Prognostic impact of myosteatosis in patients with colorectal cancer undergoing curative surgery: an updated systematic review and meta-analysis.

Background: Colorectal cancer (CRC) is a global health concern, and identifying prognostic factors can improve outcomes. Myosteatosis is fat infiltration into muscles and is a potential predictor of the survival of patients with CRC. Methods: This systematic review and meta-analysis aimed to assess the prognostic role of myosteatosis in CRC. PubMed, Embase, and Cochrane CENTRAL were searched up to 1 August 2023, for relevant studies, using combinations of the keywords CRC, myosteatosis, skeletal muscle fat infiltration, and low skeletal muscle radiodensity. Case-control, prospective, and retrospective cohort studies examining the association between myosteatosis and CRC outcomes after curative intent surgery were eligible for inclusion. Primary outcomes were overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). Results: A total of 10 studies with a total of 9,203 patients were included. The pooled hazard ratio (HR) for OS (myosteatosis vs. no myosteatosis) was 1.52 [95% confidence interval (CI), 1.38-1.67); for CSS, 1.67 (95% CI, 1.40-1.99); and for DFS, 1.89 (95% CI, 1.35-2.65). Conclusion: In patients with CRC undergoing curative intent surgery, myosteatosis is associated with worse OS, CSS, and DFS. These findings underscore the importance of evaluating myosteatosis in patients with CRC to improve outcomes.

Integrated impact of multiple body composition parameters on overall survival in gastrointestinal or genitourinary cancers: A descriptive cohort study.

BACKGROUND: This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies. METHODS: In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters. RESULTS: Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index. CONCLUSION: Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings.

Skeletal muscle density performance for screening frailty in older adults with cancer and the impact of diabetes: The CARE Registry.

INTRODUCTION: Skeletal muscle density (SMD) measurements from imaging scans identify myosteatosis and could screen patients for geriatric assessment. We assessed SMD performance as a screening tool to identify older adults with cancer likely to be frail and who could benefit from in-depth assessment; we compared performance by sex and diabetes status. MATERIALS AND METHODS: We analyzed patients in the Cancer & Aging Resilience Evaluation (CARE) Registry. Frailty and diabetes were captured using a patient-reported geriatric assessment (CARE tool). Frailty was defined using CARE frailty index (CARE-FI) based on principles of deficit accumulation. SMD was calculated from computed tomography scans (L3 vertebrae). Analyses were conducted by sex and diabetes status. Scatterplots and linear regression described crude associations between SMD and frailty score. Classification performance (frail vs. non-frail) was analyzed with (1) area under the receiver operating characteristic curves (AUC) and confidence intervals (CIs); and (2) sensitivity/specificity for sex-specific SMD quartile cut-offs (Q1, median, Q3). Performance was compared between patients with and without diabetes using differences and estimated CIs (2000 bootstrap replicates). We additionally calculated positive and negative likelihood ratios (LR+, LR-). RESULTS: The analytic cohort included 872 patients (39% female, median age 68 years, 27% with diabetes) with predominately stage III/IV gastrointestinal cancer; >60% planning to initiate first-line chemotherapy. SMD was negatively associated with frailty score; models were best fit in male patients with diabetes. AUC estimates for female (range: 0.58-0.62) and male (0.58-0.68) patients were low. Q3 cut-offs had high sensitivity (range: 0.76-0.89), but poor specificity (0.25-0.34). Diabetes did not impact estimates for female patients. Male patients with diabetes had greater sensitivity estimates compared to those without (sensitivity differences: 0.23 [0.07, 0.38], 0.08 [-0.07, 0.24], and 0.11 [0.00, 0.22] for Q1, median, Q3, respectively). LR estimates were most notable for male patients with diabetes (LR+ = 2.92, Q1 cut-off; LR- = 0.46, Q3 cut-off). DISCUSSION: Using SMD alone to screen older patients for geriatric assessment requires improvement. High-sensitivity cut-off points could miss 11-24% of patients with frailty, and many non-frail patients may be flagged. Screening with SMD is practical but work is needed to understand clinical andresource impacts of different cut-off points. Future research should evaluate performance with additional clinical data and in subgroups.

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.

CD3+/CD4+ cells combined with myosteatosis predict the prognosis in patients who underwent gastric cancer surgery.

