Skeletal Muscle Cross-sectional Area Research Articles

Astaxanthin ameliorates dexamethasone-induced skeletal muscle atrophy and disorders of glucolipid metabolism

Long-term use of glucocorticoids, such as dexamethasone, can lead to skeletal muscle atrophy and disturbances in glucolipid metabolism. Astaxanthin, a ketocarotenoid, has a variety of physiological activities. In this study, we investigated the effects of astaxanthin on dexamethasone-induced skeletal muscle atrophy and disorders of glycolipid metabolism. Male C57Bl/6J mice were administered dexamethasone alone or supplemented with different doses of astaxanthin (30mg/kg/d, 60mg/kg/d, 120mg/kg/d) for 4 weeks. The results showed that astaxanthin improved locomotor performance and attenuated dexamethasone-induced reductions in skeletal muscle mass and cross-sectional area in mice. Further exploration of the mechanism revealed that astaxanthin was able to balance the catabolism and synthesis of skeletal muscle proteins and protect mitochondria by reducing the expression of the mitochondrial autophagy-associated proteins Lc3B and BNIP3. In addition, astaxanthin reduced the accumulation of fatty acid metabolites and visceral fat and improved the ability of skeletal muscle to utilize sugars, suggesting that astaxanthin may alleviate dexamethasone-induced disturbances in glycolipid metabolism. This study illustrates that astaxanthin can alleviate skeletal muscle atrophy and metabolic disturbances induced by long-term dexamethasone treatment. This suggests that astaxanthin may be a functional dietary supplement to reduce the side effects of glucocorticoid therapy.

Correlation of Sarcopenia with Coronary Artery Disease Severity and Pericoronary Adipose Tissue Attenuation: A Coronary CT Study.

To investigate the association between sarcopenia, as appraised with CT-derived muscle metrics, and cardiovascular status, as assessed via coronary CT angiography (CCTA) using the Coronary Artery Disease-Reporting and Data System (CAD-RADS) and with pericoronary adipose tissue (pCAT) metrics. A retrospective observational study conducted on patients who underwent CCTA. The cross-sectional area (CSA) and attenuation values of the paravertebral muscles at the T8 level and the pectoralis major muscles at the T6 level were measured. The patient height was employed for the normalization of the skeletal muscle CSA. The pCAT attenuation around the coronary arteries was assessed, and the CAD severity was graded using the CAD-RADS reporting system. Regression analyses were performed to assess the impact of demographics, clinical factors, and CT variables on the CAD-RADS and pCAT. A total of 220 patients were included (132 males, median age 65 years). Regression analyses showed the associations of CAD with age and sex (p < 0.001). Familiarity with CAD was related to the left anterior descending artery pCAT (p = 0.002) and circumflex artery pCAT (p = 0.018), whereas age was related to the left anterior descending artery pCAT (p = 0.032). Weak positive correlations were found between the lower muscle density and lower pCAT attenuation (ρ = 0.144-0.240, p < 0.039). This study demonstrated weak associations between the sarcopenia indicators and the cardiovascular risk, as assessed by the CAD severity and pCAT inflammation. However, these correlations were not strong predictors of CAD severity, as age and traditional cardiovascular risk factors overshadowed the impact of sarcopenia in the cardiovascular risk assessment.

Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms

BackgroundSkeletal muscle atrophy is one of the main side effects of high-dose or continuous use of glucocorticoids (such as dexamethasone). However, there are limited studies on dexamethasone-induced skeletal muscle atrophy in zebrafish and even fewer explorations of the underlying molecular mechanisms. This study aimed to construct a model of dexamethasone-induced skeletal muscle atrophy in zebrafish and to investigate the molecular mechanisms. MethodsZebrafish soaked in 0.01 % dexamethasone solution for 10 days. Loli Track (Denmark) and Loligo Swimming Respirometer were used to observe the effect of dexamethasone on swimming ability. The effects of dexamethasone on zebrafish skeletal muscle were observed by Transmission electron microscopy, H&E, and wheat germ agglutinin techniques. Enriched genes and signaling pathways were analyzed using Transcriptome sequencing. Further, the levels of mitochondrial and endoplasmic reticulum-related proteins were examined to investigate possible mechanisms. Results0.01 % dexamethasone reduced zebrafish skeletal muscle mass (p < 0.05), myofibre size and cross-sectional area (p < 0.001), and increased protein degradation (ubiquitination and autophagy) (p < 0.05). In addition, 0.01 % dexamethasone reduced the swimming ability of zebrafish, as evidenced by the reluctance to move, fewer movement trajectories, decreased total distance traveled (p < 0.001), average velocity of movement (p < 0.001), oxygen consumption (p < 0.001), critical swimming speed (p < 0.01) and increased exhaustive swimming time (p < 0.001). Further, 0.01 % dexamethasone-induced mitochondrial dysfunction (decreased mitochondrial biogenesis, disturbs kinetic homeostasis, increased autophagy) and endoplasmic reticulum stress. Conclusions0.01 % dexamethasone induces skeletal muscle atrophy and impairs the swimming ability of zebrafish through mitochondrial dysfunction and endoplasmic reticulum stress.

