (r=0.258, p, Ege University Scientific Research Projects Coordination Unit [TGA-2019-20857], The authors would like to thank Ege University Scientific Research Projects Coordination Unit for their financial support to this project (TGA-2019-20857) .

Purpose: To obtain information on characteristics, management, current objective nutritional status and perception of nutritional status of children with cerebral palsy (CP) from healthcare professionals (HCPs) and caregivers. Materials and methods: A detailed survey of several items on eight main topics (general characteristics, motor function, comorbidities, therapies, anthropometry, feeding mode and problems and perceived nutritional status) was developed and tested for the study. Correlation between nutritional status and Gross Motor Function Classification System (GMFCS) levels was assessed using continuous variables (Z-scores for weight-for-age, height-for-age, weight-for-height, and body mass index-for-age), and categorical variables (being malnourished, stunted, or wasted). HCP and caregiver perceptions of the child's nutritional status as well as agreement between perceived and objective nutritional status and agreement between perceived nutritional status and concerns about the nutritional status were analyzed. Results: Data were available for 497 participants from eight European countries. Poorer nutritional status was associated with higher (more severe) GMFCS levels. There was minimal agreement between perceived and objective nutritional status, both for HCPs and caregivers. Agreement between HCP and caregiver perceptions of the child's nutritional status was weak (weighted kappa 0.56). However, the concerns about the nutritional status of the child were in line with the perceived nutritional status. Conclusions: The risk of poor nutritional status is associated with more severe disability in children and adolescents with CP. There is a mismatch between HCP and caregiver perceptions of participants' nutritional status as well as between subjective and objective nutritional status. Our data warrant the use of a simple and objective screening tool in daily practice to determine nutritional status in children and adolescents with CP., Danone Nutricia Research, Utrecht, the Netherlands; Nutricia Advanced Medical Nutrition in Czech Republic; Nutricia Advanced Medical Nutrition in Greece; Nutricia Advanced Medical Nutrition in Hungary; Nutricia Advanced Medical Nutrition in Italy; Nutricia Advanced Medical Nutrition in Poland; Nutricia Advanced Medical Nutrition in Slovakia; Nutricia Advanced Medical Nutrition in The Netherlands; Nutricia Advanced Medical Nutrition in Turkey; Danone Nutricia Research, This study was sponsored by Danone Nutricia Research, Utrecht, the Netherlands. Local financial support was provided by the local business units of Nutricia Advanced Medical Nutrition in Czech Republic, Greece, Hungary, Italy, Poland, Slovakia, The Netherlands, and Turkey. Medical writing support was provided by Tim Kelly, Medi-Kelsey Limited, funded by Danone Nutricia Research.

Background and aims: Higher protein (HP) diets may lead to lower cardiometabolic risk, compared to lower\ud protein (LP) diets. This systematic review and meta-analysis aims to investigate the effects of HP versus LP diets\ud on cardiometabolic risk factors in adults, using the totality of the current evidence from randomised controlled\ud trials (RCTs).\ud Methods: Systematic searches were conducted in electronic databases, up to November 2020. Random effects\ud meta-analyses were conducted to pool the standardised mean differences (SMD) and 95% confidence intervals\ud (CI). The main outcomes were weight loss, body mass index (BMI), waist circumference, fat mass, systolic and\ud diastolic BP, total cholesterol, HDL-and LDL-cholesterol, triacylglycerol, fasting glucose and insulin, and glycated\ud haemoglobin.\ud Results: Fifty-seven articles reporting on 54 RCTs were included, involving 4344 participants (65% female, mean\ud age: 46 (SD 10) years, mean BMI: 33 (SD 3) kg/m2\ud ), with a mean study duration of 18 weeks (range: 4 to 156\ud weeks). Compared to LP diets (range protein (E%):10–23%), HP diets (range protein (E%): 20–45%) led to more\ud weight loss (SMD -0.13, 95% CI: -0.23, − 0.03), greater reductions in fat mass (SMD -0.14, 95% CI: -0.24, − 0.04),\ud systolic BP (SMD -0.12, 95% CI: -0.21, − 0.02), total cholesterol (SMD -0.11, 95% CI: -0.19, − 0.02), triacylglycerol (SMD -0.22, 95% CI: -0.30, − 0.14) and insulin (SMD -0.12, 95% CI: -0.22, − 0.03). No significant\ud differences were observed for the other outcomes.\ud Conclusions: Higher protein diets showed small, but favourable effects on weight loss, fat mass loss, systolic blood\ud pressure, some lipid outcomes and insulin, compared to lower protein diets.