BACKGROUND: This study aimed to investigate the predictive capacity of lymphocyte subpopulations, sarcopenia and myosteatosis for clinical outcomes in patients who underwent gastric cancer surgery. Additionally, the prognostic significance of CD3+/CD4+ cells in conjunction with myosteatosis was explored. METHODS: A cohort of 190 patients with gastric cancer who underwent surgery and received computed tomography scans between July 2016 and December 2017 at our institution was examined. Complete clinical information and peripheral lymphocyte subpopulations were available for all patients. A comprehensive array of statistical methodologies was employed to scrutinize variances in both clinical and pathological characteristics among patients, with the aim of identifying autonomous prognostic determinants requisite for the development of a nomogram. Subsequent assessment of the predictive efficacy of the nomogram was conducted via calibration curve analysis. RESULTS: The study comprised a cohort of 190 participants, encompassing 126 males (66.32%) and 64 females (33.68%), with a mean age of 58.47 (±11.37) years. Patients were stratified into three groups based on CD3+/CD4+ cells and myosteatosis, with 24 in Group 1, 87 in Group 2 and 79 in Group 3. Notably, patients in the third group exhibited significantly shorter progression-free survival (PFS) (hazard ratio [HR] = 0.208, P < 0.001) and overall survival (OS) (HR = 0.193, P < 0.001). The subset of peripheral blood lymphocytes exhibited elevated levels of CD3+/CD4+ cells (HR = 2.485, P < 0.001) and heightened CD4+/CD8+ ratios (HR = 1.705, P = 0.038), whereas diminished CD19+ cell counts (HR = 0.210, P = 0.032) correlated with improved OS in patients. The individuals presenting with sarcopenia (HR = 4.089, P = 0.023) and myosteatosis (HR = 2.857, P < 0.001) displayed reduced OS. The multivariate Cox regression analysis showed that pathological tumour-node-metastasis stage, CD19+ cells, sarcopenia and CD3+/CD4+ cell-myosteatosis were identified as independent prognostic factors for PFS and OS in patients. The constructed nomograms for PFS and OS yielded C-index values of 0.839 (95% confidence interval [CI]: 0.798-0.880) and 0.836 (95% CI: 0.792-0.879), respectively. The calibration analysis demonstrated that the nomograms accurately predicted the 3- and 5-year survival rates of PFS and OS in patients. CONCLUSIONS: Lymphocyte subsets, including CD3+/CD4+ cells, CD4+/CD8+ ratio and CD19+ cells, are indicative of clinical prognosis in gastric cancer surgery patients. Body composition parameters, such as sarcopenia and myosteatosis, are also associated with the patient's prognosis. The combination of CD3+/CD4+ cells with myosteatosis demonstrates enhanced prognostic value, enabling the identification of patients at high risk of post-operative metastasis and recurrence.

Preoperative Bone Loss Predicts Decreased Survival Associated with Microvascular Invasion after Resection of Hepatocellular Carcinoma.

BACKGROUND: Osteopenia is a well-known risk factor for survival in patients with hepatocellular carcinoma; however, it is unclear whether osteopenia can apply to both genders and how osteopenia is associated with cancer progression. The aim of this study was to elucidate whether osteopenia predicts reduced survival in regression models in both genders and whether osteopenia is associated with the pathological factors associated with reduced survival. METHODS: This study included 188 consecutive patients who underwent hepatectomy. Bone mineral density was assessed using computed tomography (CT) scan images taken within 3 months before surgery. Non-contrast CT scan images at the level of the 11th thoracic vertebra were used. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. Overall survival (OS) curves and recurrence-free survival (RFS) were constructed using the Kaplan-Meier method, as was a log-rank test for survival. The hazard ratio and 95% confidence interval for overall survival were calculated using Cox's proportional hazard model. RESULTS: In the regression analysis, age predicted bone mineral density. The association in females was greater than that in males. The OS and RFS of osteopenia patients were shorter than those for non-osteopenia patients. According to univariate and multivariate analyses, osteopenia was an independent risk factor for OS and RFS. The sole pathological factor associated with osteopenia was microvascular portal vein invasion. CONCLUSION: Models suggest that osteopenia may predict decreased OS and RFS in patients undergoing resection of hepatocellular carcinoma due to the mechanisms mediated via microvascular portal vein invasion.

Sarcopenia is independently associated with poor preoperative physical fitness in patients undergoing colorectal cancer surgery.

