Skeletal Muscle Quantity Research Articles

Association between heart failure in asymptomatic stages and skeletal muscle function assessed by ultrasonography in community-dwelling older adults

BackgroundSymptomatic heart failure (HF) negatively affects the quantity and quality of skeletal muscles. However, the association between asymptomatic HF and skeletal muscle function remains unclear. We aimed to use ultrasonography to elucidate the association between asymptomatic HF and skeletal muscle function in community-dwelling older adults.MethodsThis cross-sectional study comprised community-dwelling older adults aged ≥ 60 years who could perform activities of daily living independently and had never had symptomatic HF (n = 52, 76.3 ± 6.1 years). The participants were classified into three groups namely, non-HF (n = 26), stage A (n = 19), and stage B (n = 7) according to the HF stage criteria of the American Heart Association /American College of Cardiology /Heart Failure Society of America guideline. Skeletal muscle quantity and quality were assessed using ultrasonography (thickness and echo intensity) of the rectus femoris (RF) and vastus intermedius (VI) muscles. The group effects on muscle thickness and echo intensity in each group were assessed using a multivariate analysis.ResultsBoth muscles consistently demonstrated significant group effects on the thickness and echo intensity. Thicknesses of the RF (p = 0.020) and VI (p = 0.035) were lower in the stage B group than that in the non-HF group. The echo intensities in the RF (p = 0.006) and VI (p = 0.009) were higher in the stage B group than that in the non-HF group.ConclusionAsymptomatic HF negatively associated with the characteristics of skeletal muscle function, as assessed by ultrasonography in community-dwelling older adults. The stage B HF contributes to reduced skeletal muscle function as well as symptomatic HF.

Impedance Spectroscopy Measures of Whole and Segmental Skeletal Muscle Quantity Associated With Strength and Power in Collegiate Ice Hockey Players.

Otremba, JR, Heesch, AJ, Morgan, RM, Poolman, MA, Schindler, GD, and Fitzgerald, JS. Bioelectrical impedance spectroscopy measures of whole and segmental skeletal muscle quantity associated with strength and power in collegiate ice hockey players. J Strength Cond Res XX(X): 000-000, 2024-Bioelectrical impedance spectroscopy (BIS) is a promising monitoring tool for body water compartment assessment, particularly intracellular water (ICW), in which acute decreases are associated with increased muscle damage and reduced function, and chronic changes are associated with muscle quantity. Because little is known about the predictive utility of BIS-derived measures in athletes, this study aimed to assess the association between whole-body and segmental compartment water measured by BIS and maximal-intensity exercise performance in athletes. Twenty-five National Collegiate Athletic Association Division I collegiate hockey players completed 2 consecutive testing sessions. Body water and composition were assessed using a SOZO BIS device. Strength and explosive strength were measured on a force platform during the isometric belt squat and squat jump, respectively. Peak power was assessed using the 6-Second Test on a Wattbike. Pearson's r and partial correlation were used to assess relationships. Select body water and composition BIS variables were strong correlates of strength ( r = 0.51-0.63, p < 0.05), moderate correlates of power ( r = 0.41-0.44, p < 0.05), and lacked association with explosive strength. Segmental leg variables tended to be the strongest correlates of strength and power. Body water and traditional lean mass variables expressed similar predictive utility. Intracellular water/extracellular water lacked associated with exercise performance in bivariate and adjusted models. We provide evidence of the criterion validity of whole-body (i.e., ICW, fat-free mass, skeletal muscle mass [SMM]) and segmental (i.e., leg ICW, leg SMM) BIS variables, related to the quantity of SMM, to predict body-size dependent maximal-intensity exercise performance. Practitioners can use this information to determine which variables to track for performance readiness monitoring.

Glucagon-like peptide-1 receptor agonist-based agents and weight loss composition: Filling the gaps.

Excess adiposity is at the root of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as first-line treatments for T2D based on significant weight loss results. The composition of weight loss using most diets consists of <25% fat-free mass (FFM) loss, with the remainder from fat stores. Higher amounts of weight loss (achieved with metabolic bariatric surgery) result in greater reductions in FFM. Our aim was to assess the impact that GLP-1RA-based treatments have on FFM. We analysed studies that reported changes in FFM with the following agents: exenatide, liraglutide, semaglutide, and the dual incretin receptor agonist tirzepatide. We performed an analysis of various weight loss interventions to provide a reference for expected changes in FFM. We evaluated studies using dual-energy X-ray absorptiometry (DXA) for measuring FFM (a crude surrogate for skeletal muscle). In evaluating the composition of weight loss, the percentage lost as fat-free mass (%FFML) was equal to ΔFFM/total weight change. The %FFML using GLP-1RA-based agents was between 20% and 40%. In the 28 clinical trials evaluated, the proportion of FFM loss was highly variable, but the majority reported %FFML exceeding 25%. Our review was limited to small substudies and the use of DXA, which does not measure skeletal muscle mass directly. Since FFM contains a variable amount of muscle (approximately 55%), this indirect measure may explain the heterogeneity in the data. Assessing quantity and quality of skeletal muscle using advanced imaging (magnetic resonance imaging) with functional testing will help fill the gaps in our current understanding.

