Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.

BACKGROUND & AIMS: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.

Prognostic Value of Myosteatosis and Creatinine-to-Cystatin C Ratio in Patients with Pancreatic Cancer Who Underwent Radical Surgery.

BACKGROUND: Myosteatosis is correlated with poor prognosis in some malignancies. The creatinine-to-cystatin ratio (CCR) is revealed to predict gastric cancer prognosis. However, the prognostic abilities of CCR and the combination of CCR and myosteatosis in patients with pancreatic cancer (PC) who underwent radical surgery remains unclear. METHODS: The retrospective cohort study included 215 patients with PC who underwent radical surgery (January 2016-October 2021). Clinicopathological and serological data were collected on admission. Myosteatosis and other body composition indices were assessed by using computed tomography. The cutoff value of CCR was determined by using the Youden index. Risk factors responsible for poor overall survival (OS) and disease-free survival (DFS) were determined by the Cox proportional hazards model. RESULTS: The myosteatosis group included 104 patients (average age, 61.3 ± 9.1 years). The best cutoff value for CCR was 1.09. CCR ≤ 1.09 was an independent predictive biomarker inversely corelated with OS (P = 0.036). Myosteatosis was an independent risk factor associated with OS and DFS (P = 0.032 and P = 0.004, respectively). Patients with concomitant myosteatosis and CCR ≤ 1.09 had the worst OS (P = 0.016). CONCLUSIONS: Myosteatosis and CCR are prognostic biomarkers for survival in PC patients who underwent radical surgery. Patients with the coexistence of myosteatosis and CCR ≤ 1.09 deserve more attention.

Fatty infiltration of gastrocnemius-soleus muscle complex: Considerations for myosteatosis rehabilitation.

Although previous studies have reported fatty infiltration of the gastrocnemius-soleus complex, little is known about the volumetric distribution and patterns of fatty infiltration. The purpose of this anatomical study was to document and quantify the frequency, distribution, and pattern of fatty infiltration of the gastrocnemius-soleus complex. One hundred formalin-embalmed specimens (mean age 78.1 ± 12.3 years; 48F/52M) were serially dissected to document the frequency, distribution, and pattern of fatty infiltration in the medial and lateral heads of gastrocnemius and soleus muscles. Fatty infiltration was found in 23% of specimens, 13 unilaterally (8F/5M) and 10 (5M/5F) bilaterally. The fatty infiltration process was observed to begin medially from the medial aspect of the medial head of gastrocnemius and medial margin of soleus and then progressed laterally throughout the medial head of gastrocnemius and the marginal, anterior, and posterior soleus. The lateral head of gastrocnemius remained primarily muscular in all specimens. Microscopically, the pattern of infiltration was demonstrated as intramuscular with intact aponeuroses, and septa. The remaining endo-, peri-, and epimysium preserved the overall contour of the gastrocnemius-soleus complex, even in cases of significant fatty replacement. Since the external contour of the calf is preserved, the presence of fatty infiltration may be underdiagnosed in the clinic without imaging. Myosteatosis is associated with gait and balance challenges in the elderly, which can impact quality of life and result in increased risk of falling. The findings of the study have implications in the rehabilitation management of elderly patients with sarcopenia and myosteatosis.

Independent association of thigh muscle fat density with vascular events in Korean adults.

BACKGROUND: We aimed to explore the associations between thigh muscle fat density and vascular events. METHODS: A total of 3,595 adults (mean age, 57.2 years; women, 1,715 [47.7%]) without baseline cardiovascular events from the Korean Atherosclerosis Study-2 were included. Muscle and fat area at the mid-thigh level were measured by computed tomography (CT) using the following Hounsfield Unit range: 0-30 for low density muscle (LDM); 31-100 for normal density muscle (NDM); and - 250 to - 50 for fat. RESULTS: During a median follow-up period of 11.8 (4.3-13.9) years, vascular events occurred in 11.6% of men and 5.9% of women. Individuals with vascular events had a larger LDM area (men: 48.8 ± 15.5 cm2 vs. 44.6 ± 14.5 cm2; women: 39.4 ± 13.2 cm2 vs. 35.0 ± 11.8 cm2, both P < 0.001) compared with those who did not have vascular events during the follow-up of at least 5 years. The LDM/NDM ratio was also independently associated with vascular events after adjusting for cardiometabolic risk factors. Moreover, the LDM/NDM ratio improved the prognostic value for vascular events when added to conventional risk factors. CONCLUSIONS: The current study suggests that a higher thigh muscle fat infiltration is associated with an increased risk of developing vascular events among Korean adults.

