Significant Muscle Loss Research Articles

Dietary protein in the ICU in relation to health outcomes.

Critical care nutrition guidelines recommend provision of higher protein doses than recommended in health. These recommendations have been predominately based on lower quality evidence and physiological rationale that greater protein doses may attenuate the significant muscle loss observed in critically ill patients. This review discusses the mechanistic action of protein in the critically ill, details results from recent trials on health outcomes, discusses considerations for interpretation of trial results, and provides an overview of future directions. Two recent large clinical trials have investigated different protein doses and the effect on clinical outcome. Important findings revealed potential harm in certain sub-groups of patients. This harm must be balanced with the potential for beneficial effects on muscle mass and physical function given that two recent systematic reviews with meta-analyses demonstrated attenuation of muscle loss with higher protein doses. Utilizing biological markers such as urea: creatinine ratio or urea levels may prove useful in monitoring harm from higher protein doses. Future research should focus on prospectively investigating biological signatures of harm as well as taking into the consideration elements that will likely enhance the effectiveness of protein dose.

Measuring Body Composition and Functional Strength: Implications for the Clinical Assessment of Skeletal Muscle

Skeletal muscle represents the largest single component of the body, comprising up to 50% of total mass in healthy individuals. Body composition assessment has largely focused on overweight and obese individuals, but healthy skeletal muscle is also an important indicator of health and wellbeing. We hypothesized that estimates of lean body mass and empirical measures of functional strength should be directly correlated with one another. In the current study, we estimated body composition using two different field methods. Bioimpedance spectroscopy (BIS) employs 256 frequencies of low energy electrical current to estimate body composition. We used BIS (Impedimed SFB7) to determine percent body fat and fat free mass in physically active volunteers, ranging in age from 18 – 62 years. In addition, we used the Jackson and Pollock 3-site skin fold method to estimate these parameters from the same individuals. We also measured functional strength with a whole body dynamometer to determine mid-thigh pull strength, and a grip dynamometer to assess grip strength (Baseline Evaluation Instruments). Data collected from more than 75 men and women revealed significant correlations between fat-free mass (FFM) and both measures of functional strength. Interestingly, men and women fell along the same trend line, with women exhibiting similar strength for a given FFM. Moreover, functional strength standardized to FFM provides an objective measure of relative strength that was not different between men and women. The American Medical Association released a new policy statement about body mass index (BMI) in June of 2023, highlighting that BMI is an imprecise measure of body composition and recommending that alternative measures, such as more precise measurement of body composition, also be used. Indeed, we found that for individuals with a BMI of less than 30, there was direct relationship between FFM and functional strength. By contrast, percent body fat was not correlated with BMI within this range. We suggest that FFM and functional strength could be used to assess healthy weight, in conjunction with BMI. These measures could also be used to screen for sarcopenia, cachexia, and other conditions associated with significant muscle loss. Skeletal muscle represents an often underappreciated component of health and a more precise assessment of muscle mass and strength should be used as a measure of overall health. This work was supported by a Keenan Award at St. Bonaventure University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Nutrition considerations for patients with persistent critical illness: A narrative review.

Critically ill patients experience high rates of malnutrition and significant muscle loss during their intensive care unit (ICU) admission, impacting recovery. Nutrition is likely to play an important role in mitigating the development and progression of malnutrition and muscle loss observed in ICU, yet definitive clinical trials of nutrition interventions in ICU have failed to show benefit. As improvements in the quality of medical care mean that sicker patients are able to survive the initial insult, combined with an aging and increasingly comorbid population, it is anticipated that ICU length of stay will continue to increase. This review aims to discuss nutrition considerations unique to critically ill patients who have persistent critical illness, defined as an ICU stay of >10 days. A discussion of nutrition concepts relevant to patients with persistent critical illness will include energy and protein metabolism, prescription, and delivery; monitoring of nutrition at the bedside; and the role of the healthcare team in optimizing nutrition support.

A retrospective evaluation of individual thigh muscle volume disparities based on hip fracture types in followed-up patients: an AI-based segmentation approach using UNETR.