The Effect of Lower Limb Combined Neuromuscular Electrical Stimulation on Skeletal Muscle Cross-Sectional Area and Inflammatory Signaling.

In individuals with a spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre- and post-intervention. The results suggest a potential preservation of muscle CSA in the Comb-NMES group compared to a control group. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI may attenuate inflammatory pathways linked to muscle atrophy and promote muscle repair. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.

Relative muscle indices and healthy reference values for sarcopenia assessment using T10 through L5 computed tomography skeletal muscle area

Sarcopenia is the age-related loss of skeletal muscle mass and function. Computed tomography (CT) assessments of sarcopenia utilize measurements of skeletal muscle cross-sectional area (SMA), radiation attenuation (SMRA), and intramuscular adipose tissue (IMAT). Unadjusted SMA is strongly correlated with both height and body mass index (BMI); therefore, SMA must be adjusted for body size to assess sarcopenic low muscle mass fairly in individuals of different heights and BMI. SMA/height (rather than SMA/height2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$SMA/height^2$$\\end{document}) provides optimal height adjustment, and vertebra-specific relative muscle index (RMI) equations optimally adjust for both height and BMI. Since L3 measurement is not available in all CT scans, sarcopenic low muscle mass may be assessed using other levels. Both a mid-vertebral slice and an inferior slice have been used to define ‘L3 SMA’, but the effect of vertebral slice location on SMA measurements is unexplored. Healthy reference values for skeletal muscle measures at mid- and inferior vertebra slices between T10 and L5, have not yet been reported. We extracted T10 through L5 SMA, SMRA, and IMAT at a mid-vertebral and inferior slice using non-contrast-enhanced CT scans from healthy, adult kidney donor candidates between age 18 and 73. We compared paired differences in SMA between the mid-vertebral slice versus the inferior slice. We calculated the skeletal muscle gauge as SMGHT=SMRA∗SMIHT\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$SMG_{HT}=SMRA*SMI_{HT}$$\\end{document}. We used allometric analysis to find the optimal height scaling power for SMA. To enable comparisons with other published reference cohorts, we computed two height-adjusted measures; SMIHT=SMA/height\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$SMI_{HT}=SMA/height$$\\end{document} (optimal) and SMIHT2=SMA/height2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$SMI_{HT2}=SMA/height^2$$\\end{document} (traditional). Using the young, healthy reference cohort, we utilized multiple linear regression to calculate relative muscle index z-scores (RMIHT\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$RMI_{HT}$$\\end{document}, RMIHT2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$RMI_{HT2}$$\\end{document}), which adjust for both height and BMI, at each vertebra level. We assessed Pearson correlations of each muscle area measure versus age, height, weight, and BMI separately by sex and vertebra number. We assessed the differences in means between age 18–40 versus 20–40 as the healthy, young adult reference group. We reported means, standard deviations, and sarcopenia cutpoints (mean-2SD and 5th percentile) by sex and age group for all measures. Sex-specific allometric analysis showed that height to the power of one was the optimal adjustment for SMA in both men and women at all vertebra levels. Differences between mid-vertebra and inferior slice SMA were statistically significant at each vertebra level, except for T10 in men. SMIHT\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$SMI_{HT}$$\\end{document} was uncorrelated with height, whereas SMIHT2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$SMI_{HT2}$$\\end{document} was negatively correlated with height at all vertebra levels. Both SMIHT\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$SMI_{HT}$$\\end{document} and SMIHT2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$SMI_{HT2}$$\\end{document} were positively correlated with BMI at all vertebra levels. RMIHT\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$RMI_{HT}$$\\end{document} was uncorrelated with BMI, weight, and height (minimal positive correlation in women at L3inf\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {L3}_{inf}$$\\end{document}, L4mid\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {L4}_{mid}$$\\end{document}, and L5inf\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {L5}_{inf}$$\\end{document}) whereas RMIHT2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$RMI_{HT2}$$\\end{document} was uncorrelated with BMI, but negatively correlated with height and weight at all levels. There were no significant differences in SMA between 18–40 versus 20–40 age groups. Healthy reference values and sarcopenic cutpoints are reported stratified by sex, vertebra level, and age group for each measure. Height to the power of one (SMA/height) is the optimal height adjustment factor for SMA at all levels between T10mid\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {T10}_{mid}$$\\end{document} through L5inf\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {L5}_{inf}$$\\end{document}. The use of SMA/height2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$SMA/height^2$$\\end{document} should be discontinued as it retains a significant negative correlation with height and is therefore biased towards identifying sarcopenia in taller individuals. Measurement of SMA at a mid-vertebral slice is significantly different from measurement of SMA at an inferior aspect slice. Reference values should be used for the appropriate slice. We report sarcopenic healthy reference values for skeletal muscle measures at the mid-vertebral and inferior aspect slice for T10 through L5 vertebra levels. Relative muscle index (RMI) equations developed here minimize correlation with both height and BMI, producing unbiased assessments of relative muscle mass across the full range of body sizes. We recommend the use of these RMI equations in other cohorts.

