Significant Loss Of Muscle Mass Research Articles

Optimal nutritional therapy in critically ill patients: a narrative review

Inadequate nutrition delivery remains a pervasive issue in critically ill patients, with significant challenges in accurately measuring nutritional requirements and personalising nutrition. Current medical nutrition therapy is constrained by difficulty in objectively measuring nutritional requirements and patient responses. Both enteral and parenteral nutrition are effective, but achieving and assessing nutritional targets pose substantial challenges. The adoption of computerised nutrition monitoring is on the rise, with future strategies potentially incorporating advanced muscle monitoring tools such as ultrasound and bioelectrical impedance analysis (BIA). Early enteral nutrition has been shown to reduce complications and shorten ICU stays; however, it should be delayed in specific conditions such as gastrointestinal bleeding. When EN is not feasible, PN serves as a safe alternative. Indirect calorimetry offers a method to measure energy expenditure and guide nutritional interventions, though larger trials are necessary to validate its benefits in personalised nutrition strategies. Significant muscle mass loss is prevalent in ICU patients, necessitating optimal amino acid delivery. Protein intake should be tailored to lean mass rather than total body weight, and bedside techniques like BIA and muscle ultrasound can aid in personalising protein delivery. While high protein intake may help mitigate muscle loss, its effect on clinical outcomes remains debated. Further trials are essential to enhance personalised ICU nutrition and improve patient outcomes throughout their ICU and post-ICU care journey.

The Wound Environment Agent-based Model (WEABM): a digital twin platform for characterization and complex therapeutic discovery for volumetric muscle loss.

Volumetric Muscle Loss (VML) injuries are characterized by significant loss of muscle mass, usually due to trauma or surgical resection, often with a residual open wound in clinical settings and subsequent loss of limb function due to the replacement of the lost muscle mass with non-functional scar. Being able to regrow functional muscle in VML injuries is a complex control problem that needs to override robust, evolutionarily conserved healing processes aimed at rapidly closing the defect in lieu of restoration of function. We propose that discovering and implementing this complex control can be accomplished by the development of a Medical Digital Twin of VML. Digital Twins (DTs) are the subject of a recent report from the National Academies of Science, Engineering and Medicine (NASEM), which provides guidance as to the definition, capabilities and research challenges associated with the development and implementation of DTs. Specifically, DTs are defined as dynamic computational models that can be personalized to an individual real world "twin" and are connected to that twin via an ongoing data link. DTs can be used to provide control on the real-world twin that is, by the ongoing data connection, adaptive. We have developed an anatomic scale cell-level agent-based model of VML termed the Wound Environment Agent Based Model (WEABM) that can serve as the computational specification for a DT of VML. Simulations of the WEABM provided fundamental insights into the biology of VML, and we used the WEABM in our previously developed pipeline for simulation-based Deep Reinforcement Learning (DRL) to train an artificial intelligence (AI) to implement a robust generalizable control policy aimed at increasing the healing of VML with functional muscle. The insights into VML obtained include: 1) a competition between fibrosis and myogenesis due to spatial constraints on available edges of intact myofibrils to initiate the myoblast differentiation process, 2) the need to biologically "close" the wound from atmospheric/environmental exposure, which represents an ongoing inflammatory stimulus that promotes fibrosis and 3) that selective, multimodal and adaptive local mediator-level control can shift the trajectory of healing away from a highly evolutionarily beneficial imperative to close the wound via fibrosis. Control discovery with the WEABM identified the following design principles: 1) multimodal adaptive tissue-level mediator control to mitigate pro-inflammation as well as the pro-fibrotic aspects of compensatory anti-inflammation, 2) tissue-level mediator manipulation to promote myogenesis, 3) the use of an engineered extracellular matrix (ECM) to functionally close the wound and 4) the administration of an anti-fibrotic agent focused on the collagen-producing function of fibroblasts and myofibroblasts. The WEABM-trained DRL AI integrates these control modalities and provides design specifications for a potential device that can implement the required wound sensing and intervention delivery capabilities needed. The proposed cyber-physical system integrates the control AI with a physical sense-and-actuate device that meets the tenets of DTs put forth in the NASEM report and can serve as an example schema for the future development of Medical DTs.