Hip fractures are a common and debilitating condition, particularly among older adults. Loss of muscle mass and strength is a common consequence of hip fractures, which further contribute to functional decline and increased disability. Assessing changes in individual thigh muscles volume in follow-up patients can provide valuable insights into the quantitative recovery process and guide rehabilitation interventions. However, accurately measuring anatomical individual thigh muscle volume can be challenging due to various, labor intensive and time-consuming. This study aimed to evaluate differences in thigh muscle volume in followed-up hip fracture patients computed tomography (CT) scans using an AI based automatic muscle segmentation model. The study included a total of 18 patients at Gyeongsang National University, who had undergone surgical treatment for a hip fracture. We utilized the automatic segmentation algorithm which we have already developed using UNETR (U-net Transformer) architecture, performance dice score = 0.84, relative absolute volume difference 0.019 ± 0.017%. The results revealed intertrochanteric fractures result in more significant muscle volume loss (females: -97.4 cm3, males: -178.2 cm3) compared to femoral neck fractures (females: -83 cm3, males: -147.2 cm3). Additionally, the study uncovered substantial disparities in the susceptibility to volume loss among specific thigh muscles, including the Vastus lateralis, Adductor longus and brevis, and Gluteus maximus, particularly in cases of intertrochanteric fractures. The use of an automatic muscle segmentation model based on deep learning algorithms enables efficient and accurate analysis of thigh muscle volume differences in followed up hip fracture patients. Our findings emphasize the significant muscle loss tied to sarcopenia, a critical condition among the elderly. Intertrochanteric fractures resulted in greater muscle volume deformities, especially in key muscle groups, across both genders. Notably, while most muscles exhibited volume reduction following hip fractures, the sartorius, vastus and gluteus groups demonstrated more significant disparities in individuals who sustained intertrochanteric fractures. This non-invasive approach provides valuable insights into the extent of muscle atrophy following hip fracture and can inform targeted rehabilitation interventions.

Functional Chimeric Double-barrel Fibula and Reinnervated Peroneus Brevis Osteomyocutaneous Flap for One-stage Forearm Reconstruction.

Reconstructing a mangled limb is complex and requires expertise in both bone and soft-tissue reconstruction, particularly when there is significant muscle loss. Typically, multistage surgery is necessary, starting with soft-tissue coverage, followed by bone grafting and tendon transfers. Sometimes, microsurgical techniques such as vascularized bone grafts and free functional muscle transfers are necessary, especially when there is a bone defect of over 6 cm; the soft-tissue environment is infected, scarred, or poorly vascularized; or there are extensive musculotendinous injuries. We treated a 34-year-old man who had a crushed left forearm resulting in an 18 × 8 cm open wound, 5-cm radius and 7-cm ulna bone defects, loss of the extensor pollicis longus and brevis muscles, and extensive injuries to the other musculotendinous structures of the forearm. To accomplish a one-stage reconstruction, we used a chimeric fibula osteomyocutaneous flap that included a 20 × 10 cm skin flap, peroneus brevis muscle with its motor nerve, and two segments of fibula. The proximal and distal fibula segments were used for ulnar and radial bone reconstruction, respectively, preserving forearm supination and pronation. The peroneus brevis tendon was sutured to the extensor pollicis longus tendon, and its motor nerve was coaptated with the posterior interosseous nerve to restore thumb extension. The skin flap provided complete coverage of all exposed bone and tendon structures. At the 12-month follow-up, the patient regained full extension of the thumb, and there were no difficulties with forearm supination and pronation or with foot eversion and plantar flexion at the donor leg.

Nutrition Assessment and Management of Late-Onset Tay-Sachs Disease: A Clinical Case Report.

Tay-Sachs disease is a sphingolipidoses disorder characterized by failure to produce enzymes necessary for the degradation of sphingolipids in lysosomes, which leads to muscle weakness, ataxia, and mental and speech disorders. The treatment for such disorders commonly includes the use of miglustat, a medication that may cause several side effects (e.g., diarrhea and weight loss) that can contribute to the development of malnutrition. To our knowledge, no reports are available in the literature on the nutritional assessment and intervention recommended for those with Tay-Sachs disease. This case report aimed to describe the case of a female patient diagnosed with late-onset Tay-Sachs disease. The patient presented with diarrhea (adverse effect to treatment) and malnutrition when referred to the dietitian. She had significant muscle loss, asthenia, and weakness. The nutritional interventions prescribed were: dietary modification; supplementation with beta-hydroxymethyl-butyrate (HMB); use of lactase enzyme; probiotic (Saccharomyces boulardii); and oral nutritional supplement with low osmolarity. Recommendations aimed to meet the patient's nutritional requirements, including energy needs. In response to the nutrition intervention, the patient progressed with diarrhea cessation, weight recovery, and improvement in physical function measured by the dynamometer. As patients undergoing treatment for Tay-Sachs disease quickly progress to malnutrition, and given the lack of guidelines to inform healthcare providers on nutritional recommendations for this cohort, the description of a case that had positive progression may inform healthcare providers and help to initiate a discussion on the need to conduct research in this field for the development of therapeutic protocols and nutrition recommendations.