Skeletal Muscle Segmentation at the Level of the Third Lumbar Vertebra (L3) in Low-Dose Computed Tomography: A Lightweight Algorithm.

The cross-sectional area of skeletal muscles at the level of the third lumbar vertebra (L3) measured from computed tomography (CT) images is an established imaging biomarker used to assess patients' nutritional status. With the increasing prevalence of low-dose CT scans in clinical practice, accurate and automated skeletal muscle segmentation at the L3 level in low-dose CT images has become an issue to address. This study proposed a lightweight algorithm for automated segmentation of skeletal muscles at the L3 level in low-dose CT images. This study included 57 patients with rectal cancer, with both low-dose plain and contrast-enhanced pelvic CT image series acquired using a radiotherapy CT scanner. A training set of 30 randomly selected patients was used to develop a lightweight segmentation algorithm, and the other 27 patients were used as the test set. A radiologist selected the most representative axial CT image at the L3 level for both the image series for all the patients, and three groups of observers manually annotated the skeletal muscles in the 54 CT images of the test set as the gold standard. The performance of the proposed algorithm was evaluated in terms of the Dice similarity coefficient (DSC), precision, recall, 95th percentile of the Hausdorff distance (HD95), and average surface distance (ASD). The running time of the proposed algorithm was recorded. An open source deep learning-based AutoMATICA algorithm was compared with the proposed algorithm. The inter-observer variations were also used as the reference. The DSC, precision, recall, HD95, ASD, and running time were 93.2 ± 1.9% (mean ± standard deviation), 96.7 ± 2.9%, 90.0 ± 2.9%, 4.8 ± 1.3 mm, 0.8 ± 0.2 mm, and 303 ± 43 ms (on CPU) for the proposed algorithm, and 94.1 ± 4.1%, 92.7 ± 5.5%, 95.7 ± 4.0%, 7.4 ± 5.7 mm, 0.9 ± 0.6 mm, and 448 ± 40 ms (on GPU) for AutoMATICA, respectively. The differences between the proposed algorithm and the inter-observer reference were 4.7%, 1.2%, 7.9%, 3.2 mm, and 0.6 mm, respectively, for the averaged DSC, precision, recall, HD95, and ASD. The proposed algorithm can be used to segment skeletal muscles at the L3 level in either the plain or enhanced low-dose CT images.

SP4.10 - Comparison of the Global Leadership Initiative on Malnutrition (GLIM) Phenotypic Criteria in Patients with Oesophagogastric Cancer

Abstract Aim The Global Leadership Initiative on Malnutrition (GLIM) consensus proposed that patients should meet one of three phenotypic criteria for a diagnosis of malnutrition. This study examined the association between these criteria and survival in oesophagogastric cancer. Methods Consecutive patients newly diagnosed with oesophagogastric cancer were identified from a prospectively maintained regional database between 2019-2020. Data were collected regarding the GLIM phenotypical criteria: involuntary weight loss (≥5% in 6 months or ≥10% in &amp;gt;6 months), body mass index (&amp;lt;20kg/m2 (&amp;lt;70 years) or &amp;lt;22kg/m2 (&amp;gt;70 years)) and reduced muscle mass via body composition analysis. Cross-sectional area of skeletal muscle was measured at mid-L3 on staging CT imaging. This was normalised for height to create skeletal muscle index (SMI), with low SMI being defined as per Martin et al. The outcome of interest was overall survival. Results Overall, 465 patients (median 71 years, n=311 males) were identified. Weight loss (p=0.022), BMI (p&amp;lt;0.001) and SMI (p=0.005) cut-offs were all associated with reduced ECOG performance status. BMI and SMI were also associated with increased age. A higher proportion of patients with advanced stage malignancy met the weight loss threshold (p=0.001). Each phenotypical criterion was associated with worsened overall survival (all p&amp;lt;0.001). While all three were prognostic, following adjustment for confounders, low SMI (aHR:1.76 (95%CI:1.39-2.22)) was more strongly associated with poor survival than low BMI (aHR:1.57 (95%CI:1.18-2.08)) or weight loss (aHR:1.46 (95%CI:1.17-1.81)). Conclusion While each of the GLIM phenotypical criteria are adversely prognostic in oesophagogastric cancer, low SMI is most strongly associated with poor survival.

