Evaluating the efficacy of immunotherapy in gastric cancer: Insights from immune checkpoint inhibitors.

The emergence of immunotherapy, particularly immune checkpoint inhibitors (ICIs), represents a groundbreaking approach to treating gastric cancer (GC). However, the prognosis of GC patients receiving ICI treatment is influenced by various factors. This manuscript identified sarcopenia and myosteatosis as inde-pendent prognostic factors impacting the outcomes of GC patients treated with ICIs. Additionally, this study introduced a visual predictive model to estimate the prognosis of GC patients. If confirmed by further studies, this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.

Diagnosis of Sarcopenia and Myosteatosis by Computed Tomography in Patients with Esophagogastric and Pancreatic Cancer.

The increase in the global incidence of cancer highlights the need to continue advancing in the techniques of diagnosis and nutritional assessment of cancer patients, given the prognostic and therapeutic impact of nutritional status. In this study, sarcopenia was evaluated as an independent predictor of morbidity and mortality. Data from 45 patients diagnosed with esophagogastric or pancreatic cancer were analyzed. Body composition was determined using computed tomography images, and functionality tests were performed. Sarcopenia was present in 22.2% of the patients, while only 31.1% had correct musculature. A reduction in muscle mass or function was observed in 46.7% of the patients. Likewise, the prevalence of myosteatosis reached 60% of the patients. No significant differences were found with regard to the presence of sarcopenia according to BMI classifications, so it is necessary to evaluate the patient with body composition techniques that include the evaluation of the different muscle and fat compartments. In conclusion, a comprehensive intervention is necessary to improve the detection of sarcopenia/myosteatosis and, in the future, to be able to carry out an approach that improves the quality of life and survival rates of patients.

Effect of contrast phase on quantitative analysis of skeletal muscle and adipose tissue by computed tomography.

OBJECTIVES: Significant variability exists in the contrast phases applied during computed tomography (CT) studies when assessing morphometric measurements of muscle area (CT-assessed sarcopenia) and density (CT-assessed myosteatosis) and visceral adipose tissue area (CT-assessed visceral obesity). This study explored the impact of contrast phase timing on changes in morphometric measurements of body composition. METHODS: This single-center retrospective cohort study included 459 patients undergoing a multiphase CT scan. Morphometric measurements were obtained at the third lumbar vertebra level. Patients were classified as sarcopenic, myosteatotic, or visceral obese using predefined cutoff values. The intraclass correlation coefficient was used to assess correlations across different enhancement phases, and Cohen's κ measured the inter-enhancement agreement for sarcopenia, myosteatosis, and visceral obesity. RESULTS: Significant differences were observed in mean visceral adipose tissue area, muscle density, and muscle area (P < 0.001). The intraclass correlation coefficient between unenhanced and arterial phases was 0.987 (95% confidence interval [CI], 0.759-0.996) for adipose tissue, 0.995 (95% CI, 0.989-0.997) for muscle area, and 0.850 (95% CI, 0.000-0.956) for muscle density. However, when morphometric measurements were categorized using predefined cutoffs, the κ agreement was considerably lower, particularly for CT-assessed myosteatosis, ranging from 0.635 (unenhanced to arterial) to 0.331 (unenhanced to late venous phase). CONCLUSIONS: Different CT contrast phases induce small but clinically significant alterations in the measurements of muscle area and density and visceral fat. Such minor changes can result in misclassification issues when fixed cutoff values are used to diagnose myosteatosis with CT. This underscores the importance of reporting absolute values and the specific contrast phase used in future studies.

Association between atherogenic dyslipidemia and muscle quality defined by myosteatosis.