INTRODUCTION: Protein energy wasting (PEW) is the most important risk factor for morbidity and mortality in hemodialysis patients. Inadequate dietary protein intake is a frequent cause of PEW. Recent studies have identified fibroblast growth factor 21 (FGF21) as an endocrine protein sensor. This study aims to investigate the potential of FGF21 as a biomarker for protein intake and PEW and to investigate intradialytic FGF21 changes.METHODS: Plasma FGF21 was measured using an enzyme-linked immunoassay. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h urea excretion and protein intake. Muscle mass was assessed using the creatinine excretion rate and fatigue was assessed using the Short Form 36 and the Checklist Individual Strength.RESULTS: Out of 59 hemodialysis patients (65 ± 15 years, 63% male), 39 patients had a low protein intake, defined as a protein intake less than 0.9 g/kg/24-h. Patients with a low protein intake had nearly twofold higher plasma FGF21 compared to those with an adequate protein intake (FGF21 1370 [795-4034] pg/mL versus 709 [405-1077] pg/mL;P < 0.001). Higher plasma FGF21 was associated with higher odds of low protein intake (Odds Ratio: 3.18 [1.62-7.95] per doubling of FGF21; P = 0.004), independent of potential confounders. Higher plasma FGF21 was also associated with lower muscle mass (std β: -0.34 [-0.59;-0.09];P = 0.009), lower vitality (std β: -0.30 [-0.55;-0.05];P = 0.02), and more fatigue (std β: 0.32 [0.07;0.57];P = 0.01). During hemodialysis plasma FGF21 increased by 354 [71-570] pg/mL, corresponding to a 29% increase.CONCLUSION: Higher plasma FGF21 is associated with higher odds of low protein intake in hemodialysis patients. Secondarily, plasma FGF21 is also associated with lower muscle mass, less vitality, and more fatigue. Lastly, there is an intradialytic increase in plasma FGF21. FGF21 could be a valuable marker allowing for objective assessment of PEW.

Zusammenfassung Kachexie wird als multifaktorielles Syndrom definiert, das durch einen unfreiwillig fortschreitenden Gewichtsverlust infolge einer Verringerung der Skelettmuskelmasse mit oder ohne Reduktion des Fettgewebes gekennzeichnet ist. Der Abbau von Muskelgewebe wird als Sarkopenie bezeichnet. Diese wird klinisch als Verlust von Muskelmasse und/oder Muskelkraft definiert, wobei der Verlust von Muskelkraft im Vordergrund steht. Mit Sarkopenie verbunden ist der Zustand der Myosteatose, der durch eine Zunahme der intra- und extrazellularen Fettspeicher gekennzeichnet ist und mit einer verminderten Muskelfunktion einhergeht. Kachexie ist fur den Tod von mindestens 20% aller Krebspatienten mitverantwortlich. Die Inzidenz variiert bei diesen Patienten je nach Art der Erkrankung zwischen 80% fur Patienten mit Magen- und Bauchspeicheldrusenkrebs, 50% fur Patienten mit Lungen-, Dickdarm- und Prostatakrebs sowie etwa 40% fur Patienten mit Brustkrebs oder Leukamie. Hierbei ist eine Unterscheidung zwischen tumorassoziierter Kachexie und einer durch Nebenwirkungen und Komplikationen der onkologischen Therapie bedingten Kachexie oft schwierig. Das wesentliche klinische Merkmal der Kachexie ist ein unfreiwilliger Gewichtsverlust, der sich jedoch nicht immer klinisch manifestiert, sodass die Identifizierung von Risikopatienten erheblich erschwert ist. Nicht nur das Langzeit-Outcome der Patienten wird von Kachexie und Sarkopenie beeinflusst. Auch die unmittelbaren postoperativen Komplikationsraten (Morbiditat) werden erhoht und haben tiefgreifende Auswirkungen auf die Krankheitslast und das Leiden der Patienten nach einer chirurgischen Behandlung. Kachexie, Sarkopenie und Myosteatose sind somit fur den klinischen Alltag hochrelevante Parameter, die einen signifikanten Einfluss auf das postoperative Outcome der Patienten haben. Es wurden verschiedene Methoden entwickelt, um die fruhzeitige Identifizierung von Patienten mit einem erhohten Risiko zu verbessern. Diese bieten die Moglichkeit, ungewollten Gewichtsverlust, verringerte Muskelkraft und die Fitness der Patienten zu testen. Derartige Ma ss nahmen sollten Teil unserer taglichen klinischen Routine werden, um diejenigen Patienten mit dem hochsten postoperativen Risiko zu erkennen. Entsprechend konnen neuartige Prakonditionierungskonzepte fur bestimmte Patientengruppen in der Lage sein, die postoperative Morbiditat zu verringern.Abstract Cachexia is defined as a multifactorial syndrome characterised by involuntary progressive weight loss due to a decrease in skeletal muscle mass, with or without a reduction in adipose tissue. The breakdown of muscle tissue is known as sarcopenia. This is clinically defined as loss of muscle mass and/or muscle strength, with loss of muscle strength being more important than muscle mass. Cachexia is responsible for the death of at least 20% of all cancer patients. The incidence in these patients varies, depending on the type of disease, between 80% for patients with gastric and pancreatic cancer, 50% for patients with lung, colon and prostate cancer, and about 40% for patients with breast cancer or leukemia. It is often difficult to distinguish between tumour-associated cachexia and cachexia caused by side effects and complications of oncological therapy. The main clinical feature of cachexia is involuntary weight loss, but this does not always manifest itself clinically, making it much more difficult to identify patients at risk. Not only the long-term outcome of the patient is influenced by cachexia and sarcopenia. Immediate postoperative complication rates (morbidity) are also increased and have profound effects on the burden of disease and the suffering of patients after surgical treatment. Cachexia, sarcopenia and myosteatosis are therefore highly relevant parameters for everyday clinical practice, which have a significant influence on the postoperative outcome of the patient. Several tools have been developed to aid the identification of patients with nutritional risk, i.e. involuntary weight loss, reduced muscle strength and physical condition. Such measures should be a part of our daily clinical routine to ensure the identification of patients with the highest postoperative risk. Novel preconditioning treatment may be beneficial to certain patient groups to reduce postoperative morbidity.

