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Novel High-Quality Sonographic Methods to Diagnose Muscle Wasting in Long-Stay Critically Ill Patients: Shear Wave Elastography, Superb Microvascular Imaging and Contrast-Enhanced Ultrasound.
Hernández-Socorro, CR, Saavedra, P, López-Fernández, JC, Lübbe-Vazquez, F, Ruiz-Santana, S
Nutrients. 2021;(7)
Abstract
Novel ultrasound (US) methods are required to assess qualitative changes in the quadriceps rectus femoris (QRF) muscle when evaluating mechanically ventilated, long-stay ICU patients with suspected neuromuscular acquired weakness (ICUAW). Our aim was to analyze novel US muscle assessment methods in these patients versus healthy controls by carrying out a prospective observational study. Shear wave elastography (SWE) showed, with a receiver operating characteristic (ROC) curve of 0.972 (95% confidence interval (CI) = 0.916-1.000), that patients increased muscle stiffness associated with muscle fibrosis when diagnosed with ICUAW. We also performed, for the first time, superb microvascular imaging (SMI), which is an innovative US technique designed for imaging microvascularization unseen with color Doppler US, and observed that 53.8% of cases had significantly lower QRF muscle microvascular angiogenic activity than controls (p < 0.001). Finally, we used contrast-enhanced ultrasound (CEUS) to analyze maximum and minimum QRF muscle perfusion and obtained a ROC curve of 0.8, but when used as markers for SMI, their diagnostic capacity increased to 0.988 (CI = 0.965-1) and 0.932 (CI = 0.858-1), respectively. These findings show, for the first time, that these novel sonographic muscle methods should be used for their diagnostic capacity when assessing sarcopenic processes associated with this group of critically ill patients.
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Dietary protein intake does not modulate daily myofibrillar protein synthesis rates or loss of muscle mass and function during short-term immobilization in young men: a randomized controlled trial.
Kilroe, SP, Fulford, J, Jackman, S, Holwerda, A, Gijsen, A, van Loon, L, Wall, BT
The American journal of clinical nutrition. 2021;(3):548-561
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Abstract
BACKGROUND Short-term (<1 wk) muscle disuse lowers daily myofibrillar protein synthesis (MyoPS) rates resulting in muscle mass loss. The understanding of how daily dietary protein intake influences such muscle deconditioning requires further investigation. OBJECTIVES To assess the influence of graded dietary protein intakes on daily MyoPS rates and the loss of muscle mass during 3 d of disuse. METHODS Thirty-three healthy young men (aged 22 ± 1 y; BMI = 23 ± 1 kg/m2) initially consumed the same standardized diet for 5 d, providing 1.6 g protein/kg body mass/d. Thereafter, participants underwent a 3-d period of unilateral leg immobilization during which they were randomly assigned to 1 of 3 eucaloric diets containing relatively high, low, or no protein (HIGH: 1.6, LOW: 0.5, NO: 0.15 g protein/kg/d; n = 11 per group). One day prior to immobilization participants ingested 400 mL deuterated water (D2O) with 50-mL doses consumed daily thereafter. Prior to and immediately after immobilization upper leg bilateral MRI scans and vastus lateralis muscle biopsies were performed to measure quadriceps muscle volume and daily MyoPS rates, respectively. RESULTS Quadriceps muscle volume of the control legs remained unchanged throughout the experiment (P > 0.05). Immobilization led to 2.3 ± 0.4%, 2.7 ± 0.2%, and 2.0 ± 0.4% decreases in quadriceps muscle volume (P < 0.05) of the immobilized leg in the HIGH, LOW, and NO groups (P < 0.05), respectively, with no significant differences between groups (P > 0.05). D2O ingestion resulted in comparable plasma free [2H]-alanine enrichments during immobilization (∼2.5 mole percentage excess) across groups (P > 0.05). Daily MyoPS rates during immobilization were 30 ± 2% (HIGH), 26 ± 3% (LOW), and 27 ± 2% (NO) lower in the immobilized compared with the control leg, with no significant differences between groups (P > 0.05). CONCLUSIONS Three days of muscle disuse induces considerable declines in muscle mass and daily MyoPS rates. However, daily protein intake does not modulate any of these muscle deconditioning responses.Clinical trial registry number: NCT03797781.