Background: Myosteatosis, ectopic fat accumulation in skeletal muscle, is a crucial component of sarcopenia, linked to various cardiometabolic diseases. This study aimed to analyze the association between dyslipidemia and myosteatosis using abdominal computed tomography (CT) in a large population. Methods: This study included 11,823 patients not taking lipid-lowering medications with abdominal CT taken between 2012 and 2013. Total abdominal muscle area (TAMA), measured at the L3 level, was segmented into skeletal muscle area (SMA) and intramuscular adipose tissue. SMA was further classified into normal attenuation muscle area (NAMA: good quality muscle) and low attenuation muscle area (poor quality muscle). NAMA divided by TAMA (NAMA/TAMA) represents good quality muscle. Atherosclerotic dyslipidemia was defined as high-density lipoprotein cholesterol (HDL-C) less than 40 mg/dL in men and 50 mg/dL in women, low-density lipoprotein cholesterol (LDL-C) greater than 160 mg/dL, triglycerides (TG) greater than 150 mg/dL, small dense LDL-C (sdLDL-C) greater than 50.0 mg/dL, or apolipoprotein B/A1 (apoB/A1) greater than 0.08. Results: The adjusted odds ratios (ORs) of dyslipidemia according to the HDL-C and sdLDL definitions were greater in both sexes in the lower quartiles (Q1~3) of NAMA/TAMA compared with Q4. As per other definitions, the ORs were significantly increased in only women for LDL-C and only men for TG and ApoB/A1. In men, all lipid parameters were significantly associated with NAMA/TAMA, while TG and ApoB/A1 did not show significant association in women. Conclusion: Myosteatosis measured in abdominal CT was significantly associated with a higher risk of dyslipidemia. Myosteatosis may be an important risk factor for dyslipidemia and ensuing cardiometabolic diseases.

Myosteatosis predicts bariatric surgery response: A longitudinal study in patients with morbid obesity.

CONTEXT: Data on the preoperative factors for bariatric surgery response in patients with morbid obesity are limited, and there are no studies on the relationship between myosteatosis and surgery response. OBJECT: We investigated the preoperative factors determining bariatric surgery response and the impact of preoperative muscle fat infiltration on bariatric surgery response. METHODS: This retrospective longitudinal cohort study included 125 individuals (37 men, 88 women) with morbid obesity who underwent bariatric surgery. Muscle fat infiltration (skeletal muscle fat index [SMFI]) was evaluated using computed tomography-based psoas muscle mass and density at the 4th lumbar level. A bariatric surgery response was defined as ≥50% excessive weight loss at one year postoperatively. RESULTS: Before bariatric surgery, the patient mean body weight and body mass index (BMI) were 107.0 kg and 39.0 kg/m2, respectively. After one year, the mean body weight was 79.6 kg. The mean excessive weight loss at one year was 75.6% and 102 (81.6%) patients were categorized as responders. There were no statistically significant differences in initial BMI, age, sex, or proportion of diabetes between responders and non-responders. Responders were more likely to have lower SMFI and triglyceride and glycated hemoglobin A1c levels than non-responders at baseline (P<0.05). Multiple logistic regression analysis showed that a lower baseline SMFI was associated with bariatric surgery response (odds ratio=0.31, 95% confidence interval=0.14-0.69, P=0.004). CONCLUSIONS: Preoperative myosteatosis may determine the response to bariatric surgery.

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.

Myosteatosis: an underrecognized risk factor for mortality in non-dialysis chronic kidney disease patients.