BACKGROUND: Accurate preoperative risk assessment for major colorectal cancer (CRC) surgery remains challenging. Body composition (BC) and cardiopulmonary exercise testing (CPET) can be used to evaluate risk. The relationship between BC and CPET in patients undergoing curative CRC surgery is unclear. METHODS: Consecutive patients undergoing CPET prior to CRC surgery between 2010 and 2020 were identified between two different UK hospitals. Body composition phenotypes such as sarcopenia, myosteatosis, and visceral obesity were defined using widely accepted thresholds using preoperative single axial slice CT image at L3 vertebrae. Relationships between clinicopathological, BC, and CPET variables were investigated using linear regression analysis. RESULTS: Two hundred eighteen patients with stage I-III CRC were included. The prevalence of sarcopenia, myosteatosis, and visceral obesity was 62%, 33%, and 64%, respectively. The median oxygen uptake at anaerobic threshold (VO2 at AT) was 12.2 mL/kg/min (IQR 10.6-14.2), and oxygen uptake at peak exercise (VO2 peak) was 18.8 mL/kg/min (IQR 15.4-23). On univariate linear regression analysis, male sex (P < 0.001) was positively associated with VO2 at AT. While ASA grade (P < 0.001) and BMI (P = 0.007) were negatively associated with VO2 at AT, on multivariate linear regression analysis, these variables remained significant (P < 0.05). On univariate linear regression analysis, male sex (P < 0.001) was positively associated with VO2 peak, whereas age (P < 0.001), ASA grade (P < 0.001), BMI (P = 0.003), sarcopenia (P = 0.015), and myosteatosis (P < 0.001) were negatively associated with VO2 peak. On multivariate linear regression analysis age (P < 0.001), ASA grade (P < 0.001), BMI (P < 0.001), and sarcopenia (P = 0.006) were independently and negatively associated with VO2 peak. CONCLUSIONS: The novel finding that sarcopenia is independently associated with reduced VO2 peak performance in CPET supports the supposition that reduced muscle mass relates to poor physical function in CRC patients. Further work should be undertaken to assess whether sarcopenia diagnosed on CT can act as suitable surrogate for CPET to further enhance personalized risk stratification.

Impact of Peroxisome Proliferator-Activated Receptor Agonists on Myosteatosis in the Context of Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), and more specifically steatohepatitis may be associated with fat infiltration of skeletal muscles which is known as myosteatosis. Pan-peroxisome proliferator-activated receptor (PPAR) agonists have been shown to promote metabolic dysfunction-associated steatohepatitis (MASH) remission. However, the effect of PPAR agonists on myosteatosis remains to be determined. The aim of this review is to evaluate the effect that PPAR agonists alone or in combination, have on myosteatosis in the context of MASLD. METHODS: Original research reports concerning the impact of PPAR agonists on muscle fat in MASLD were screened from PUBMED and EMBASE databases following the PRISMA methodology. RESULTS: Eleven original manuscripts were included in this review. Two preclinical studies assessed the impact of the PPARα agonist on fat content in the quadriceps muscle and the liver by extracting triglycerides in rats fed a high-fat diet and in insulin-resistant mice. Both models showed muscle and liver triglyceride content reduction using WY14643. Fenofibrate had no significant impact on soleus intramyocellular lipids or liver fat content in insulin-resistant subjects based on proton magnetic resonance spectroscopy. Treatment with PPARδ agonists increased the expression of genes involved in fatty acid oxidation in two studies on muscle cell culture. PPARγ agonists were investigated in two preclinical studies and one clinical study using spectroscopy and computed tomography respectively. In the first preclinical study in Zucker diabetic fatty rats, rosiglitazone reduced muscle lipids and hepatic steatosis. In a second preclinical study using the same animal model, pioglitazone reduced tibialis anterior intramyocellular lipids. In contrast, computed tomography analyses in patients with type 2 diabetes revealed a surface area increase of low-density muscles (suggesting an increase in muscle fat content) after a one-year treatment with rosiglitazone. Varying combinations of PPAR agonists (cevoglitazar, fenofibrate/pioglitazone and muraglitazar) were evaluated in two preclinical studies and one clinical study. In rats, these treatments showed variable results for muscle and liver depending on the combinations studied. In type 2 diabetic patients, treatment with muraglitazar (a PPARα/γ agonist) reduced the intramyocellular lipid content of tibialis anterior as well as liver fat content following spectroscopy assessment. CONCLUSION: The combination of different PPAR agonists could have a positive impact on reducing myosteatosis, in addition to their effect on the liver. Some discrepancies could be explained by the different techniques used to assess muscle lipid content, the muscles assessed and the possible adipogenic effect of PPARγ agonists. Further clinical research is needed to fully assess the efficacy of these treatments on both MASLD progression and associated myosteatosis.