Myosteatosis predicts postoperative complications and long-term survival in robotic gastrectomy for gastric cancer: A propensity score analysis.

BACKGROUND: Robotic gastrectomy is increasingly utilized for gastric cancer, but high morbidity remains a concern. Myosteatosis or low skeletal muscle density reflecting fatty infiltration, associates with complications after other cancer surgeries but has not been evaluated for robotic gastrectomy. METHODS: This retrospective study analysed 381 patients undergoing robotic gastrectomy for gastric cancer from September 2019 to October 2022. Myosteatosis was quantified on preoperative computed tomography (CT) images at lumbar 3 (L3). Propensity score matching addressed potential confounding between myosteatosis and non-myosteatosis groups. Outcomes were postoperative complications, 30 days mortality, 30 days readmissions and survival. RESULTS: Myosteatosis was present in 33.6% of patients. Myosteatosis associated with increased overall (47.7% vs. 26.5%, p < 0.001) and severe complications (12.4% vs. 4.9%, p < 0.001). After matching, myosteatosis remained associated with increased overall complications, major complications, intensive care unit (ICU) transfer and readmission (all p < 0.05). Myosteatosis independently predicted overall [odds ratio (OR) = 2.86, 95% confidence interval (CI): 1.57-5.20, p = 0.001] and severe complications (OR = 4.81, 95% CI: 1.51-15.27, p = 0.008). Myosteatosis also associated with reduced overall (85.0% vs. 93.2%, p = 0.015) and disease-free survival (80.3% vs. 88.4%, p=0.029). On multivariate analysis, myosteatosis independently predicted poorer survival [hazard ratio (HR) = 2.83, 95% CI: 1.32-6.08, p=0.012] and disease-free survival (HR = 1.83, 95% CI: 1.01-3.30, p=0.032). CONCLUSION: Preoperative CT-defined myosteatosis independently predicts increased postoperative complications and reduced long-term survival after robotic gastrectomy for gastric cancer. Assessing myosteatosis on staging CT could optimize preoperative risk stratification.

Chitinase-3 like-protein-1, a prognostic biomarker in patients with hepatocellular carcinoma and concomitant myosteatosis.

BACKGROUND: Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). METHODS: This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman's rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104). CONCLUSIONS: Elevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention.

Impact of sarcopenia on postoperative outcomes after hepatectomy in older patients with intrahepatic cholangiocarcinoma: A multicentre cohort study.

BACKGROUND AND AIMS: Sarcopenia is associated with poor prognosis, but its role in older patients with intrahepatic cholangiocarcinoma (ICC) is unclear. We aimed to evaluate the impact of sarcopenia on the prognosis of older patients with ICC undergoing hepatectomy. METHODS: A total of 363 patients with ICC following hepatectomy from 2015 to 2021 were retrospectively reviewed at five institutions. Sarcopenia was evaluated using skeletal muscle index by computed tomography images. Patients were divided into four subgroups according to sarcopenia and age. Postoperative outcomes including complication, overall survival (OS) and recurrence-free survival (RFS) were evaluated. Risk factors were identified through univariate and multivariate Cox regression analyses. RESULTS: 302 patients were included in the analysis. The median age was 63 years and there were 128 patients (42.4%) aged over 65 years. 192 patients (63.6%) were diagnosed with sarcopenia, while 180 patients (59.6%) experienced myosteatosis. Older patients experienced a higher incidence of sarcopenia and myosteatosis, and worse postoperative outcomes than younger patients. In the subgroup of patients with sarcopenia, older patients experienced a significant shorter OS than younger patients, which was not observed in patients without sarcopenia. According to the multivariate Cox regression analysis, lymphatic metastasis (p < .001), blood transfusion (p = .004), low serum albumin (p = .051), sarcopenia (p = .024), and myosteatosis (p = .004) were identified as independent risk factors of OS in older patients, meanwhile tumour size (p = .013) and lymphatic metastasis (p < .001) were independent risk factors of RFS. CONCLUSIONS: Sarcopenia and myosteatosis have a significant adverse impact on postoperative outcomes in older patients with ICC undergoing hepatectomy.