BMP-7 Attenuates Sarcopenia and Adverse Muscle Remodeling in Diabetic Mice via Alleviation of Lipids, Inflammation, HMGB1, and Pyroptosis.

Diabetic myopathy involves hyperglycemia, oxidative stress, and inflammation. However, the role of hypercholesterolemia-induced inflammation-mediated pathological mechanisms leading to fibrosis, sarcopenia, deterioration of muscle, and muscle dysfunction in diabetes is not well understood. In this study, we investigated the novel role of bone morphogenetic protein-7 (BMP-7) in ameliorating metabolic alterations, inflammation, pyroptosis, TGF-β/SMAD cell signaling mechanisms, and progression of diabetic myopathy. C57BL/6J mice were treated with saline, streptozotocin (STZ), or STZ+BMP-7. Diabetes was confirmed by increased fasting glucose levels and a glucose tolerance test. Gastrocnemius muscle and blood samples were collected for lipid and tissue analysis using various methods. A significant increase in hyperglycemia resulted in an increase in lipid accumulation, monocyte infiltration, and inflammation, as well as an increase in pyroptotic markers and signaling markers in diabetic muscle myocytes. A structural analysis showed significant muscle loss, and increased muscle deterioration and fibrosis leading to muscle dysfunction. BMP-7 attenuated pathological processes that resulted in significantly improved muscle function. We report, for the first time, that increased hyperlipidemia aggravates inflammation-induced pyroptosis, resulting in significant muscle loss, sarcopenia, and adverse skeletal muscle remodeling in diabetic muscle myopathy. Interventional treatment with BMP-7 attenuates hypercholesterolemia-induced inflammation-mediated sarcopenia and adverse muscle remodeling, suggesting BMP-7 could be a potential treatment option for diabetic muscle myopathy.

A Study of Muscle Mass Change at Onset and 2 Weeks Post Onset in Stroke Patients

[Purpose] The purpose of this study was to compare the body composition of stroke victims at the time of stroke onset and 2 weeks after stroke onset, and to examine the causes of differences. [Participants and Methods] Thirty-three patients with acute stroke were included. Body Mass Index (BMI), body fat percentage, Skeletal Muscle Mass Index (SMI), trunk muscle mass, paralytic upper limb muscle mass, paralytic lower limb muscle mass, non-paralytic upper limb muscle mass, and non-paralytic lower limb muscle mass were measured within 3 days of onset and at 2 weeks ± 2 days after onset, and the effect size calculated. [Results] Two weeks after onset, BMI had decreased significantly, but SMI, lower limb muscle mass, and body fat percentage showed no significant decrease. Significant muscle loss occurred in the trunk and both upper limbs, and the size was large and moderate to severe. [Conclusion] Acute stroke patients tend to lose muscle mass in both upper limbs and the trunk in the two weeks after stroke onset.

Laparoscopic liver resection is associated with less significant muscle loss than the conventional open approach

BackgroundLaparoscopic liver resections (LLR) have been shown a treatment approach comparable to open liver resections (OLR) in hepatocellular carcinoma (HCC). However, the influence of procedural type on body composition has not been investigated. The aim of the current study was to compare the degree of skeletal muscle loss between LLR and OLR for HCC.MethodsBy using propensity score matching (PSM) analysis, 64 pairs of patients were enrolled. The change of psoas muscle index (PMI) after the operation was compared between the matched patients in the LLR and OLR. Risk factors for significant muscle loss (defined as change in PMI > mean change minus one standard deviation) were further investigated by multivariate analysis.ResultsAmong patients enrolled, there was no significant difference in baseline characteristics between the two groups. The PMI was significantly decreased in the OLR group (P = 0.003). There were also more patients in the OLR group who developed significant muscle loss after the operations (P = 0.008). Multivariate analysis revealed OLR (P = 0.023), type 2 diabetes mellitus, indocyanine green retention rate at 15 min (ICG-15) > 10%, and cancer stage ≧ 3 were independent risk factors for significant muscle loss. In addition, significant muscle loss was associated with early HCC recurrence (P = 0.006). Metabolomic analysis demonstrated that the urea cycle may be decreased in patients with significant muscle loss.ConclusionLLR for HCC was associated with less significant muscle loss than OLR. Since significant muscle loss was a predictive factor for early tumor recurrence and associated with impaired liver metabolism, LLR may subsequently result in a more favorable outcome.

