Progress in the study of muscle wasting in heart failure patients

Background Muscle wasting is a common clinical phenomenon that affects at least 20 percent of patients with heart failure. The exercise capacity of heart failure patients is limited; if left unchecked, which can form ca- chexia, seriously affecting the quality of life of patients with heart failure. This paper summarizes the clinical manifestations, pathophysiological mechanisms and its latest research direction including microRNA-regulated networks, and potential therapeutic strategies of muscle wasting in heart failure. Our goal is to provide a basis for clinicians to further understand and treat the muscle wasting in heart failure patients.

The mechanism by which noncoding RNAs regulate muscle wasting in cancer cachexia

Cancer cachexia(CC)is a complex metabolic syndrome that accelerates muscle wasting and affects up to 80%of patients with cancer;however,timely diagnostic methods and effective cures are lacking.Although a considerable number of studies have focused on the mechanism of CC-induced muscle atrophy,few novel therapies have been applied in the last decade.In recent years,noncoding RNAs(ncRNAs)have attracted great attention as many differentially expressed ncRNAs in cancer cachectic muscles have been reported to participate in the inhibition of myogenesis and activation of proteolysis.In addition,extracellular vesicles(EVs),which function as ncRNA carriers in intercellular communication,are closely involved in changing ncRNA expression profiles in muscle and promoting the development of muscle wasting;thus,EV-related ncRNAs may represent potential therapeutic targets.This review comprehensively describes the process of ncRNA transmission through EVs and summarizes the pathways and targets of ncRNAs that lead to CC-induced muscle atrophy.

Passive Strategies for the Prevention of Muscle Wasting During Recovery from Sports Injuries

Background Recovery from sport injuries commonly involves a muscle disuse situation(i.e.,reduction in physical activity levels sometimes preceded by joint immobilization)with subsequent negative effects on muscle mass and function.Purpose To summarize the current body of knowledge on the effectiveness of different physical strategies that are currently available to mitigate the negative effects of muscle disuse during recovery from sports injury.Methods A narrative review was conducted to summarize the information available on neuromuscular electrical stimulation(NMES),blood flow restriction(BFR)and vibration intervention.Results The concomitant application of BFR and low-intensity exercise has shown promising results in the prevention of disuse-induced muscle atrophy.Some benefits might also be obtained with BFR alone(i.e.,with no exercise),but evidence is still inconclusive.NMES,which can be applied both passively and synchronously with exercise,can also attenuate most of the negative changes associated with disuse periods.In turn,the mechanical stimulus elicited by vibration seems effec-tive to reduce the loss of bone mineral density that accompanies muscle disuse and could also provide some benefits at the muscle tissue level.Conclusions Different physical strategies are available to attenuate disuse-induced negative consequences during recovery from injury.These interventions can be applied passively,which makes them feasible during the first stages of the recovery.However,it would be advisable to apply these strategies in conjunction with low-intensity voluntary exercise as soon as this is feasible.

Sonographic muscle mass assessment in patients after cardiac surgery

BACKGROUND Patients undergoing cardiac surgery particularly those with comorbidities and frailty,experience frequently higher rates of post-operative morbidity,mortality and prolonged hospital length of stay.Muscle mass wasting seems to play important role in prolonged mechanical ventilation(MV)and consequently in intensive care unit(ICU)and hospital stay.AIM To investigate the clinical value of skeletal muscle mass assessed by ultrasound early after cardiac surgery in terms of duration of MV and ICU length of stay.METHODS In this observational study,we enrolled consecutively all patients,following their admission in the Cardiac Surgery ICU within 24 h of cardiac surgery.Bedside ultrasound scans,for the assessment of quadriceps muscle thickness,were performed at baseline and every 48 h for seven days or until ICU discharge.Muscle strength was also evaluated in parallel,using the Medical Research Council(MRC)scale.RESULTS Of the total 221 patients enrolled,ultrasound scans and muscle strength assessment were finally performed in 165 patients(patients excluded if ICU stay<24 h).The muscle thickness of rectus femoris(RF),was slightly decreased by 2.2%[(95%confidence interval(CI):-0.21 to 0.15),n=9;P=0.729]and the combined muscle thickness of the vastus intermedius(VI)and RF decreased by 3.5%[(95%CI:-0.4 to 0.22),n=9;P=0.530].Patients whose combined VI and RF muscle thickness was below the recorded median values(2.5 cm)on day 1(n=80),stayed longer in the ICU(47±74 h vs 28±45 h,P=0.02)and remained mechanically ventilated more(17±9 h vs 14±9 h,P=0.05).Moreover,patients with MRC score≤48 on day 3(n=7),required prolonged MV support compared to patients with MRC score≥49(n=33),(44±14 h vs 19±9 h,P=0.006)and had a longer duration of extracorporeal circulation was(159±91 min vs 112±71 min,P=0.025).CONCLUSION Skeletal quadriceps muscle thickness assessed by ultrasound shows a trend to a decrease in patients after cardiac surgery post-ICU admission and is associated with prolonged duration of MV and ICU length of stay.