Background Anemia and suboptimal gestational weight gain (GWG) are associated with adverse maternal and birth outcomes. Limited research indicates that balanced energy-protein (BEP) supplements reduce the incidence of inadequate GWG. Objectives We assessed the efficacy of a micronutrient-fortified BEP supplement on the secondary outcomes of anemia, GWG, GWG rate, and GWG in relation to the Institute of Medicine (IOM)'s recommendations, as compared with an iron-folic acid (IFA) tablet. Methods We conducted a randomized controlled trial in Burkina Faso, among pregnant women (15-40 y old) enrolled at

This study was conducted to assess the impacts of prolonged fasting (70 and 120days) on the morphological, biochemical, oxidative stress responses, immune-related gene expression, histopathology, and DNA damage in rainbow trout. Final weight (FW), hepatosomatic index (HSI), and condition factor (CF) significantly decreased in both 70 and 120days of fasting compared to the pre-fasting group (p p p

Introduction It is unclear whether adiposity leads to changes in movement behaviors, and there is a lack of compositional analyses of longitudinal data which focus on these associations. Using a compositional approach, this study aimed to examine the associations between baseline adiposity and 7-year changes in physical activity (PA) and sedentary behavior (SB) among elderly women. We also explored the longitudinal associations between change in adiposity and change in movement-behavior composition. Methods This longitudinal study included 176 older women (mean baseline age 62.8 (4.1) years) from Central Europe. Movement behavior was assessed by accelerometers and adiposity was measured by bioelectrical impedance analysis at baseline and follow-up. A set of multivariate least-squares regression analyses was used to examine the associations of baseline adiposity and longitudinal changes in adiposity as explanatory variables with longitudinal changes in a 3-part movement-behavior composition consisting of SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) as outcome variables. Results No significant associations were found between baseline adiposity and longitudinal changes in the movement-behavior composition (p > 0.05). We found significant associations of changes in body mass index (BMI) and fat mass percentage (FM%) with changes in the movement-behavior composition. An increase in BMI was associated with an increase of SB at the expense of LPA and MVPA (β = 0.042, p = 0.009) and with a decrease of MVPA in favor of SB and LPA (β = − 0.059, p = 0.037). An increase in FM% was significantly associated only with an increase of SB at the expense of LPA and MVPA (β = 0.019, p = 0.031). Conclusions This study did not support the assumption that baseline adiposity is associated with longitudinal changes in movement behaviors among elderly women, but we found evidence for change-to-change associations, suggesting that a 7-year increase in adiposity is associated with a concurrent increase of SB at the expense of LPA and MVPA and with a concurrent decrease of MVPA in favor of LPA and SB. Public health interventions are needed to simultaneously prevent weight gain and promote physically active lifestyle among elderly women.

