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Sarcopenia is the age-related loss of skeletal muscle mass and function. Computed tomography (CT) assessments of sarcopenia utilize measurements of skeletal muscle cross-sectional area (SMA), radiation attenuation (SMRA), and intramuscular adipose tissue (IMAT). Unadjusted SMA is strongly correlated with both height and body mass index (BMI); therefore, SMA must be adjusted for body size to assess sarcopenic low muscle mass fairly in individuals of different heights and BMI. SMA/height (rather than S M A / h e i g h t 2 ) provides optimal height adjustment, and vertebra-specific relative muscle index (RMI) equations optimally adjust for both height and BMI. Since L3 measurement is not available in all CT scans, sarcopenic low muscle mass may be assessed using other levels. Both a mid-vertebral slice and an inferior slice have been used to define 'L3 SMA', but the effect of vertebral slice location on SMA measurements is unexplored. Healthy reference values for skeletal muscle measures at mid- and inferior vertebra slices between T10 and L5, have not yet been reported. We extracted T10 through L5 SMA, SMRA, and IMAT at a mid-vertebral and inferior slice using non-contrast-enhanced CT scans from healthy, adult kidney donor candidates between age 18 and 73. We compared paired differences in SMA between the mid-vertebral slice versus the inferior slice. We calculated the skeletal muscle gauge as S M G HT = S M R A ∗ S M I HT . We used allometric analysis to find the optimal height scaling power for SMA. To enable comparisons with other published reference cohorts, we computed two height-adjusted measures; S M I HT = S M A / h e i g h t (optimal) and S M I H T 2 = S M A / h e i g h t 2 (traditional). Using the young, healthy reference cohort, we utilized multiple linear regression to calculate relative muscle index z-scores ( R M I HT , R M I H T 2 ), which adjust for both height and BMI, at each vertebra level. We assessed Pearson correlations of each muscle area measure versus age, height, weight, and BMI separately by sex and vertebra number. We assessed the differences in means between age 18-40 versus 20-40 as the healthy, young adult reference group. We reported means, standard deviations, and sarcopenia cutpoints (mean-2SD and 5th percentile) by sex and age group for all measures. Sex-specific allometric analysis showed that height to the power of one was the optimal adjustment for SMA in both men and women at all vertebra levels. Differences between mid-vertebra and inferior slice SMA were statistically significant at each vertebra level, except for T10 in men. S M I HT was uncorrelated with height, whereas S M I H T 2 was negatively correlated with height at all vertebra levels. Both S M I HT and S M I H T 2 were positively correlated with BMI at all vertebra levels. R M I HT was uncorrelated with BMI, weight, and height (minimal positive correlation in women at L3 inf , L4 mid , and L5 inf ) whereas R M I H T 2 was uncorrelated with BMI, but negatively correlated with height and weight at all levels. There were no significant differences in SMA between 18-40 versus 20-40 age groups. Healthy reference values and sarcopenic cutpoints are reported stratified by sex, vertebra level, and age group for each measure. Height to the power of one (SMA/height) is the optimal height adjustment factor for SMA at all levels between T10 mid through L5 inf . The use of S M A / h e i g h t 2 should be discontinued as it retains a significant negative correlation with height and is therefore biased towards identifying sarcopenia in taller individuals. Measurement of SMA at a mid-vertebral slice is significantly different from measurement of SMA at an inferior aspect slice. Reference values should be used for the appropriate slice. We report sarcopenic healthy reference values for skeletal muscle measures at the mid-vertebral and inferior aspect slice for T10 through L5 vertebra levels. Relative muscle index (RMI) equations developed here minimize correlation with both height and BMI, producing unbiased assessments of relative muscle mass across the full range of body sizes. We recommend the use of these RMI equations in other cohorts., (© 2024. The Author(s).)