Rethinking the physiological cross-sectional area of skeletal muscle reveals the mechanical advantage of pennation

The shape of skeletal muscle varies remarkably—with important implications for locomotor performance. In many muscles, the fibres are arranged at an angle relative to the tendons’ line of action, termed the pennation angle. These pennate muscles allow more sarcomeres to be packed side by side, enabling the muscle to generate higher maximum forces for a given muscle size. Historically, the physiological cross-sectional area (PCSA) has been used to capture both the size and arrangement of muscle fibres, and is one of the best predictors of a muscles capacity to produce force. However, the anatomical and mechanical implications of PCSA remain ambiguous as misinterpretations have limited our ability to understand the mechanical advantage of pennate muscle designs. We developed geometric models to resolve the mechanistic and functional impacts of pennation angle across a range of muscle shapes and sizes. Comparisons among model predictions and empirical data on human lower limb muscles demonstrated how a pennate arrangement of fibres allows muscles to produce up to six times more isometric force when compared with non-pennate muscles of the same volume. We show that in muscles much longer than thick, an optimal pennation angle exists at which isometric force is maximized. Using empirically informed geometric models we demonstrate the functional significance of a pennate muscle design and provide a new parameter, pennation mechanical advantage, which quantifies this performance improvement.

Thoracic sarcopenia was a poor prognostic predictor in patients receiving immunotherapy retain-->for advanced non-small-cell retain-->lung cancer

Sarcopenia, as measured at the level of the third lumbar (L3) has been shown to predict the survival of cancer patients. However, many patients with advanced non-small cell lung cancer (NSCLC) do not undergo routine abdominal imaging. The objective of this study was to investigate the association of thoracic sarcopenia with survival outcomes among patients who underwent immunotherapy for NSCLC. In this retrospective study, patients who initiated immunotherapy for advanced NSCLC from 2019 to 2022 were enrolled. and detailed patient data were collected. Cross sectional skeletal muscle area was calculated at the fifth thoracic vertebra (T5) on pretreatment chest computed tomography (CT) scan. Gender-specific lowest quartile values was used to define sarcopenia. The risk factors were analyzed using Cox analyses. The log-rank test and the random survival forest (RSF) were used to compare progression free survival (PFS). The model's performance was assessed using calibration curve and the receiver operating characteristic curve (ROC). A total of 242 patients was included (discovery cohort n=194, validation cohort n=48). In the discovery cohort, patients with sarcopenia exhibited significantly poorer PFS (p<0.001) than patients without sarcopenia. Univariate cox regression revealed that sarcopenia, lung cancer stage, body mass index, smoking status, and neutrophil-to-lymphocyte ratio were predictors of poor PFS. A RSF model was constructed based on the aforementioned parameters, to evaluate the model's efficacy, the ROC curve was utilized. with an area under the curve for predicting 6-month PFS of 0.68 and for 12-month PFS of 0.69. The prediction models for survival outcomes built by the discovery cohort showed similar performance in the validation cohort. Sarcopenia at T5 is independent prognostic factors in patients who received immunotherapy for advanced NSCLC.

