Skeletal Muscle Area Research Articles

Visceral adiposity in cirrhosis: Association with disease severity and impact of liver transplantation.

Changes in adipose tissue distribution in liver cirrhosis are poorly characterized and may affect clinical outcomes. Adult liver transplant (LT) January 2008-August 2017 recipients with abdominal MRI within 6 months pre-LT were retrospectively assessed. Visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle area (cm2) were determined at L3. Visceral-to-subcutaneous adipose tissue ratio (VSR) was used to define relative adipose distribution, stratified by sex. Correlation was tested with Pearson. Body composition measures were compared by Child-Turcotte-Pugh (CTP) class, before and after LT, and evaluated as predictors of clinical outcomes. A total of 318 patients were studied. Mean age was 56 years, 33.64% were female, and 47.80% had CTP C cirrhosis. CTP C was associated with a 0.42-point increase in VSR compared with CTP A (95% CI = 0.13-0.71, p < 0.01), adjusting for age, sex, diabetes, and HCC. Among the 79 (24.84%) patients with repeat MRI 1-2 years after LT, VSR significantly improved from before LT (1.31 vs. 0.95, p < 0.01). In adjusted analysis, CTP C was associated with a 0.86-point decrease in post-LT VSR compared with pre-LT VSR (95% CI = -1.27 to -0.44, p < 0.01). Body mass index poorly correlated with VSR before and after LT. Elevated pre-LT VSR trended toward an association with a 7.17-point decrease in pre-LT glomerular filtration rate (95% CI = -14.35 to -0.02, p = 0.05), adjusting for CTP C, age, sex, diabetes, hypertension, pre-LT sarcopenia, and hepatocellular carcinoma. Elevated pre-LT VSR did not affect 3-year post-LT mortality (log-rank p = 0.24). Poorly represented by body mass index, visceral adiposity is increased in cirrhosis and is associated with CTP class. However, this adipose redistribution may be modifiable by LT.

Racial differences in muscle measures and survival among older adults with GI malignancies.

12044 Background: Sarcopenia (low muscle mass) and myosteatosis (fat infiltration of muscle) can be assessed from routinely obtained Computed tomography (CT) images and are independent predictors of chemotherapy toxicities and survival among patients with gastrointestinal (GI) malignancies. However, most studies to date have consisted of predominantly white populations. Therefore, the role of sarcopenia and myosteatosis among racial minority populations is unknown. Our objective was to examine racial differences in muscle measures and their association with survival among older adults with GI malignancies. Methods: This is a prospective cohort study of older adults with GI cancers from the University of Alabama at Birmingham. Single slices of axial CT images from L3 segments were analyzed using Slice-O-Matic software. Skeletal muscle area (cm2) was divided by height to obtain the skeletal muscle index (SMI, cm2/m2). Skeletal muscle radiodensity (SMD) in Hounsfield units (HU) was used to approximate muscle composition. Sarcopenia (low SMI) and myosteatosis (low SMD) were defined based on standard cut-offs developed in a cohort of GI malignancies (Martin et al., JCO 2013). We compared differences in muscle measures between non-Hispanic (NH) White and NH Black participants. We utilized Cox models, separated by race, to examine the impact of muscle measures on survival. We adjusted for age, sex, education, cancer type, cancer stage, lines of therapy, and comorbidities. Results: Six hundred sixty patients were included, 76% NH White and 24% NH Black. The median age was 69.4 years, 35% had colorectal cancer, and 42% had stage IV disease. NH Black patients had higher SMD (41.7 vs. 38.3 HU; p &lt; 0.001) and lower rates of myosteatosis (40% vs. 27%; p = 0.04) but similar SMI (42.3 vs. 41.1 cm2/m2) and rates of sarcopenia (58% vs. 55%). In stratified Cox models, each 5 HU unit increase in SMD was associated with reduced risk of all-cause mortality of NH black patients (HR 0.88; 95% CI 0.80-0.98 p = 0.02) and not in NH White patients (HR 0.95; 95% CI-0.88-1.01; p = 0.14). Meanwhile, each 5-unit increase in SMI was associated with improved survival in NH White patients (HR 0.91; CI 0.85-0.98; p = 0.03) but not in NH Black patients (HR 0.89 CI0.78-1.03 p = 0.13). When using existing cut points for sarcopenia and myosteatosis, NH White patients with sarcopenia had worse survival (HR 1.42; CI 1.04-1.92; p = 0.02), but sarcopenia among NH black patients was not associated with worse survival (HR 1.16 95% CI 0.62-2.16 p = 0.64). Myosteatosis was not associated with worse survival in either NH white (HR 95%CI 0.95-1.68 p = 0.10) or NH black patients (HR 1.61 95%CI 0.88-2.95 p = 0.12). Conclusions: Muscle measures may differ by race and have different associations with survival by racial group. Therefore, it is essential to develop cut points for muscle measures incorporating race.