Sarcopenia diagnosis in patients with colorectal cancer: a review of computed tomography-based assessments and emerging ways to enhance practicality.

Traditionally, cancer treatment has focused on the stages of the disease; however, recent studies have highlighted the importance of considering the overall health status of patients in the prognosis of cancer. Loss of skeletal muscle, known as sarcopenia, has been found to significantly affect outcomes in many different types of cancers, including colorectal cancer. In this review, we discuss the guidelines for diagnosing sarcopenia, with a specific focus on CT-based assessments. Many groups worldwide, including those in Europe and Asia, have introduced their own diagnostic guidelines for sarcopenia. Seemingly similar yet subtle discrepancies, particularly in the cutoff values used, limit the use of these guidelines in the general population, warranting a more universal guideline. Although CT-based measurements, such as skeletal muscle index and radiodensity, have shown promise in predicting outcomes, the lack of standardized values in these measurements hinders their universal adoption. To overcome these limitations, innovative approaches are being developed to assess changes in muscle mass trajectories and introduce new indices, such as skeletal and appendicular muscle gauges. Additionally, machine learning models have shown superior performance in predicting sarcopenic status, providing an alternative to CT-based diagnosis, particularly after surgery. CT has tremendous benefits and a significant role in visually as well as quantitatively retrieving information on patient body composition. In order to compensate for the limitation of standard cutoff value, 3-dimensional analysis of the CT, artificial intelligence-based body composition analysis, as well as machine learning algorithms for data interpretation and analysis have been proposed and are being utilized. In conclusion, despite the varying definitions of sarcopenia, CT-based measurements coupled with machine-learning models are promising for evaluating patients with cancer. Standardization efforts can improve diagnostic accuracy, reduce the reliance on CT examinations, and make sarcopenia assessments more accessible in clinical settings.

The effects of myosteatosis on skeletal muscle function in older adults.

Myosteatosis, or the infiltration of fatty deposits into skeletal muscle, occurs with advancing age and contributes to the health and functional decline of older adults. Myosteatosis and its inflammatory milieu play a larger role in adipose tissue dysfunction, muscle tissue dysfunction, and increased passive muscle stiffness. Combined with the age-related decline of sex hormones and development of anabolic resistance, myosteatosis also contributes to insulin resistance, impaired muscle mechanics, loss of force production from the muscle, and increased risk of chronic disease. Due to its highly inflammatory secretome and the downstream negative effects on muscle metabolism and mechanics, myosteatosis has become an area of interest for aging researchers and clinicians. Thus far, myosteatosis treatments have had limited success, as many lack the potency to completely rescue the metabolic and physical consequences of myosteatosis. Future research is encouraged for the development of reliable assessment methods for myosteatosis, as well as the continued exploration of pharmacological, nutritional, and exercise-related interventions that may lead to the success in attenuating myosteatosis and its clinical consequences within the aging population.

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.

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.

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.

Progressive sarcopenia and myosteatosis predict prognosis of advanced HCC patients treated with immune checkpoint inhibitors.

Background: Immunotherapy stands as a pivotal modality in the therapeutic landscape for the treatment of advanced hepatocellular carcinoma, yet responses vary among patients. This study delves into the potential impact of sarcopenia, myosteatosis and adiposity indicators, as well as their changes during immunotherapy, on treatment response and prognosis in patients with advanced hepatocellular carcinoma treated with immune checkpoint inhibitors. Methods: In this retrospective analysis, 116 patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors were recruited. Skeletal muscle, intramuscular, subcutaneous, and visceral adipose tissue were assessed by computed tomography at the level of the third lumbar vertebrae before and after 3 months of treatment. Sarcopenia and myosteatosis were evaluated by skeletal muscle index and mean muscle density using predefined threshold values. Patients were stratified based on specific baseline values or median values, along with alterations observed during the treatment course. Overall survival (OS) and progression-free survival (PFS) were compared using the log-rank test and a multifactorial Cox proportional risk model. Results: A total of 116 patients were recruited and divided into two cohorts, 81 patients for the training set and 35 patients for the validating set. In the overall cohort, progressive sarcopenia (P=0.021) and progressive myosteatosis (P=0.001) were associated with objective response rates, whereas progressive myosteatosis (P<0.001) was associated with disease control rates. In the training set, baseline sarcopenia, myosteatosis, and subcutaneous and visceral adipose tissue were not significantly associated with PFS and OS. In multivariate analysis adjusting for sex, age, and other factors, progressive sarcopenia(P=0.002) and myosteatosis (P=0.018) remained independent predictors of PFS. Progressive sarcopenia (P=0.005), performance status (P=0.006) and visceral adipose tissue index (P=0.001) were all independent predictors of OS. The predictive models developed in the training set also had good feasibility in the validating set. Conclusion: Progressive sarcopenia and myosteatosis are predictors of poor clinical outcomes in patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors, and high baseline visceral adiposity is associated with a poorer survival.