Age-induced changes in skeletal muscle mitochondrial DNA synthesis, quantity, and quality in genetically unique rats

AbstractMitochondrial genomic integrity is a key element of physiological processes and health. Changes in the half-life of the mitochondrial genome are implicated in the generation and accumulation of age-induced mitochondrial DNA (mtDNA) mutations, which are implicated in skeletal muscle aging and sarcopenia. There are conflicting data on the half-life of mtDNA, and there is limited information on how aging affects half-life in skeletal muscle. We hypothesized that skeletal muscle mtDNA synthesis rates would decrease with age in both female and male rats concomitant with changes in mtDNA integrity reflected in mtDNA copy number and mutation frequency. We measured mitochondrial genome half-life using stable isotope labeling over a period of 14 days and assessed mtDNA copy number and deletion mutation frequency using digital PCR in the quadriceps muscle of 9-month-old and 26-month-old male and female OKC-HET rats. We found a significant age-related increase in mtDNA half-life, from 132 days at 9 months to 216 days at 26 months of age in OKC-HET quadriceps. Concomitant with the increase in mtDNA half-life, we found an age-related increase in mtDNA deletion mutation frequency in both male and female rats. Notably, 26-month-old female rats had a lower mutation frequency than male rats, and there were no changes in mtDNA copy number with sex, age, or mitochondrial genotype. These data reveal several key findings: (1) mtDNA turnover in rat skeletal muscle decreases with age, (2) mtDNA half-lives in skeletal muscle are approximately an order of magnitude longer than what is reported for other tissues, and (3) muscle mtDNA turnover differs significantly from the turnover of other mitochondrial macromolecules including components of the mitochondrial nucleoid. These findings provide insight into the factors driving age-induced mtDNA mutation accumulation, which contribute to losses of mitochondrial genomic integrity and may play a role in skeletal muscle dysfunction.

A sex-oriented analysis concerning skeletal muscle quantity and quality and associations to quality of life in hospitalized patients with cirrhosis

BackgroundThere is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities.MethodsTotally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity.ResultsThe study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P < 0.001) and SMI (48.8 versus 42.2 cm2/m2, P < 0.001) were significantly higher in males relative to females, with comparable myosteatosis prevalence (15.3 versus 16.7%, P = 0.708). Self-care, usual activities and pain within EQ-5D scale were more prevalent in the sarcopenia compared with non-sarcopenia groups across entire population and stratified by sex. The SMI values exhibited a significantly linear correlation with EQ-5D utility index in male but not female patients (P for non-linearity = 0.281). In multiple analysis, SMI or the presence of sarcopenia was both significantly associated with EQ-5D utility index. Subgroup analyses unveiled no discernible interactions between sarcopenia and EQ-5D utility index.ConclusionsMuscle quantity measured by SMI was associated with declined HRQoL in males rather than females, whereas no associations were found regarding muscle quality measured by IMAC in both sexes. It is tempting to manage sarcopenia by increasing SMI levels as high as possible in hopes of achieving better health consequence. Our findings represent the importance of connecting CT-demarcated body composition abnormalities to meaningful patient-centered outcomes. Future targeted studies with sizable multi-center populations are warranted to clarify this causality, and in consequence develop optimized intervention against sarcopenia/myosteatosis or key determinants concerning impaired HRQoL.

Phase angle measured by bioelectrical impedance analysis in patients with chronic obstructive pulmonary disease: Associations with physical inactivity and frailty

BackgroundFactors associated with early-stage frailty (pre-frailty) in patients with chronic obstructive pulmonary disease (COPD) remain unestablished. In addition to skeletal muscle quantity, skeletal muscle dysfunction can be estimated using an angular metric from bioelectrical impedance analyzer (BIA), termed the phase angle, that reflects cell membrane reactance representing the structural stability. This study examined whether the phase angle was more closely associated with pre-frailty compared with skeletal muscle quantity in patients with COPD. MethodsThis cross-sectional analysis included stable smokers with and without COPD whose frailty status was assessed using the Japanese version of the Cardiovascular Health Study criteria. The phase angle and skeletal muscle index (SMI) were measured using BIA, and physical activity over one week was assessed using triaxial accelerometers. ResultsA total of 159 patients were categorized into robust, pre-frail, and frail groups (n = 38, 92, and 29, respectively). The phase angle was significantly smaller in the pre-frail and frail groups than in the robust group after adjusting for age, sex, height, body mass index, smoking history, and lung function. In contrast, SMI did not differ between the robust and pre-frail groups. When combining the pre-frail and frail groups into a non-robust group, 4.8° was determined as the cutoff phase angle value to identify non-robust status. A phase angle <4.8° was associated with shorter durations of moderate-intensity physical activity but not with light physical activity. ConclusionsA smaller phase angle was associated with pre-frailty and impaired moderate-intensity physical activity in smokers with and without COPD.