Background & Aims: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction., Methods: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included., Results: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses., Conclusions: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis., Lay Summary: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized., Competing Interests: Conflict of interest MP is funded by BONFOR-Forschungskommission der Medizinischen Fakultät Bonn and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy–EXC2151–390873048 and Ernst-und-Berta Grimmke Foundation. TB: Grants: Abbvie, BMS, Gilead, Humedics, Intercept, Janssen, MSD/Merck, Merz, Novartis, and Sequana Medical; Consulting or advisory board: Abbvie, Alexion, Bayer, BMS, Gilead, Intercept, Janssen, MSD/Merck, Merz, Novartis, Sequana Medical, and Spring Bank; Speaker: Abbvie, Alexion, Bayer, BMS, Eisai, Gilead, Intercept, Ipsen, Janssen, MSD/Merck, Merz, Novartis, Sirtex and Sequana Medical in the past 2 years. JT was supported by grants of Deutsche Forschungsgemeinschaft (SFB TRR57 P18, CRC 1382 A09), the European Union’s Horizon 2020 research and innovation program’s GALAXY study (No. 668031), LIVERHOPE (No. 731875), MICROB-PREDICT (No. 825694), DECISION (No. 84794) and the Cellex Foundation (PREDICT). JT: Grants: Gore; Consultant: Martins Pharma, Ironwood, Gore, Alexion, BMS, Grifols, Sequana Medicals, Versantis; Sponsored lectures (National or International): Gilead Sciences, Gore, Alexion, BMS, Grifols, Sequana Medicals, Norgine, Intercept. FJ: Speaker: Gilead Sciences, MSD and Ascletis. Consulting or advisory board: Gilead Sciences and MSD. MHN: Grants: Gilead, Pfizer, Enanta, Vir, Glycotest, National Cancer Institute, B. K. Kee Foundation, Exact Sciences; Helio Health; Consulting or advisory board: Intercept, Gilead, Exact Sciences, Laboratory of Advanced Medicine, Bayer, Eisai, GSK, Novartis. All other authors report no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Sarcopenia has been shown to be an independent negative predictor in various diseases. The measurement of pre-defined criteria of skeletal muscle in patients with acute disease is usually unavailable. Therefore, we evaluate the psoas muscle area based on computed tomography (CT) imaging as an alternative for sarcopenia in an Asian trauma population., Methods: 939 trauma patients were enrolled and had CT imaging performed primarily for trauma indications. The cross-sectional area of psoas muscle at the base of the fourth lumbar vertebral was measured on these CTs. Psoas muscle index (PMI) was calculated and analyzed to determine sex-specific cut-off values to define the "extremely low psoas muscle index" (ELPMI) group., Results: Psoas muscle index was significantly higher in males (1065.09 ± 230.51 mm 2 /m 2  in males vs 719.57 ± 147.39 mm 2 /m 2  in females, p < 0.001) and decreased gradually with aging (p < 0.001). PMI of the subset of patients aged 18-40 (n = 462) weas analyzed to determine sex-specific cut-off values for ELPMI. PMI cut-off values for ELPMI (2 SD below mean) were 675 mm 2 /m 2 for males and 490 mm 2 /m 2 for females. The entire trauma cohort was further analyzed, and ELPMI was identified as an independent risk factor for a longer length of intensive unit stay (β coefficient = 3.881, p = 0.011)., Conclusion: Data from young trauma adults were used to establish cut-off values for ELPMI, which is a longer ICU stay predictor. These cut-off values for ELPMI may apply to other acute disease entities., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Frailty has been shown to be an independent negative predictor of surgical outcomes in geriatric patients. Traditional measurements of muscle strength and mass are impractical in emergency settings, and computed tomography (CT)-measured skeletal muscle mass has been proposed as an alternative. However, the cutoff values for low muscle mass are still unknown, and their impact on abdominal emergencies in the elderly population is unclear., Methods: A total of 462 young trauma patients aged 18-40 years were analyzed to establish sex-specific reference cutoff values for the CT-measured muscle index (MI) and muscle gauge (MG) values. The impacts of low MI and MG values were investigated in 1192 elderly patients (aged ≥ 65 years) undergoing abdominal surgery., Results: The sex-specific cutoff values for MI and MG were determined by adopting European Working Group on Sarcopenia in Older People 2 guidelines. The correlation between MG and aging was significantly stronger than that between MI and ageing. With regard to the MG, the L4 psoas muscle