Significant muscle loss after stereotactic body radiotherapy predicts worse survival in patients with hepatocellular carcinoma

The relationship between sarcopenia and treatment outcomes, especially in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiotherapy (SBRT) has not been well-explored. This study aimed to investigate the effects of sarcopenia on the survival and toxicity after SBRT in patients with HCC. We included 137 patients with HCC treated with SBRT between 2008 and 2018. Sarcopenia was defined as a skeletal muscle index (SMI) of < 49 cm2/m2 for men and < 31 cm2/m2 for women using computed tomography images at the mid-level of the third lumbar vertebra. The SMI change was presented as the change per 90 days. The Kaplan–Meier method was used for survival estimation, and the Cox regression was used to determine prognosticators. Sarcopenia was present in 67 of 137 eligible patients. With the median follow-up of 14.1 months and 32.7 months in the entire cohort and in those alive, respectively, patients with pre-SBRT sarcopenia or SMI loss ≥ 7% after SBRT had worse overall survival than their counterparts. Significant survival predictors on multivariate analysis were SMI loss ≥ 7% after SBRT [hazard ratio (HR): 1.96, p = 0.013], presence of extrahepatic metastasis (HR: 3.47, p < 0.001), neutrophil-to-lymphocyte ratio (HR: 1.79, p = 0.027), and multiple tumors (HR: 2.19, p = 0.003). Separate Cox models according to the absence and presence of pre-SBRT sarcopenia showed that SMI loss ≥ 7% remained a significant survival predictor in patients with sarcopenia (HR: 3.06, p = 0.017) compared with those without sarcopenia. SMI loss ≥ 7% is also a predictor of the Child–Pugh score increase by ≥ 2 points after SBRT. SMI loss ≥ 7% after SBRT is a significant prognostic factor for worse survival and is associated with liver toxicity compared with pre-SBRT sarcopenia.

Impact of skeletal muscle loss during conversion therapy on clinical outcomes in lavage cytology positive patients with gastric cancer.

BackgroundThe relationship between sarcopenia and clinical outcomes during conversion therapy in patients with lavage cytology positive gastric cancer (GC-CY1) remains unclear. This study aimed to investigate the impact of sarcopenia and skeletal muscle loss on the efficacy of conversion therapy, tumour response and survival in GC-CY1 patients.MethodsRetrospective analysis of data from a prospective trial of conversion therapy conducted between April 2018 and August 2019 in patients with GC-CY1 (NCT03718624). Skeletal muscle index (SMI) was measured at the level of the third lumbar (L3) vertebra and the sarcopenia was defined using published cut-off points in all patients. We defined ΔSMI (%)/50 days above 9.53% for men and ΔSMI (%)/50 days above 8.81% for women as significant muscle loss (SML) and analysed the changes in skeletal muscle during conversion therapy in relation to treatment efficacy, survival and tumour response.ResultsOf the 36 patients, 7 patients (19.44%) developed sarcopenia before conversion therapy, 6 (16.67%) developed new sarcopenia after conversion therapy, and 8 (22.22%) developed SML during treatment. Multivariate analysis showed that sarcopenia before treatment [Odds Ratio (OR) =8.923, 95%CI: 1.341-25.321, p=0.002] and SML during treatment (OR=7.803, 95%CI: 1.106-16.189, p=0.001) had a negative impact on the success rate of conversion therapy. Cox multifactorial analysis found that pre-treatment sarcopenia [overall survival (OS): Hazard Ratio (HR) =6.341, 95%CI: 1.269-18.943, p=0.001; progression-free survival (PFS): HR=8.212, 95%CI: 1.569-36.582, p=0.001], newly developed sarcopenia after conversion therapy (OS: HR=3.189, 95%CI: 1.023-9.811, p=0.012; PFS: HR=3.084, 95%CI: 1.042-14.236, p=0.013) and the presence of SML during treatment (OS: HR=10.234, 95%CI: 2.532-54.231, p=0.002; PFS: HR=9.562, 95%CI: 2.341-38.092, p=0.002) were independent risk factor for OS and PFS in GC-CY1 patients.ConclusionPre-treatment sarcopenia and the presence of SML during treatment are strongly correlated with the immediate and long-term outcomes of GC-CY1 patients and can be used as imaging markers to predict the treatment efficacy and prognosis of patients in clinical practice.

Effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes in patients with locally advanced GIST

BackgroundCurrently, the effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes in patients with locally advanced gastrointestinal stromal tumors (LA-GIST) remains unclear. This study aims to investigate the relationship between changes in skeletal muscle and postoperative complications, survival and tumor response in patients with LA-GIST during neoadjuvant therapy with imatinib.MethodsWe retrospectively analyzed pre- and post-treatment computed tomography images of 57 GIST patients who underwent radical surgery after neoadjuvant therapy with imatinib from January 2013 to March 2019. Skeletal muscle index (SMI) was measured at the L3 vertebral level in all patients. A cut-off value (SMI < 52.3 cm2/m2 and < 38.6 cm2/m2 for men and women, respectively) published in a previous study was used to define sarcopenia. Based on gender, we defined ΔSMI (%)/250 days above 9.69% for men and ΔSMI (%)/250 days above 7.63% for women as significant muscle loss (SML). Factors associated with postoperative complications and tumor response were analyzed using logistic regression, and predictors affecting patient prognosis were analyzed using Cox regression.ResultsOf the 57 patients, sarcopenia was present before and after neoadjuvant therapy in 20 (35.09%) and 28 (49.12%) patients, respectively. It was not associated with immediate or long-term clinical outcomes. However, patients with SML during neoadjuvant therapy had a higher incidence of postoperative complications (60.00% vs. 25.00%, p = 0.008), worse pathological regression (44.00% vs. 75.00%, p = 0.017) and worse 3-year survival (Male, 68.75% vs. 95.45%, p = 0.027; Female, 66.67% vs. 100.00%, p = 0.046) than patients without SML.ConclusionThe development of SML during neoadjuvant therapy in LA-GIST patients, rather than pre- and post-treatment sarcopenia, is a major prognostic factor for the long-term prognosis and is also associated with recent postoperative complication rates and pathological regression.

Ultrasonography for Assessment of Sarcopenia: A Primer.

The human skeletal muscle has a pivotal role in preserving health by maintaining mobility, balance, and metabolic homeostasis. Significant muscle loss as a part of aging and accelerated by disease leads to sarcopenia which becomes an important predictor of quality of life in older persons. Therefore, clinical screening for sarcopenia and validation by precise qualitative and quantitative measurement of skeletal muscle mass (MM) and function is at the center-stage of translational research. Many imaging modalities are available, each having their strengths and limitations, either in interpretation, technical processes, time constraints, or expense. B-mode ultrasonography (US) is a relatively novel approach to evaluating muscle. It can measure several parameters such as MM and architecture simultaneously including muscle thickness, cross-sectional area, echogenicity, pennate angle, and fascicle length. It can also evaluate dynamic parameters like muscle contraction force and muscle microcirculation. US has not gained global attention due to a lack of consensus on standardization and diagnostic threshold values to diagnose sarcopenia. However, it is an inexpensive and widely available technique with clinical applicability. The ultrasound-derived parameters correlate well with strength and functional capacity and provide potential prognostic information. Our aim is to present an update on the evidence-based role of this promising technique in sarcopenia, its advantages over the existing modalities, and its limitations in actual practice with the hope that it may emerge as the "stethoscope" for community diagnosis of sarcopenia.

AKT controls protein synthesis and oxidative metabolism via combined mTORC1 and FOXO1 signalling to govern muscle physiology.