BACKGROUND: Low muscle mass quantity and quality (myosteatosis) can be evaluated by computed tomography (CT) by measuring skeletal muscle area and muscular attenuation, respectively, at the third lumbar vertebra. We aimed to define cut-off points of skeletal muscle area and muscular attenuation to predict mortality in non-dialysis chronic kidney disease (CKD) patients. METHODS: We conducted a retrospective study including non-dialysis CKD patients over two years, who underwent an opportunistic computed tomography within a two year period, and for whom creatinine was measured within 90 days of CT. Skeletal muscle area was normalized for stature to calculate the skeletal muscle index. Area under the receiver operating characteristic (AuROC) curve and Youden's index were used, to identify the cut-point, separately according to sex. RESULTS: One hundred sixty-seven patients (50.9% male, mean age of 68.3 ± 16.4 years) were included, most with CKD stages 3 and 4. During a median follow-up of 4.9 (4.2) years, 39 (23.4%) patients died. Muscular attenuation showed a better ability to predict mortality (AuROC curve 0.739 [95% CI 0.623-0.855] in women and 0.744 in men [95% CI 0.618-0.869]) than skeletal muscle index (AuROC curve 0.491 [95% CI 0.332-0.651] in women and 0.711 [95% CI 0.571-0.850] in men). For muscular attenuation, the best cut-off values to predict mortality were 27.56 Hounsfield units in women and 24.58 Hounsfield units in men. For skeletal muscle index, the best cut-off values were 38.47 cm2/m2 in women and 47.81 cm2/m2 in men. In univariable Cox-regression both low muscle mass and myosteatosis were associated with increased mortality. In multivariable Cox-regression models only myosteatosis maintained a significant association with mortality (Hazard Ratio 2.651 (95% CI 1.232-5.703, p = 0.013)). CONCLUSIONS: We found sex-specific cut-off values for muscle parameters using CT analysis in non-dialysis CKD patients that were associated with mortality. In this population, myosteatosis may be more closely associated with mortality than muscle quantity.

The Role of Combined Muscle Ultrasound and Bioimpedentiometry Parameters for Sarcopenia Diagnosis in a Population of Hospitalized Older Adults.

BACKGROUND: For the study of quantitative and qualitative muscle parameters, ultrasound and bioelectric impedance analysis are reliable, non-invasive, and reproducible. The aim of this study was to test the combined role of those techniques for the diagnosis of sarcopenia in a population of hospitalized older males and females. METHODS: A total of 70 subjects were recruited, including 10 healthy adults and 60 hospitalized elderly patients with a good level of independence and cooperation, with and without sarcopenia. The rectus femoris cross-sectional area (CSA), thickness, echogenicity, and compressibility were measured with ultrasound echography. The phase angles (PhAs) and skeletal muscle mass were calculated by bioimpedence analysis. The muscle quality index (MQI) was calculated as the product of CSA and PhA. RESULTS: Muscle compressibility was greater and PhA was lower in sarcopenic when compared with non-sarcopenic subjects. The threshold values for sarcopenia diagnosis in both sexes of CSA, of PhA, and of the MQI were identified. The obtained CSA values showed an AUC of 0.852 for women and 0.867 for men, PhA of 0.792 in women and 0.898 in men, while MQI was 0.900 for women and 0.969 for men. CONCLUSIONS: The newly calculated cut-off values of CSA, PhA, and MQI predicted the presence of sarcopenia with good sensitivity and specificity values. The use of the MQI proved to be more promising than the separate use of CSA and PhA in both male and female subjects.

The relationship between imaging-based body composition abnormalities and long-term mortality in patients with liver cirrhosis.

BACKGROUND: Emerging evidence on cirrhosis suggests a close correlation between abnormality in body composition characteristics and poor prognosis. This study aimed to evaluate the impact of dynamic changes in body composition on the prognostic outcomes in patients with cirrhosis. METHODS: This retrospective analysis included 158 patients diagnosed as cirrhosis from January 2018 to August 2023. Skeletal muscle mass, muscle quality, visceral and subcutaneous adiposity were evaluated using computed tomography (CT) imaging at the third lumbar vertebra level. Competing risk model was performed four different body composition status (i.e., normal, only sarcopenia, only myosteatosis, and combined status) for liver-related mortality. We also explored the relationship between the dynamic change in body composition and long-term prognosis by applying Gray's test. RESULTS: Of the 158 cirrhotic patients (mean [SD] age, 57.1 [12.6] years), sarcopenia was present in 85 (60.1 %) patients, while 22 (13.9 %) patients had sarcopenic obesity and 68 (43.0 %) had myosteatosis. Patients solely diagnosed with sarcopenia exhibited a higher mortality rate compared to those with normal body composition (Gray's test, P=0.006), while patients solely diagnosed with myosteatosis or with a combination of sarcopenia and myosteatosis did not reach statistical significance (Gray's test, P=0.076; P=0.140). Multivariable analysis also revealed that VSR (HR=1.10 [1.01∼1.20]; P=0.028), sarcopenia (HR=2.73 [1.20∼6.22], P=0.017) and myosteatosis (HR=2.39 [1.10∼5.18], P=0.028) were significant independent predictors of liver-related deaths. Otherwise, patients exhibiting aggravating body composition during follow-up period were associated with a significantly higher mortality risk compared to those with normal or remission body composition status (HR=7.63 [1.12∼51.14]; P=0.036). CONCLUSION: Progressive alterations in body composition status appears to be associated with liver-related mortality in individuals with liver cirrhosis. Focusing on the management of skeletal muscle, along with visceral and subcutaneous adiposity, may contribute to improving the prognosis of cirrhotic patients.

