ABSTRACT
BACKGROUND: Cachexia is a condition characterized as a loss in body mass or metabolic dysfunction and is associated with several prevalent chronic health conditions including many cancers, COPD, HIV, and kidney disease, with between 10 and 50% of patients with these conditions having cachexia. Currently there is little research into cachexia and our objective is to characterize cachexia patients, their healthcare utilization, and associated hospitalization costs. Given the increasing prevalence of chronic diseases, it is important to better understand cachexia so that the condition can be better diagnosed and managed. METHODS: We utilized one year (2009) of the Nationwide Inpatient Sample (NIS). The NIS represents all inpatient stays at a random 20% sample of all hospitals within the United States. We grouped cachexia individuals by primary or secondary discharge diagnosis and then compared those with cachexia to all others in terms of length of stay (LOS) and total cost. Finally we looked into factors predicting increased LOS using a negative binomial model. RESULTS: We estimated US prevalence for cachexia-related inpatient admissions at 161,898 cases. Cachexia patients were older, with an average age of 67.95 versus 48.10 years in their non-cachexia peers. Hospitalizations associated with cachexia had an increased LOS compared to non-cachexia patients (6 versus 3 days), with average costs per stay $4641.30 greater. Differences were seen in loss of function (LOF) with cachexia patients, mostly in the major LOF category (52.60%), whereas non-cachexia patients were spread between minor, moderate, and major LOF (36.28%, 36.11%, and 21.26%, respectively). Significant positive predictors of increased LOS among cachexia patients included urban hospital (IRR=1.21, non-teaching urban; IRR=1.23, teaching urban), having either major (IRR=1.41) or extreme (IRR=2.64) LOF, and having a primary diagnosis of pneumonia (IRR=1.15). CONCLUSION: We have characterized cachexia and seen it associated with increased length of stay, increased cost, and more severe loss of function in patients compared to those without cachexia.
ABSTRACT
Canonical Wnt signaling is important in skeletal muscle repair but has not been well characterized in response to physiological stimuli. The objective of this study was to assess the effect of downhill running (DHR) on components of Wnt signaling. Young, male C57BL/J6 mice were exposed to DHR. Muscle injury and repair (MCadherin) were measured in soleus. Gene and protein expression of Wnt3a, active ß-catenin, GSK3ß, and LEF1 were measured in gastrocnemius. Muscle injury increased 6 days post-DHR and MCadherin protein increased 5 days post-DHR. Total and active GSK3ß protein decreased 3 days (9-fold and 3.6-fold, respectively) post-DHR. LEF1 protein increased 6 days (5-fold) post-DHR. DHR decreased GSK3ß and increased LEF1 protein expression, but did not affect other components of Wnt signaling. Due to their applicability, using models of physiological stimuli such as DHR will provide significant insight into cellular mechanisms within muscle.
Subject(s)
Down-Regulation/physiology , Glycogen Synthase Kinase 3/metabolism , Lymphoid Enhancer-Binding Factor 1/metabolism , Muscle, Skeletal/metabolism , Physical Conditioning, Animal/physiology , Running/physiology , Up-Regulation/physiology , Animals , Cadherins/metabolism , Glycogen Synthase Kinase 3 beta , Male , Mice , Mice, Inbred C57BL , Models, Animal , Time Factors , Wnt Signaling Pathway/physiology , Wnt3A Protein/metabolism , beta Catenin/metabolismABSTRACT
The age-related loss of skeletal muscle mass and function that is associated with sarcopenia can result in ultimate consequences such as decreased quality of life. The causes of sarcopenia are multifactorial and include environmental and biological factors. The purpose of this review is to synthesize what the literature reveals in regards to the cellular regulation of sarcopenia, including impaired muscle regenerative capacity in the aged, and to discuss if physiological stimuli have the potential to slow the loss of myogenic potential that is associated with sarcopenia. In addition, this review article will discuss the effect of aging on Notch and Wnt signaling, and whether physiological stimuli have the ability to restore Notch and Wnt signaling resulting in rejuvenated aged muscle repair. The intention of this summary is to bring awareness to the benefits of consistent physiological stimulus (exercise) to combating sarcopenia as well as proclaiming the usefulness of contraction-induced injury models to studying the effects of local and systemic influences on aged myogenic capability.