23 Pre-surgical visceral adipose tissue may be a novel pre-surgical risk factor for acute kidney injury among clear cell renal cell cancer patients undergoing radical nephrectomy

Abstract Background Patients with renal cancer undergoing partial (PN) or radical nephrectomy (RN) are at risk for acute kidney injury (AKI). Established risk factor for AKI include baseline comorbidities (e.g., obesity, hypertension), normal renal parenchymal loss, and ischemia-reperfusion injury. Pre-surgical body composition may be an overlooked modifiable patient characteristic that influences risk of AKI. We hypothesized that patients with higher visceral adipose tissue quantity or lower skeletal muscle quantity would have a higher risk of AKI. Methods The RESOLVE study at Memorial Sloan Kettering Cancer Center is a retrospective study of 1239 patients with stage I-III clear cell renal cell carcinoma (ccRCC) undergoing PN or RN from 2000 to 2020. We excluded from analysis patients with solitary kidney, those without preoperative serum creatinine (sCr) measurements, and those without a sCr measurement within seven days following nephrectomy, yielding a study population of 1,200 ccRCC patients with longitudinal sCr assessment (n=754 PN; n=446 PN). AKI was defined as a binary variable using the Kidney Disease – Improving Global Outcomes (KDIGO) criteria, based on a threshold of either a 1.5x relative or 0.3 mg/dl absolute increase in sCr within seven days. The cross-sectional areas and radiodensities of visceral adipose and skeletal muscle tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. We used generalized linear models with a binomial family and identity link to estimate seven-day risk differences (RD) and 95% confidence intervals in subgroups defined by surgery type. Results AKI was more frequent among patients undergoing RN (66% vs 26% among PN). Male patients, those with higher eGFR prior to surgery, those with lower stage/smaller tumors, and those with a history of hyperlipidemia more frequently experienced AKI in the post-operative period. No associations were observed with other reported comorbidities (diabetes, hypertension). While no association was observed between BMI and risk of AKI, visceral adipose and skeletal muscle variables were significantly associated with risk of AKI in univariate models. After adjustment for age, sex, comorbidities, and other body composition variables, only higher visceral adipose tissue quantity remained significantly associated with increased risk of AKI [RD per 40 unit increase (95% CI): 5.2 (1.3, 9.2)]. Muscle characteristics were not associated with AKI in multivariable models. Among patients undergoing PN, we observed a higher frequency of AKI among male patients, those with higher stage/larger tumors, and those with longer ischemia times. No significant associations were observed with comorbidity histories. In univariate models, visceral adipose tissue quantity and quality as well as skeletal muscle quantity were associated with AKI risk; however, after adjustment for age, sex, comorbidities, and other body composition variables, we observed no significant associations between any body composition feature and AKI in patients undergoing PN. Conclusions Associations between pre-surgical body composition and risk of AKI vary by surgery type. Visceral adipose tissue quantity was associated with risk of AKI among patients undergoing RN, but not PN. This finding may be relevant for patient counseling, consideration for nephron-sparing surgery, and development of interventions to lower visceral adipose tissue quantity. Future studies should evaluate the impact of both pre-surgical and post-surgical change in body composition in relation on chronic kidney disease after nephrectomy.

53 Associations between body composition, ClearCode34, and clinical outcomes in localized clear cell renal cell carcinoma

