Varying Impact of Lenvatinib or Sorafenib Therapy on Skeletal Muscle Loss in Patients with Hepatocellular Carcinoma.

INTRODUCTION: Lenvatinib and sorafenib are key therapeutic agents for hepatocellular carcinoma (HCC). However, there are no useful biomarkers for selecting molecular-targeted agents (MTAs). Skeletal muscle volume is associated with the clinical outcomes in these patients. We investigated the effects of lenvatinib and sorafenib on the skeletal muscles of patients with HCC. METHODS: We evaluated the impact of skeletal muscle changes over a 3-month period for each MTA (n = 117; lenvatinib/sorafenib, 45/72). The skeletal muscle mass index (SMI) was measured at the third lumbar vertebra. Furthermore, we evaluated the direct effect of each MTA on primary human skeletal muscle cells by estimating muscle protein synthesis using western blot analysis. RESULTS: The median change in SMI was -0.7% (p = 0.959) and -5.9% (p < 0.001) for the lenvatinib and sorafenib groups, respectively. Sorafenib had a greater effect on skeletal muscle loss than lenvatinib (p < 0.001). Additionally, SMI significantly decreased in the sorafenib group regardless of initial skeletal muscle volume (p < 0.001), whereas no significant differences were observed in the lenvatinib group. Sorafenib therapy (odds ratio [OR], 2.98; p = 0.023) and non-muscle depletion (OR, 3.31; p = 0.009) were associated with a decreased SMI. In vitro analysis showed that sorafenib negatively affected muscle synthesis compared to lenvatinib. CONCLUSIONS: Sorafenib may have a more negative effect on skeletal muscle than lenvatinib.

Assessment of skeletal muscle dynamics and milk production across a 300-day lactation in multiparous dairy cattle.

The objective of this study was to evaluate changes in longissimus dorsi muscle depth (LDD) across lactation (0 to 300 DIM) and identify the impact of low versus high muscle reserves immediately after parturition on body weight and body reserve changes as well as production variables across a 300-d lactation. Forty multiparous cows were classified as high muscle (HM; LDD > 5.0 cm; n = 18) or low muscle (LM; LDD ≤ 5.0 cm; n = 22) based on LDD measurements collected within 24 h of parturition. Body weights (BW) and ultrasound scans to assess LDD and back fat depth (BFD) were collected monthly from parturition until 300 DIM. Ultrasound scans captured and measured using available software. Blood samples were taken at 7, 150 and 300 DIM, and plasma was analyzed for markers of metabolic status by measuring insulin, nonesterified fatty acids (NEFA), creatinine, and 3-methylhistidine (3-MH). Milk yield was recorded daily and milk components were analyzed monthly. Data analysis was performed and the statistical models included the fixed effect of muscle group, time, their interaction, and the random effect of cow nested within muscle group with repeated measures using a first-order autoregressive covariance structure. Muscle group was not related with BW or BFD for any of the time points measured. Cows lost BW from 0 to 60 DIM and gained weight from 60 to 300 DIM. Similarly, BFD decreased between 0 to 90 DIM and increased BFD after 90 DIM until 300 DIM. A muscle group by time interaction was observed for LDD. The HM cows had more muscle at 0 DIM, indicative of treatment assignment (1.34 cm more), and 300 DIM (0.78 cm more) and tended to have more muscle at 60 DIM (0.66 cm more) compared with LM. After 240 DIM, both muscle groups began net accretion of muscle reserves until 300 DIM. No differences were observed for blood metabolites measured based on muscle group. However, there were significant time effects for creatinine, 3-MH, and NEFA concentrations, which reflected the observed changes in BFD and LDD measured in ultrasound scans. For statistical analysis of daily milk production, observations were grouped into 3 stages of lactation, early (0-60 DIM), mid (60-240 DIM), and late lactation (240-300 DIM). There was a muscle group by stage of lactation interaction, where in early and mid-lactation, HM cows produced, on average, 1.9 kg more milk/d; however, in late lactation, LM cows produced 1.8 kg more milk/d. Our results indicate that muscle reserves are depleted in early lactation, and accreted in late lactation, whereas BW and BFD started to increase by 90 DIM. Data also supports that cows with more extensive muscle depletion in early lactation had greater milk production, however, substantial muscle accretion in late lactation may result in reduced milk production.

Prognostic value of muscle depletion assessed by computed tomography for surgical outcomes of cancer patients undergoing total esophagectomy and gastrectomy.