Differences in muscle composition and functionality: Exploring CT anatomical points and SARC-F components

PurposeOur study aimed to 1) investigate the differences of muscle parameters in relation to each SARC-F component/question; and 2) explore the relationship between SARC-F score with these muscle parameters using various landmarks derived from computed tomography (CT) scans of patients with cancer. MethodsThis study is a cross-sectional analysis of a cohort comprised of consecutive patients with cancer, displaying CT scans. SARC-F questionnaire was utilized as a proxy for muscle functionality, with a score ≥4 indicating a poor status. Muscle assessment via CT measurements was performed using single cross-sectional images at the level of the third lumbar vertebrae (L3) in the abdominal region, the thigh region, and the total gluteal region at the level of the second sacral vertebrae. Skeletal muscle (SM) cross-sectional area, SM index (normalized to height2), and SM radiodensity (SMD) were evaluated for all anatomical landmarks. ResultsA total of 128 patients were included in this analysis (53.1% females, 61.7% older adults). Patients with SARC-F scores ≥4 demonstrated significantly lower values of SMD across all landmarks assessed. Those reporting difficulties related to strength (P = 0.039), requiring assistance in walking (P = 0.033), and climbing stairs (P = 0.012) exhibited significantly lower SMD values at the L3 landmark. At gluteus and thigh levels, only patients experiencing difficulty climbing stairs (P = 0.012) showed significantly lower values of SMD. Only SMD at gluteus level was independently associated with SARC-F score (βadjusted –0.09, 95% CI –0.16 to –0.02). ConclusionsOur findings suggest that individuals with poor muscle composition may experience a higher risk of sarcopenia/poor muscle functionality.

Sarcopenia shortens overall survival of patients with platinum-resistant recurrent ovarian cancer: inverse probability of treatment-weighting analysis

ObjectiveThe association between sarcopenia and prognosis in patients with platinum-resistant recurrent ovarian cancer remains unclear. This study investigated whether sarcopenia is a prognostic factor in patients with platinum-resistant recurrent ovarian...

Association between remote resistance exercises programs delivered by a smartphone application and skeletal muscle mass among elderly patients with type 2 diabetes- a retrospective real-world study.

We aimed to explore the relationship between remote resistance exercise programs delivered via a smartphone application and skeletal muscle mass among elderly patients with type 2 diabetes, utilizing real-world data. The resistance exercises were provided through Joymotion®, a web-based telerehabilitation smartphone application (Shanghai Medmotion Medical Management Co., Ltd). The primary outcome was the changes in skeletal muscle index (SMI) before and after the remote resistance exercises programs. The secondary outcomes were changes in skeletal muscle cross-sectional area (SMA), skeletal muscle radiodensity (SMD) and intermuscular adipose tissue (IMAT). A total of 101 elderly patients with type 2 diabetes were analyzed. The participants had an average age of 72.9 ± 6.11 years for males and 74.4 ± 4.39 years for females. The pre- and post-intervention SMI mean (± SE) was 31.64 ± 4.14 vs. 33.25 ± 4.22 cm2/m2 in male, and 22.72 ± 3.24 vs. 24.28 ± 3.60 cm2/m2 in female respectively (all P < 0.001). Similarly, a statistically significant improvement in SMA, IMAT, and SMD for both male and female groups were also observed respectively (P < 0.001). Multiple linear regression models showed potential confounding factors of baseline hemoglobin A1c and duration of diabetes with changes in SMI in male, while hemoglobin A1c and high density lipoprotein cholesterol with changes in SMI in female. Remote resistance exercises programs delivered by a smartphone application were feasible and effective in helping elderly patients with type 2 diabetes to improve their skeletal muscle mass.

Blood flow restriction Exercise in the perioperative setting to Prevent loss of muscle mass in patients with pancreatic, biliary tract, and liver cancer: study protocol for the PREV-Ex randomized controlled trial

BackgroundPatients diagnosed with pancreatic, biliary tract, and liver cancer often suffer from a progressive loss of muscle mass. Given the considerable functional impairments in these patients, high musculoskeletal weight loads may not be well tolerated by all individuals. The use of blood-flow restricted resistance training (BFR-T) which only requires low training loads may allow for a faster recovery of muscle due to avoidance of high levels of mechanical muscle stress associated with high-load resistance exercise. This study aims to investigate whether BFR-T can prevent or slow down the loss of skeletal muscle mass and enhance the functional capacity and mental health of patients with pancreatic, biliary tract, and liver cancer.MethodsThe PREV-Ex exercise trial is a multicenter two-armed randomized controlled trial. Patients will be randomized to an exercise program consisting of home-based low-load BFR-T during a combined pre- and postoperative period for a total of 6–10 weeks (prehabilitation and rehabilitation), or to a control group. Protein supplementation will be given to both groups to ensure adequate protein intake. The primary outcomes, skeletal muscle thickness and muscle cross-sectional area, will be assessed by ultrasound. Secondary outcomes include the following: (i) muscle catabolism-related and inflammatory bio-markers (molecular characteristics will be assessed from a vastus lateralis biopsy and blood samples will be obtained from a sub-sample of patients); (ii) patient-reported outcome measures (self-reported fatigue, health-related quality of life, and nutritional status will be assessed through validated questionnaires); (iii) physical fitness/performance/activity (validated tests will be used to evaluate physical function, cardiorespiratory fitness and maximal isometric muscle strength. Physical activity and sedentary behavior (assessed using an activity monitor); (iv) clinical outcomes: hospitalization rates and blood status will be recorded from the patients’ medical records; (v) explorative outcomes of patients’ experience of the exercise program which will be evaluated using focus group/individual interviews.DiscussionIt is worthwhile to investigate new strategies that have the potential to counteract the deterioration of skeletal muscle mass, muscle function, strength, and physical function, all of which have debilitating consequences for patients with pancreatic, biliary tract, and liver cancer. The expected findings could improve prognosis, help patients stay independent for longer, and possibly reduce treatment-related costs.Trial registrationClinicalTrials.gov NCT05044065. Registered on September 14, 2021.