gauge (L4 PMG) was further investigated in an elderly cohort owing to its high predictive value and ease of use in the clinical setting. A low L4 PMG value was an independent risk factor for overall complications and mortality in elderly patients with abdominal emergencies., Conclusion: The current study was the largest study investigating the correlations between MG values and aging in the Asian population. A low L4 PMG value may help surgeons during preoperative decision making regarding geriatric patients with abdominal emergencies., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Measurements of skeletal muscle cross-sectional area (SMA) at the level of the third lumbar (L3) vertebra derived from clinical computed tomography (CT) scans are commonly used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. As SMA is correlated with height and Body Mass Index (BMI), body size adjustment is necessary to fairly assess sarcopenic low muscle mass in individuals of different height and BMI. The skeletal muscle index, a widely used measure, adjusts for height as [Formula: see text] but uses no BMI adjustment. There is no agreed upon standard for body size adjustment. We extracted L3 SMA using non-contrast-enhanced CT scans from healthy adults, split into 'Under-40' and 'Over-40' cohorts. Sex-specific allometric analysis showed that height to the power of one was the optimal integer coefficient for height adjusted SMA in both males and females. We computed two height-adjusted measures [Formula: see text] and [Formula: see text], comparing their Pearson correlations versus age, height, weight, and BMI separately by sex and cohort. Finally, in the 'Under-40' cohort, we used linear regression to convert each height-adjusted measure into a z-score ([Formula: see text], [Formula: see text]) adjusted for BMI. [Formula: see text] was less correlated with height in both males and females ([Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text]) than [Formula: see text] ([Formula: see text] and [Formula: see text], [Formula: see text]). [Formula: see text] was uncorrelated with BMI and weight, and minimally correlated with height in males and females ([Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text]). The final [Formula: see text] equation was: [Formula: see text], where [Formula: see text], [Formula: see text], [Formula: see text], and sex = 1 if male, 0 if female. We propose [Formula: see text] for optimal height adjustment and the [Formula: see text] score for optimal height and BMI adjustment. By minimizing correlations with height and BMI, the [Formula: see text] score produces unbiased assessments of relative L3 skeletal muscle area across the full range of body sizes.

Background: Frailty and sarcopenia are associated with mortality and poor outcomes among patients with cirrhosis. Frailty is multifactorial but due in part to sarcopenia and cognitive dysfunction. Data are limited regarding the correlation of bedside frailty and cognitive function measures with sarcopenia., Aims: To evaluate the correlations between frailty measures and muscle indices from computed tomography (CT)., Methods: We prospectively enrolled 106 patients with clinically compensated cirrhosis (and no prior hepatic encephalopathy). All patients underwent CT scan and cognitive testing (via inhibitory control test, ICT), and were subject to hand grip, 30-s chair stands, mid-arm muscle area (MAMA), and a four-question algorithm based on the Sickness Impact Profile (SIP) predictive of minimal HE. We evaluated Spearman correlations between all measures as well as the sensitivity and specificity of each measure for falls., Results: In total, 106 (35.3%) patients (55 men) had CT scans to measure skeletal muscle area and quality. Hand grip correlated strongly with skeletal muscle area (correlation coefficient 0.64, p < 0.001) and mildly with ICT performance (0.34, p = 0.002). However, for women, the strongest correlation with hand grip was ICT performance (0.60, p < 0.001). Chair stand performance correlated best with SIP (correlation coefficient - 0.35, p < 0.001). MAMA was not correlated with CT-based muscle indices among women but was for men. Poor chair stand performance (< 10/30-s) had a sensitivity/specificity for falls of 73%/54%; low muscle radiation attenuation (density) was 40%/80% sensitive/specific., Conclusion: Bedside measures of physical function, muscle bulk, and cognitive performance are correlated with CT-based muscle measures. Bedside measures of frailty may provide an advantage over sarcopenia for outcome assessment that should be confirmed prospectively.