Development of an Exercise-based EV Therapy to Improve Skeletal Muscle Recovery After Immobilization

Introduction: Immobilization is necessary for recovery from illness or bone fractures; however, prolonged immobilization can result in significant loss of muscle mass and function. It is critical to recover muscle mass quickly following immobilization as severe muscle atrophy is correlated with increased likelihood of metabolic disorders, disability, and mortality. Physical rehabilitation can improve outcomes but is not always feasible. The purpose is to determine the extent to which EVs circulating in blood after endurance exercise training (EnVs) act as a safe and effective therapy to recover skeletal muscle mass following disuse. Methods: Donor C57BL/6 mice (n = 8-10, 4-month-old) were provided access to horizontal running wheels in a locked (sedentary) or unlocked (exercise) condition. After 4 weeks of voluntary running, EVs (SedVs or EnVs) were isolated from plasma using size exclusion chromatography according to manufactures guidelines, and concentration confirmed via nanoparticle tracking analysis (NanoSight NS3000). Recipient C57BL6/J mice (n = 5-8, 4-month-old) were subjected to single limb immobilization for 14 days. Upon remobilization, mice received a single intramuscular injection of PBS, SedVs, EnVs, or endurance plasma proteins, and remobilized for 3 and 14 days. Muscle samples were collected after remobilization and assessed for muscle cross-sectional-area (CSA) and capillarization. Results: Upon 3-day remobilization, EnVs did not significantly recover global fiber CSA and fiber-type specific CSA (Type IIa, Type IIx or Type IIb) or capillarization. Upon 14-day remobilization, EnVs did not significantly improve global fiber CSA and fiber-type specific CSA. However, a significant treatment effect was observed for capillary density (P = 0.0445), with increases observed for both SedV (P = 0.034) and EnV (P = 0.0117). Conclusion: EVs isolated from plasma after exercise can significantly improve skeletal muscle vascularization after immobilization, which may represent an important step toward full recovery of skeletal muscle mass. Partially support by NIH (NIAMS R01AR072735). 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.

Translatability of mouse muscle-aging for humans: the role of sex

Muscle-aging drives sarcopenia and is a major public health issue. Mice are frequently used as a model for human muscle-aging, however, research investigating their translational value is limited. In addition, mechanisms underlying muscle-aging may have sex-specific features in humans, but it is not yet assessed whether these are recapitulated in mice. Here, we studied the effects of aging on a functional, histological and transcriptional level at multiple timepoints in male and female mice (4, 17, 21 and 25 months), with particular emphasis on sex-differences. The effects of natural aging on the transcriptome of quadriceps muscle were compared to humans on pathway level. Significant loss of muscle mass occurred late, at 25 months, in both male (-17%, quadriceps) and female mice (-10%, quadriceps) compared to young control mice. Concomitantly, we found in female, but not male mice, a slower movement speed in the aged groups compared to the young mice (P < 0.001). Consistently, weighted gene co-expression network analysis revealed a stronger association between the aging-related reduction of movement and aging-related changes in muscle transcriptome of female compared to male mice (P < 0.001). In male, but not female mice, major distinctive aging-related changes occurred in the last age group (25 months), which highlights the necessity for careful selection of age using mice as a muscle-aging model. Furthermore, contrasting to humans, more aging-related changes were found in the muscle transcriptome of male mice compared to female mice (4090 vs. 2285 differentially expressed genes at 25 months, respectively). Subsequently, male mice recapitulated more muscle-aging related pathways characteristic for both male and female humans. In conclusion, our data show that sex has a critical effect on the mouse muscle-aging trajectory, although these do not necessarily reflect sex differences observed in the human muscle-aging trajectory.

Blood flow restriction training in the pre- and postoperative phases of joint surgery

AbstractOrthopedic patients are frequently affected by temporary phases of immobility during the course of traumatic/degenerative joint diseases and particularly after joint surgery. These phases are usually accompanied by a significant loss of muscle mass and strength. However, since the patients’ load capacity is usually reduced, physicians and physiotherapists are often faced with the dilemma of not being able to offer an adequate therapeutic strategy for muscle preservation or early muscle building, since the high mechanical loads required for this in the training process are usually not feasible or even contraindicated for a certain period of time. In recent years, a training technique originating from sports science, called blood flow restriction (BFR) training, has increasingly been used in preoperative therapy or for rehabilitation. As the BFR method uses special blood pressure cuffs to occlude venous outflow from the exercising limb during exclusively low mechanical load strength training, the significant effects of muscle hypertrophy demonstrated by this method are of greatest interest to rehabilitation research. This article focuses on the training technique, the underlying mechanisms and potential risks, as well as integration of the technique into the clinical rehabilitation process based on existing data. Furthermore, this article provides the basis for a future consensus paper to validate the usability and effectiveness of BFR training in the conservative and rehabilitative therapeutic phases of joint surgery.