INTRODUCTION: Considering the high morbimortality rate in oncologic surgeries of the gastrointestinal tract, especially in patients with malnutrition, the use of predictive tools is necessary, since preoperative strategies could improve postoperative outcomes. OBJECTIVES: To evaluate body composition by computed tomography and its association with morbimortality post esophagectomy and total gastrectomy. METHODS: Prospective cohort study (n = 80). Sociodemographic, diagnostic, treatment and postoperative data were collected. Anthropometric and biochemical (hemoglobin, transferrin, and albumin) data were evaluated. The muscle mass was calculated through two methods, the muscle mass index (MMI) and the psoas total area (PTA). For postoperative complications classification, the Clavien-Dindo scale was used. RESULTS: The prevalence of muscle depletion found was 33.8% by MMI and 61% by PTA (poor agreement, kappa = 0.25). Complication rates were 18.5% in gastrectomies and 50% in esophagectomies. No statistically significant difference was found between the presence of muscle depletion and complications. However, when stratified by surgery, a borderline association was found between the MMI and post esophagectomies complications (P = .05). CONCLUSION: Despite the high prevalence of muscle loss, it was not possible to correlate it with surgical outcomes for gastrectomies, but for esophagectomies, there may be relevance due to borderline association, although patients received nutritional therapy.

Sex differences in postsurgical skeletal muscle depletion after donation of living-donor liver transplantation, although minimal, should not be ignored.

BACKGROUND: Donor safety is the top priority in living-donor liver transplantation. Splenic hypertrophy and platelet count decrease after donor surgery are reported to correlate with the extent of hepatectomy, but other aftereffects of donor surgeries are unclear. In this study, we evaluated the surgical effects of donor hepatectomy on skeletal muscle depletion and their potential sex differences. METHODS: Among a total of 450 consecutive donor hepatectomies performed from April 2001 through March 2017, 277 donors who completed both preoperative and postoperative (60-119 days postsurgery) evaluation by computed tomography were the subjects of this study. Donors aged 45 years or older were considered elderly donors. Postoperative skeletal muscle depletion was assessed on the basis of the cross-sectional area of the psoas major muscle. Postoperative changes in the spleen volume and platelet count ratios were also analysed to evaluate the effects of major hepatectomy. RESULTS: The decrease in the postoperative skeletal muscle mass in the overall donor population was slight (99.4 ± 6.3%). Of the 277 donors, 59 (21.3%) exhibited skeletal muscle depletion (i.e., < 95% of the preoperative value). Multivariate analysis revealed that elderly donor (OR:2.30, 95% C.I.: 1.27-4.24) and female donor (OR: 1.94, 95% C.I. 1.04-3.59) were independent risk factors for postoperative skeletal muscle depletion. Stratification of the subjects into four groups by age and sex revealed that the elderly female donor group had significantly less skeletal muscle mass postoperatively compared with the preoperative values (95.6 ± 6.8%), while the other three groups showed no significant decrease. Due to their smaller physical characteristics, right liver donation was significantly more prevalent in the female groups than in the male groups (112/144, 77.8% vs 65/133, 48.9%; p < 0.001). The estimated liver resection rate correlated significantly with the splenic hypertrophy ratio (r = 0.528, p < 0.001) and the extent of the platelet count decrease (r = - 0.314, p < 0.001), but donor age and sex did not affect these parameters. CONCLUSION: Elderly female donors have a higher risk of postoperative skeletal muscle depletion. Additionally, female donors are more likely to donate a right liver graft, whose potential subclinical risks include postoperative splenic enlargement and a platelet count decrease.

Effect of loop diuretics on skeletal muscle depletion in patients with liver cirrhosis.

AIM: Sarcopenia, the loss of skeletal muscle mass, impairs prognosis of patients with liver cirrhosis. The aim of this study was to investigate the effect of loop diuretics, which are frequently used to treat hepatic edema/ascites, on skeletal muscle depletion and the prognosis in patients with liver cirrhosis. METHODS: This retrospective study evaluated 226 patients with liver cirrhosis. The skeletal muscle cross-sectional area at the level of the third lumbar vertebra was measured using computed tomography. The relative change in skeletal muscle area per year (ΔSMA) was calculated, and the association between ΔSMA and therapeutic dosage of loop diuretics was examined. RESULTS: The therapeutic dosage of loop diuretics was inversely correlated with ΔSMA by simple (r = -0.27, P < 0.0001) and multiple regression analyses (t = -3.07, P = 0.002). During a median follow-up period of 49 months, 82 patients died. Overall survival rates were lower in patients treated with loop diuretics at >20 mg than in those who received ≤20 mg (median, 66 vs. 97 months; P = 0.002). Multivariate analysis revealed that loop diuretics of >20 mg (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.03-3.24; P = 0.039) and ΔSMA of ≤-3.1% (HR, 3.87; 95% CI, 2.32-6.60; P < 0.0001) were independently associated with mortality. CONCLUSIONS: A higher dose of loop diuretic use was associated with more rapid skeletal muscle depletion and poor survival in patients with liver cirrhosis, independent of the severity of liver disease.