Age and body composition of patients receiving treatment for locally advanced esophageal cancer.

e16094 Background: Standard of care for locally advanced esophageal cancer consists of chemoradiation (chemoRT) followed by esophagectomy. Fewer patients in older populations with locally advanced esophageal cancer undergo esophagectomy when compared to their younger counterparts. Furthermore, frail patients frequently forgo surgery after chemoRT. The current study examined the relationship between age, body composition, and treatment decision-making in locally advanced esophageal cancer. Methods: Patients with clinical stage T2-4, N0-2, and M0 adenocarcinoma or squamous cell carcinoma of the mid or distal esophagus diagnosed between 2010-2021 were included from 11 hospitals across our healthcare system. Treatment decision-points included receipt of chemoRT versus non-curative therapy, unresectable disease after chemoRT defined by metastatic disease or upper mediastinal lymphadenopathy, and receipt of surgery stratified by histology. Sociodemographic data including age, race, sex, insurance status, socioeconomic status, body composition data from CT imaging (skeletal muscle gauge [SMG]), and outcome data were collected. Skeletal Muscle Gauge was calculated as the product of skeletal muscle cross-sectional area at L3 normalized for height and muscle density. Fisher's exact test was used for categorical variables and Kruskal-Wallis for continuous variables. Results: 513 patients were included in the analysis, of which 399 (78%) had adenocarcinoma and 114 (22%) had squamous cell carcinoma. Median age was 66. Of the 513 patients, 472 (92%) underwent chemoRT (366 [78%] adenocarcinoma, 106 [22%] squamous cell carcinoma). Patients who were over the age of 75 were less likely to undergo chemoRT when compared to their younger counterparts (85% vs. 94%, p = 0.002). After the completion of chemoRT, 419 (89%) patients were deemed resectable, 330 adenocarcinoma and 89 with squamous cell carcinoma. Among resectable patients with adenocarcinoma, those &gt; 75 years old and lower SMG were less likely to receive surgery (p &lt; 0.001 and p =0.001). Age and body composition associated with lower receipt of surgery in locally advanced esophageal cancer patients was significant on both univariate and multivariate analyses. Conclusions: Patients over 75 are less likely to undergo chemoRT and surgical resection for locally advanced esophageal cancer. Among patients with resectable disease who have completed chemoRT, those with unfavorable body composition as measured by low SMG on CT imaging are also less likely to undergo surgical resection. These measures may be helpful in surgical decision-making in patients with locally-advanced esophageal cancer. Further study is warranted to more precisely define the relationship between age, body composition, and risk of surgery in esophageal cancer.

Body composition measures as a determinant of alpelisib-related toxicity.

e13093 Background: Body composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity. Methods: A retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, and hospitalizations. Results: Sarcopenia was observed in half of the patients (n=19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P=0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P=0.04) and hospitalizations (P=0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity. Conclusions: Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to predict toxicity, allowing for personalized therapeutic observation and intervention.

A randomised controlled intervention trial to study the effect of a personalised lifestyle programme on cancer-related fatigue among colorectal cancer survivors: protocol for the SoFiT study.