BackgroundSkeletomuscular diseases result in significant muscle loss and decreased performance, paralleled by a loss in mitochondrial and oxidative capacity. Insulin and insulin‐like growth factor‐1 (IGF‐1) are two potent anabolic hormones that activate a host of signalling intermediates including the serine/threonine kinase AKT to influence skeletal muscle physiology. Defective AKT signalling is associated with muscle pathology, including cachexia, sarcopenia, and disuse; however, the mechanistic underpinnings remain unresolved.MethodsTo elucidate the role of AKT signalling in muscle mass and physiology, we generated both congenital and inducible mouse models of skeletal muscle‐specific AKT deficiency. To understand the downstream mechanisms mediating AKT's effects on muscle biology, we generated mice lacking AKT1/2 and FOXO1 (M‐AKTFOXO1TKO and M‐indAKTFOXO1TKO) to inhibit downstream FOXO1 signalling, AKT1/2 and TSC1 (M‐AKTTSCTKO and M‐indAKTTSCTKO) to activate mTORC1, and AKT1/2, FOXO1, and TSC1 (M‐QKO and M‐indQKO) to simultaneously activate mTORC1 and inhibit FOXO1 in AKT‐deficient skeletal muscle. Muscle proteostasis and physiology were assessed using multiple assays including metabolic labelling, mitochondrial function, fibre typing, ex vivo physiology, and exercise performance.ResultsHere, we show that genetic ablation of skeletal muscle AKT signalling resulted in decreased muscle mass and a loss of oxidative metabolism and muscle performance. Specifically, deletion of muscle AKT activity during development or in adult mice resulted in a significant reduction in muscle growth by 30–40% (P < 0.0001; n = 12–20) and 15% (P < 0.01 and P < 0.0001; n = 20–30), respectively. Interestingly, this reduction in muscle mass was primarily due to an ~40% reduction in protein synthesis in both M‐AKTDKO and M‐indAKTDKO muscles (P < 0.05 and P < 0.01; n = 12–20) without significant changes in proteolysis or autophagy. Moreover, a significant reduction in oxidative capacity was observed in both M‐AKTDKO (P < 0.05, P < 0.01 and P < 0.001; n = 5–12) and M‐indAKTDKO (P < 0.05 and P < 0.01; n = 4). Mechanistically, activation and inhibition of mTORC1/FOXO1, respectively, but neither alone, were sufficient to restore protein synthesis, muscle oxidative capacity, and muscle function in the absence of AKT in vivo. In a mouse model of disuse‐induced muscle loss, simultaneous activation of mTORC1 and inhibition of FOXO1 preserved muscle mass following immobilization (~5–10% reduction in casted M‐indFOXO1TSCDKO muscles vs. ~30–40% casted M‐indControl muscles, P < 0.05 and P < 0.0001; n = 8–16).ConclusionsCollectively, this study provides novel insights into the AKT‐dependent mechanisms that underlie muscle protein homeostasis, function, and metabolism in both normal physiology and disuse‐induced muscle wasting.

MP61-17 CHARACTERIZING CHANGES IN MUSCLE MASS AFTER RADICAL NEPHRECTOMY FOR STAGE II-IV CLEAR CELL RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance III (MP61)1 Sep 2021MP61-17 CHARACTERIZING CHANGES IN MUSCLE MASS AFTER RADICAL NEPHRECTOMY FOR STAGE II-IV CLEAR CELL RENAL CELL CARCINOMA Mouneeb Choudry, Suzanne Lange, Matthew Covington, Jacob Ambrose, Heidi Hanson, Christopher Dechet, Brock O'Neil, Helena Furberg, Adriana Coletta, Jennifer Ose, Jeffrey Yap, Cornelia Ulrich, Jonathan Chipman, and Alejandro Sanchez Mouneeb ChoudryMouneeb Choudry More articles by this author , Suzanne LangeSuzanne Lange More articles by this author , Matthew CovingtonMatthew Covington More articles by this author , Jacob AmbroseJacob Ambrose More articles by this author , Heidi HansonHeidi Hanson More articles by this author , Christopher DechetChristopher Dechet More articles by this author , Brock O'NeilBrock O'Neil More articles by this author , Helena FurbergHelena Furberg More articles by this author , Adriana ColettaAdriana Coletta More articles by this author , Jennifer OseJennifer Ose More articles by this author , Jeffrey YapJeffrey Yap More articles by this author , Cornelia UlrichCornelia Ulrich More articles by this author , Jonathan ChipmanJonathan Chipman More articles by this author , and Alejandro SanchezAlejandro Sanchez More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002101.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Sarcopenia (low skeletal muscle mass) is a poor prognostic factor in patients undergoing nephrectomy for localized renal cancer. However, little is known about the trajectory of muscle mass change after surgery. Here, we characterize post-operative changes in muscle mass using a retrospective cohort of patients with clear cell renal cell carcinoma (ccRCC). METHODS: A total of 117 patients with stage II-IV ccRCC who underwent radical nephrectomy from 02/2014-09/2019 at the University of Utah were included. Skeletal muscle (SM) mass area and measures of adiposity (visceral and subcutaneous tissue area) were quantified using standard of care computed tomography (CT) images and Slice-o-matic software (Montreal, Canada). Sarcopenia (yes/no) was classified according to gender-specific international consensus definitions (SMI of <55cm2/m2 for men and <39 cm2/m2 for women). CT images were obtained within 4 months of surgery and at least one scan within 18 months after surgery. RESULTS: Median age 64 (IQR: 56-71), 74% male, 87% White, 69% had stage II-III and 31% had stage IV disease. At baseline, 48% were obese and 54% were considered sarcopenic. Among 80 patients with evaluable skeletal muscle area, 62 patients maintained muscles mass (± 1 SD, 78%) after surgery and 5 had significant muscle deterioration (≥ 2 SD, 6%). CONCLUSIONS: Among patients with stage II-IV clear cell renal cancer undergoing nephrectomy, post-operative muscle loss was present among 22% of patients and significant muscle loss in 6%. Patients with post-operative muscle wasting after surgery may be an ideal group to target with lifestyle interventions. Among a larger cohort of patients, we plan to assess the association of muscle loss with survival outcomes. Source of Funding: The research reported in this publication was supported by Huntsman Cancer Foundation. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1090-e1090 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mouneeb Choudry More articles by this author Suzanne Lange More articles by this author Matthew Covington More articles by this author Jacob Ambrose More articles by this author Heidi Hanson More articles by this author Christopher Dechet More articles by this author Brock O'Neil More articles by this author Helena Furberg More articles by this author Adriana Coletta More articles by this author Jennifer Ose More articles by this author Jeffrey Yap More articles by this author Cornelia Ulrich More articles by this author Jonathan Chipman More articles by this author Alejandro Sanchez More articles by this author Expand All Advertisement Loading ...