Abstract Background Emerging evidence suggests that pre-surgical body composition is a prognostic factor for cancer outcomes. Lower skeletal muscle quantity and radiodensity have been associated with renal cell carcinoma (RCC) outcomes in other studies, while reports of the relationship between visceral adipose tissue and RCC outcomes have been inconsistent. Mechanisms underlying these associations are unclear but may relate to tumor biology. We leveraged a large molecular epidemiology study of localized clear cell renal cell carcinoma (ccRCC) patients to examine how pre-surgical body composition features were associated with survival post-nephrectomy as well as ClearCode34 status, a previously validated prognostic gene expression signature. Methods The RESOLVE study at Memorial Sloan Kettering Cancer Center is a retrospective study of 1,239 patients with stage I-III ccRCC undergoing nephrectomy without systemic therapy. Pre-surgical CT scans at the third lumbar vertebrae were segmented for the cross-sectional areas and radiodensities of skeletal muscle, subcutaneous adipose and visceral adipose tissues using Automatica software. Formalin-fixed, paraffin-embedded tumor tissue samples were available for 929 patients, which were sent to the University of North Carolina at Chapel Hill and assayed for gene expression. RNA was extracted from these samples and analyzed using the Nanostring nCounter system on a custom panel of 356 genes, including the 34 genes used in the ClearCode34 assay. Of the 929 patients with tumor tissue available, gene expression data from 837 patients (90.1%) passed RNA extraction and data QC. Samples were classified into either ccA or ccB ClearCode34 classes using a reference data set and PAM (prediction analysis of microarrays) centroid-based classification. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) within five years of diagnosis using Cox proportional hazards models for both body composition variables and ClearCode34 subtype. We also estimated odds ratios (ORs) and 95% CIs for associations between ClearCode34 subtype and body composition with logistic regression. All multivariable models were adjusted for age, sex, and all body composition variables. Results Of the 837 patients in our analytic sample, 219 (26%) had ccB tumors. Men, patients with high stage or grade tumors, and patients with chronic kidney disease prior to nephrectomy were more likely to present with ccB tumors. Lower skeletal muscle density (SMD) was significantly associated with lower five-year DFS [HR (95% CI) per 10 HU decrease in SMD: 1.7 (1.2, 2.3)]. While no other body composition features were significantly associated, we also observed non-significantly increased HRs for VATI and VATD [HR (95% CIs): 1.3 (0.8, 2.0) and 1.5 (0.9, 2.7), respectively]. ClearCode34 subtype was significantly associated with five-year DFS, where patients with ccB tumors had poorer DFS [HR (95% CI): 1.7 (1.1, 2.5)] compared to patients with ccA tumors. Notably, we observed no significant associations between any body composition feature and ClearCode34 in univariable analyses. However, in multivariable models that accounted for all body composition variables simultaneously as well as age and sex, lower SMD emerged as significantly associated with ccB subtype [OR (95% CI) per 10 HU decrease in SMD: 1.3 (1.0, 1.7)]. Conclusions Our findings suggest that the associations observed between body composition features and clinical outcomes in ccRCC may be related to tumor biology. Lower pre-surgical SMD, which may represent myosteatosis and metabolic dysregulation in ccRCC patients, was associated with both decreased five-year DFS and an increased likelihood of presenting with a more aggressive ccB tumor. Future studies should investigate body composition features related to ccRCC prognosis and additional markers of tumor biology, such as immune-related gene expression patterns, to extend these findings.

Association between metabolic dysfunction-associated steatotic liver disease and myosteatosis measured by computed tomography.

In 2023, the concept of metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced as an alternative to non-alcoholic fatty liver disease (NAFLD). We aimed to assess the quantity and quality of skeletal muscle using each of these diagnostic classifications. This cross-sectional study included 18154 participants (11551 [63.6%] men and 6603 [36.4%] women, mean age 53.0±8.8). The participants were classified into four categories: neither steatotic liver disease (SLD), NAFLD only, MASLD only or both SLDs. An appendicular skeletal muscle mass adjusted for body mass index of <0.789 for men and <0.512 for women was defined as sarcopenia. The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area and intermuscular/intramuscular adipose tissue. Myosteatosis was defined by a T-score<-1.0 of the NAMA/TAMA index, which was calculated by dividing the NAMA by the TAMA and multiplying by 100. Using subjects with neither SLD as a reference, the multivariable-adjusted odds ratios (ORs) for sarcopenia were significantly increased in those with MASLD, with adjusted ORs (95% confidence interval [CI]) of 2.62 (1.94-3.54) in the MASLD-only group and 2.33 (1.92-2.82) in the both SLDs group, while the association was insignificant in those with NAFLD only (adjusted OR [95% CI]: 2.16 [0.67-6.94]). The OR for myosteatosis was also elevated in the MASLD groups, with an OR (95% CI) of 1.75 (1.52-2.02) in subjects with MASLD only and 1.70 (1.57-1.84) in those with both SLDs, while it was slightly decreased in subjects with NAFLD only (0.52 [0.29-0.95]). Employing the MASLD concept rather than that of the NAFLD proved to be more effective in distinguishing individuals with reduced muscle mass and compromised muscle quality.

Changes in skeletal muscle function during chemotherapy and related factors in patients with acute leukemia.

Skeletal muscle function is an important prognostically relevant indicator in patients with acute leukemia (AL), but skeletal dysfunction during chemotherapy is not well understood. This study aimed to investigate the factors that influence changes in skeletal muscle function from before the start of chemotherapy to before allogeneic hematopoietic stem cell transplantation (allo-HSCT). This was a retrospective cohort study that included 90 patients with AL who underwent chemotherapy before transplantation to perform allo-HSCT (men, 67.3%; median age, 53years). The outcome measure was defined as changes in skeletal muscle function from before chemotherapy to before allo-HSCT, and was assessed by measuring the psoas muscle index (PMI) as skeletal muscle quantity and computed tomography values (CTV) as skeletal muscle quality using a computed tomography scanner. We examined the differences in PMI and CTV before chemotherapy and allo-HSCT, and the factors associated with changes in PMI. The mean PMI for before chemotherapy and allo-HSCT were 4.6 ± 1.4 cm2/m2 and 4.0 ± 1.3 cm2/m2 and significant differences were observed (p < 0.001). However, the mean CTV before chemotherapy and allo-HSCT were 47.3 ± 4.5 HU and 47.4 ± 5.0 HU, respectively, and no significant differences were found (p = 0.798). In stepwise multiple regression analysis, age and sex were identified as factors related to changes in PMI (age, p = 0.019; sex, p = 0.001). We found that skeletal muscle quantity decreased during chemotherapy in patients with AL and was influenced by male sex and older age. TRIAL REGISTRATION NUMBER: 34-096(11,243). Date of registration: September 11, 2023.