Metabolic Impact of Frailty Changes Diabetes Trajectory

Diabetes mellitus prevalence increases with increasing age. In older people with diabetes, frailty is a newly emerging and significant complication. Frailty induces body composition changes that influence the metabolic state and affect diabetes trajectory. Frailty appears to have a wide metabolic spectrum, which can present with an anorexic malnourished phenotype and a sarcopenic obese phenotype. The sarcopenic obese phenotype individuals have significant loss of muscle mass and increased visceral fat. This phenotype is characterised by increased insulin resistance and a synergistic increase in the cardiovascular risk more than that induced by obesity or sarcopenia alone. Therefore, in this phenotype, the trajectory of diabetes is accelerated, which needs further intensification of hypoglycaemic therapy and a focus on cardiovascular risk reduction. Anorexic malnourished individuals have significant weight loss and reduced insulin resistance. In this phenotype, the trajectory of diabetes is decelerated, which needs deintensification of hypoglycaemic therapy and a focus on symptom control and quality of life. In the sarcopenic obese phenotype, the early use of sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists is reasonable due to their weight loss and cardio-renal protection properties. In the malnourished anorexic phenotype, the early use of long-acting insulin analogues is reasonable due to their weight gain and anabolic properties, regimen simplicity and the convenience of once-daily administration.

Limited physician knowledge of sarcopenia: A survey.

Sarcopenia, a reduction in skeletal muscle mass and function, is a condition that contributes to functional decline and disability in older adults. Although research on this geriatric condition has developed rapidly in recent years, little work has been done to document whether practicing physicians are incorporating sarcopenia into their clinical practice. An online survey of 253 practicing U.S. physicians assessed knowledge of sarcopenia, use of the term in practice, motivation for screening patients, and diagnostic and treatment approaches. They were board certified in four practice areas: internal medicine (n=69), family medicine (n=69), geriatrics (n=40), or physical medicine and rehabilitation (PM&R) (n=75). Less than 20% of internists and family medicine physicians reported being very familiar with the term sarcopenia, with substantially higher familiarity at this level reported among geriatricians (70%) and among PM&R specialists (41%). Two additional findings pointed to deficiencies in sarcopenia knowledge and practice: participants substantially overestimated the prevalence of sarcopenia in older adults (44% of participants reported an expected prevalence of >25%) compared to findings from published studies (indicating 10% of older adults experience sarcopenia); over 75% reported not typically using specific diagnostic criteria or being unsure if their approach utilized any specific criteria. When asked what terminology they use in a medical chart for a patient presenting with significant loss of muscle mass and strength, only 8% said sarcopenia. Sarcopenia, a condition that can have a major impact on older adults as they age, has not been fully incorporated into the knowledge base and practices of active physicians. The survey data suggest that improving physician familiarity with sarcopenia and having universal agreement on criteria for diagnosis may increase the screening for and treatment of sarcopenia.

Incidence of muscle wasting in the critically ill: a prospective observational cohort study

Loss of muscle mass occurs rapidly during critical illness and negatively affects quality of life. The incidence of clinically significant muscle wasting in critically ill patients is unclear. This study aimed to assess the incidence of and identify predictors for clinically significant loss of muscle mass in this patient population. This was a single-center observational study. We used ultrasound to determine the rectus femoris cross-sectional area (RFcsa) on the first and seventh day of ICU stay. The primary outcome was the incidence of significant muscle wasting. We used a logistic regression model to determine significant predictors for muscle wasting. Ultrasound measurements were completed in 104 patients. Sixty-two of these patients (59.6%) showed ≥ 10% decreases in RFcsa. We did not identify any predictor for significant muscle wasting, however, age was of borderline significance (p = 0.0528). The 28-day mortality rate was higher in patients with significant wasting, but this difference was not statistically significant (30.6% versus 16.7%; p = 0.165). Clinically significant muscle wasting was frequent in our cohort of patients. Patient age was identified as a predictor of borderline significance for muscle wasting. The results could be used to plan future studies on this topic.Trial registration: ClinicalTrials.gov NCT03865095, date of registration: 06/03/2019.