Towards bioengineered skeletal muscle: recent developments in vitro and in vivo.

Skeletal muscle is a functional tissue that accounts for approximately 40% of the human body mass. It has remarkable regenerative potential, however, trauma and volumetric muscle loss, progressive disease and aging can lead to significant muscle loss that the body cannot recover from. Clinical approaches to address this range from free-flap transfer for traumatic events involving volumetric muscle loss, to myoblast transplantation and gene therapy to replace muscle loss due to sarcopenia and hereditary neuromuscular disorders, however, these interventions are often inadequate. The adoption of engineering paradigms, in particular materials engineering and materials/tissue interfacing in biology and medicine, has given rise to the rapidly growing, multidisciplinary field of bioengineering. These methods have facilitated the development of new biomaterials that sustain cell growth and differentiation based on bionic biomimicry in naturally occurring and synthetic hydrogels and polymers, as well as additive fabrication methods to generate scaffolds that go some way to replicate the structural features of skeletal muscle. Recent advances in biofabrication techniques have resulted in significant improvements to some of these techniques and have also offered promising alternatives for the engineering of living muscle constructs ex vivo to address the loss of significant areas of muscle. This review highlights current research in this area and discusses the next steps required towards making muscle biofabrication a clinical reality.

Persistent Uncontrolled Asthma: Long-Term Impact on Physical Activity and Body Composition

RationaleAsthma, obesity and physical activity (PA) are interrelated. However, longitudinal data with objective PA measures and direct assessment of body composition are still lacking.ObjectiveTo study the impact of symptom control on PA and body composition.MethodsIn a longitudinal cohort study of the German Center for Lung Research, we assessed the body composition of 233 asthma patients and 84 healthy controls using bioelectrical impedance analysis. PA (ie average daily steps and time of at least moderate activity, steps/min) was measured by accelerometry for one week. Asthma control was assessed by ACT score, ACQ-5 score and history of severe exacerbations. After two years of follow-up, we studied changes in physical activity and body composition in relation to asthma control.ResultsPatients with uncontrolled asthma had increased fat mass and decreased muscle mass compared to patients with controlled asthma or healthy controls. Both fat mass and muscle mass correlated better with asthma control than the body mass index (BMI). In multivariate regressions adjusted for age and sex, asthma control and physical activity were independent predictors of body composition (R2 = 0.61, p < 0.001). Persistent uncontrolled asthma patients (n=64) had lower physical activity at both baseline (6614 steps/118 min) and follow-up (6195/115). Despite having stable BMI, they also had significant muscle loss (−1.2%, −0.88 kg, p<0.01) and fat accumulation (+1%, +1.1 kg, p<0.01). By contrast, temporarily uncontrolled or controlled asthma patients had higher physical activity at baseline (8670/156) and follow -up (9058/153) with almost unchanged body composition.ConclusionPersistent uncontrolled asthma is associated with sustained physical inactivity and adverse changes in body composition that might be overlooked by relying solely on BMI. Physical activity is an independent predictor of body composition and reliable long-term marker of symptom control.

Longitudinal Observation of Muscle Mass over 10 Years According to Serum Calcium Levels and Calcium Intake among Korean Adults Aged 50 and Older: The Korean Genome and Epidemiology Study.