The coexistence of myosteatosis and the creatinine/cystatin C ratio are determinants of outcomes in cholangiocarcinoma patients undergoing curative surgery.

Background: Myosteatosis is a well-established predictor of poor prognosis in many types of cancer, and a decreased Creatinine/Cystatin C ratio (CCR) is a known indicator of unfavorable outcomes in patients with metabolic disorders and cancer. Despite this knowledge, the significance of concurrent CCR and myosteatosis in predicting the prognosis of patients with cholangiocarcinoma (CCA) who undergo radical surgery remains uncertain. Method: Data from 757 patients with cholangiocarcinoma who underwent the first radical resection in the Affiliated Hospital of Qingdao University from January 2017 to March 2022 were collected. According to the inclusion and exclusion criteria, 149 patients were finally included in the retrospective study cohort. Various clinicopathological, serological, and radiological data were collected at admission. Myosteatosis was evaluated using sliceOmatic software on computed tomography (CT) images. The study used receiver operating characteristic (ROC) curve analysis to determine the critical value of CCR, which predicts overall survival (OS) based on the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were employed to identify the risk factors associated with OS and RFS confidently. Results: The group identified as the myosteatosis cohort consisted of 79 patients with an average age of 64.3 ± 7.8 years. The ROC curve analysis revealed an optimal critical CCR value of 10.834. A low CCR ≤ 10.834 and myosteatosis were found to be associated with poor OS and RFS outcomes (P = 0.022; P = 0.017; P = 0.038; P = 0.030 respectively). Moreover, patients with myosteatosis and a CCR ≤ 10.834 had the worst OS and RFS outcomes (P = 0.035; P = 0.027). Conclusion: After radical excision in CCA patients, the presence of myosteatosis and CCR had a negative correlation with prognosis. A more accurate prediction of OS and RFS was possible by combining CCR and myosteatosis, compared to CCR alone.

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.

Low serum manganese as a noninvasive marker predicting the presence of myosteatosis among hospitalized patients with cirrhosis.

Emerging evidence expands on a close connection between trace elements and muscular abnormalities, mostly focusing on sarcopenia. We hypothesized an association between concentrations of serum trace elements and myosteatosis, given that myosteatosis has a more pronounced clinical implication relative to sarcopenia, but there is a paucity of data in patients with cirrhosis. Consecutive patients were hospitalized for cirrhosis-associated complications. Serum trace elements (zinc, copper, manganese [Mn], magnesium, calcium, and iron) were measured by inductively coupled plasma mass spectrometry. The presence of myosteatosis was defined according to computed tomography-demarcated intramuscular adipose tissue content. In total, the 295 patients with cirrhosis analyzed had a median age of 63 years and 53.6% were male. Among them, 42 patients presented with myosteatosis (14.2%) and concomitant higher Model for End-stage Liver Disease-Sodium and triglyceride concentrations and lower neutrophil counts and serum Mn concentrations (all P < .05). No differences were found regarding other 5 trace elements in patients with versus without myosteatosis. The median serum Mn concentrations were 1.16 µg/L, and this population was categorized into high-Mn and low-Mn groups. The proportion of myosteatosis was significantly lower in high-Mn group than that in low-Mn group (8.1% vs 20.4%, P < .001). Univariable binary logistic regression indicated that low Mn was associated with myosteatosis (odds ratio, 2.906; 95% confidence interval, 1.424-5.932; P = .003) in the context of cirrhosis. This result was validated according to multivariable analysis by adjusting for confounding factors. In conclusion, low serum Mn can be predictive of myosteatosis, a novel muscular abnormality representing more clinical relevance and close relation to inferior outcomes among cirrhosis.

Evaluation of muscle mass and intramuscular fatty infiltration in dogs with hypercortisolism and their association with prognosis.