Morphomic phenotyping of oncologic populations.

e13572 Background: We have previously identified body and organ composition measures in pre-treatment CT scans that predict post-treatment mortality or disease recurrence in melanoma as well as esophageal, pancreatic, hepatocellular and lung cancers within single institution cohorts in the US. Similar trends can be identified in Asian cohorts although the absolute range of these body composition measures differ substantially from those in the US. We have also identified body and organ composition measures that predict drug tissue distribution and optimal dosing. The qualitative and relative nature of body and organ composition measures to date have limited their utility for precision treatment of oncologic populations. We have therefore refined the precision, granularity and reliability of these measures (morphomics) in oncologic and reference populations. Methods: Analytic Morphomics, our group’s imaging analysis platform, extracts granular, anatomically-indexed body and organ composition measures from medical imaging. This platform has been updated to use artificial intelligence and nested, supervised machine learning algorithms. Our digital morphomics “assays” are 100% reproducible due to our extensive use of deterministic software algorithms and scalable due to our use of efficient ML algorithms and software code. Our ML models have been trained using state-of-the art techniques in 2D and 3D convolutional neural networks (CNNs) for image segmentation, utilizing repeated randomization cross-validation, hold-out sets, and ensemble modeling methods, with large, broadly representable training image sets, and verified by extensive user testing on clinical scans from nearly 200,000 live subjects. Results: We analyzed curated cohorts reflecting the general United States and Taiwanese population (Ns=5,286; 1,459). In addition, we analyzed oncological cohorts reflecting patients with colon (N=95), ovarian (216), pancreatic (156), and esophageal cancers (Ns=333, 344). Validated morphomic measures include bone mineral density (BMD), visceral fat area (VAT, subcutaneous fat area (SAT), skeletal muscle area (SMA), skeletal muscle density (MD) at multiple vertebral levels. When referenced against measures taken from general non-oncologic (trauma) populations to adjust for non-specific changes due to age and gender, these referenced morphomic measures gain predictive power for mortality and cancer recurrence. Conclusions: The unprecedented level of granularity and precision of these raw and referenced morphomic measures shows clinical utility for improved patient selection, drug dosing as well as evaluation of treatment response and toxicity.

P-222 Prognostic value of skeletal muscle area at diagnosis in patients with metastatic colorectal cancer: A single institution experience

P-222 Prognostic value of skeletal muscle area at diagnosis in patients with metastatic colorectal cancer: A single institution experience

Association between thoracic and third lumbar CT-derived muscle mass and density in Caucasian patients without chronic disease: a proof-of-concept study