The awareness of the presence and consequences of sarcopenia has significantly increased over the past decade. Sarcopenia is defined as gradual loss of muscle mass and strength and ultimately loss of physical performance associated with aging and chronic disease. The prevalence of sarcopenia is higher in chronic obstructive pulmonary disease (COPD) compared to age-matched controls. Current literature suggests that next to physical inactivity, COPD-specific alterations in physiological processes contribute to accelerated development of sarcopenia. Sarcopenia in COPD can be assessed according to current guidelines, but during physical performance testing, ventilatory limitation should be considered. Treatment of muscle impairment can halt or even reverse sarcopenia, despite respiratory impairment. Exercise training and protein supplementation are currently at the basis of sarcopenia treatment. Furthermore, effective current and new interventions targeting the pulmonary system (eg, smoking cessation, bronchodilators and lung volume reduction surgery) may also facilitate muscle maintenance. Better understanding of disease-specific pathophysiological mechanisms involved in the accelerated development of sarcopenia in COPD will provide new leads to refine nutritional, exercise and physical activity interventions and develop pharmacological co-interventions.

The awareness of the presence and consequences of sarcopenia has significantly increased over the past decade. Sarcopenia is defined as gradual loss of muscle mass and strength and ultimately loss of physical performance associated with aging and chronic disease. The prevalence of sarcopenia is higher in chronic obstructive pulmonary disease (COPD) compared to age-matched controls. Current literature suggests that next to physical inactivity, COPD-specific alterations in physiological processes contribute to accelerated development of sarcopenia. Sarcopenia in COPD can be assessed according to current guidelines, but during physical performance testing, ventilatory limitation should be considered. Treatment of muscle impairment can halt or even reverse sarcopenia, despite respiratory impairment. Exercise training and protein supplementation are currently at the basis of sarcopenia treatment. Furthermore, effective current and new interventions targeting the pulmonary system (eg, smoking cessation, bronchodilators and lung volume reduction surgery) may also facilitate muscle maintenance. Better understanding of disease-specific pathophysiological mechanisms involved in the accelerated development of sarcopenia in COPD will provide new leads to refine nutritional, exercise and physical activity interventions and develop pharmacological co-interventions.

Background and aimsHigher protein (HP) diets may lead to lower cardiometabolic risk, compared to lower protein (LP) diets. This systematic review and meta-analysis aims to investigate the effects of HP versus LP diets on cardiometabolic risk factors in adults, using the totality of the current evidence from randomised controlled trials (RCTs).MethodsSystematic searches were conducted in electronic databases, up to November 2020. Random effects meta-analyses were conducted to pool the standardised mean differences (SMD) and 95% confidence intervals (CI). The main outcomes were weight loss, body mass index (BMI), waist circumference, fat mass, systolic and diastolic BP, total cholesterol, HDL-and LDL-cholesterol, triacylglycerol, fasting glucose and insulin, and glycated haemoglobin.ResultsFifty-seven articles reporting on 54 RCTs were included, involving 4344 participants (65% female, mean age: 46 (SD 10) years, mean BMI: 33 (SD 3) kg/m2), with a mean study duration of 18 weeks (range: 4 to 156 weeks). Compared to LP diets (range protein (E%):10–23%), HP diets (range protein (E%): 20–45%) led to more weight loss (SMD -0.13, 95% CI: -0.23, −0.03), greater reductions in fat mass (SMD -0.14, 95% CI: -0.24, −0.04), systolic BP (SMD -0.12, 95% CI: -0.21, −0.02), total cholesterol (SMD -0.11, 95% CI: -0.19, −0.02), triacylglycerol (SMD -0.22, 95% CI: -0.30, −0.14) and insulin (SMD -0.12, 95% CI: -0.22, −0.03). No significant differences were observed for the other outcomes.ConclusionsHigher protein diets showed small, but favourable effects on weight loss, fat mass loss, systolic blood pressure, some lipid outcomes and insulin, compared to lower protein diets.

In head and neck cancer (HNC) there is a need for more personalized treatment based on risk assessment for treatment related adverse events (i.e. toxicities and complications), expected survival and quality of life. Sarcopenia, defined as a condition characterized by loss of skeletal muscle mass and function, can predict adverse outcomes in HNC patients. A review of the literature on the measurement of sarcopenia in head and neck cancer patients and its association with frailty was performed. Skeletal muscle mass (SMM) measurement only is often used to determine if sarcopenia is present or not. SMM is most often assessed by measuring skeletal muscle cross-sectional area on CT or MRI at the level of the third lumbar vertebra. As abdominal scans are not always available in HNC patients, measurement of SMM at the third cervical vertebra has been developed and is frequently used. Frailty is often defined as an age-related cumulative decline across multiple physiologic systems, with impaired homeostatic reserve and a reduced capacity of the organism to withstand stress, leading to increased risk of adverse health outcomes. There is no international standard measure of frailty and there are multiple measures of frailty. Both sarcopenia and frailty can predict adverse outcomes and can be used to identify vulnerable patients, select treatment options, adjust treatments, improve patient counselling, improve preoperative nutritional status and anticipate early on complications, length of hospital stay and discharge. Depending on the definitions used for sarcopenia and frailty, there is more or less overlap between both conditions. However, it has yet to be determined if sarcopenia and frailty can be used interchangeably or that they have additional value and should be used in combination to optimize individualized treatment in HNC patients.