Unveiling the detrimental vicious cycle linking skeletal muscle and COVID-19: A systematic review and meta-analysis.

Skeletal muscle catabolism supports multiple organs and systems during severe trauma and infection, but its role in COVID-19 remains unclear. This study investigates the interactions between skeletal muscle and COVID-19. The PubMed, EMbase, and The Cochrane Library databases were systematically searched from January 2020 to August 2023 for cohort studies focusing on the impact of skeletal muscle on COVID-19 prevalence and outcomes, and longitudinal studies examining skeletal muscle changes caused by COVID-19. Skeletal muscle quantity (SMQN) and quality (SMQL) were assessed separately. The random-effect model was predominantly utilized for statistical analysis. Seventy studies with moderate to high quality were included. Low SMQN/SMQL was associated with an increased risk of COVID-19 infection (OR=1.62, p<0.001). Both the low SMQN and SMQL predicted COVID-19-related mortality (OR=1.53, p=0.016; OR=2.18, p=0.001, respectively). Mortality risk decreased with increasing SMQN (OR=0.979, p=0.009) and SMQL (OR=0.972, p=0.034). Low SMQN and SMQL were also linked to the need for intensive care unit/mechanical ventilation, increased COVID-19 severity, and longer hospital stays. Significant skeletal muscle wasting, characterized by reduced volume and strength, was observed during COVID-19 infection and the pandemic. This study reveals a detrimental vicious circle between skeletal muscle and COVID-19. Effective management of skeletal muscle could be beneficial for treating COVID-19 infections and addressing the broader pandemic. These findings have important implications for the management of future virus pandemics. PROSPERO CRD42023395476.

Skeletal muscle quantity and quality evaluation in heart failure: comparing thoracic versus abdominopelvic CT approaches

Given the critical role of skeletal muscle in healthy aging, low muscle mass (myopenia) and quality (myosteatosis) can be used as predictors of poor functional and cardiometabolic outcomes. Myopenia is also a part of sarcopenia and malnutrition diagnostic criteria. However, there is limited evidence for using chest computed tomography (CT) to evaluate muscle health. We aimed to compare chest CT landmarks to the widely used L3 vertebra for single-slice skeletal muscle evaluation in patients with heart failure (HF). Patients admitted for acute decompensated HF between January 2017 and December 2018 were retrospectively analyzed. Body composition measurements were made on CT of the chest and abdomen/pelvis with or without contrast one month before discharge. Skeletal muscle index (SMI) and intermuscular adipose tissue percentage (IMAT%) were calculated at several thoracic levels (above the aortic arch, T8, and T12) and correlated to the widely used L3 level. A total of 200 patients were included, 89 (44.5%) female. The strongest correlation of thoracic SMI (for muscle quantity) and IMAT% (for muscle quality) with L3 was at the T12 level (r = 0.834, p < 0.001 and r = 0.757, p < 0.001, respectively). Cutoffs to identify low muscle mass for T12 SMI (derived from the lowest sex-stratified L3 SMI tertile) were 31.1 cm²/m² in men and 26.3 cm²/m² in women. SMI and IMAT% at T12 had excellent correlations with the widely used L3 level for muscle quantity and quality evaluation in patients with HF.

Artificial intelligence–based skeletal muscle estimates and outcomes of EUS-guided treatment of pancreatic fluid collections

Background and AimsSkeletal muscle status may impact clinical outcomes of a variety of pancreatic diseases. Skeletal muscle quality and quantity have not been fully examined in relation to the outcomes of endoscopic ultrasound (EUS)-guided treatment of pancreatic fluid collections (PFCs). MethodsUsing a multi-institutional cohort of 372 patients receiving EUS-guided treatment of PFCs in 2010-2020, we examined the association of skeletal muscle status with adverse outcomes including clinical treatment failure and in-hospital mortality. Utilizing an in-house deep learning-based platform for pre-procedural computed tomography images, we calculated skeletal muscle density (SMD) and skeletal muscle index (SMI, height-adjusted muscle area) as surrogates for muscular quality and quantity, respectively. Multivariable logistic regression analysis was conducted to calculate odds ratios (ORs) for adverse outcomes. ResultsLower-level SMD was associated with higher risks of clinical failure and in-hospital mortality (Ptrend < 0.001). The adjusted OR for clinical failure comparing the extreme quartiles was 3.64 (95% confidence interval, 1.52-8.72). Compared with patients in the top two quartiles, patients in the lowest quartile had an adjusted OR for in-hospital mortality of 12.4 (95% confidence interval, 3.43-44.8). We observed no effect modification by the PFC types on the SMD-outcome relationship (Pinteraction > 0.16). SMD was not associated with the risk of procedure-related adverse events or PFC recurrence. SMI was not associated with adverse outcomes (Ptrend > 0.39). ConclusionsIn patients with endoscopically managed PFCs, SMD, but not SMI, was associated with the risks of clinical failure and in-hospital mortality, supporting the prognostic role of skeletal muscle quality.