Observational studies suggest that a healthy diet in combination with ample physical activity is associated with a lower prevalence of cancer-related fatigue. The SoFiT trial (SoFiT: Study on Fatigue: a lifestyle intervention among colorectal cancer survivors) will assess the effect of a personalised lifestyle programme on cancer-related fatigue in a randomised study. We designed a programme that aims to increase adherence to lifestyle recommendations on diet and physical activity. The programme was person-centred with regard to the lifestyle and personal characteristics of participants, to the determinants of behaviour of that participant, and to the preferences, opportunities and barriers of the participant. The effect of the programme was tested in the SoFiT trial: a two-armed, parallel, randomised controlled trial among adult stage I-III colorectal cancer survivors, who experience cancer-related fatigue after treatment completion; intended sample size n=184. Participants randomised to the intervention group received the personalised lifestyle programme. During 6 months, participants in the intervention group had individual sessions with a lifestyle coach of which four sessions were face-to-face and eight sessions were remote. After 6 months, participants randomised to the control group had access to two lifestyle coaching sessions and to the same materials that the intervention group also received. The primary endpoint of the trial is cancer-related fatigue. Secondary endpoints are sleep quality and duration, health-related quality of life, physical performance, depression and anxiety, skeletal muscle echo intensity and cross-sectional area, and gut microbiota composition. This trial will show the effects of a personalised lifestyle programme on cancer-related fatigue and on an extensive set of secondary outcomes. Clinicaltrials.gov: NCT05390398.

#2439 The association between vitamin D deficiency and sarcopenia in patients with pre-dialysis CKD

Abstract Background and Aims Sarcopenia is characterized by a progressive and widespread loss of skeletal muscle, leading to muscle weakness and frailty. While primary sarcopenia is linked to aging, secondary sarcopenia can independently occur, especially in chronic conditions like chronic kidney disease (CKD). Investigating sarcopenia in CKD patients has become a focal point in research due to its significant impact on the quality of life, morbidity, and mortality of these individuals. Despite reports connecting vitamin D deficiency, prevalent in CKD, to sarcopenia in the general population, there is limited information regarding the specific relationship between vitamin D and sarcopenia in CKD. This study aims to explore the association between vitamin D deficiency and sarcopenia in patients with pre-dialysis CKD. Method This cross-sectional study enrolled 569 patients with pre-dialysis chronic kidney disease (CKD), defined as having an estimated glomerular filtration rate (eGFR) less than 60 ml/min/m2. Sarcopenia was assessed using computed tomography (CT)-derived skeletal muscle index (SMI), calculated based on the cross-sectional area of skeletal muscles at the 3rd lumbar vertebra. Using Korean-specific SMI cutoffs, patients were categorized into sarcopenic and non-sarcopenic groups. Logistic regression analyses were employed to explore associations between sarcopenia and baseline variables, including active vitamin D, specifically 1,25-dihydroxyvitamin D [1,25(OH)2D] level. Results Among the 569 patients, 278 had CKD stage 3, 198 had CKD stage 4, and 93 had CKD stage 5. The prevalence of sarcopenia increased with advancing CKD stage (CKD stage 3 vs. stage 4 vs. stage 5: 20.1% vs. 31.3% vs. 41.9%, P &amp;lt; 0.001). Univariate logistic regression analysis revealed an association between 1,25(OH)2D levels and sarcopenia. Additionally, age, male sex, diabetes, body mass index, eGFR, urinary albumin excretion levels, and serum levels of albumin, high-sensitive C-reactive protein (hsCRP), and intact parathyroid hormone were associated with sarcopenia. In multivariable logistic regression analysis, 1,25(OH)2D levels remained independently associated with sarcopenia (per 1 pg/dl increase, odds ratio [OR]: 0.84; 95% confidence interval [CI]: 0.80–0.87, P &amp;lt; 0.001). Age (per 1 year increase, OR: 1.04, 95% CI: 1.02–1.07, P &amp;lt; 0.001), diabetes (vs. non-diabetes, OR: 2.33, 95% CI: 1.39–3.89, P = 0.001), serum albumin (per 1 mg/dl increase, OR: 0.39, 95% CI: 0.22–0.71, P = 0.0023), and hsCRP (per 1 mg/dl increase, OR: 1.91, 95% CI: 1.25–2.92, P = 0.003) were also independently associated with sarcopenia. Conclusion This study revealed an independent association between 1,25(OH)2D levels and sarcopenia derived from CT scans in pre-dialysis CKD patients. This association retained significance even after adjusting for traditional risk factors for sarcopenia, such as age, diabetes, serum albumin, and hsCRP. Further prospective studies are necessary to determine whether therapy with exogenous 1,25(OH)2D drugs can improve sarcopenia in these patients.

Sarcopenia is independently associated with mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy.