The main objective of this study was to study predictors of vascular health with focus on adiposity-related factors. Glucose metabolism, blood lipids, inflammatory markers and body composition were assessed 15 years before assessment of vascular health which was assessed with pulse wave velocity (PWV) in 660 subjects born 1934–44. In a univariate analysis in women the strongest association with PWV was seen for age, systolic blood pressure, dysglycemia, dyslipidemia, inflammatory markers and body fat percentage measured in late midlife and PWV measured 15 years later. In men age, body mass index (BMI), systolic blood pressure, dysglycemia, and body fat percentage in late midlife were associated with PWV. One novel finding was that adiposity-related factors were strong predictors of vascular health, something not fully encapsulated in BMI, lean body mass or body fat percentage alone. A higher fat mass index was associated with worse vascular health, which was not ameliorated by a higher lean mass index. Our findings stress the importance to study body composition and fat and lean body mass simultaneously because of their close interaction with each other also in relation to vascular health.

Background: Visceral obesity is associated with the metabolic syndrome. The metabolic risk differs per ethnicity, but reference values for visceral obesity for body composition analyses using Computed Tomography (CT) scans in the Caucasian population are lacking. Therefore, the aim of this study was to define gender specific reference values for visceral obesity in a Caucasian cohort based upon the association between the amount of visceral adipose tissue (VAT) and markers of increased metabolic risk.Methods: Visceral Adipose Tissue Area Index (VATI cm(2)/m(2)) at the level of vertebra L3 was analyzed using CT scans of 416 healthy living kidney donor candidates. The use of antihypertensive drugs and/or statins was used as an indicator for increased metabolic risk. Gender specific cut-off values for VATI with a sensitivity >= 80% were calculated using receiver operating characteristic (ROC) curves.Results: In both men and women who used antihypertensive drugs, statins or both, VATI was higher than in those who did not use these drugs (p = 38.7 cm(2)/m(2) and >= 24.9 cm(2)/m(2) was associated with increased metabolic risk with a sensitivity of 80%. ROC analysis showed that VATI was a better predictor of increased metabolic risk than BMI (area under ROC curve (AUC) = 0.702 vs AUC = 0.556 in males and AUC = 0.757 vs AUC = 0.630 in females).Conclusion: Gender and ethnicity specific cut-off values for visceral obesity are important in body composition research, although further validation is needed. This study also showed that quantification of VATI is a better predictor for metabolic risk than BMI. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.