A new diagnostic index for sarcopenia and its association with short-term postoperative complications in patients undergoing surgery for colorectal cancer.

AIM: Sarcopenia is a robust prognostic indicator of outcomes after surgery for colorectal cancer (CRC). However, there are no serum markers routinely available for estimating skeletal muscle mass (SMM). The present study aimed to describe a new sarcopenia index (SI), serum creatinine (Scr) × cystatin C-based glomerular filtration rate, and investigate its association with short-term complications after curative resection of CRC. METHOD: Consecutive patients who underwent curative resection of CRC from December 2011 to January 2017 were retrospectively identified. Skeletal muscle cross-sectional area was analysed on L3 computed tomographic images. Receiver operating characteristic curve analysis showed that the cutoff points of SI for sarcopenia were below 56.1 in men and below 43.7 in women. Patients were classified into low and high SI groups in accordance with these cutoff values. The association between SI and body composition and the impact of preoperative SI on postoperative outcomes were analysed. RESULTS: Among 417 patients, SI showed a stronger correlation with skeletal muscle area (SMA) (r = 0.537, P < 0.001) than with the Scr/cystatin C ratio (r = 0.469, P < 0.001) and Scr (r = 0.447, P < 0.001). The low SI group had a lower SMA, lower preoperative haemoglobin, a higher prevalence of sarcopenia and experienced more postoperative complications compared with the high SI group (all P < 0.001). Multivariate logistic regression analysis showed that the independent risk factors for overall complications were low preoperative haemoglobin, low SI, sarcopenia and American Society of Anesthesiologists grade ≥ 3. CONCLUSION: This new SI is a simple and useful surrogate marker for estimating SMM, and is associated with outcomes after CRC surgery.

Association between Skeletal Muscle Depletion and Sorafenib Treatment in Male Patients with Hepatocellular Carcinoma: A Retrospective Cohort Study.

The effect of skeletal muscle mass (SMM) on the outcomes of sorafenib treatment for hepatocellular carcinoma (HCC) has not been established. We measured the SMM in HCC patients treated with sorafenib, evaluated the patients' survival, and evaluated the association between skeletal muscle depletion and sorafenib treatment. Of the 97 HCC patients treated with sorafenib at our institution in the period from July 2009 to February 2015, our study included 69 patients (51 males, 18 females) who had received sorafenib for ≥ 8 weeks and whose follow-up data were available. SMM was calculated from computed tomography images at the mid-L3 level (cm2) and normalized to height (m2) to yield the L3 skeletal muscle index (L3-SMI, cm2/m2). The median L3-SMI value was higher in the males (43 cm2/m2) compared to the females (36 cm2/m2). In the males only, the multivariate Cox regression identified an L3-SMI <43 cm2/m2 as independently associated with higher mortality compared to an L3-SMI ≥43 cm2/m2 (hazard ratio 2.315, 95% confidence interval: 1.125-4.765, p=0.023). Skeletal muscle depletion is a factor predicting poor prognosis for male patients with advanced HCC treated with sorafenib.

A combination of resistance and endurance training increases leg muscle strength in COPD: An evidence-based recommendation based on systematic review with meta-analyses.

Resistance training (RT) is thought to be effective in preventing muscle depletion, whereas endurance training (ET) is known to improve exercise capacity and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD). Our objectives were to assess the efficiency of combining RT with ET compared with ET alone. We identified eligible studies through a systematic multi-database search. One author checked titles and abstracts for relevance using broad inclusion criteria, whilst two independent authors checked the full-text copies for eligibility. Two authors independently extracted data, and we assessed the risk of bias and quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation guidelines. We included 11 randomized controlled trials (331 participants) and 2 previous systematic reviews. The meta-analyses showed equal improvements in HRQoL, walking distance and exercise capacity. However, we found moderate quality evidence of a significant increase in leg muscle strength favouring a combination of RT and ET (standardized mean difference of 0.69 (95% confidence interval: 0.39-0.98). In conclusion, we found significantly increased leg muscle strength favouring a combination of RT with ET compared with ET alone. Therefore, we recommend that RT should be incorporated in rehabilitation of COPD together with ET.