Loss of muscle mass in women with premature ovarian insufficiency as compared with healthy controls.

Menopausal transition has been known to be associated with the loss of muscle mass. However, muscle health in women with premature menopause, that is, premature ovarian insufficiency (POI), remains unclear. We aimed to investigate and compare muscle mass parameters and the prevalence of low muscle mass between patients with spontaneous POI and healthy controls. In this cross-sectional study, 59 women with spontaneous POI and 57 premenopausal controls with normal ovarian function were enrolled at the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) from June 17, 2020, to August 20, 2021. Muscle mass parameters were measured by dual-energy x-ray absorptiometry, and low muscle mass was diagnosed using the Asian Working Group for Sarcopenia criteria. In addition, participants provided their sociodemographic data, menstrual and reproductive history, lifestyle factors, and medical history. Multivariate linear regression analysis was conducted. Muscle mass parameters, including appendicular skeletal muscle mass (ASM), ASM/height2, ASM/weight, ASM/body mass index, total skeletal muscle mass (TSM), and TSM/weight, were significantly lower in women with POI as compared with healthy controls (ASM: 14.62 ± 2.08 vs 15.97 ± 1.78, P < 0.001; ASM/height2: 5.71 ± 0.64 vs 6.15 ± 0.62, P < 0.001; ASM/weight: 0.27 [0.25, 0.28] vs 0.28 [0.27, 0.29], P = 0.002; ASM/BMI: 0.68 ± 0.07 vs 0.73 ± 0.06, P = 0.001; TSM: 33.85 ± 4.08 vs 36.43 ± 3.56, P < 0.001; TSM/weight: 0.63 [0.59, 0.65] vs 0.64 [0.61, 0.67], P = 0.02). The prevalence of low muscle mass in POI patients was significantly higher than that in controls (32.20% vs 8.77%, χ2 = 9.70, P = 0.002). Furthermore, multivariate linear regression analyses demonstrated that POI status was an independent risk factor for ASM (β = -1.13; 95% CI, -1.62 to -0.65), ASM/height2 (-0.35, -0.47 to -0.22), ASM/weight (-0.01, -0.02 to -0.009), ASM/BMI (-0.05, -0.07 to -0.02), TSM (-2.16, -3.14 to -1.17), and TSM/weight (-0.03, -0.04 to -0.02). Women with POI exhibit significant loss of muscle mass as compared with healthy controls. Early diagnosis and long-term health management in POI patients are important.

WE4.6 Postoperative muscle atrophy: an overlooked cause of morbidity

Abstract Aims A significant proportion of patients never fully recover baseline activity levels following major abdominal surgery. Postoperative muscle atrophy may be a major contributing factor to this, but is often overlooked. This study aimed to quantify the degree of muscle loss in patients undergoing routine recovery following major abdominal surgery and in patients admitted to critical care. Methods Fifteen patients undergoing major open colorectal resection were recruited. Cross surface area (CSA) and muscle thickness (MT) of a quadriceps muscle, Vastus Lateralis (VL) were measured pre-operatively and on post-operative day (POD) 5 using ultrasound. Knee extension strength was also measured pre-operatively and on POD5 using a handheld dynamometer. A systematic literature review was performed to identify studies reporting muscle loss in patients admitted to an intensive treatment unit (ITU), with pooled means of changes in quadriceps muscle CSA calculated. Results By POD 5 VL CSA had decreased by 9.16% (± 2.0), and MT had decreased by 8.14% (± 5.93). Associated with this, knee extensor strength decreased by 19.69% (± 12.91). Systematic review identified 4 studies reporting muscle loss in ITU patients, including a total of 126 patients. Pooled mean of quadriceps CSA in patient admitted to ITU decreased by 13.9% (-12.5% -20.75%) by POD7. Conclusions Major abdominal surgery is associated with a significant loss of muscle mass and function. Losses are larger in patients requiring ITU admission. This may have a significant impact on patients’ full recovery to baseline function and further work is required to investigate this.