Background: There is a need for a type of physical activity that could address the challenging cycle of physical inactivity, impaired health-related fitness, and type 2 diabetes mellitus (T2DM) conditions. Yoga could be one type of exercise to overcome the barriers to adhere to regular physical activity. The current study aimed to systematically review the effect of yoga on health-related fitness, including cardiorespiratory fitness, muscle strength, body composition, balance, and flexibility, among patients with T2DM. Methods: We systematically searched four databases and two registries (Pubmed, Scopus, Cochrane, Embase, WHO-ITCRP, and Clinicaltrials.gov) in September 2021, following a registered protocol on PROSPERO (CRD42022276225). Study inclusion criteria were T2DM patients with or without complication, yoga intervention as a single component or as a complement compared to other kinds of exercise or an inactive control, health-related fitness, and a randomized, controlled trial or quasi-experimental with control group design. The ROBINS-I tool and ROB 2.0 tool were used to assess the risk of bias in the included studies. A vote-counting analysis and meta-analysis computed using random effects’ models were conducted. Results: A total of 10 records from 3 quasi-experimental and 7 randomized, controlled trials with 815 participants in total were included. The meta-analysis favored yoga groups compared to inactive controls in improving muscle strength by 3.42 (95% confidence interval 2.42 to 4.43), repetitions of chair stand test, and improving cardiorespiratory fitness by 6.6% (95% confidence interval 0.4 to 12.8) improvement of baseline forced vital capacity. The quality of evidence for both outcomes was low. Conclusion: Low-quality evidence favored yoga in improving health-related fitness, particularly muscle strength and cardiorespiratory fitness, among patients with T2DM. Funding: All authors in this systematic review received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Background: There is a need for a type of physical activity that could address the challenging cycle of physical inactivity, impaired health-related fitness, and type 2 diabetes mellitus (T2DM) conditions. Yoga could be one type of exercise to overcome the barriers to adhere to regular physical activity. The current study aimed to systematically review the effect of yoga on health-related fitness, including cardiorespiratory fitness, muscle strength, body composition, balance, and flexibility, among patients with T2DM. Methods: We systematically searched four databases and two registries (Pubmed, Scopus, Cochrane, Embase, WHO-ITCRP, and Clinicaltrials.gov) in September 2021, following a registered protocol on PROSPERO (CRD42022276225). Study inclusion criteria were T2DM patients with or without complication, yoga intervention as a single component or as a complement compared to other kinds of exercise or an inactive control, health-related fitness, and a randomized, controlled trial or quasi-experimental with control group design. The ROBINS-I tool and ROB 2.0 tool were used to assess the risk of bias in the included studies. A vote-counting analysis and meta-analysis computed using random effects' models were conducted. Results: A total of 10 records from 3 quasi-experimental and 7 randomized, controlled trials with 815 participants in total were included. The meta-analysis favored yoga groups compared to inactive controls in improving muscle strength by 3.42 (95% confidence interval 2.42 to 4.43), repetitions of chair stand test, and improving cardiorespiratory fitness by 6.6% (95% confidence interval 0.4 to 12.8) improvement of baseline forced vital capacity. The quality of evidence for both outcomes was low. Conclusion: Low-quality evidence favored yoga in improving health-related fitness, particularly muscle strength and cardiorespiratory fitness, among patients with T2DM. Funding: All authors in this systematic review received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Context Circulating levels of liver-enriched antimicrobial peptide 2 (LEAP2), a ghrelin receptor antagonist, decrease under caloric restriction and increase in obesity. The role of LEAP2 in male puberty, a phase with accelerated energy demand, is unclear. Objective This work aimed to investigate whether circulating LEAP2 levels are downregulated in boys following the onset of puberty to respond to the energy need required for growth. Methods We determined circulating LEAP2 levels in 28 boys with constitutional delay of growth and puberty (CDGP) who participated in a randomized controlled trial (NCT01797718), and were treated with letrozole (n = 15) or intramuscular low-dose testosterone (T) (n = 13) for 6 months. Blood sampling and dual-energy x-ray absorptiometry–measured body composition were performed at 0-, 6-, and 12-month visits. Results Serum LEAP2 levels decreased statistically significantly during pubertal progression (0-6 months: mean decrease –4.3 [10.3] ng/mL, P = .036 and 0-12 months: –3.9 [9.3] ng/mL, P = .033). Between 0 and 6 months, the changes in serum LEAP2 levels correlated positively with changes in percentage of body fat (rs = 0.48, P = .011), and negatively with growth velocity and estradiol levels (rs = –0.43, P = .022, rs = –0.55, P = .003, respectively). In the T group only, the changes in serum LEAP2 correlated negatively with changes in T and estradiol levels. Between 0 and 12 months, the change in LEAP2 levels correlated negatively with the change in high-density lipoprotein levels (rs = –0.44, P = .022) and positively with the change in insulin (rs = 0.50, P = .009) and HOMA-IR (rs = 0.51, P = .007) levels. Conclusion Circulating LEAP2 levels decreased after induction of puberty reciprocally with increased growth rate and energy demand, reflecting the metabolic state of the adolescent. Further, the results suggest that estradiol levels may have a permissive role in downregulating circulating LEAP2 levels.

Purpose of Review: Sports nutrition guidelines typically state that athletes desiring weight gain follow a regimen that includes increasing energy intake by ~ 300–500 kcal/day with an emphasis on adequate protein and carbohydrate and judicious inclusion of energy-dense foods, in combination with rigorous resistance training. This regimen is thought to promote weekly gains of ~ 0.45 kg (1 lb), mostly as lean body mass (LBM). This review summarizes the evidence supporting these intentional weight gain regimens in athletes. Recent Findings: Although some research has been conducted in the past 5 years, research on intentional weight gain is lacking. Summary: Currently, available data suggests that weekly weight gain of 0.45 kg (1 lb), primarily as LBM, may be difficult for some athletes to achieve. Available evidence, however, suggests that commonly recommended strategies to promote calorie surplus, including consuming larger portions, incorporating energy-dense foods, and prioritizing liquid over solid foods, may prove helpful. Accepted version