BACKGROUND: Muscle atrophy and intramuscular fatty infiltration, as well as their association with prognosis, have not been quantified in dogs with spontaneous hypercortisolism (HC). OBJECTIVE: To quantitatively evaluate muscle atrophy and IM fatty infiltration in dogs with HC and determine their prognostic impact. ANIMALS: Fifty-three dogs with HC and 66 control dogs without HC. METHODS: Retrospective cohort study. Medical records and computed tomography images obtained between 2014 and 2021 were evaluated. Kaplan-Meier curves and log-rank tests were used to analyze the effect of muscle atrophy and IM fatty infiltration on the prognosis of dogs with HC. RESULTS: Dogs with HC showed lower visually measured cross-sectional area (VCSA) and cross-sectional area based on attenuation (HCSA) than control dogs (median [interquartile range {IQR}]: 50.3 mm2/mm [36.2-67.8] vs 66.7 mm2/mm [48.0-85.9]; P < .001; 30.4 mm2/mm [13.7-57.2] vs 54.8 mm2/mm [39.7-71.5]; P < .001, respectively). Dogs with HC had lower epaxial muscle attenuation (L3HU) than control dogs (median [IQR]: 21.2 Hounsfield [HU] [12.4-28.2] vs 33.2 HU [22.6-43.6]; P < .001). Dogs with HC with lower HCSA or L3HU had shorter survival (median [IQR]: 670 days [222-673] vs 949 days [788-1074], P < .01; 523 days [132-670] vs 949 days [756-1074], P < .01, respectively) but not lower VCSA (median [IQR]: 673 days [132-788] vs 949 days [523 to not applicable]; P = .30). CONCLUSION AND CLINICAL IMPORTANCE: Hypercortisolism in dogs causes muscle atrophy and IM fatty infiltration and is associated with poor prognosis.

Abdominal CT metrics in 17,646 patients reveal associations between myopenia, myosteatosis, and medical phenotypes: a phenome-wide association study.

BACKGROUND: Deep learning facilitates large-scale automated imaging evaluation of body composition. However, associations of body composition biomarkers with medical phenotypes have been underexplored. Phenome-wide association study (PheWAS) techniques search for medical phenotypes associated with biomarkers. A PheWAS integrating large-scale analysis of imaging biomarkers and electronic health record (EHR) data could discover previously unreported associations and validate expected associations. Here we use PheWAS methodology to determine the association of abdominal CT-based skeletal muscle metrics with medical phenotypes in a large North American cohort. METHODS: An automated deep learning pipeline was used to measure skeletal muscle index (SMI; biomarker of myopenia) and skeletal muscle density (SMD; biomarker of myosteatosis) from abdominal CT scans of adults between 2012 and 2018. A PheWAS was performed with logistic regression using patient sex and age as covariates to assess for associations between CT-derived muscle metrics and 611 common EHR-derived medical phenotypes. PheWAS P values were considered significant at a Bonferroni corrected threshold (α = 0.05/1222). FINDINGS: 17,646 adults (mean age, 56 years ± 19 [SD]; 57.5% women) were included. CT-derived SMI was significantly associated with 268 medical phenotypes; SMD with 340 medical phenotypes. Previously unreported associations with the highest magnitude of significance included higher SMI with decreased cardiac dysrhythmias (OR [95% CI], 0.59 [0.55-0.64]; P < 0.0001), decreased epilepsy (OR, 0.59 [0.50-0.70]; P < 0.0001), and increased elevated prostate-specific antigen (OR, 1.84 [1.47-2.31]; P < 0.0001), and higher SMD with decreased decubitus ulcers (OR, 0.36 [0.31-0.42]; P < 0.0001), sleep disorders (OR, 0.39 [0.32-0.47]; P < 0.0001), and osteomyelitis (OR, 0.43 [0.36-0.52]; P < 0.0001). INTERPRETATION: PheWAS methodology reveals previously unreported associations between CT-derived biomarkers of myopenia and myosteatosis and EHR medical phenotypes. The high-throughput PheWAS technique applied on a population scale can generate research hypotheses related to myopenia and myosteatosis and can be adapted to research possible associations of other imaging biomarkers with hundreds of EHR medical phenotypes. FUNDING: National Institutes of Health, Stanford AIMI-HAI pilot grant, Stanford Precision Health and Integrated Diagnostics, Stanford Cardiovascular Institute, Stanford Center for Digital Health, and Stanford Knight-Hennessy Scholars.