Doctor of Philosophy

dissertationIntramuscular adipose tissue (IMAT) is an important negative predictor of muscle and mobility function in older adults. While IMAT has been theorized to increase with aging, more recent evidence suggests that IMAT may be a byproduct of inactivity rather than aging per se. The mechanism of IMAT's influence on muscle and mobility function is unknown but similar to the negative consequences attributed to other ectopic fat depots, may involve an inflammatory pathway. In order to clarify if IMAT is an obligatory consequence of age or if it is related to inactivity, the primary aim of this study was to compare IMAT, muscle and mobility function, and muscular inflammation in age and BMI matched older frail and nonfrail adults. A secondary aim was to examine the relationship of IMAT and visceral adipose tissue (VAT), muscular inflammation, muscle function and mobility function in a subgroup of older adults. Two groups of older nonobese adults were recruited. A sedentary frail group was classified as at least moderately frail with modified physical performance test scores of 32. Magnetic resonance imaging (MRI) was used to determine mean cross sectional area of thigh IMAT and VAT. Maximal voluntary isometric contractions were used to determine muscle function, and 6 minute walk and stair ascent time were used to determine mobility function. A sub group of participants from both groups who were free from disease and medications known to influence inflammation underwent percutaneous muscle biopsies iv of the vastus lateralis. Western blot and real time polymerase chain reaction were used to determined local muscular expression of mRNA and protein for the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis alpha (TNF-a). We found significant differences in IMAT, and IL-6 mRNA and protein expression between frail and nonfrail adults. We also found significant correlations between IMAT, VAT, IL-6, and muscle and mobility function. These findings suggest that IMAT is a product of inactivity and disease rather then aging alone and provide a potential mechanistic link between increased IMAT and decreased muscle and mobility function in older adults

Intermuscular fat: a review of the consequences and causes

pre-printMuscle's structural composition is an important factor underlying muscle strength and physical function in older adults. There is an increasing amount of research to support the clear disassociation between the loss of muscle lean tissue mass and strength with aging. This disassociation implies that factors in addition to lean muscle mass are responsible for the decreases in strength and function seen with aging. Intermuscular adipose tissue (IMAT) is a significant predictor of both muscle function and mobility function in older adults and across a wide variety of comorbid conditions such as stroke, spinal cord injury, diabetes, and COPD. IMAT is also implicated in metabolic dysfunction such as insulin resistance. The purpose of this narrative review is to provide a review of the implications of increased IMAT levels in metabolic, muscle, and mobility function. Potential treatment options to mitigate increasing levels of IMAT will also be discussed

Intramuscular Adipose Tissue, Sarcopenia, and Mobility Function in Older Individuals

Objective. Intramuscular adipose tissue (IMAT) and sarcopenia may adversely impact mobility function and physical activity. This study determined the association of locomotor muscle structure and function with mobility function in older adults. Method. 109 older adults with a variety of comorbid disease conditions were examined for thigh muscle composition via MRI, knee extensor strength via isometric dynamometry, and mobility function. The contribution of strength, quadriceps lean tissue, and IMAT to explaining the variability in mobility function was examined using multivariate linear regression models. Results. The predictors as a group contributed 27–45% of the variance in all outcome measures; however, IMAT contributed between 8–15% of the variance in all four mobility variables, while lean explained only 5% variance in only one mobility measure. Conclusions. Thigh IMAT, a newly identified muscle impairment appears to be a potent muscle variable related to the ability of older adults to move about in their community

Alterations in Muscle Architecture: A Review of the Relevance to Individuals After Limb Salvage Surgery for Bone Sarcoma

© Copyright © 2020 Nelson, Marchese, Rock, Henshaw and Addison. Osteosarcoma and Ewing\u27s sarcoma are the most common primary bone malignancies affecting children and adolescents. Optimal treatment requires a combination of chemotherapy and/or radiation along with surgical removal when feasible. Advances in multiple aspects of surgical management have allowed limb salvage surgery (LSS) to supplant amputation as the most common procedure for these tumors. However, individuals may experience significant impairment after LSS, including deficits in range of motion and strength that limit function and impact participation in work, school, and the community, ultimately affecting quality of life. Muscle force and speed of contraction are important contributors to normal function during activities such as gait, stairs, and other functional tasks. Muscle architecture is the primary contributor to muscle function and adapts to various stimuli, including periods of immobilization-protected weightbearing after surgery. The impacts of LSS on muscle architecture and how adaptations may impact deficits within the rehabilitation period and into long-term survivorship is not well-studied. The purpose of this paper is to [1] provide relevant background on bone sarcomas and LSS, [2] highlight the importance of muscle architecture, its measurement, and alterations as seen in other relevant populations and [3] discuss the clinical relevance of muscle architectural changes and the impact on muscle dysfunction in this population. Understanding the changes that occur in muscle architecture and its impact on long-term impairments in bone sarcoma survivors is important in developing new rehabilitation treatments that optimize functional outcomes

Rehabilitation Outcomes among Frail Older Adults in the United States

Background: Current rehabilitation care paradigms are not well aligned with the needs of frail older adults, but the resultant impact on rehabilitation outcomes is unclear. Understanding how frailty may impact rehabilitation outcomes, and understanding some of the underlying mechanisms, may help inform payment policy changes. Design: This study was a cross-sectional analysis of data from Round 5 of the National Health and Aging and Trends Study (NHATS). We identified older adults who had completed one or more episodes of rehabilitation care and used a validated 5-item NHATS Fried Frailty scale to categorize patients as frail (3/5 or more) or non-frail (≤2/5). We then evaluated the association between frailty status and three key patient outcomes: (1) achievement of rehabilitation goals, (2) functional improvement during rehabilitation episodes, and (3) discontinuation of therapy after exhausting insurance benefits. Lastly, we used multivariable, survey-weighted logistic regression models to estimate adjusted relationships between frailty and rehabilitation outcomes. Results: An estimated 5.6 million survey-weighted older adults in the United States (95% CI 5.1 to 6.0 million) completed an episode of rehabilitation in the past year, an estimated 1,271,290 (95% CI 921,758 to 1,620,822; weighted: 22.8%) of whom were frail. Frail rehabilitation recipients were generally older, had a greater comorbidity burden, and had a higher prevalence of dementia. In adjusted models, frailty was associated with poorer functional outcomes, a lower probability of meeting rehabilitation goals and a greater likelihood of exhausting rehabilitation insurance benefits. Conclusions: Exercise is a well-supported intervention for the management of frailty, but our results suggest that frail older adults are not getting the volume or intensity of rehabilitation treatment needed to maximally improve outcomes—in part due to limited payer coverage of rehabilitation services in the United States

Skeletal Muscle Measurements in Pediatric Hematology and Oncology: Essential Components to a Comprehensive Assessment

Children with hematologic and oncologic health conditions are at risk of impaired skeletal muscle strength, size, and neuromuscular activation that may limit gross motor performance. A comprehensive assessment of neuromuscular function of these children is essential to identify the trajectory of changes in skeletal muscle and to prescribe therapeutic exercise and monitor its impact. Therefore, this review aims to (a) define fundamental properties of skeletal muscle; (b) highlight methods to quantify muscle strength, size, and neuromuscular activation; (c) describe mechanisms that contribute to muscle strength and gross motor performance in children; (d) recommend clinical assessment measures; and (e) illustrate comprehensive muscle assessment in children using examples of sickle cell disease and musculoskeletal sarcoma