Thoracic sarcopenia measured by Hounsfield unit average calculation predicts morbidity and mortality in coronary artery bypass grafting.

OBJECTIVES: The aim of the study was to investigate the potential prognostic role of preoperative measurement of erector spinae myosteatosis with Hounsfield unit average calculation as a marker for sarcopenia and frailty in patients undergoing coronary bypass surgery. METHODS: Preoperative computer tomography-derived measurements of 479 consecutive patients undergoing coronary bypass surgery between January 2017 and December 2019 were retrospectively performed. The erector spinae muscle at the level of the 12th vertebra was manually outlined bilaterally on the axial computer tomography slices and Hounsfield unit average calculation was performed. The lower quartile of muscle density values was defined as myosteatotic and thus sarcopenic. Sarcopenic (n = 121) versus non-sarcopenic patients (n = 358) were compared regarding postoperative morbidity and short- and long-term mortality. Results were adjusted for age, body mass index, atrial fibrillation and hypertension using inverse probability weighting. RESULTS: Sarcopenia was associated with higher 30-day mortality (4.1% vs 0.8%; P = 0.012), mid-term mortality after 1 year (9.3% vs 3.1%; P = 0.047) and 2 years (10.8% vs 4.2%; P = 0.047). Long-term mortality (5 years) was 20.8% for sarcopenic and 13.0% for non-sarcopenic patients but was not found to be significantly different (P = 0.089). Sarcopenia was associated with higher rates of reintubation (7.5% vs 1.1%; P < 0.001), sternal wound infections (7.5% vs 2.8%; P = 0.039) and acute kidney injury requiring haemodialysis (2.5% vs 0.4%; P = 0.021). CONCLUSIONS: In patients undergoing coronary bypass surgery, sarcopenia was associated with increased short-term mortality, mid-term mortality and morbidity. The measurement of erector spinae myosteatosis could be an easy and useful parameter in preoperative risk assessment.

Prognostic impact of myosteatosis on survival with immune checkpoint inhibitors: A systematic review and meta-analysis.

BACKGROUND: Myosteatosis has emerged as a promising prognostic biomarker for survival outcomes in patients with advanced cancer. However, recent research has yielded conflicting results on the association between myosteatosis and survival in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we performed this systematic review and meta-analysis to evaluate the association between myosteatosis and survival outcomes in patients treated with ICIs. METHODS: We conducted a systematic review using Pubmed, Web of Science, and Scopus databases for studies published until June 10, 2024. This protocol was registered in the PROSPERO database (Registration Number: CRD42023466337). We performed the meta-analyses with the generic inverse-variance method with a random effects model. RESULTS: Eleven studies involving 1362 patients were included. The pooled analysis showed that patients with myosteatosis had a significantly higher risk of death compared to patients without myosteatosis (HR: 1.61, 95% CI: 1.23-2.12, p < 0.001). Subgroup analysis revealed this association was stronger in melanoma patients (HR: 2.07, 95% CI: 1.09-3.94, p = 0.030). Furthermore, patients with myosteatosis had an increased risk of progression or death than those without myosteatosis (HR: 1.31, 95% CI: 1.05-1.64, p = 0.020). CONCLUSION: Myosteatosis is associated with a higher risk of death in ICI-treated patients. Further research in larger cohorts is needed to standardize the definition of myosteatosis as well as the true mechanistic association between myosteatosis and survival in patients treated with ICIs.