Unlocking liver health: Can tackling myosteatosis spark remission in metabolic dysfunction-associated steatotic liver disease?

Myosteatosis is highly prevalent in metabolic dysfunction-associated steatotic liver disease (MASLD) and could reciprocally impact liver function. Decreasing muscle fat could be indirectly hepatoprotective in MASLD. We conducted a review to identify interventions reducing myosteatosis and their impact on liver function. Non-pharmacological interventions included diet (caloric restriction or lipid enrichment), bariatric surgery and physical activity. Caloric restriction in humans achieving a mean weight loss of 3% only reduces muscle fat. Lipid-enriched diet increases liver fat in human with no impact on muscle fat, except sphingomyelin-enriched diet which reduces both lipid contents exclusively in pre-clinical studies. Bariatric surgery, hybrid training (resistance exercise and electric stimulation) or whole-body vibration in human decrease both liver and muscle fat. Physical activity impacts both phenotypes by reducing local and systemic inflammation, enhancing insulin sensitivity and modulating the expression of key mediators of the muscle-liver-adipose tissue axis. The combination of diet and physical activity acts synergistically in liver, muscle and white adipose tissue, and further decrease muscle and liver fat. Several pharmacological interventions (patchouli alcohol, KBP-089, 2,4-dinitrophenol methyl ether, adipoRon and atglistatin) and food supplementation (vitamin D or resveratrol) improve liver and muscle phenotypes in pre-clinical studies by increasing fatty acid oxidation and anti-inflammatory properties. These interventions are effective in reducing myosteatosis in MASLD while addressing the liver disease itself. This review supports that disturbances in inter-organ crosstalk are key pathophysiological mechanisms involved in MASLD and myosteatosis pathogenesis. Focusing on the skeletal muscle might offer new therapeutic strategies to treat MASLD by modulating the interactions between liver and muscles.

Shining a spotlight on sarcopenia and myosteatosis in liver disease and liver transplantation: Potentially modifiable risk factors with major clinical impact.

Muscle-wasting and disease-related malnutrition are highly prevalent in patients with chronic liver diseases (CLD) as well as in liver transplant (LT) candidates. Alterations of body composition (BC) such as sarcopenia, myosteatosis and sarcopenic obesity and associated clinical frailty were tied to inferior clinical outcomes including hospital admissions, length of stay, complications, mortality and healthcare costs in various patient cohorts and clinical scenarios. In contrast to other inherent detrimental individual characteristics often observed in these complex patients, such as comorbidities or genetic risk, alterations of the skeletal muscle and malnutrition are considered as potentially modifiable risk factors with a major clinical impact. Even so, there is only limited high-level evidence to show how these pathologies should be addressed in the clinical setting. This review discusses the current state-of-the-art on the role of BC assessment in clinical outcomes in the setting of CLD and LT focusing mainly on sarcopenia and myosteatosis. We focus on the disease-related pathophysiology of BC alterations. Based on these, we address potential therapeutic interventions including nutritional regimens, physical activity, hormone and targeted therapies. In addition to summarizing existing knowledge, this review highlights novel trends, and future perspectives and identifies persisting challenges in addressing BC pathologies in a holistic way, aiming to improve outcomes and quality of life of patients with CLD awaiting or undergoing LT.

Dual-Energy CT muscle fat fraction as a new imaging biomarker of body composition and survival predictor in critically ill patients.