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Pre- and Post-Surgical Nutrition for Preservation of Muscle Mass, Strength, and Functionality Following Orthopedic Surgery.
Hirsch, KR, Wolfe, RR, Ferrando, AA
Nutrients. 2021;(5)
Abstract
Nutritional status is a strong predictor of postoperative outcomes and is recognized as an important component of surgical recovery programs. Adequate nutritional consumption is essential for addressing the surgical stress response and mitigating the loss of muscle mass, strength, and functionality. Especially in older patients, inadequate protein can lead to significant muscle atrophy, leading to a loss of independence and increased mortality risk. Current nutritional recommendations for surgery primarily focus on screening and prevention of malnutrition, pre-surgical fasting protocols, and combating post-surgical insulin resistance, while recommendations regarding macronutrient composition and timing around surgery are less established. The goal of this review is to highlight oral nutrition strategies that can be implemented leading up to and following major surgery to minimize atrophy and the resultant loss of functionality. The role of carbohydrate and especially protein/essential amino acids in combating the surgical stress cascade and supporting recovery are discussed. Practical considerations for nutrient timing to maximize oral nutritional intake, especially during the immediate pre- and post- surgical periods, are also be discussed.
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Supplement Use in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Systematic Review.
Greif, DN, Emerson, CP, Allegra, P, Arizpe, A, Mansour, KL, Cade, WH, Baraga, MG
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2020;(9):2537-2549
Abstract
PURPOSE To assess whether a standardized dietary supplementation can help to decrease postoperative muscle atrophy and/or improve rehabilitation outcomes in patients who underwent anterior cruciate ligament reconstruction (ACLR). METHODS A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). MEDLINE, Scopus, and Cochrane Library databases were searched, and articles that examined protein or amino acid, vitamin, or any other type of supplementation in ACLR were reviewed. Two independent reviewers conducted the search using pertinent Boolean operations. RESULTS A total of 1818 articles were found after our database search. Ten studies fulfilled our inclusion criteria and only assessed patients undergoing ACLR. Four studies assessed protein-based supplementation. One study assessed creatine as a supplement. Four studies assessed vitamin-based supplementation. One study assessed testosterone supplementation. Protein and amino acid supplementation showed potential benefits; multiple authors demonstrated a combination of improved achievement of rehabilitation benchmarks, graft maturation, muscular hypertrophic response, and peak dynamic muscle strength. When we examined creatine, vitamin, or hormone-based protocols, none demonstrated results, suggesting these factors may attenuate muscle atrophy after surgery. Vitamin C and E demonstrated potentially increased local inflammation in skeletal muscle, which runs contrary to the belief that antioxidant vitamin-based supplementation may decrease the inflammatory response that plays a role in the post injury/operative period. CONCLUSIONS Protein-based supplementation may play a role in mitigating muscle atrophy associated with ACLR, as multiple authors demonstrated a combination of improved achievement of rehabilitation benchmarks, thigh hypertrophic response, and peak dynamic muscle strength. However, based on current literature, it is not possible to recommend a specific protein-based supplementation protocol at this time for patients undergoing ACLR. Limited evidence suggests no benefit for creatine, vitamin, or hormone-based protocols. LEVEL OF EVIDENCE II, a systematic review of level I-II studies.
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High-dose leucine supplementation does not prevent muscle atrophy or strength loss over 7 days of immobilization in healthy young males.