Shared and Divergent Epigenetic Mechanisms in Cachexia and Sarcopenia.

Significant loss of muscle mass may occur in cachexia and sarcopenia, which are major causes of mortality and disability. Cachexia represents a complex multi-organ syndrome associated with cancer and chronic diseases. It is often characterized by body weight loss, inflammation, and muscle and adipose wasting. Progressive muscle loss is also a hallmark of healthy aging, which is emerging worldwide as a main demographic trend. A great challenge for the health care systems is the age-related decline in functionality which threatens the independence and quality of life of elderly people. This biological decline can also be associated with functional muscle loss, known as sarcopenia. Previous studies have shown that microRNAs (miRNAs) play pivotal roles in the development and progression of muscle wasting in both cachexia and sarcopenia. These small non-coding RNAs, often carried in extracellular vesicles, inhibit translation by targeting messenger RNAs, therefore representing potent epigenetic modulators. The molecular mechanisms behind cachexia and sarcopenia, including the expression of specific miRNAs, share common and distinctive trends. The aim of the present review is to compile recent evidence about shared and divergent epigenetic mechanisms, particularly focusing on miRNAs, between cachexia and sarcopenia to understand a facet in the underlying muscle wasting associated with these morbidities and disclose potential therapeutic interventions.

Oyster Hydrolysates Attenuate Muscle Atrophy via Regulating Protein Turnover and Mitochondria Biogenesis in C2C12 Cell and Immobilized Mice.

Sarcopenia, also known as skeletal muscle atrophy, is characterized by significant loss of muscle mass and strength. Oyster (Crassostrea gigas) hydrolysates have anti-cancer, antioxidant, and anti-inflammation properties. However, the anti-sarcopenic effect of oyster hydrolysates remains uninvestigated. Therefore, we prepared two different oyster hydrolysates, namely TGPN and PNY. This study aimed to determine the anti-muscle atrophy efficacy and molecular mechanisms of TGPN and PNY on both C2C12 cell lines and mice. In vitro, the TGPN and PNY recovered the dexamethasone-induced reduction in the myotube diameters. In vivo, TGPN and PNY administration not only improved grip strength and exercise endurance, but also attenuated the loss of muscle mass and muscle fiber cross-sectional area. Mechanistically, TGPN and PNY increased the expression of protein synthesis-related protein levels via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of the rapamycin pathway, and reduced the expression of protein degradation-related protein levels via the PI3K/Akt/forkhead box O pathway. Also, TGPN and PNY stimulated NAD-dependent deacetylase sirtuin-1(SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), nuclear respiratory factor 1,2, mitochondrial transcription factor A, along with mitochondrial DNA content via SIRT1/PGC-1α signaling. These findings suggest oyster hydrolysates could be used as a valuable natural material that inhibits skeletal muscle atrophy via regulating protein turnover and mitochondrial biogenesis.

Синдром персистирующего воспаления, иммуносупрессии и катаболизма: механизмы саркопении и пути коррекции

Благодаря прогрессу в области интенсивной терапии многие пациенты с тяжелой патологией выписываются из отделений интенсивной терапии. Однако у части больных сохраняется длительное слабой степени воспаление, восстановление является затяжным, и у них развивается хроническое критическое состояние. Кроме того, у некоторых пациентов наряду с устойчивым воспалением возникают иммуносупрессия и катаболизм. В 2012 году это состояние было выделено в отдельный синдром, который может наблюдаться после тяжелой травмы и ожогов, сепсиса, некротического панкреатита. Один из ведущих клинических проявлений при этом — значительная потеря мышечной массы тела, плохо поддающаяся коррекции. При использовании литературы из базы MedLine описываются современные представления о механизмах саркопении при синдроме устойчивого воспаления, иммуносупрессии и катаболизма и возможные пути оптимальной анаболической поддержки.