OBJECTIVE: To analyze changes in the muscular fat fraction (FF) during immobilization at the intensive care unit (ICU) using dual-energy CT (DECT) and evaluate the predictive value of the DECT FF as a new imaging biomarker for morbidity and survival. METHODS: Immobilized ICU patients (n = 81, 43.2% female, 60.3 ± 12.7 years) were included, who received two dual-source DECT scans (CT1, CT2) within a minimum interval of 10 days between 11/2019 and 09/2022. The DECT FF was quantified for the posterior paraspinal muscle by two radiologists using material decomposition. The skeletal muscle index (SMI), muscle radiodensity attenuation (MRA), subcutaneous-/ visceral adipose tissue area (SAT, VAT), and waist circumference (WC) were assessed. Reasons for ICU admission, clinical scoring systems, therapeutic regimes, and in-hospital mortality were noted. Linear mixed models, Cox regression, and intraclass correlation coefficients were employed. RESULTS: Between CT1 and CT2 (median 21 days), the DECT FF increased (from 20.9% ± 12.0 to 27.0% ± 12.0, p = 0.001). The SMI decreased (35.7 cm2/m2 ± 8.8 to 31.1 cm2/m2 ± 7.6, p < 0.001) as did the MRA (29 HU ± 10 to 26 HU ± 11, p = 0.009). WC, SAT, and VAT did not change. In-hospital mortality was 61.5%. In multivariable analyses, only the change in DECT FF was associated with in-hospital mortality (hazard ratio (HR) 9.20 [1.78-47.71], p = 0.008), renal replacement therapy (HR 48.67 [9.18-258.09], p < 0.001), and tracheotomy at ICU (HR 37.22 [5.66-245.02], p < 0.001). Inter-observer reproducibility of DECT FF measurements was excellent (CT1: 0.98 [0.97; 0.99], CT2: 0.99 [0.96-0.99]). CONCLUSION: The DECT FF appears to be suitable for detecting increasing myosteatosis. It seems to have predictive value as a new imaging biomarker for ICU patients. CLINICAL RELEVANCE STATEMENT: The dual-energy CT muscular fat fraction appears to be a robust imaging biomarker to detect and monitor myosteatosis. It has potential for prognosticating, risk stratifying, and thereby guiding therapeutic nutritional regimes and physiotherapy in critically ill patients. KEY POINTS: The dual-energy CT muscular fat fraction detects increasing myosteatosis caused by immobilization. Change in dual-energy CT muscular fat fraction was a predictor of  in-hospital morbidity and mortality. Dual-energy CT muscular fat fraction had a predictive value superior to established CT body composition parameters.

Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease is associated with heterogeneous pattern of fat infiltration in skeletal muscles.

OBJECTIVES: To evaluate the association between fat infiltration in skeletal muscles (myosteatosis) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In a cross-sectional cohort of 72 histologically proven NAFLD patients (n = 38 with non-alcoholic steatohepatitis; NASH), among which 20 had HCC diagnosed on biopsy, we used proton density fat fraction (PDFF) at MRI to evaluate myosteatosis in skeletal muscles (mean fat fraction and first order radiomic-based pattern) at the third lumbar level, namely in erector spinae (ES), quadratus lumborum (QL), psoas, oblique, and rectus muscles. RESULTS: PDFFES was 70% higher in patients with HCC when compared to those without HCC (9.6 ± 5.5% versus 5.7 ± 3.0%, respectively, p < 0.001). In multivariate logistic regression, PDFFES was a significant predictor of the presence of HCC (AUC = 0.72, 95% CI 0.57-0.86, p = 0.002) independently from age, sex, visceral fat area, and liver fibrosis stage (all p < 0.05). The relationship between PDFFES and HCC was exacerbated in patients with NASH (AUC = 0.79, 95% CI 0.63-0.86, p = 0.006). In patients with NASH, radiomics features of heterogeneity such as energy and entropy in any of the paraspinal muscles (i.e., ES, QL, or psoas) were independent predictors of HCC. EnergyES identified patients with HCC (n = 13) in the NASH population with AUC = 0.92 (95% CI 0.82-1.00, p < 0.001). CONCLUSION: In patients with NAFLD, and more specifically in those with NASH, the degree and heterogeneity of myosteatosis is independently associated with HCC irrespective of liver fibrosis stage. CLINICAL RELEVANCE STATEMENT: Our data suggest that myosteatosis could be used as a biomarker of HCC in the ever-expanding NAFLD population and pave the way for further investigation in longitudinal studies. KEY POINTS: • HCC in patients with non-alcoholic fatty liver disease, and more specifically in those with non-alcoholic steatohepatitis, is independently associated with severe fatty infiltration (myosteatosis) of paravertebral skeletal muscles. • Association between myosteatosis and HCC is independent from liver fibrosis stage. • Histogram-based radiomics features of myosteatosis predicts the risk of HCC in patients with non-alcoholic steatohepatitis.