Edwards, SJ, Smeuninx, B, Mckendry, J, Nishimura, Y, Luo, D, Marshall, RN, Perkins, M, Ramsay, J, Joanisse, S, Philp, A, et al
The American journal of clinical nutrition. 2020;(5):1368-1381
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BACKGROUND Unavoidable periods of disuse lead to muscle atrophy and functional decline. Preventing such declines can reduce the risk of re-injury and improve recovery of normal physiological functioning. OBJECTIVES We aimed to determine the effectiveness of high-dose leucine supplementation on muscle morphology and strength during 7 d of unilateral lower-limb immobilization, and the role of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis in disuse atrophy. METHODS Sixteen healthy males (mean ± SEM age: 23 ± 1 y) underwent 7 d of unilateral lower-limb immobilization, with thrice-daily leucine (LEU; n = 8) or placebo (PLA; n = 8) supplementation (15 g/d). Before and after immobilization, muscle strength and compartmental tissue composition were assessed. A primed continuous infusion of l-[ring-13C6]-phenylalanine with serial muscle biopsies was used to determine postabsorptive and postprandial (20 g milk protein) MyoPS and MitoPS, fiber morphology, markers of protein turnover, and mitochondrial function between the control leg (CTL) and the immobilized leg (IMB). RESULTS Leg fat-free mass was reduced in IMB (mean ± SEM: -3.6% ± 0.5%; P = 0.030) but not CTL with no difference between supplementation groups. Isometric knee extensor strength declined to a greater extent in IMB (-27.9% ± 4.4%) than in CTL (-14.3% ± 4.4%; P = 0.043) with no difference between groups. In response to 20 g milk protein, postprandial MyoPS rates were significantly lower in IMB than in CTL (-22% ± 4%; P < 0.01) in both LEU and PLA. Postabsorptive MyoPS rates did not differ between legs or groups. Postabsorptive MitoPS rates were significantly lower in IMB than in CTL (-14% ± 5%; P < 0.01) and postprandial MitoPS rates significantly declined in response to 20 g milk protein ingestion (CTL: -10% ± 8%; IMB: -15% ± 10%; P = 0.039), with no differences between legs or groups. There were no significant differences in measures of mitochondrial respiration between legs, but peroxisome proliferator-activated receptor γ coactivator 1-α and oxidative phosphorylation complex II and III were significantly lower in IMB than in CTL (P < 0.05), with no differences between groups. CONCLUSIONS High-dose leucine supplementation (15 g/d) does not appear to attenuate any functional declines associated with 7 d of limb immobilization in young, healthy males.This trial was registered at clinicaltrials.gov as NCT03762278.
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2020 Chitranjan S. Ranawat Award: Perioperative essential amino acid supplementation suppresses rectus femoris muscle atrophy and accelerates early functional recovery following total knee arthroplasty.
Ueyama, H, Kanemoto, N, Minoda, Y, Taniguchi, Y, Nakamura, H
The bone & joint journal. 2020;(6_Supple_A):10-18
Abstract
AIMS: The aim of this study was to assess the effectiveness of perioperative essential amino acid (EAA) supplementation to prevent rectus femoris muscle atrophy and facilitate early recovery of function after total knee arthroplasty (TKA). METHODS The study involved 60 patients who underwent unilateral TKA for primary knee osteo-arthritis (OA). This was a double-blind, placebo-controlled, randomized control trial with patients randomly allocated to two groups, 30 patients each: the essential amino acid supplementation (9 g daily) and placebo (lactose powder, 9 g daily) groups. Supplementation and placebo were provided from one week before to two weeks after surgery. The area of the rectus femoris muscle were measured by ultrasound imaging one month before surgery and one, two, three, and four weeks postoperatively. The serum albumin level, a visual analogue knee pain score, and mobility were also measured at each time point. The time to recovery of activities of daily living (ADLs) was recorded. Postoperative nutrition and physiotherapy were identical in both groups. RESULTS The mean relative change from baseline was as follows for the amino acid group: 116% in rectus femoris muscle area (71% to 206%); 95% in serum albumin (80% to 115%) and 39% in VAS pain (0% to 100%) at four weeks after surgery. These values in the placebo group were: 97% in muscle area (68 to 155); 89% in serum albumin (71% to 100%) and 56% in VAS pain four weeks after surgery (0% to 100%). All changes were statistically significant (p < 0.05). The mean time to recovery of ADLs was shorter in the amino acid group compared with the placebo group (p = 0.005). CONCLUSION Perioperative essential amino acid supplementation prevents rectus femoris muscle atrophy and accelerates early functional recovery after TKA. Cite this article: Bone Joint J 2020;102-B(6 Supple A):10-18.