The Impact of Imaging-Diagnosed Sarcopenia on Long-term Prognosis After Curative Resection for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: Recent research suggests that sarcopenia potentially influences the long-term postoperative prognosis of malignant tumors. Thus, the primary objective of this study was to investigate the impact of imaging-diagnosed sarcopenia on the long-term prognosis of hepatocellular carcinoma (HCC) patients after curative resection. METHODS: In our approach, all studies incorporated in this study employed Cox proportional hazards models with multivariable adjusted hazard ratios. The meta-analysis was performed using R statistical software. The primary outcomes were quantified using hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: This study analyzed 30 studies, involving 7352 HCC patients after curative resection (2695 in the sarcopenia group and 4657 in the non-sarcopenia group). The meta-analysis of 28 studies indicated that patients in the sarcopenia group demonstrated notably inferior overall survival (OS) compared with the non-sarcopenia group (HR=2.20; 95% CI, 1.88-2.58; p < 0.01). Similarly, sarcopenia exhibits a significant association with poor recurrence-free survival (RFS) and disease-free survival (DFS) based on 16 and 6 studies (HR=1.50; 95% CI, 1.39-1.63; p < 0.01 and HR=1.96; 95% CI, 1.83-2.10; p < 0.01, respectively). CONCLUSION: In conclusion, imaging-diagnosed sarcopenia adversely affects the long-term prognosis, including OS, RFS, and DFS, in HCC patients after curative resection. The findings hold considerable importance in guiding comprehensive healthcare procedures for HCC patients after surgery.

Blood biomarkers for sarcopenia: A systematic review and meta-analysis of diagnostic test accuracy studies.

Biomarkers are emerging as a potential tool for screening or diagnosing sarcopenia. We aimed to summarize the current evidence on the diagnostic test accuracy of biomarkers for sarcopenia. We comprehensively searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials up to January 2023 and only included diagnostic test accuracy studies. We identified 32 studies with 23,840 participants (women, 58.26%) that assessed a total of 30 biomarkers. The serum creatinine to cystatin C ratio (Cr/CysC) demonstrated a pooled sensitivity ranging from 51% (95% confidence interval [CI] 44-59%) to 86% (95% CI 70-95%) and a pooled specificity ranged from 55% (95% CI 38-70%) to 76% (95% CI 63-86%) for diagnosing sarcopenia defined by five different diagnostic criteria (11 studies, 7240 participants). The aspartate aminotransferase to alanine aminotransferase ratio demonstrated a pooled sensitivity of 62% (95% CI 56-67%) and a pooled specificity of 66% (95% CI 60-72%) (3 studies, 11,146 participants). The other 28 blood biomarkers exhibited low-to-moderate diagnostic accuracy for sarcopenia regardless of the reference standards. In conclusion, none of these biomarkers are optimal for screening or diagnosing sarcopenia. Well-designed studies are needed to explore and validate novel biomarkers for sarcopenia.

Impact of Skeletal Muscle Depletion on Patients with Myelodysplastic Syndrome Treated with Azacitidine.

BACKGROUND: Azacitidine (AZA) is the standard treatment for patients with high-risk myelodysplastic syndromes (MDS). The impact of skeletal muscle depletion (SMD), which is associated with outcomes of hematological malignancies, on the clinical course of MDS patients treated with AZA was investigated. METHODS: This retrospective, observational study included 50 MDS patients treated with AZA. Muscle mass was evaluated using the skeletal muscle index (SMI), which is the area of muscle mass at the third lumbar vertebra on CT images divided by the square of the height. RESULTS: Of the enrolled patients, 39 were males, and their median age was 69.5 years. Twenty-seven (20 male and 7 female) patients showed SMD. The median survival was 13.4 months in the SMD group and 15.2 months in the non-SMD group, with no significant difference and no significant association between the response rate or severe non-hematological toxicities and the presence of SMD. By contrast, grade 3-4 anemia and thrombocytopenia were significantly more frequent in the SMD group than in the non-SMD group. SMD was associated with severe anemia and thrombocytopenia in MDS patients treated with AZA. CONCLUSION: Reduced skeletal muscle mass may predict severe hematological toxicity in MDS patients treated with AZA.

Validated Tools for Screening Sarcopenia: A Scoping Review.