Myosteatosis and not low muscle mass is associated with lower survival in kidney transplant recipients

AbstractBackgroundMyosteatosis, that is muscle fat infiltration, is an important marker of muscle quality, affecting quality of life and survival in patients with chronic kidney disease (CKD). However, the connection between myosteatosis, skeletal muscle index (SMI) and survival in kidney transplant (KTx) recipients remains unclear.MethodsThis retrospective observational study included a cohort of consecutive adult kidney recipients transplanted between 2010 and 2017 in Stockholm. Preoperative abdominal computed tomography (CT) images obtained after diagnosis of CKD 5 and within 36 months of transplantation were collected. Using established criteria, we measured muscle area at the third lumbar vertebra (L3 level) and identified low attenuation muscle, indicating myosteatosis. Each area was divided by height squared providing the SMI, and fatty muscle index (FMI). Given that there is no commonly accepted definition of sarcopenia, two cut‐offs for SMI were used to define low muscle mass, Cut‐off 1 (≤32.8 for women and ≤44.7 for men) and Cut‐off 2 (≤38.5 for women and ≤52.4 for men). Average radiodensity of skeletal muscle and Charlson comorbidity index were calculated for each patient. The influence on survival from SMI, FMI, SMI/FMI ratio, and radiodensity was analysed.ResultsOut of 582 KTx recipients, 266 (46%) had a pre‐transplant abdominal CT available. Applying SMI Cut‐off 1, 30 recipients (11%) had sarcopenia compared with 106 (40%) with Cut‐off 2. Neither SMI nor FMI was associated with survival. Yet there was an association between SMI/FMI ratio and survival, patients with the lowest quintile SMI/FMI ratio having a significantly lower survival when compared with the highest quintile, both in the crude model and when adjusted for age, gender, and comorbidity. Additionally, FMI, radiodensity, and SMI/FMI, but not SMI, were significantly associated with Charlson comorbidity index (P &lt; 0.01).ConclusionsThe SMI/FMI ratio may be associated with both pre‐transplant comorbidity and post‐transplant survival even though the significance of SMI is unclear. This suggests that SMI/FMI ratio is a better indicator of muscular impairment than skeletal muscle quantity alone. The finding may reflect the complex interplay between muscle mass, muscular fat infiltration and metabolic health, all important determinants of wellness and longevity. In summary, our study underscores the potential of the SMI/FMI ratio as a predictor of outcome after KTx, a finding possibly transferable to other patient populations.

Investigating the effects of synbiotic supplementation on functional movement, strength and muscle health in older Australians: a study protocol for a double-blind, randomized, placebo-controlled trial

BackgroundAging has been associated with a progressive loss of skeletal muscle quality, quantity and strength, which may result in a condition known as sarcopenia, leading to a decline in physical performance, loss of independence and reduced quality of life. While the cause of impaired physical functioning observed in elderly populations appears to be multifactorial, recent evidence suggests that age-associated alterations in gut microbiota could be a contributing factor. The primary objective will be to assess the effects of a dietary synbiotic formulation on sarcopenia-related functional outcomes such as handgrip strength, gait speed and physical performance within older individuals living independently. The secondary objective will be to examine associations between changes in gut microbiota composition, functional performance and lean muscle mass.MethodsSeventy-four elderly (60–85 years) participants will be randomized in a double-blind, placebo-controlled fashion to either an intervention or control group. The intervention group (n = 37) will receive oral synbiotic formulation daily for 16 weeks. The control group (n = 37) will receive placebo. Assessments of physical performance (including Short Physical Performance Battery, handgrip strength and timed up-and-go tests) and muscle ultrasonography will be performed at 4 time points (baseline and weeks 8, 16 and 20). Likewise, body composition via bioelectric impedance analysis and blood and stool samples will be collected at each time point. Dual-energy X-ray absorptiometry will be performed at baseline and week 16. The primary outcomes will be between-group changes in physical performance from baseline to 16 weeks. Secondary outcomes include changes in body composition, muscle mass and architecture, fecal microbiota composition and diversity, and fecal and plasma metabolomics.DiscussionGut-modulating supplements appear to be effective in modifying gut microbiota composition in healthy older adults. However, it is unclear whether these changes translate into functional and/or health improvements. In the present study, we will investigate the effects of a synbiotic formulation on measures of physical performance, strength and muscle health in healthy older populations.Trial registrationThis study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000652774) in May 2022.