Sarcopenia upon admission to the intensive care unit (ICU) consistently correlates with adverse outcomes, including heightened mortality, in critically ill patients. This study aims to investigate the independent association of sarcopenia with both mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury (SIAKI) undergoing continuous renal replacement therapy (CRRT). This retrospective study included 618 patients with SIAKI who underwent CRRT in our ICU. All patients had abdominal computed tomography (CT) scans within 3 days preceding ICU admission. The cross-sectional area of skeletal muscles at the third lumbar vertebra was quantified, and the skeletal muscle index (SMI), a normalized measure of skeletal muscle mass, was computed. Using Korean-specific SMI cutoffs, patients were categorized into sarcopenic and non-sarcopenic groups. Among the 618 patients, 301 expired within 28 days of ICU admission. Multivariable Cox regression analysis revealed that sarcopenia independently predicted 28-day mortality. Among survivors, sarcopenia was independently associated with recovery from dialysis within 28 days after ICU admission. Kaplan-Meier analysis illustrated that sarcopenic patients had a higher mortality rate and a lower rate of recovery from dialysis within 28 days after ICU admission compared to non-sarcopenic patients. This study underscores the independent association of sarcopenia, assessed via CT-derived SMI, with both mortality and recovery from dialysis in critically ill patients with SIAKI undergoing CRRT. The inclusion of sarcopenia assessment could serve as a valuable tool for physicians in effectively stratifying the risk of adverse outcomes in these patients.

Peripheral quantitative computed tomography is a valid imaging technique for tracking changes in skeletal muscle cross-sectional area.

Peripheral quantitative computed tomography (pQCT) has recently expanded to quantifying skeletal muscle, however its validity to determine muscle cross-sectional area (mCSA) compared to magnetic resonance imaging (MRI) is unknown. Eleven male participants (age: 22 ± 3 y) underwent pQCT and MRI dual-leg mid-thigh imaging before (PRE) and after (POST) 6 weeks of resistance training for quantification of mid-thigh mCSA and change in mCSA. mCSA agreement at both time points and absolute change in mCSA across time was assessed using Bland-Altman plots for mean bias and 95% limits of agreement (LOA), as well as Lin's concordance correlation coefficients (CCC). Both pQCT and MRI mCSA increased following 6 weeks of resistance training (∆mCSApQCT: 6.7 ± 5.4 cm2, p < 0.001; ∆mCSAMRI: 6.0 ± 6.4 cm2, p < 0.001). Importantly, the change in mCSA was not different between methods (p = 0.39). Bland-Altman analysis revealed a small mean bias (1.10 cm2, LOA: -6.09, 8.29 cm2) where pQCT tended to overestimate mCSA relative to MRI when comparing images at a single time point. Concordance between pQCT and MRI mCSA at PRE and POST was excellent yielding a CCC of 0.982. For detecting changes in mCSA, Bland-Altman analysis revealed excellent agreement between pQCT and MRI (mean bias: -0.73 cm2, LOA: -8.37, 6.91 cm2). Finally, there was excellent concordance between pQCT and MRI mCSA change scores (CCC = 0.779). Relative to MRI, pQCT imaging is a valid technique for measuring both mid-thigh mCSA at a single time point and mCSA changes following a resistance training intervention.

Impact of cachexia on disease recurrence and survival outcomes in endometrial cancer patients

ObjectiveCancer cachexia is progressive weight loss due to muscle/adipose tissue wasting and inadequate intake that occurs in response to malignancy. It is an independent predictor of disease recurrence and reduced survival in several cancers. However, cachexia’s relationship with gynecologic malignancy outcomes has only been examined in small studies with limited follow-up and inconsistent definitions of cachexia. This study investigated the impact of cachexia on disease recurrence and overall survival in high-risk endometrial carcinoma patients. MethodsThis retrospective cohort study examined data from patients with high-risk non-metastatic primary endometrial carcinoma treated at a single institution from 2015 to 2020. Treatment for all subjects included total hysterectomy, surgical staging, pelvic external beam radiotherapy with or without adjuvant chemotherapy. Radiation planning CT datasets were used to measure skeletal musculature at the L3 vertebral level. Skeletal muscle index (SMI) was defined as total L3 skeletal muscle cross sectional area (cm2)/height2 (m2), and cachexia was defined based on SMI. Results55 patients were eligible for analysis. Several SMI thresholds were used to define cachexia, and analysis was performed for each definition. Kaplan-Meier and Cox-proportional hazards regression analysis yielded no significant reduction in overall survival (OS) or progression-free survival (PFS) in patients with cachexia, regardless of threshold chosen. However, 4 of 13 definitions of cachexia showed significantly improved OS in patients without cachexia, relative to those with cachexia. There were no significant differences in disease recurrence. ConclusionsCachexia as defined in this study was not associated with poor outcomes in endometrial carcinoma patients based on OS, PFS, or disease recurrence.