OBJECTIVE: Choosing the optimal sarcopenia screening tool for a specific clinical scenario is challenging. We aimed to summarize all validated sarcopenia screening tools with diagnostic accuracy tested in one or more study populations. DESIGN: Scoping review. SETTING AND PARTICIPANTS: Hospitals, nursing homes, communities, or health checkups. METHODS: We systematically searched 3 databases in April 2022: MEDLINE, EMBASE, and CENTRAL. Two review authors independently performed the study selection and data extraction. The included tools' contents, characteristics, and number of citations were summarized and visualized. RESULTS: We summarized 102 diagnostic accuracy studies involving 53 screening tools, classified into 7 groups: questionnaires (n = 13); serum biomarkers (n = 10); formulas, algorithms, and models (n = 9); physical ability tests (n = 9); integration tools (n = 7); anthropometric indices (n = 3); and ultrasound or bioimpedance analysis (n = 2). The most commonly used questionnaire was SARC-F (770 citations), followed by SARC-CalF (254 citations) and MSRA-7 (61 citations). Handgrip strength and Ishii score were the most widely used physical performance tests (331 citations) and formulas (294 citations), respectively. Sarcopenia index (based on serum cystatin C and creatinine) and calf circumference were the most commonly used serum biomarkers (123 citations) and anthropometric indexes (127 citations), respectively. Ultrasound was the most commonly used imaging tool for screening sarcopenia (57 citations). The included tools varied significantly in content. Various tools assessed some or all components of sarcopenia with different methods, and others assessed different domains, such as age, body mass index, falls, diet, and even mental health. We also summarized the screening tools that were validated in different clinical settings (hospitals, communities, nursing homes, and health checkups). CONCLUSIONS AND IMPLICATIONS: More than 50 validated tools are currently available for screening sarcopenia in different clinical settings. The results of this review may help clinicians and researchers in selecting optimal tools for sarcopenia in different clinical scenarios and in developing future tools.

Impact of sarcopenia and sarcopenic obesity on survival in patients with primary liver cancer: a systematic review and meta-analysis.

Background: Sarcopenia and sarcopenic obesity are associated with an increased possibility of adverse clinical outcomes; however, the effects of sarcopenia and sarcopenic obesity on patients with primary liver cancer remain controversial. Therefore, the present study aimed to determine the impact of sarcopenia and sarcopenic obesity on survival in patients with primary liver cancer. Methods: We searched studies published in English in PubMed, Embase, Web of Science, and Cochrane Library databases up to 13 November 2022. Cohort studies that reported the association among sarcopenia, sarcopenic obesity, and patient survival were included. Results: A total of 64 cohort studies with data on 11,970 patients with primary liver cancer were included in the meta-analysis. Sarcopenia was associated with poor overall survival in patients with primary liver cancer [adjusted hazard ratio (HR) 2.11, 95% confidence interval (CI): 1.89-2.36, P < 0.0001], with similar findings for sarcopenic obesity (adjusted HR: 2.87, 95% CI: 2.23-3.70, P < 0.0001). Sarcopenia was also associated with poor overall survival across the subgroups analyzed by ethnicity, type of liver cancer, treatment modalities, method used to define sarcopenia, and etiology of liver cancer. We also found a negative correlation among sarcopenia, sarcopenic obesity, and recurrence-free/disease-free survival (adjusted HR: 1.73, 95% CI: 1.50-1.99, P < 0.001; adjusted HR: 2.28, 95% CI: 1.54-3.35, P < 0.001, respectively). Conclusion: Sarcopenia and sarcopenic obesity were significantly associated with poor overall survival and recurrence-free/disease-free survival in patients with primary liver cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=378433, PROSPERO [42022378433].

Diagnostic test accuracy of ultrasound for sarcopenia diagnosis: A systematic review and meta-analysis.