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

BACKGROUND: There 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. METHODS: Totally, 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. RESULTS: The 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. CONCLUSIONS: Muscle 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.

Assessment of myosteatosis and functionality in pretreatment gynecological cancer patients.

PURPOSE: We aimed to investigate the relationship between pretreatment gynecologic cancer survival and the physical function of patients with myosteatosis. Understanding this relationship prior to treatment would help healthcare providers identify and refer patients with poor muscle quality to an exercise program prior to treatment. METHODS: We conducted a cross-sectional analysis of 73 GC patients. Physical function was quantified using handgrip strength and an adapted version of the Senior Fitness Test (aerobic endurance not included). The EORTC QLC-C30 was used to evaluate general health quality. Myosteatosis (values below the median muscle radiodensity), muscle mass, and adipose tissue variables were calculated from the computed tomography (CT) scan at the third lumbar vertebra using specific software. RESULTS: Seventy patients (50.9 ± 15.2) were included; 41.5% had stage III or IV disease, and 61.4% had cervical cancer. The myosteatosis group was 11.9 years older and showed reduced functioning compared to the normal-radiodensity group. Age and Timed Up and Go (TUG) test results were shown to be the most reliable predictors of muscle radiodensity in pretreatment gynecological patients according to multivariate regression analysis (R2 = 0.314). CONCLUSION: Gynecological healthcare professionals should be aware that prompt exercise programs might be especially beneficial for older patients with reduced TUG performance to preserve muscle function and quality.

Age-adjusted Charlson comorbidity index and its association with body composition and overall survival in patients with colorectal cancer.

OBJECTIVE: To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). RESEARCH METHODS AND PROCEDURES: In this cohort study, patients (≥ 18 years old) with CRC were followed for 36 months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. RESULTS: A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2 years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). CONCLUSION: The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.

Albumin-myosteatosis gauge as a prognostic factor in patients with advanced pancreatic cancer undergoing first-line chemotherapy.

BACKGROUND: Sarcopenia and myosteatosis have been associated with a poor prognosis for several cancers. The albumin-myosteatosis gauge (AMG) is a novel integrated measure proposed to assess myosteatosis along with serum albumin level as a surrogate of systemic inflammation and malnutrition. The aim of this study was to investigate the prognostic value of AMG in patients with advanced pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with advanced PDAC treated with chemotherapy between 2013 and 2022 were evaluated. Skeletal muscle radiodensity (SMD) and skeletal muscle index (SMI) were calculated using computed tomography at the level of the L3 vertebra. The AMG was defined as albumin x SMD and expressed as an arbitrary unit (AU). Patients were first categorized by sex-specific quartiles and then dichotomized at the sex-specific median value of the AMG. RESULTS: A total of 196 patients were included. The median age (interquartile range) was 62 (54-67), and 128 (65.3%) were male. With regard to AMG, 142.86 and 114.15 AU were identified as cutoff values for males and females, respectively. In multivariable analyses, lower AMG values (G1-G2 vs. G3-G4) (HR: 1.61, 95% CI 1.17-2.21, p = 0.003), higher ECOG performance score (> 0 vs. 0) (HR: 1.51, 95% CI 1.10-2.06, p = 0.009) and metastatic disease (vs. locally advanced) (HR: 1.88, 95% CI 1.27-2.79, p = 0.001) were associated with OS. CONCLUSION: The study findings suggest the prognostic value of AMG in patients with advanced PDAC undergoing first-line chemotherapy. Further studies are warranted to validate these findings and assess potential predictive role of AMG in guiding treatment selection.