The aim of this study was to investigate the longitudinal change in muscle mass over 10 years according to serum calcium levels and calcium intake. A total of 1497 men and 1845 women aged 50 years and older were included. Significant muscle loss (SML) was defined as a 5% or greater loss from baseline, while time-dependent development of SML was assessed according to quartiles for corrected calcium level and daily calcium intake using Cox regression models. The incidence of SML was 6.7 and 7.7 per 100-person-years among men and women, respectively. Groups with the lowest corrected calcium levels had more prominent SML than those with higher calcium levels, regardless of sex. The relationship between SML and calcium intake was significant only among women. The hazard ratio for SML per 1 mmol/L increase in corrected calcium level was 0.236 and 0.237 for men and women, respectively. In conclusion, low serum calcium levels may predict SML among adults aged ≥ 50 years, while low calcium intake may be a predictor for muscle loss among women. Therefore, encouraging dietary calcium intake among middle-aged and older adults for preservation of muscle mass should be considered.

Metabolic profiling shows pre-existing mitochondrial dysfunction contributes to muscle loss in a model of ICU-acquired weakness.

BackgroundSurgery can lead to significant muscle loss, which increases recovery time and associates with increased mortality. Muscle loss is not uniform, with some patients losing significant muscle mass and others losing relatively little, and is likely to be accompanied by marked changes in circulating metabolites and proteins. Determining these changes may help understand the variability and identify novel therapeutic approaches or markers of muscle wasting.MethodsTo determine the association between muscle loss and circulating metabolites, we studied 20 male patients (median age, 70.5, interquartile range, 62.5–75) undergoing aortic surgery. Muscle mass was determined before and 7 days after surgery and blood samples were taken before surgery, and 1, 3, and 7 days after surgery. The circulating metabolome and proteome were determined using commercial services (Metabolon and SomaLogic).ResultsTen patients lost more than 10% of the cross‐sectional area of the rectus femoris (RFCSA) and were defined as wasting. Metabolomic analysis showed that 557 circulating metabolites were altered following surgery (q < 0.05) in the whole cohort and 104 differed between wasting and non‐wasting patients (q < 0.05). Weighted genome co‐expression network analysis, identified clusters of metabolites, both before and after surgery, that associated with muscle mass and function (r = −0.72, p = 6 × 10−4 with RFCSA on Day 0, P = 3 × 10−4 with RFCSA on Day 7 and r = −0.73, P = 5 × 10−4 with hand‐grip strength on Day 7). These clusters were mainly composed of acyl carnitines and dicarboxylates indicating that pre‐existing mitochondrial dysfunction contributes to muscle loss following surgery. Surgery elevated cortisol to the same extent in wasting and non‐wasting patients, but the cortisol:cortisone ratio was higher in the wasting patients (Day 3 P = 0.043 and Day 7 P = 0.016). Wasting patients also showed a greater increase in circulating nucleotides 3 days after surgery. Comparison of the metabolome with inflammatory markers identified by SOMAscan® showed that pre‐surgical mitochondrial dysfunction was associated with growth differentiation factor 15 (GDF‐15) (r = 0.79, P = 2 × 10−4) and that GDF‐15, interleukin (IL)‐8), C‐C motif chemokine 23 (CCL‐23), and IL‐15 receptor subunit alpha (IL‐15RA) contributed to metabolic changes in response to surgery.ConclusionsWe show that pre‐existing mitochondrial dysfunction and reduced cortisol inactivation contribute to muscle loss following surgery. The data also implicate GDF‐15 and IL‐15RA in mitochondrial dysfunction.

Effects of acute oral feeding on protein metabolism and muscle protein synthesis in individuals with cancer.

Weight loss and muscle loss are common in individuals living with cancer, with ≤50% experiencing involuntary weight loss at any time point in their cancer journey, and between 11% and 74% having sarcopenia or significant muscle loss. These changes in body composition are related to poor outcomes such as increased treatment toxicity, impaired quality of life, and reduced survival duration. Poor outcomes are not restricted to those who are underweight with severe weight loss; sarcopenia alone has been shown to be a prognostic marker across all body mass index categories, ranging from underweight to obesity To understand the mechanism of nutrition interventions in cancer and to develop effective future interventions, it is necessary to look at the acute effects of feeding on the response of the body and the ability to reach an anabolic response. The aim of this study was to explore and summarize the emerging evidence on metabolic effects of acute oral interventions on whole body protein kinetics and muscle protein synthesis in individuals with cancer.