Muscle ultrasound is an emerging tool for diagnosing sarcopenia. This review aims to summarize the current knowledge on the diagnostic test accuracy of ultrasound for the diagnosis of sarcopenia. We collected data from Ovid Medline, Embase and the Cochrane Central Register of Controlled Trials. Diagnostic test accuracy studies using muscle ultrasound to detect sarcopenia were included. Bivariate random-effects models based on sensitivity and specificity pairs were used to calculate the pooled estimates of sensitivity, specificity and the area under the curves (AUCs) of summary receiver operating characteristic (SROC), if possible. We screened 7332 publications and included 17 studies with 2143 participants (mean age range: 52.6-82.8 years). All included studies had a high risk of bias. The study populations, reference standards and ultrasound measurement methods varied across the studies. Lower extremity muscles were commonly studied, whereas muscle thickness (MT) was the most widely measured parameter, followed by the cross-sectional area (CSA). The MTs of the gastrocnemius, rectus femoris, tibialis anterior, soleus, rectus abdominis and geniohyoid muscles showed a moderate diagnostic accuracy for sarcopenia (SROC-AUC 0.83, 8 studies; SROC-AUC 0.78, 5 studies; AUC 0.82, 1 study; AUC 0.76-0.78, 2 studies; AUC 0.76, 1 study; and AUC 0.79, 1 study, respectively), whereas the MTs of vastus intermedius, quadriceps femoris and transversus abdominis muscles showed a low diagnostic accuracy (AUC 0.67-0.71, 3 studies; SROC-AUC 0.64, 4 studies; and AUC 0.68, 1 study, respectively). The CSA of rectus femoris, biceps brachii muscles and gastrocnemius fascicle length also showed a moderate diagnostic accuracy (AUC 0.70-0.90, 3 studies; 0.81, 1 study; and 0.78-0.80, 1 study, respectively), whereas the echo intensity (EI) of rectus femoris, vastus intermedius, quadriceps femoris and biceps brachii muscles showed a low diagnostic accuracy (AUC 0.52-0.67, 2 studies; 0.48-0.50, 1 study; 0.43-0.49, 1 study; and 0.69, 1 study, respectively). The combination of CSA and EI of biceps brachii or rectus femoris muscles was better than either CSA or EI alone for diagnosing sarcopenia. Muscle ultrasound shows a low-to-moderate diagnostic test accuracy for sarcopenia diagnosis depending on different ultrasound parameters, measured muscles, reference standards and study populations. The combination of muscle quality indicators (e.g., EI) and muscle quantity indicators (e.g., MT) might provide better diagnostic test accuracy.

Correlation of skeletal muscle depletion with acute toxicities for cervical cancer patients undergoing concurrent chemoradiation: A prospective study.

Context: Pelvic radiation with concurrent chemotherapy is associated with toxicities that worsen the cachectic state of the patient. Aims: : The aim of this study is to quantify skeletal muscle changes on computed tomography (CT) images helps in assessing the same which could be correlated with the toxicities. Settings and Design: The study design was s prospective study. Subjects and Methods: Forty-one patients were treated with chemoradiation followed by brachytherapy (BT) for cervical cancer. Preexternal beam and preBT CT scans were used to assess skeletal muscle index (SMI). The changes in the SMI were correlated with enteritis, dyselectrolytemia, and hematological toxicities. Statistical Analysis Used: Paired t-test was used to compare pre- and post-treatment SMI. Chi-square test would be used to study the association between toxicity and SMI change. Results: The mean SMI was 57.41 cm2/m2 (42.5-73) in the preexternal beam radiotherapy (EBRT) scans and 54.5 cm2/m2 (40.9-71.07) in the post-EBRT scans. Twenty-two patients (53.7%), 14 patients (34.1%), and five patients (12.2%) belonged to <5%, 5%-10%, and >10% loss in SMI groups, respectively. Grade III enteritis was seen in 31.7% of the patients, hyponatremia in 26.8% of the patients in the 4th week, and leukopenia and neutropenia were seen in 26.8% of cases in the 5th week. Enteritis correlated significantly with the change in SMI (P = 0.047). Conclusion: Patients with cancer cachexia are at higher risk for radiation enteritis during chemoradiation for cervical cancer.

Skeletal muscle depletion predicts death in severe community-acquired pneumonia patients entering ICU.

BACKGROUND: Sarcopenia, or skeletal muscle depletion, was common in the elderly and often led to a poor prognosis of diseases. The area of the psoas muscle in abdominal computed tomography (CT) is the most common used for diagnosing sarcopenia. However, patients with pneumonia routinely only undergo chest CT. OBJECTIVES: This study aimed to determine whether paraspinal muscle area (PMA) obtained by chest CT can predict death for community-acquired pneumonia (SCAP) patients entering intensive care unit (ICU). METHODS: This study enrolled 208 SCAP patients admitted to ICU after undergoing chest CT. PMA, paraspinal muscle radiodensity (PMD), and lean paraspinal muscle area (LPMA) were calculated on chest CT images. The main outcome was mortality during hospitalization. Logistic regression, receiver operating characteristic (ROC) curve, and Kaplan-Meier curves were used to evaluate forecasting effectiveness. RESULTS: The primary outcome occurred in 76 (36.53%) patients. In multivariate logistic regression, PMA, lactic dehydrogenase (LDH), invasive mechanical ventilation (IMV), red blood cell (RBC) and age≥ 65 years were independent risk factors predicting death during hospitalization (adjusted Odds Ratio [OR]: 0.886, 1.002, 3.178, 0.612 and 2.003, respectively). The area under curve (AUC) of PMA to predict death was 0.720 (P< 0.001). During hospitalization, the median survival time of high-PMA (51.00 days) and low-PMA groups (20.00 days) was statistically significant (P< 0.001). CONCLUSION: Lower PMA was associated with an increased risk of death for SCAP patients admitted to the ICU. In other words, PMA may help early identify adverse prognosis of SCAP patients admitted to ICU.