Introduction: It is widely known that dialysis patients have significantly impaired functional outcomes and arterial stiffness, but still few studies have investigated the effects of dialysis longitudinally by a multidimensional approach. We aimed to assess longitudinal patterns of physical activity (PA), physical functioning (PF), health-related quality of life (HrQoL), body composition (BC), and arterial stiffness in prevalent dialysis patients. Materials and Methods: Thirty-nine prevalent dialysis patients (23 conventional hemodialysis [CHD] and 16 peritoneal dialysis) with a mean vintage of 25.7 (±22.1) months were included in this observational prospective study with a 2-year follow-up, and at baseline 20 healthy controls were included. Measurements were performed every 6 months. HrQoL was assessed using the Short Form-36 (SF-36) questionnaire. PA was assessed using the SenseWear™ Pro3 accelerometer. PF was assessed by walking speed, the PF subscale of the SF-36, and handgrip strength (HGS). BC was assessed using the Body Composition Monitor® and arterial stiffness by measuring carotid-femoral pulse wave velocity (PWV). The longitudinal trend was assessed using linear mixed models, correcting for sex, age, and dialysis vintage. For PWV, the trend was additionally corrected for diabetes and systolic blood pressure. Results: After correction, no statistically significant changes over time were observed for the parameters of PA, PF, HrQoL, and BC. In the combined group and in the group of CHD patients only, a significant change was observed for PWV (overall trend: p = 0.007 and p = 0.008, respectively). A statistically significant difference at baseline was observed between dialysis patients and healthy controls in all parameters, except for HGS and PWV. Discussion/Conclusion: We observed no statistically significant changes in functional outcomes during a 2-year follow-up period, but a significant increase was observed for arterial stiffness. These results might suggest that after a certain period in time, a relatively stable course is present in functional outcomes, but an ongoing deterioration in arterial stiffness occurs, which might increase the risk of cardiovascular disease and all-cause mortality in these patients.

Obesity is the consequence of a positive energy balance and characterized by enlargement of the adipose tissue, which in part is due to hyperplasia and hypertrophy of the adipocytes. Not much is known about the transition of normal mature adipocytes to the hypertrophic state, which in vivo is very hard to study. Here, we have maintained mature human SGBS cells as a surrogate for adipocytes, changes of morphological and molecular metabolism of the adipocytes were monitored over the first 4 days and the last 4 days. In total, 393 cellular proteins and 246 secreted proteins were identified for further analysis. During the first 4 days of high glucose and insulin, the adipocytes seemed to prefer pyruvate as energy source, whereas beta‐oxidation was down‐regulated supporting lipid loading. Over time, lipid droplet fusion instead of lipid uptake became relatively important for growth of lipid droplets during the last 4 days. Moreover, ECM production shifted towards ECM turnover by the up‐regulation of proteases over eight days. The present in vitro system provides insight into the metabolic changes of adipocytes under conditions of high glucose and insulin, which may help to understand the process of in vivo adipocyte hypertrophy during the development of obesity.

Background In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. Aims The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. Methods This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. Results The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. Conclusion The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

BACKGROUND: Low skeletal muscle radiation attenuation (SM-RA) is indicative of myosteatosis and diminished muscle function. It is predictive of poor outcome following oncological surgery in several cancer types. Postoperative pneumonia is a known risk factor for increased postoperative mortality. We hypothesized that low SM-RA of the respiratory muscles at the 4th thoracic-vertebra (T4) is associated with postoperative pneumonia following liver surgery.METHODS: Postoperative pneumonia was identified using prospective infection control data. Computed tomography body composition analysis was performed at the L3-and T4 level to determine SM-RA. Body composition variables were corrected for confounders and related to postoperative pneumonia and admission time by multivariable logistic regression.RESULTS: Body composition analysis of 180 patients was performed. Twenty-one patients developed postoperative pneumonia (11.6%). Multivariable analysis showed that low T4 SM-RA as well as low L3 SM-RA were significantly associated with postoperative pneumonia (OR 3.65, 95% CI 1.41-9.49, p < 0.01) and (OR 3.22, 95% CI 1.20-8.61, p = 0.02, respectively).CONCLUSION: Low SM-RA at either the L3-or T4-level is associated with a higher risk of postoperative pneumonia following CLRM resection.