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The Role of Muscle Decline in Type 2 Diabetes Development: A 5-Year Prospective Observational Cohort Study.
Maliszewska, K, Adamska-Patruno, E, Goscik, J, Lipinska, D, Citko, A, Krahel, A, Miniewska, K, Fiedorczuk, J, Moroz, M, Gorska, M, et al
Nutrients. 2019;(4)
Abstract
The major risk factors of T2DM (type 2 diabetes mellitus) development are still under investigation. We evaluate the possible risk factors associated with type 2 diabetes (T2DM) in adult subjects during a five-year prospective cohort study. We recruited 1160 subjects who underwent oral glucose tolerance test, anthropometric measurements, and body composition and body fat distribution analysis at a baseline visit and again at follow-up after approximately five years. The conclusions of this study are based on observation of 219 subjects who attended both the first and follow-up visits. The fasting serum insulin was measured, and HOMA-IR (homeostatic model assessment of insulin resistance) was calculated. During the follow-up period, T2DM was diagnosed in 7.4% of participants, impaired fasting glucose in 37.7%, and impaired glucose tolerance in 9.3%. Logistic regression models, adjusted for age, were constructed. The changes in glucose concentration, visceral fat tissue content, insulin resistance, and %loss of muscle mass were chosen as the potential predictors for T2DM development. A set of independent variables was extracted. The constructed feature set comprised change in HOMA-IR (OR (odds ratio) = 1.01, p < 0.01) and change in %loss of muscle mass (OR = 0.84, p < 0.03). With an aim to validate the prediction capability using the selected attributes, a support vector machine classifier and leave-one-out cross-validation procedure was applied, yielding 92.78% classification accuracy. Our results show the correlation between the %loss of muscle mass and T2DM development in adults, independent of changes in insulin resistance.
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A nutrient cocktail prevents lipid metabolism alterations induced by 20 days of daily steps reduction and fructose overfeeding: result from a randomized study.
Damiot, A, Demangel, R, Noone, J, Chery, I, Zahariev, A, Normand, S, Brioche, T, Crampes, F, de Glisezinski, I, Lefai, E, et al
Journal of applied physiology (Bethesda, Md. : 1985). 2019;(1):88-101
Abstract
Physical inactivity and sedentary behaviors are independent risk factors for numerous diseases. We examined the ability of a nutrient cocktail composed of polyphenols, omega-3 fatty acids, vitamin E, and selenium to prevent the expected metabolic alterations induced by physical inactivity and sedentary behaviors. Healthy trained men ( n = 20) (averaging ∼14,000 steps/day and engaged in sports) were randomly divided into a control group (no supplementation) and a cocktail group for a 20-day free-living intervention during which they stopped exercise and decreased their daily steps (averaging ∼3,000 steps/day). During the last 10 days, metabolic changes were further triggered by fructose overfeeding. On days 0, 10, and 20, body composition (dual energy X-ray), blood chemistry, glucose tolerance [oral glucose tolerance test (OGTT)], and substrate oxidation (indirect calorimetry) were measured. OGTT included 1% fructose labeled with (U-13C) fructose to assess liver de novo lipogenesis. Histological changes and related cellular markers were assessed from muscle biopsies collected on days 0 and 20. While the cocktail did not prevent the decrease in insulin sensitivity and its muscular correlates induced by the intervention, it fully prevented the hypertriglyceridemia, the drop in fasting HDL and total fat oxidation, and the increase in de novo lipogenesis. The cocktail further prevented the decrease in the type-IIa muscle fiber cross-sectional area and was associated with lower protein ubiquitination content. The circulating antioxidant capacity was improved by the cocktail following the OGTT. In conclusion, a cocktail of nutrient compounds from dietary origin protects against the alterations in lipid metabolism induced by physical inactivity and fructose overfeeding. NEW & NOTEWORTHY This is the first study to test the efficacy of a novel dietary nutrient cocktail on the metabolic and physiological changes occurring during 20 days of physical inactivity along with fructose overfeeding. The main findings of this study are that 1) reduction in daily steps leads to decreased insulin sensitivity and total fat oxidation, resulting in hyperlipemia and increased de novo lipogenesis and 2) a cocktail supplement prevents the alterations on lipid metabolism.