Loss of skeletal muscle mass can be predicted by sarcopenia and reflects poor functional recovery at one year after surgery for geriatric hip fractures

IntroductionHip fractures in the elderly impact negatively on functional dependence, and carry great social costs and morbidity. We assessed the decline in muscle mass and functional outcomes following hip fracture surgery . Material and methodsThirty patients with a hip fracture (mean age: 80.8 years) were assessed using dual-energy X-ray absorptiometry and reassessed for changes in body composition 1 year after hip surgery. Baseline demographic data, sarcopenia, and bone mineral density were recorded. Body mass index (BMI), handgrip strength, appendicular skeletal muscle mass (ASM), total body fat percentage, and responses to questionnaires measuring quality of life and activities of daily living (ADL) before injury and 1 year after hip surgery were analyzed to identify changes. Associations with changes in ADL or quality of life were analyzed with time-variant independent variables. ResultsSignificant losses in ADL were identified at the 1-year follow-up, at which time only 43% of patients had regained their preinjury ADL status. Additionally, the participants had lost an average of 4.63% of ASM. ASM loss was significantly higher in patients with baseline sarcopenia than in those without (mean loss: 9.18% and 1.15%, respectively). When confounders were controlled for, a greater loss of ASM and handgrip strength and larger increase in BMI were associated with greater decrease in ADL 1 year after hip surgery. ConclusionGeriatric hip fracture patients may experience a significant loss of muscle mass, associated with impaired functional recovery 1 year after hip surgery, highlighting a potential treatment target of maintaining muscle mass to improve prognosis in these patients.

Longitudinal Changes in Body Composition Following Hematopoietic Cell Transplantation

Sarcopenia, the loss of skeletal muscle tissue, has been identified as a potential risk factor for adverse outcomes in hematopoietic cell transplantation (HCT) recipients. However, much remains unknown about longitudinal changes in body composition following HCT. We retrospectively evaluated computed tomography (CT) imaging from 315 lymphoma patients undergoing HCT at our institution between 2000 and 2014. Two HCT cohorts were established: auto-HCT (did not receive allo-HCT, n=218) and allo-HCT (may have received previous auto-HCT, n=97). Cross-sectional area of lean muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were measured at the level of the third lumbar vertebral body (L3) on an axial CT image prior to HCT, 1 year post-HCT, and 2.5 years post-HCT. Lean muscle was normalized for height and reported as L3 skeletal muscle index (L3SMI). Sarcopenia was defined as L3SMI ≤39 cm2/m2 for women and ≤55 cm2/m2for men.Sarcopenia prior to HCT was observed in 50% of HCT recipients, 47% in the auto-HCT cohort and 57% in the allo-HCT cohort. The number of lines of therapy prior to HCT was predictive of sarcopenia prior to HCT (OR=1.29, p=.01). There was a significant decline in skeletal muscle mass over time for patients in the allo-HCT cohort when compared to the trend in the auto-HCT cohort (-6.52 cm2/imaging interval, p=<0.01) (Figure 1). In the allo-HCT cohort, the association between the change in muscle mass (per cm2) from prior to HCT to 2.5 years post-HCT and moderate-severe chronic GVHD did meet statistical significance (OR 1.04, p=0.03). The incidence of sarcopenia increased over time in all patients receiving HCT (OR=1.55; p=0.02), particularly driven by patients undergoing allo-HCT who experienced an increased rate of sarcopenia over time compared to auto-HCT (OR=1.66, p=0.02). The incidence of sarcopenia reached 66% at 2.5 years post-HCT in the allo-HCT cohort (Figure 2). In the allo-HCT cohort, the association between sarcopenia at 2.5 years post-HCT and moderate-severe chronic GVHD did not meet statistical significance (OR 3.32, p=0.07). Adipose tissue analysis showed allo-HCT recipients had lower measurements of SAT at all time point when compared to patients in the auto-HCT cohort. There was a significant increase in both VAT and SAT experienced by recipients of auto-HCT and allo-HCT when comparing CT images from 1 year post-HCT and 2.5 years post-HCT (p<0.05). However, there was no significant difference in change in SAT or VAT over time when comparing auto-HCT and allo-HCT cohorts.In conclusion, retrospective analysis of CT imaging revealed significant loss of muscle mass and an increased incidence of sarcopenia following HCT, especially in patients undergoing allo-HCT. Future studies are needed to further characterize changes in body composition in HCT recipients and investigate its impact on HCT outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Longitudinal partially ordered data analysis for preclinical sarcopenia.