Aim Loss of skeletal muscle mass is a common clinical finding in cancer patients. The purpose of this meta‐analysis and systematic review was to quantify the effect of doxorubicin on skeletal muscle and report on the proposed molecular pathways possibly leading to doxorubicin‐induced muscle atrophy in both human and animal models. Methods A systematic search of the literature was conducted in PubMed, EMBASE, Web of Science and CENTRAL databases. The internal validity of included studies was assessed using SYRCLE’s risk of bias tool. Results Twenty eligible articles were identified. No human studies were identified as being eligible for inclusion. Doxorubicin significantly reduced skeletal muscle weight (ie EDL, TA, gastrocnemius and soleus) by 14% (95% CI: 9.9; 19.3) and muscle fibre cross‐sectional area by 17% (95% CI: 9.0; 26.0) when compared to vehicle controls. Parallel to negative changes in muscle mass, muscle strength was even more decreased in response to doxorubicin administration. This review suggests that mitochondrial dysfunction plays a central role in doxorubicin‐induced skeletal muscle atrophy. The increased production of ROS plays a key role within this process. Furthermore, doxorubicin activated all major proteolytic systems (ie calpains, the ubiquitin‐proteasome pathway and autophagy) in the skeletal muscle. Although each of these proteolytic pathways contributes to doxorubicin‐induced muscle atrophy, the activation of the ubiquitin‐proteasome pathway is hypothesized to play a key role. Finally, a limited number of studies found that doxorubicin decreases protein synthesis by a disruption in the insulin signalling pathway. Conclusion The results of the meta‐analysis show that doxorubicin induces skeletal muscle atrophy in preclinical models. This effect may be explained by various interacting molecular pathways. Results from preclinical studies provide a robust setting to investigate a possible dose‐response, separate the effects of doxorubicin from tumour‐induced atrophy and to examine underlying molecular pathways. More research is needed to confirm the proposed signalling pathways in humans, paving the way for potential therapeutic approaches.

Bone strength and fracture risk do not only depend on bone density, but also on bone structure. The trabecular bone score (TBS) evaluates homogeneity of bone microarchitecture indirectly by measuring gray-level variations of two-dimensional (2D) DXA images. Although TBS is well-established for adults, there have been only few publications in pediatrics. In this monocentric retrospective analysis, we investigated TBS in children and adolescents with cerebral palsy (CP), a patient group vulnerable to low bone mineral mass due to impaired mobility. The influence of different parameters on TBS and areal BMD (aBMD) were evaluated, as well as the relationship between TBS and aBMD. We compared TBS values of our study population to a reference population. A total of 472 lumbar spine-dual-energy X-ray absorptiometry (LS-DXA) scans of children and adolescents with CP (205 female), aged between 4 and 18 years, were analyzed. The DXA-scans were part of the routine examination. The children had no records of fractures or specific bone diseases. Our study population with CP had similar TBS as the reference population. TBS did not increase with age until an inflection point at 10 years in females, and 12 years in males. Girls had significantly higher TBS than boys (p = .049) and pubertal girls aged 8 to 13 years had significantly higher TBS than prepubertal girls (p = .009). TBS standard deviation score for age (SDS-TBS) and aBMD Z-scores correlated weakly (p < .001; R = 0.276 [males], R = 0.284 [females]). Other than for aBMD Z-scores, SDS-TBS was not influenced by age-adjusted height Z-scores and there was no significant difference in SDS-TBS when grouped by mobility levels, using the Gross Motor Function Classification System (GMFCS). Our results indicate that children with CP have a similar homogeneous distribution of trabecular microarchitecture as controls. Puberty initiation appears to be essential for increase of TBS with age and for sex differences. TBS seems less influenced by body composition, height, and mobility than aBMD. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Aim Loss of skeletal muscle mass is a common clinical finding in cancer patients. The purpose of this meta-analysis and systematic review was to quantify the effect of doxorubicin on skeletal muscle and report on the proposed molecular pathways possibly leading to doxorubicin-induced muscle atrophy in both human and animal models.Methods A systematic search of the literature was conducted in PubMed, EMBASE, Web of Science and CENTRAL databases. The internal validity of included studies was assessed using SYRCLE's risk of bias tool.Results Twenty eligible articles were identified. No human studies were identified as being eligible for inclusion. Doxorubicin significantly reduced skeletal muscle weight (ie EDL, TA, gastrocnemius and soleus) by 14% (95% CI: 9.9; 19.3) and muscle fibre cross-sectional area by 17% (95% CI: 9.0; 26.0) when compared to vehicle controls. Parallel to negative changes in muscle mass, muscle strength was even more decreased in response to doxorubicin administration. This review suggests that mitochondrial dysfunction plays a central role in doxorubicin-induced skeletal muscle atrophy. The increased production of ROS plays a key role within this process. Furthermore, doxorubicin activated all major proteolytic systems (ie calpains, the ubiquitin-proteasome pathway and autophagy) in the skeletal muscle. Although each of these proteolytic pathways contributes to doxorubicin-induced muscle atrophy, the activation of the ubiquitin-proteasome pathway is hypothesized to play a key role. Finally, a limited number of studies found that doxorubicin decreases protein synthesis by a disruption in the insulin signalling pathway.Conclusion The results of the meta-analysis show that doxorubicin induces skeletal muscle atrophy in preclinical models. This effect may be explained by various interacting molecular pathways. Results from preclinical studies provide a robust setting to investigate a possible dose-response, separate the effects of doxorubicin from tumour-induced atrophy and to examine underlying molecular pathways. More research is needed to confirm the proposed signalling pathways in humans, paving the way for potential therapeutic approaches.