Advances in pharmacotherapies in cancer-related cachexia

Cancer-related cachexia is highly prevalent in patients with advanced cancer, affecting approximately 50%–80% of patients and seriously interfering with active therapy, quality of life, and survival time. There arecurrently no effective treatments for cachexia. Therefore, new therapeutic strategies are required. In recentyears, advances in understanding the mechanisms underlying cachexia have been made, and new drugshave been developed to combat cachexia muscle wasting and weight loss due to cancer. In this systematicreview, we discuss these novel targets and drug treatments.

Recent Advances in Metabolomics and Therapeutics for Cancer Cachexia

Cancer Cachexia afflicts 50 - 80 percent of cancer patients with roughly 20 percent of all cancer patients dying of cachexia. Metabolomics is the study of different metabolites, their location in the body, and the timing of their appearance and disappearance. As a result, this science of Metabolomics can be applied to solve the problem of Cancer Cachexia. In this review, I examine recent studies on metabolism that use Metabolomics as their instrument of discovery. Further, this review details potential therapeutic interventions at the cellular, animal, and human level that show promise for attenuating Cancer Cachexia.

Resistance Exercise to Mitigate Cancer Cachexia: Molecular Mechanisms and Practical Applications

Background: Fifty-eighty percent of all cancer patients are afflicted by cancer cachexia and 20 percent die due to cancer cachexia. Purpose: From this narrative review, I will make a case for utilizing resistance exercise training from a molecular mechanistic standpoint and provide insight in how it can be used in a hospital setting. Method: PubMed Search and review of the literature. Discussion: The loss of about 9 percent of lean body mass is related to lower survival in metastatic colorectal cancer. Chemotherapy is also related to muscle mass loss. Resistance exercise training increases muscle protein synthesis and net muscle protein balance towards anabolism in healthy volunteers. Resistance exercise has shown to reduce the secretion of proinflammatory cytokines from monocytes and reduce toll-like receptor-4 expression on monocytes. Resistance exercise training has been shown to reduce lean body mass losses and improve function in cancer patients. Conclusion: All in all, resistance exercise training has been shown to alter molecular mechanisms that lead to muscle protein gains and is an effective means to improve function and reduce lean body mass losses in cancer with few side effects.

Muscle mitochondria and oxidative metabolism as targets against cancer cachexia

Cancer cachexia is a debilitating syndrome mainly characterized by muscle and fat wasting, leading to the progressive loss of body weight and complicating the management of cancer patient. In particular, the loss of muscle weight is a negative prognostic factor, being associated with chemotherapy toxicity and reduced survival. Increased inflammation and protein dysmetabolism are some of the impairments that lead to muscle wasting in cancer patients. Together with these alterations, tumor growth and chemotherapy administration may affect mitochondrial function, impinging on the muscle energy metabolism. Indeed, therapeutic approaches poised to correct both hypercatabolism and mitochondrial alterations could be effective in preventing cancer-induced muscle wasting. Among the non-pharmacological approaches, exercise training is one of the best modulator of muscle physiology able to impinge on both protein and energy metabolism. However, the wasting phenotype that characterizes cancer patients could be not compatible with physical training, prompting the development of different strategies to improve muscle metabolism. The aim of this mini-review is to discuss both the beneficial effects and the limitations of exercise training in cancer cachexia and the adoption of drugs able to modulate exercise-induced pathways.

Preclinical and clinical studies on cancer-associated cachexia

BACKGROUND： Cancer cachexia is the wasting condition that is often seen in advanced stage cancer patients. This wasting is largely attributable to a systemic and progressive loss of skeletal muscle mass that greatly hinders performance of normal daily activities, resulting in reduced quality of life. Moreover, it negatively influences the prognosis of cancer patients. A general consensus in the field is that the loss of muscle mass is due both to an increase in protein degradation and a decrease in protein synthesis. Recent studies using preclinical models for studying cachexia have been useful in identifying the contribution of inflammatory cytokines （e.g. tumor necrosis factor-a and Interleukin-6）, and myostatin receptors （e.g. the type IIB activin receptor） to cachexia development, and have led to several clinical trials. However, many questions remain about the molecular mechanisms thought to play a role in the development of cachexia. METHODS： We conducted a literature search using search engines, such as PubMed and Google Scholar to identify publications within the cancer cachexia field. RESULTS- We summarized our current knowledge of： 1） the driving mechanisms of cancer cachexia, 2） the preclinical models available for studying the condition, and 3） the findings of recent clinical trials. CONCLUSION： Cancer cachexia is a complex and variable condition that currently has no standard effective therapeutic treatment. Further studies are desperately needed to better understand this condition and develop effective combination treatments for patients.