Low skeletal muscle radiodensity is a risk factor for adjuvant chemotherapy discontinuation in colorectal cancer.

BACKGROUND: Previously, we reported SMR (skeletal muscle radiodensity) as a potential prognostic marker for colorectal cancer. However, there have been limited studies on the association between SMR and the continuation of adjuvant chemotherapy in colorectal cancer. METHODS: In this retrospective study, 143 colorectal cancer patients underwent curative surgery and adjuvant chemotherapy using the CAPOX regimen. Patients' SMRs were measured from preoperative CT images and divided into low (bottom quarter) and high (top three quarters) SMR groups. We compared chemotherapy cycles, capecitabine and oxaliplatin doses, and adverse effects in each group. RESULTS: The low SMR group had significantly fewer patients completing adjuvant chemotherapy compared to the high SMR group (44% vs. 68%, P < 0.01). Capecitabine and oxaliplatin doses were also lower in the low SMR group. Incidences of Grade 2 or Grade 3 adverse effects did not differ between groups, but treatment discontinuation due to adverse effects was significantly higher in the low SMR group. Logistic regression analysis revealed Stage III disease (odds ratio 18.09, 95% CI 1.41-231.55) and low SMR (odds ratio 3.26, 95% CI 1.11-9.56) as factors associated with unsuccessful treatment completion. Additionally, a higher proportion of low SMR patients received fewer than 2 cycles of chemotherapy (50% vs. 12%). CONCLUSION: The low SMR group showed higher treatment incompletion rates and received lower drug doses during adjuvant chemotherapy. Low SMR independently contributed to treatment non-completion in colorectal cancer patients.

Utilizing a novel MRI technique to identify adverse muscle composition in end-stage liver disease: A pilot study.

INTRODUCTION AND OBJECTIVES: Sarcopenia is a common complication of end-stage liver disease (ESLD), but its exact relationship to myosteatosis and frailty remains unclear. In this pilot study, we tested the feasibility of a specialized MRI protocol and automated image analysis in patients with ESLD. MATERIALS AND METHODS: In a single-center prospective study, adult liver transplant candidates with ESLD underwent assessment of muscle composition between 3/2022 and 6/2022 using the AMRA® MAsS Scan. The primary outcome of interest was feasibility of the novel MRI technique in patients with ESLD. We also tested if thigh muscle composition correlated with validated measures of frailty and sarcopenia. RESULTS: Eighteen subjects (71 % male, mean age 59 years) were enrolled. The most common etiologies of cirrhosis were alcohol-related liver disease (44 %) and non-alcohol-associated fatty liver disease (33 %), with a mean MELD-Na of 13 (± 4). The mean time needed to complete the MRI protocol was 14.9 min and only one patient could not complete it due to metal hardware in both knees. Forty-one percent of patients had adverse muscle composition (high thigh fat infiltration and low-fat free muscle volume) and these patients were more likely to have undergone a recent large volume paracentesis (43 % vs. 0 %, p < 0.02). The adverse muscle composition group performed significantly worse on the 6-minute walk test compared to the remainder of the cohort (379 vs 470 m, p < 0.01). CONCLUSIONS: The AMRA® MAsS Scan is feasible to perform in patients with ESLD and can be used to quantify myosteatosis, a marker of muscle quality and potentially muscle functionality in ESLD.

Sarcopenia and Ageing.