Chest computed tomography-derived muscle mass and quality indicators, in-hospital outcomes, and costs in older inpatients.

BACKGROUND: Muscle mass and muscle quality assessed by computed tomography (CT) have been associated with poor prognosis in oncology and surgery patients, but the relevant evidence was limited in older patients. We hypothesized that muscle mass and muscle quality indicators derived from opportunistic chest CT images at the 12th thorax vertebra level (T12) could predict in-hospital death, length of hospital stay (hospital LOS), and hospital costs among older patients in acute care wards. METHODS: We conducted a prospective cohort study. Older patients admitted to the acute geriatric wards of a teaching hospital were continuously recruited. Chest CT images were analysed using SliceOmatic software. The skeletal muscle area, skeletal muscle radiodensity, and intermuscular adipose tissue (IMAT) at the T12 level were measured. Skeletal muscle index (SMI) was calculated using skeletal muscle area divided by body height squared. RESULTS: We included 1135 older patients with a median age of 80 years (interquartile range, 73 to 85 years), 498 (44%) were women, 148 (13%) patients died during hospitalization. The SMI and SMD were negatively correlated to age (ρ = -0.11, P < 0.001, ρ = -0.30, P < 0.001, respectively), whereas the IMAT was positively correlated to age (ρ = 0.27, P < 0.001). Compared with survivors, dead patients had significantly lower SMI in men (P < 0.001) but not in women (P = 0.760). After adjusting for sex and other potential confounders, the SMI [increased per 1 cm2 /m2 , odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93 to 0.99] and SMD (increased per 1 Hounsfield unit, OR 0.93, 95% CI 0.90 to 0.96) were negatively and independently associated with in-hospital death, whereas the IMAT (increased per 1 cm2 , OR 1.09, 95% CI 1.05 to 1.14) was independently and positively associated with in-hospital death. None of the SMI, SMD, or IMAT was significantly related to long hospital LOS or increased hospital costs. CONCLUSIONS: Chest CT-derived muscle mass indicator (T12 SMI) and muscle quality indicators (T12 SMD and T12 IMAT) may serve as prognostic factors for predicting in-hospital death among older inpatients. Opportunistic chest CT images might be an overlooked resource for measuring muscle mass and muscle quality and for predicting short-term prognosis in older inpatients.

Prevalence and role of low skeletal muscle mass (LSMM) in hepatocellular carcinoma. A systematic review and meta-analysis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor disease in the world. The impact of sarcopenia on survival outcomes in patients with HCC has been studied, but the extent of the impact remains unclear. This systematic review and meta-analysis aimed to analyze the prevalence of low skeletal muscle mass (LSMM) as a surrogate parameter for sarcopenia in patients with HCC and its influence on survival parameters after various treatments in a large study population. METHODS: Different databases such as MEDLINE, Cochrane database, and SCOPUS were screened for studies on sarcopenia, respectively LSMM and survival in HCC up to March 2021. Twenty-seven studies met the inclusion criteria. The methodological quality was analyzed via QUADAS-2. We investigated the prevalence of LSMM and its impact on overall and recurrence/disease-free survival. RESULTS: The prevalence of LSMM, defined by different cut-off values, was 38.5%. In patients with LSMM, overall survival (OS) was strongly impaired in univariable and multivariable analyses: HR = 1.84, 95% CI = 1.64-2.07, p < 0.00001 and HR = 1.89, 95% CI = 1.61-2.23, p < 0.00001, respectively. Subanalyses on patients treated with kinase inhibitors such as Sorafenib or Lenvatinib (4 studies) or hepatectomy (6 studies) showed lower overall survival in multivariable regression with HR = 2.24, 95% = 1.60-3.14, p < 0.00001 and HR = 2.17, 95% CI = 1.48-3.19, p < 0.00001, respectively. Patients with LSMM post-resection also showed lower recurrence-free survival with HR = 1.79, 95% CI = 1.28-2.50, p < 0.00001 in multivariable analysis. CONCLUSION: LSMM is very frequent in patients with HCC. Due to its impact on survival, there is a need for adequate treatment and prevention, which proves to be challenging due to its multifactorial nature. For future investigation, one should focus on prospective study protocols as well as standardized assessment methods and cut-off values.