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.

Impact of CT-relevant skeletal muscle parameters on post-liver transplantation survival in patients with hepatocellular carcinoma.

BACKGROUND: The specific CT-related skeletal muscle parameters predictive of postoperative survival in liver transplant (LT) patients with hepatocellular carcinoma (HCC) remain unclear. There is increasing evidence supporting the role of fatty acids and their lipid intermediates in regulating skeletal muscle mass and function, the relationship between lipoprotein subfractions and body composition remains unclear. METHODS: Adult patients with HCC who underwent LT between January 2015 and September 2022 were retrospectively analyzed. CT parameters, including skeletal muscle index (SMI), psoas muscle index (PMI), skeletal muscle density (SMD), visceral and subcutaneous adipose tissue (VAT and SAT), and the VAT/SAT ratio at the L3 level, and lipid profiles, were assessed prior to LT. RESULTS: Of the 284 LT patients with HCC, 224 underwent CT (L3 level) within 3 months of LT, and 82 (37%) were diagnosed with myosteatosis. Patients with myosteatosis exhibited significantly lower 1- and 3-year survival rates (p = 0.002, p = 0.01), a trend persisting even beyond the Milan criteria (p = 0.004, p = 0.04). After adjusting for covariates, SMD demonstrated a significant negative correlation with post-transplant survival (HR: 0.90, [95% Confidence Interval(CI): 0.83-0.98], C-statistic: 0.78, p = 0.009). Pearson's correlation analysis revealed a positive correlation between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(ApoA1) levels and SMD. Multivariate stepwise regression analysis demonstrated that every 10 Hounsfield unit decrease in SMD was associated with a 0.16 mmol/L decrease in HDL-C and a 0.18 g/L decrease in ApoA1. CONCLUSION: Routine abdominal CT scans for assessing skeletal muscle density before LT were significantly associated with post-transplant mortality. Furthermore, abnormal HDL-C and ApoA1 levels before LT were associated with myosteatosis.

Skeletal muscle quality predicts overall survival in advanced liver hepatocellular carcinoma treated with SIRT and sorafenib: A subanalysis of the SORAMIC trial.

BACKGROUND AND AIMS: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC. METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis. RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04. CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS. IMPACT AND IMPLICATIONS: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.

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.

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.

Cardiometabolic Characteristics of Obesity Phenotypes in Persons With HIV.

Background: In the general population, it is established that adipose tissue depots pose various risks for cardiometabolic diseases. The interaction among obesity, HIV, and antiretroviral treatment promotes even greater risk for persons with HIV (PWH). As obesity is a heterogeneous condition, determining the specific obesity phenotypes present and their characteristics is critical to personalize care in PWH. Methods: Visceral, sarcopenic, myosteatotic, hepatosteatotic, and metabolically healthy obesity phenotypes were determined by pre-established cut points after segmentation of computed tomography scans at the L3 vertebra. Multivariable linear regression modeling included anthropometrics, clinical biomarkers, and inflammatory factors while controlling for age, sex, race, and body mass index (BMI). Results: Of 187 PWH, 86% were male, and the mean ± SD age and BMI were 51.2 ± 12.3 years and 32.6 ± 6.3 kg/m2. Overall, 59% had visceral obesity, 11% sarcopenic obesity, 25% myosteatotic obesity, 9% hepatosteatotic obesity, and 32% metabolically healthy obesity. The strongest predictor of visceral obesity was an elevated triglyceride:high-density lipoprotein (HDL) ratio. Increased subcutaneous fat, waist circumference, and HDL cholesterol were predictors of sarcopenic obesity. Diabetes status and elevated interleukin 6, waist circumference, and HDL cholesterol predicted myosteatotic obesity. An increased CD4+ count and a decreased visceral:subcutaneous adipose tissue ratio predicted hepatosteatotic obesity, though accounting for only 28% of its variability. Participants with metabolically healthy obesity were on average 10 years younger, had higher HDL, lower triglyceride:HDL ratio, and reduced CD4+ counts. Conclusions: These findings show that discrete obesity phenotypes are highly prevalent in PWH and convey specific risk factors that measuring BMI alone does not capture. These clinically relevant findings can be used in risk stratification and optimization of personalized treatment regimens. This study is registered at ClinicalTrials.gov (NCT04451980).