Musculoskeletal ageing is a major health challenge as muscles and bones constitute around 55-60% of body weight. Ageing muscles will result in sarcopenia that is characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes. In recent years, a few consensus panels provide new definitions for sarcopenia. It was officially recognized as a disease in 2016 with an ICD-10-CM disease code, M62.84, in the International Classification of Diseases (ICD). With the new definitions, there are many studies emerging to investigate the pathogenesis of sarcopenia, exploring new interventions to treat sarcopenia and evaluating the efficacy of combination treatments for sarcopenia. The scope of this chapter is to summarize and appraise the evidence in terms of (1) clinical signs, symptoms, screening, and diagnosis, (2) pathogenesis of sarcopenia with emphasis on mitochondrial dysfunction, intramuscular fat infiltration and neuromuscular junction deterioration, and (3) current treatments with regard to physical exercises and nutritional supplement.

Myosteatosis in multiple myeloma: a key determinant of survival beyond sarcopenia.

OBJECTIVE: Fatty infiltration of skeletal muscle (Myosteatosis) is associated with increased frailty, decreased muscle and mobility function, which seems fairly prevalent in multiple myeloma (MM) patients. This study aimed to determine the prognostic value of myosteatosis assessed by CT for progression-free survival (PFS) and overall survival (OS). MATERIALS AND METHODS: This IRB-approved cohort study included patients with newly diagnosed MM who were treated at a single university hospital and received CT at baseline. Geriatric assessment was performed via International Myeloma Working Group frailty score and Revised Myeloma Comorbidity Index. Myosteatosis was determined through measurement of paravertebral muscle radiodensity. Statistical analyses included uni- and multivariable Cox proportional hazard models and the Kaplan-Meier-method. RESULTS: A total of 226 newly diagnosed MM patients (median age: 65 years [range: 29-89], 63% males, mean BMI: 25 [14-42]) were analyzed. The prevalence of myosteatosis was 51%. Muscle radiodensity was significantly decreased in individuals with International Staging System stage III vs. I (p < 0.001), indicating higher fatty muscle infiltration in patients with advanced disease. Both PFS and OS were significantly decreased in patients with myosteatosis (PFS: median 32.0 months (95% CI 20.5.5-42.2) vs. 66.4 months without myosteatosis (95% CI 42.5-not reached), p < .001); OS: median 58.6 (95% CI 51.3-90.2) vs. not reached, p < .001). Myosteatosis remained an independent predictor of OS in multivariable analyses (HR: 1.98; 95%-CI: 1.20-3.27). CONCLUSION: Myosteatosis seems fairly prevalent in patients with newly diagnosed MM and associated with impaired overall survival. Prospective clinical trials are required to better understand the role of myosteatosis in MM patients.

Myosteatosis as a novel predictor of new-onset diabetes mellitus after kidney transplantation.

OBJECTIVES: We evaluate the effect of myosteatosis on new-onset diabetes mellitus after kidney transplantation. METHODS: Consecutive patients who had renal transplant between 2006 and 2021 were reviewed, and 219 patients were finally included. Psoas muscle index was used to evaluate sarcopenia and average total psoas density (calculated by computed tomography before surgery) for myosteatosis. We used Cox proportional regression analyses in investigation of whether skeletal muscle depletion before surgery inclusive of sarcopenia and myosteatosis is a new additional predictor of new-onset diabetes mellitus. RESULTS: Median recipient age and body mass index were 45 years and 21.1 kg/m2 , respectively, and 123 patients (56%) were male. Preoperative impaired glucose tolerance was present in 58 patients (27%) and new-onset diabetes mellitus in 30 patients (14%), with median psoas muscle index of 6 cm2 /m2 and average total psoas density of 41 Hounsfield Unit. In multivariate analysis, significant risk factors were body mass index ≥25 kg/m2 (p < 0.01), impaired glucose tolerance (p < 0.01), and average total psoas density < 41.9 Hounsfield Unit (p = 0.03). New-onset diabetes mellitus had incidence rates of 3.7% without risk factors, 10% with a single risk factor, 33% with two, and 60% with three. Patients with new-onset diabetes mellitus were effectively stratified by the number of risk factors (p < 0.01). CONCLUSIONS: Myosteatosis could be a new risk factor used to predict new-onset diabetes mellitus.