The psoas muscle depletion index is related to the degree of cirrhosis and skeletal muscle loss in patients with end-stage liver disease.

Objective: To establish a new psoas muscle depletion index (PDI) from healthy young donors and to explore the correlation between the PDI and the severity of cirrhosis in patients with endstage liver disease (ESLD). Methods: Clinical data of 461 healthy donors were collected during the period 2014-2019, and clinical data of 331 patients with ESLD were collected during the period 2014-2018. The patients were divided into four groups by PDI severity: PDI ≥ 0.90, PDI = 0.75-0.90, PDI = 0.50-0.75 and PDI ≤ 0.50 (Gsev). Differences in international normalised ratio (INR), total bilirubin and serum creatinine levels, and Child-Pugh (CP) and model for end-stage liver disease (MELD) scores were compared. The sarcopenia incidence according to the PDI and the psoas muscle index (PMI) in different weight groups were also compared. Results: Gsev had the highest CP (10.2 ± 2.1) and MELD (20.1 ± 7.4) scores and total bilirubin (166.3 ± 192.0 umol/L) and blood creatinine (92.9 ± 90.2 umol/L) levels and the lowest haemoglobin (93.8 ± 21.7 g/L) and blood albumin (30.9 ± 5.8 g/L) levels. Gsev showed significant changes in INR (1.74 ± 0.65) and blood sodium (135.3 ± 5.65 mmol/L). If PDI <0.75 was used as the diagnostic criterion for sarcopenia, the incidence was 53.3% in patients weighing >90 kg and 53.6% in those weighing <60 kg. This differed from the PMI, with an incidence of 3.3% in patients weighing >90 kg. Conclusions: The PDI had no significant correlation with body height, body weight or body mass index (BMI) in healthy individuals and patients with ESLD. The PDI was significantly correlated with the severity of cirrhosis and loss of skeletal muscle.

Serum creatinine and cystatin C-based diagnostic indices for sarcopenia in advanced non-small cell lung cancer.

BACKGROUND: Sarcopenia is an important prognostic factor of lung cancer. The serum creatinine/cystatin C ratio (CCR) and the sarcopenia index (SI, serum creatinine × cystatin C-based glomerular filtration rate) are novel screening tools for sarcopenia; however, the diagnostic accuracy of the CCR and SI for detecting sarcopenia remains unknown. We aimed to explore and validate the diagnostic values of the CCR and SI for determining sarcopenia in non-small cell lung cancer (NSCLC) and to explore their prognostic values for overall survival. METHODS: We conducted a prospective cohort study of adult patients with stage IIIB or IV NSCLC. Levels of serum creatinine and cystatin C were measured to calculate the CCR and SI. Sarcopenia was defined separately using CCR, SI, and the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Participants were randomly sampled into derivation and validation sets (6:4 ratio). The cutoff values for diagnosing sarcopenia were determined based on the derivation set. Diagnostic accuracy was analysed in the validation set through receiver operating characteristic (ROC) curves. Cox regression models and survival curves were applied to evaluate the impact of different sarcopenia definitions on survival. RESULTS: We included 579 participants (women, 35.4%; mean age, 58.4 ± 8.9 years); AWGS-defined sarcopenia was found in 19.5% of men and 10.7% of women. Both CCR and SI positively correlated with computed tomography-derived and bioimpedance-derived muscle mass and handgrip strength. The optimal cutoff values for CCR and SI were 0.623 and 54.335 in men and 0.600 and 51.742 in women, with areas under the ROC curves of 0.837 [95% confidence interval (CI): 0.770-0.904] and 0.833 (95% CI: 0.765-0.901) in men (P = 0.25), and 0.808 (95% CI: 0.682-0.935) and 0.796 (95% CI: 0.668-0.924) in women (P = 0.11), respectively. The CCR achieved sensitivities and specificities of 73.0% and 93.7% in men and 85.7% and 65.7% in women, respectively; the SI achieved sensitivities and specificities of 75.7% and 86.5% in men and 92.9% and 62.9% in women, respectively. CCR-defined, SI-defined, and AWGS-defined sarcopenia were independently associated with a high mortality risk [hazard ratio (HR) = 1.75, 95% CI: 1.25-2.44; HR = 1.55, 95% CI: 1.11-2.17; and HR = 1.76, 95% CI: 1.22-2.53, respectively]. CONCLUSIONS: CCR and SI have satisfactory and comparable diagnostic accuracy and prognostic values for sarcopenia in patients with advanced NSCLC. Both may serve as surrogate biomarkers for evaluating sarcopenia in these patients. However, further external validations are required.