Polygonatum sibiricum polysaccharide ameliorates skeletal muscle aging via mitochondria-associated membrane-mediated calcium homeostasis regulation

BackgroundSarcopenia, an age-related disease, is characterized by a gradual loss of muscle mass, strength, and function. It has been linked to abnormal organelle function in myotubes, including the mitochondria and endoplasmic reticulum (ER). Recent studies revealed that mitochondria-associated membranes (MAM), the sites connecting mitochondria and the ER, may be implicated in skeletal muscle aging. In this arena, the potential of Polygonatum sibiricum polysaccharide (PSP) emerges as a beacon of hope. PSP, with its remarkable antioxidant and anti-senescence properties, is on the cusp of a therapeutic revolution, offering a promising strategy to mitigate the impacts of sarcopenia. PurposeThe objective of this research is to explore the effects of PSP on age-related muscle dysfunction and the underlying mechanisms involved both in vivo and in vitro. MethodsIn this investigation, we used in vitro experiments using D-galactose (D-gal)-induced aging in C2C12 myotubes and in vivo experiments on aged mice. Key indices were assessed, including reactive oxygen species (ROS) levels, mitochondrial function, the expression of aging-related markers, and the key proteins of mitochondria and MAM fraction. Differentially expressed genes (DEGs) related to mitochondria and ER were identified, and bioinformatic analyses were performed to explore underlying mechanisms. Muscle mass and function were determined to evaluate the quantity and quality of skeletal muscle in vivo. ResultsPSP treatment effectively mitigated oxidative stress and mitochondrial malfunction caused by D-gal in C2C12 myotubes, preserving mitochondrial fitness and reducing MAM formation. Besides, PSP attenuated D-gal-induced increases in Ca2+ concentrations intracellularly by modulating the calcium-related proteins, which were also confirmed by gene ontology (GO) analysis of DEGs. In aged mice, PSP increased muscle mass and improved grip strength, hanging time, and other parameters while reducing ROS levels and increasing antioxidant enzyme activities in skeletal muscle tissue. ConclusionPSP offers protection against age-associated muscle impairments. The proposed mechanism suggests that modulation of calcium homeostasis via regulation of the MAM results in a favorable functional outcome during skeletal muscle aging. The results of this study highlight the prospect of PSP as a curative intervention for sarcopenia and affiliated pathological conditions, warranting further investigation.

Signaling pathways and regulatory networks in quail skeletal muscle development: insights from whole transcriptome sequencing

Quail, as an advantageous avian model organism due to its compact size and short reproductive cycle, holds substantial potential for enhancing our understanding of skeletal muscle development. The quantity of skeletal muscle represents a vital economic trait in poultry production. Unraveling the molecular mechanisms governing quail skeletal muscle development is of paramount importance for optimizing meat and egg yield through selective breeding programs. However, a comprehensive characterization of the regulatory dynamics and molecular control underpinning quail skeletal muscle development remains elusive. In this study, through the application of HE staining on quail leg muscle sections, coupled with preceding fluorescence quantification PCR of markers indicative of skeletal muscle differentiation, we have delineated embryonic day 9 (E9) and embryonic day 14 (E14) as the start and ending points, respectively, of quail skeletal muscle differentiation. Then, we employed whole transcriptome sequencing to investigate the temporal expression profiles of leg muscles in quail embryos at the initiation of differentiation (E9) and upon completion of differentiation (E14). Our analysis revealed the expression patterns of 12,012 genes, 625 lncRNAs, 14,457 circRNAs, and 969 miRNAs in quail skeletal muscle samples. Differential expression analysis between the E14 and E9 groups uncovered 3,479 differentially expressed mRNAs, 124 lncRNAs, 292 circRNAs, and 154 miRNAs. Furthermore, enrichment analysis highlighted the heightened activity of signaling pathways related to skeletal muscle metabolism and intermuscular fat formation, such as the ECM-receptor interaction, focal adhesion, and PPAR signaling pathway during E14 skeletal muscle development. Conversely, the E9 stage exhibited a prevalence of pathways associated with myoblast proliferation, exemplified by cell cycle processes. Additionally, we constructed regulatory networks encompassing lncRNA‒mRNA, miRNA‒mRNA, lncRNA‒miRNA-mRNA, and circRNA-miRNA‒mRNA interactions, thus shedding light on their putative roles within quail skeletal muscle. Collectively, our findings illuminate the gene and non-coding RNA expression characteristics during quail skeletal muscle development, serving as a foundation for future investigations into the regulatory mechanisms governing non-coding RNA and quail skeletal muscle development in poultry production.