Association between myosteatosis and impaired glucose metabolism: A deep learning whole-body magnetic resonance imaging population phenotyping approach.

BACKGROUND: There is increasing evidence that myosteatosis, which is currently not assessed in clinical routine, plays an important role in risk estimation in individuals with impaired glucose metabolism, as it is associated with the progression of insulin resistance. With advances in artificial intelligence, automated and accurate algorithms have become feasible to fill this gap. METHODS: In this retrospective study, we developed and tested a fully automated deep learning model using data from two prospective cohort studies (German National Cohort [NAKO] and Cooperative Health Research in the Region of Augsburg [KORA]) to quantify myosteatosis on whole-body T1-weighted Dixon magnetic resonance imaging as (1) intramuscular adipose tissue (IMAT; the current standard) and (2) quantitative skeletal muscle (SM) fat fraction (SMFF). Subsequently, we investigated the two measures for their discrimination of and association with impaired glucose metabolism beyond baseline demographics (age, sex and body mass index [BMI]) and cardiometabolic risk factors (lipid panel, systolic blood pressure, smoking status and alcohol consumption) in asymptomatic individuals from the KORA study. Impaired glucose metabolism was defined as impaired fasting glucose or impaired glucose tolerance (140-200 mg/dL) or prevalent diabetes mellitus. RESULTS: Model performance was high, with Dice coefficients of ≥0.81 for IMAT and ≥0.91 for SM in the internal (NAKO) and external (KORA) testing sets. In the target population (380 KORA participants: mean age of 53.6 ± 9.2 years, BMI of 28.2 ± 4.9 kg/m2, 57.4% male), individuals with impaired glucose metabolism (n = 146; 38.4%) were older and more likely men and showed a higher cardiometabolic risk profile, higher IMAT (4.5 ± 2.2% vs. 3.9 ± 1.7%) and higher SMFF (22.0 ± 4.7% vs. 18.9 ± 3.9%) compared to normoglycaemic controls (all P ≤ 0.005). SMFF showed better discrimination for impaired glucose metabolism than IMAT (area under the receiver operating characteristic curve [AUC] 0.693 vs. 0.582, 95% confidence interval [CI] [0.06-0.16]; P < 0.001) but was not significantly different from BMI (AUC 0.733 vs. 0.693, 95% CI [-0.09 to 0.01]; P = 0.15). In univariable logistic regression, IMAT (odds ratio [OR] = 1.18, 95% CI [1.06-1.32]; P = 0.004) and SMFF (OR = 1.19, 95% CI [1.13-1.26]; P < 0.001) were associated with a higher risk of impaired glucose metabolism. This signal remained robust after multivariable adjustment for baseline demographics and cardiometabolic risk factors for SMFF (OR = 1.10, 95% CI [1.01-1.19]; P = 0.028) but not for IMAT (OR = 1.14, 95% CI [0.97-1.33]; P = 0.11). CONCLUSIONS: Quantitative SMFF, but not IMAT, is an independent predictor of impaired glucose metabolism, and discrimination is not significantly different from BMI, making it a promising alternative for the currently established approach. Automated methods such as the proposed model may provide a feasible option for opportunistic screening of myosteatosis and, thus, a low-cost personalized risk assessment solution.

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.

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.