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Determinants of skeletal muscle protein turnover following severe burn trauma in children.
Malagaris, I, Herndon, DN, Polychronopoulou, E, Rontoyanni, VG, Andersen, CR, Suman, OE, Porter, C, Sidossis, LS
Clinical nutrition (Edinburgh, Scotland). 2019;(3):1348-1354
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BACKGROUND & AIMS Burns remain the fifth cause of non-fatal pediatric injuries globally, with muscle cachexia being a hallmark of the stress response to burns. Burn-induced muscle wasting is associated with morbidity, yet the determinants of muscle protein catabolism in response to burn trauma remains unclear. Our objective was to determine the effect of patient and injury characteristics on muscle protein kinetics in burn patients. METHODS This retrospective, observational study was performed using protein kinetic data from pediatric patients who had severe burns (>30% of the total body surface area burned) and underwent cross-limb stable isotope infusions between 1999 and 2008 as part of prospective clinical trials. Mixed multiple regression models were used to assess associations between patient/injury characteristics and muscle protein fractional synthesis rate (FSR), net balance (NB), and rates of phenylalanine appearance (Ra; index of protein breakdown) and disappearance (Rd; index of protein synthesis) across the leg. RESULTS A total of 268 patients who underwent 499 studies were analyzed. Increasing time post injury was associated with greater FSR (p < 0.001) and NB (p = 0.01). Males were more catabolic than females (as indicated by lower NB, p = 0.04 and greater Ra, p = 0.008), a consequence of higher protein breakdown rather than lower synthesis. Increasing burn size was associated with higher protein synthesis rate (as indicated by higher FSR, p = 0.019) and higher protein breakdown rates (as indicated by greater Ra, p = 0.001). FSR was negatively associated with age (p < 0.001). CONCLUSIONS Data from this large patient cohort show that injury severity, sex, and time post injury influence skeletal muscle wasting in burned children. These findings suggest that individual patient characteristics should be considered when devising therapies to improve the acute care and rehabilitation of burn survivors.
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Vitamin D, muscle recovery, sarcopenia, cachexia, and muscle atrophy.
Garcia, M, Seelaender, M, Sotiropoulos, A, Coletti, D, Lancha, AH
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:66-69
Abstract
The relevance of vitamin D to skeletal muscle metabolism has been highlighted in recent years. The interest arises from the important findings of studies demonstrating multiple effects of vitamin D on this tissue, which can be divided into genomic (direct effects) and non-genomic effects (indirect effects). Another important aspect to be considered in the study of vitamin D and muscle fiber metabolism is related to different expression of vitamin D receptor (VDR), which varies in muscle tissue depending on age, sex, and pathology. The correlation between low circulating levels of vitamin D and muscle metabolism disorders is documented in various contexts, including muscle recovery, atrophy, sarcopenia, and cachexia. The aim of this review was to analyze recent results of both in vitro and in vivo studies to address the relationship between vitamin D and skeletal muscle biology. The words muscle atrophy, muscle hypertrophy, sarcopenia, and cachexia were crossed over with vitamin D in a Pubmed search. All original contributions, along with reviews on the topic, were included, and no publications in the past 10 y were discarded. The papers retrieved different topics such as vitamin D in skeletal muscle; vitamin D in circulation; vitamin D, sarcopenia, and muscle atrophy; vitamin D and cachexia; and vitamin D and muscle recovery.