Postabsorptive and postprandial myofibrillar protein synthesis rates at rest and after resistance exercise in women with postmenopause.

Feeding and resistance exercise stimulate myofibrillar protein synthesis (MPS) rates in healthy adults. This anabolic characterization of "healthy adults" has been namely focused on males. Therefore, the purpose of this study was to examine the temporal responses of MPS and anabolic signaling to resistance exercise alone or combined with the ingestion of protein in postmenopausal females and compare postabsorptive rates with young females. Sixteen females [60 ± 7 yr; body mass index (BMI) = 26 ± 12 kg·m-2] completed an acute bout of unilateral resistance exercise before consuming either: a fortified whey protein supplement (WHEY) or water. Participants received primed continuous infusions of L-[ring-13C6]phenylalanine with bilateral muscle biopsies before and after treatment ingestion at 2 h and 4 h in nonexercised and exercised legs. Resistance exercise transiently increased MPS above baseline at 0-2 h in the water condition (P = 0.007). Feeding after resistance exercise resulted in a late phase (2-4 h) increase in MPS in the WHEY condition (P = 0.005). In both conditions, resistance exercise did not enhance the cumulative (0-4 h) MPS response. In the nonexercised leg, MPS did not differ at 0-2 h, 2-4 h, or 0-4 h of the measurement periods (all, P > 0.05). Likewise, there were no changes in the phosphorylation of p70S6K, AMPKα, or total and phosphorylated yes-associated protein on Ser127. Finally, postabsorptive MPS was lower in premenopausal versus postmenopausal females (P = 0.023). Our results demonstrate that resistance exercise-induced changes in MPS are temporally regulated, but do not result in greater cumulative (0-4 h) MPS in postmenopausal women.NEW & NOTEWORTHY An adequate quality and quantity of skeletal muscle is relevant to support physical performance and metabolic health. Muscle protein synthesis (MPS) is an established remodeling marker, which can be hypertrophic or nonhypertrophic. Importantly, protein ingestion and resistance exercise are two strategies that support healthy muscle by stimulating MPS. Our study shows postmenopause modulates baseline MPS that may diminish the MPS response to the fundamental anabolic stimuli of protein ingestion and resistance exercise in older females.

Skeletal muscle status and survival among patients with advanced biliary tract cancer

BackgroundStudies have demonstrated a prognostic role of sarcopenia (i.e., loss of skeletal muscle volume and functionality) in patients with various cancer types. In patients with biliary tract cancer, the quantity and quality of skeletal muscles and their serial changes have not been fully investigated in relation to survival outcomes.MethodsWe identified 386 patients with unresectable or recurrent biliary tract cancer and calculated skeletal muscle index (SMI) and skeletal muscle density (SMD) to estimate muscular quantity and quality, respectively, based on computed tomography images. Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) according to skeletal muscle status and its serial change.ResultsCompared to patients without sarcopenia, patients with sarcopenia were associated with shorter PFS (multivariable HR, 1.60; 95% CI, 1.15–2.22; P = 0.005), but not with OS (P = 0.027) at the adjusted α level of 0.013. SMD at baseline was associated with OS (multivariable HR comparing the extreme quartiles, 1.52; 95% CI, 1.07–2.14; Ptrend = 0.012), but not with PFS (Ptrend = 0.13). A reduction in SMI rather than that in SMD was associated with OS. Progressive disease was a risk factor for reductions in SMI and SMD.ConclusionsSkeletal muscle quantity and quality and their serial changes were associated with survival outcomes in patients with advanced biliary tract cancer. Our data highlight the importance of designing nutritional and physical interventions for improvements in skeletal muscle status.

Clinical Application of Skeletal Muscle Quantity and Quality Assessment Using Bioelectrical Impedance and Ultrasound Images.

A decline in muscle strength is a key factor responsible for physical dysfunction in older individuals. Both loss of muscle quantity and quality are associated with muscle strength decline. While the gold standard method for evaluating muscle mass and quality is magnetic resonance imaging, it is not suitable for clinical settings because of the measurement and analysis costs. Bioelectrical impedance analysis (BIA) and B-mode ultrasonography are clinically useful alternatives for skeletal muscle assessment owing to their feasibility and noninvasiveness. The recent advancements in the techniques for BIA and ultrasonography have improved their accuracy in assessing skeletal muscle quantity and quality, making them useful in detecting age-related and disease-specific alterations. This review comprehensively analyzes the advantages of using BIA and ultrasound imaging for assessing skeletal muscle quantity and quality and detecting muscle degeneration. We summarize the recent findings regarding age-related changes in muscle characteristics and the associations of muscle degeneration with physical dysfunction in patients with knee osteoarthritis. Furthermore, we discuss the clinical application of skeletal muscle assessment using BIA and ultrasound for evaluating training effects and exercise prescription.