Measurements of skeletal muscle cross-sectional area, index, and radiation attenuation utilizing clinical computed tomography (CT) scans are used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. To classify individuals as sarcopenic, sex-specific cutoffs for 'low' values are used. Conventionally, cutoffs for skeletal muscle measurements at the level of the third lumbar (L3) vertebra are used, however L3 is not included in several clinical CT protocols. Non-contrast-enhanced CT scans from healthy kidney donor candidates (age 18-40) at Michigan Medicine were utilized. Skeletal muscle area (SMA), index (SMI), and mean attenuation (SMRA) were measured at each vertebral level between the tenth thoracic (T10) and the fifth lumbar (L5) vertebra. Sex-specific means, standard deviations (s.d.), and sarcopenia cutoffs (mean-2 s.d.) at each vertebral level were computed. Associations between vertebral levels were assessed using Pearson correlations and Tukey's difference test. Classification agreement between different vertebral level cutoffs was assessed using overall accuracy, specificity, and sensitivity. SMA, SMI, and SMRA L3 cutoffs for sarcopenia were 92.2 cm 2 , 34.4 cm 2 /m 2 , and 34.3 HU in females, and 144.3 cm 2 , 45.4 cm 2 /m 2 , and 38.5 HU in males, consistent with previously reported cutoffs. Correlations between all level pairs were statistically significant and high, ranging from 0.65 to 0.95 (SMA), 0.64 to 0.95 (SMI), and 0.63 to 0.95 (SMRA). SMA peaks at L3, supporting its use as the primary site for CT sarcopenia measurements. However, when L3 is not available alternative levels (in order of preference) are L2, L4, L5, L1, T12, T11, and T10. Healthy reference values reported here enable sarcopenia assessment and sex-specific standardization of SMA, SMI, and SMRA in clinical populations, including those whose CT protocols do not include L3.

Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). Recent data suggest that body composition features strongly affect post-LT mortality. We examined the impact of body composition on post-LT mortality in patients with HCC. Data on adult LT recipients who received Model for End-Stage Liver Disease exception for HCC between February 29, 2002, and December 31, 2013, and who had a computed tomography (CT) scan any time 6 months prior to LT were reviewed (n = 118). All available CT scan Digital Imaging and Communication in Medicine files were analyzed using a semiautomated high throughput methodology with algorithms programmed in MATLAB. Analytic morphomics measurements including dorsal muscle group (DMG) area, visceral and subcutaneous fat, and bone mineral density (BMD) were taken at the bottom of the eleventh thoracic vertebral level. Thirty-two (27%) patients died during the median follow-up of 4.4 years. The number of HCC lesions (hazard ratio [HR], 2.81; P < 0.001), BMD (HR = 0.90/Hounsfield units [HU]; P = 0.03), pre-LT locoregional therapy (HR = 0.14; P < 0.001), and donor age (HR = 1.05; P < 0.001) were the independent predictors of post-LT mortality. DMG area did not affect post-LT survival. In conclusion, in addition to number of HCC lesions and pre-LT locoregional therapy, low BMD, a surrogate for bone loss rather than DMG area, was independently associated with post-LT mortality in HCC patients. Bone loss may be an early marker of deconditioning that precedes sarcopenia and may affect transplant outcomes. Liver Transplantation 22 1092-1098 2016 AASLD., (© 2016 American Association for the Study of Liver Diseases.)

Aims: Patients with low muscle mass have increased risk of paclitaxel‐induced peripheral neuropathy, which is dependent on systemic paclitaxel exposure. Dose optimization may be feasible through the secondary use of radiologic data for body composition. The objective of this study was to interrogate morphomic parameters as predictors of paclitaxel pharmacokinetics to identify alternative dosing strategies that may improve treatment outcomes. Methods: This was a secondary analysis of female patients with breast cancer scheduled to receive 80 mg/m2 weekly paclitaxel infusions. Paclitaxel was measured at the end of initial infusion to estimate maximum concentration (Cmax). Computed tomography (CT) scans were used to measure 29 body composition features for inclusion in pharmacokinetic modelling. Monte Carlo simulations were performed to identify infusion durations that limit the probability of exceeding Cmax > 2885 ng/mL, which was selected based on prior work linking this to an unacceptable risk of peripheral neuropathy. Results: Thirty‐nine patients were included in the analysis. The optimal model was a two‐compartment pharmacokinetic model with T11 skeletal muscle area as a covariate of paclitaxel volume of distribution (Vd). Simulations suggest that extending infusion of the standard paclitaxel dose from 1 hour to 2 and 3 hours in patients who have skeletal muscle area 4907–7080 mm2 and <4907 mm2, respectively, would limit risk of Cmax > 2885 ng/mL to <50%, consequently reducing neuropathy, while marginally increasing overall systemic paclitaxel exposure. Conclusion: Extending paclitaxel infusion duration in ~25% of patients who have low skeletal muscle area is predicted to reduce peripheral neuropathy while maintaining systemic exposure, suggesting that personalizing paclitaxel dosing based on body composition may improve treatment outcomes. [ABSTRACT FROM AUTHOR]