Sarcopenia is a geriatric syndrome characterized by significant loss of muscle mass. Based on a commonly used definition of the condition that involves three measurements, different subclinical and clinical states of sarcopenia are formed. These states constitute a partially ordered set (poset). This article focuses on the analysis of longitudinal poset in the context of sarcopenia. We propose an extension of the generalized linear mixed model and a recoding scheme for poset analysis such that two submodels-one for ordered categories and one for nominal categories-that include common random effects can be jointly estimated. The new poset model postulates random effects conceptualized as latent variables that represent an underlying construct of interest, that is, susceptibility to sarcopenia over time. We demonstrate how information can be gleaned from nominal sarcopenic states for strengthening statistical inference on a person's susceptibility to sarcopenia.

Neuromotor Characteristics Of Older Men With Sarcopenia

Skeletal muscle mass increases over the first three decades of life, declines steadily through middle age, and more rapidly in older age. Sarcopenia describes a condition of significant loss of muscle mass in conjunction with reduced strength and function. While the changes in mass, strength and function across the lifespan are well-documented, little is known of the underlying neuromotor changes. PURPOSE: To examine the neuromotor mechanisms that underpin changes in muscles mass and function in older men with sarcopenia. METHODS: Twenty four older men (74.4 ±5.0yrs) were recruited for testing. Muscle and fat mass were determined by DXA (Norland XR-800, USA). Functional performance was assessed via isometric knee extension strength, timed-up-and-go (TUG), 5-times sit-to-stand (5TSTS), self-selected gait speed, and hand grip strength. Neuromotor function was assessed using electrical stimulation of the tibial nerve (Digitimer DS7AH, UK) and recording of EMG activity and torque during a graded plantar flexion contraction protocol. Measures included Level of Voluntary Activation (LoVA; 20%, 40%, 60% 80%, and 100% of MVC), resting and superimposed twitch (SIT), ankle torque, and EMG activity of the plantar and dorsi flexor muscles. RESULTS: Six older men were classified as sarcopenic based on DXA-derived measures of appendicular lean mass and height (<7.25kg/m2). Differences in LoVA and SIT were observed between older men and sarcopenic men at the 60% (LoVA: OM=85.5 ±5.5% SM=77.3 ±11.7%, p<0.05; SIT: OM=2.0 ±1.0% SM=3.6 ±2.8%, p<0.05) and 80% (LoVA: OM=95.8 ±2.4% SM=92.4 ±3.3%, p<0.05; SIT: OM=0.5 ±0.3% SM=1.2 ±0.8%, p<0.05) contraction intensities. Significant differences in knee extension strength were observed between older men and sarcopenic men (OM=512.2 ±125.2N SM=328.6 ±74.4N, p=0.03), however no other differences in functional performance measures were observed. CONCLUSIONS: These preliminary findings suggest that there are underlying neuromotor changes in men with sarcopenia, particularly during submaximal muscle contractions. Interestingly, men with sarcopenia were still able to maintain a similar level of functional ability compared to older healthy men. Future work will examine neuromotor characteristics in response to fatigue.

SO018NON-INVASIVE ASSESSMENT AND MONITORING OF SKELETAL MUSCLE MASS IN CRITICALLY ILL PATIENTS WITH AKI BY QUADRICEPS MUSCLE ULTRASOUND

Abstract Background and Aims Critically ill patients undergo important muscle wasting during ICU stay, and a significant loss of muscle mass still occurs in the first few days of hospital stay. This may delay both functional recovery and weaning from mechanical ventilation, being also a well-known predictor of mortality. Quite often, muscle wasting is masked by fluid overload, increasing the risk for underestimating the presence of malnutrition, as frequently occurs in critically ill patients with AKI. An important concern in this clinical setting is the lack of adequate tools for routine bedside evaluation of the skeletal muscle mass. Lately, the use of ultrasound (US) for the assessment of muscle mass has aroused considerable interest. It is a non-invasive technique, applicable at the bedside and even in non-collaborative patients, it is economically viable, safe and do not require specialized staff. Recently, its reliability and validity have been demonstrated in critically ill patients with AKI. On this premise, in the present study, we aimed to evaluate the clinical application of US for both evaluation and monitoring of quadriceps muscle thickness in critically ill patients with AKI. Method This is an observational study, conducted in the renal ICU of the Parma University Hospital. All adult patients with AKI, with no distinction regarding the severity of AKI, admitted in the renal ICU from 15/03/2017 to 15/03/2018, with previous hospital stay less than 72h, with a likely ICU stay of at least 5 days were eligible for entering the study. The diagnosis of AKI was made according to KDIGO. Quadriceps rectus femoris and vastus intermedius thickness (QRFT and QVIT) were measured at the midpoint and at the border between the upper third and lower two-thirds between the anterior superior iliac spine (ASIS) and the upper pole of the patella. US was performed twice during ICU stay, i.e., at baseline (within 72h from admission) and after 5 days since the first measurement. Results We enrolled 30 patients, 70% (n= 21/30) were male, mean age ± SD age 74±11 years, APACHE II mean ± SD, 22 ± 5. Ultrasonography took less than 10 minutes to set up and complete image acquisition and less than 10 minutes per image to complete measurement analysis in all patients. A total of 472 images were analyzed across the 30 subjects.

The Effects of Resistance Exercise With Blood Flow Restriction on Flow-Mediated Dilation and Arterial Stiffness in Elderly People With Low Gait Speed: Protocol for a Randomized Controlled Trial.

BackgroundDuring aging, a significant loss of muscle mass, strength, and power is associated with a decline in daily functional capacities. Traditionally, resistance training is prescribed to prevent or reverse the skeletal muscle weakness, but the required training intensity may be too demanding for older people with poor physical performance. Resistance exercise with blood flow moderation (KAATSU training), originally developed in Japan, combines resistance exercise with blood flow restriction. It has been reported that KAATSU training enhances muscle hypertrophy in many populations. However, few studies have evaluated the effects of resistance exercises with blood flow restriction in elderly people and how this affects vascular structure and function.ObjectiveThe aim of this study was to evaluate (1) the acute and chronic effects of resistance exercise with blood flow restriction on vascular health in elderly people with low gait speed and (2) whether low-load resistance training with blood flow restriction elicits similar strength and gait speed gains to those elicited by conventional resistance training without blood flow restriction.MethodsThis is an ongoing randomized controlled trial in elderly people with low gait speed. Overall, two study arms of 13 participants each perform resistance exercise with and without blood flow restriction. The 2 groups are as follows: the control group will perform conventional resistance exercise (60% of 1 repetition maximum) and the KAATSU group will perform the low-load resistance exercise with blood flow restriction (20% of 1 repetition maximum) for 12 weeks. Pulse wave velocity, venous occlusion plethysmography, and flow-mediated dilation are used to assess arterial stiffness, muscle blood flow, and endothelial function, respectively. The secondary outcomes are gait speed, strength, and quality of life. All measures will be performed before and after the training program.ResultsThis research study is in progress. Recruitment has started, and data collection is expected to finish in August 2020.ConclusionsThe findings of this study will have important implications for the rehabilitation of elderly people.Trial RegistrationClinicalTrials.gov NCT03272737; https://clinicaltrials.gov/ct2/show/NCT03272737International Registered Report Identifier (IRRID)DERR1-10.2196/14691

Redox responses in skeletal muscle following denervation

Previous studies have shown a significant increase in the mitochondrial generation of hydrogen peroxide (H2O2) and other peroxides in recently denervated muscle fibers. The mechanisms for generation of these peroxides and how the muscle responds to these peroxides are not fully established. The aim of this work was to determine the effect of denervation on the muscle content of proteins that may contribute to mitochondrial peroxide release and the muscle responses to this generation. Denervation of the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles in mice was achieved by surgical removal of a small section of the peroneal nerve prior to its entry into the muscle. An increase in mitochondrial peroxide generation has been observed from 7 days and sustained up to 21 days following denervation in the TA muscle fibers. This increased peroxide generation was reduced by incubation of skinned fibers with inhibitors of monoamine oxidases, NADPH oxidases or phospholipase A2 enzymes and the muscle content of these enzymes together with peroxiredoxin 6 were increased following denervation. Denervated muscle also showed significant adaptations in the content of several enzymes involved in the protection of cells against oxidative damage. Morphological analyses indicated a progressive significant loss of muscle mass in the TA muscle from 7 days up to 21 days following denervation due to fiber atrophy but without fiber loss. These results support the possibility that, at least initially, the increase in peroxide production may stimulate adaptations in an attempt to protect the muscle fibers, but that these processes are insufficient and the increased peroxide generation over the longer term may activate degenerative and atrophic processes in the denervated muscle fibers.