BackgroundComputed tomography (CT) is increasingly used in the clinical workup, and existing scan contains unused body composition data, potentially useful in a clinical setting. However, there is no healthy reference for contrast-enhanced thoracic CT-derived muscle measures. Therefore, we aimed at investigating whether there is a correlation between each of the thoracic and third lumbar vertebra level (L3) skeletal muscle area (SMA), skeletal muscle index (SMI), and skeletal muscle density (SMD) at contrast-enhanced CT in patients without chronic disease.MethodsA proof-of-concept retrospective observational study was based on Caucasian patients without chronic disease, who received CT for trauma between 2012 and 2014. Muscle measures were assessed using a semiautomated threshold-based software by two raters independently. Pearson’s correlation between each thoracic level and third lumbar and intraclass correlation between two raters and test–retest with SMA as proxy parameters were used.ResultsTwenty-one patients (11 males, 10 females; median age 29 years) were included. The second thoracic vertebra (T2) had the highest median of cumulated SMA (males 314.7 cm2, females 118.5 cm2) and SMI (97.8 cm2/m2 and 70.4 cm2/m2, respectively). The strongest SMA correlation was observed between T5 and L3 (r = 0.970), the SMI between T11 and L3 (r = 0.938), and the SMD between the T10 and L3 (r = 0.890).ConclusionsThis study suggests that any of the thoracic levels can be valid to assess skeletal muscle mass. However, the T5 may be most favourable for measuring SMA, the T11 for SMI, and T10 for SMD when using contrast-enhanced thoracic CT.Relevance statementIn COPD patients, a CT-derived thoracic muscle mass assessment may help identify who would benefit from focused pulmonary rehabilitation: thoracic contrast-enhanced CT conducted as part of the standard clinical workup can be used for this evaluation.Key points• Any thoracic level can be used to assess thoracic muscle mass.• Thoracic level 5 is strongly associated with the 3rd lumbar muscle area.• A strong correlation between the thoracic level 11 and the 3rd lumbar muscle index.• Thoracic level 10 is strongly associated with the 3rd lumbar muscle density.Graphical

Low-quality muscle mass rather than normal-quality muscle mass determines fibrosis progression in biopsy-proven NAFLD.

Sarcopaenia is associated with advanced nonalcoholic fatty liver disease (NAFLD). However, the impact of the muscle mass categorised by muscle quality on fibrosis progression remains unclear. A total of 292 patients with biopsy-proven NAFLD who underwent serial vibration-controlled transient elastography assessments at least 1 year from baseline were selected. The skeletal muscle area (SMA) was determined on abdominal computed tomography (CT) at the third lumbar vertebra level and categorised to normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA) and intermuscular adipose tissue (IMAT) using a muscle quality map. These SMAs were normalised by the height squared to obtain the skeletal muscle index (SMI). At baseline, as the histological fibrosis stage increased, SMINAMA decreased and SMILAMA increased (p for trend = 0.014 and p for trend <0.001, respectively), which was not significant after adjustment for age, sex and obesity. During a median follow-up of 41 months, fibrosis progression was detected in 48 out of 292 patients, and higher SMILAMA quartiles independently increased the risk of fibrosis progression in a dose-dependent manner (hazard ratio [HR] per quartile: 1.41; 95% confidence interval [CI], 1.04-1.91). The highest quartile of SMILAMA increased the risk of fibrosis progression by 3.25 times compared to the lowest quartile of SMILAMA (95% CI, 1.18-8.90). SMINAMA quartiles were not associated with the risk of fibrosis progression. Increased low-quality muscle mass, but not decreased normal-quality muscle mass, as assessed by a muscle quality map in CT, predicts fibrosis progression in patients with NAFLD.

Association of chronic statin use, myopenia, myosteatosis and major morbidity in surgical patients with upper gastrointestinal cancer

Derangements of body composition affect surgical outcomes. Chronic statin use may induce muscle wasting and impair muscle tissue quality. Aim of this study was to evaluate the association of chronic statin use, skeletal muscle area (SMA), myosteatosis and major postoperative morbidity. Between 2011 and 2021, patients undergoing pancreatoduodenectomy or total gastrectomy for cancer, and using statins since at least 1 year, were retrospective studied. SMA and myosteatosis were measured at CT scan. The cut-off for SMA and myosteatosis were determined using ROC curve and considering severe complications as the binary outcome. The presence of myopenia was defined when SMA was lower that the cut-off. A multivariable logistic regression was applied to assess the association between several factors and severe complications. After a matching procedure (1:1) for key baseline risk factors (ASA; age; Charlson comorbidity index; tumor site; intraoperative blood loss), a final sample of 104 patients, of which 52 treated and 52 not treated with statins, was obtained. The median age was 75 years, with an ASA score ≥ 3 in 63% of the cases. SMA (OR 5.119, 95% CI 1.053–24.865) and myosteatosis (OR 4.234, 95% CI 1.511–11.866) below the cut-off values were significantly associated with major morbidity. Statin use was predictive of major complication only in patients with preoperative myopenia (OR 5.449, 95% CI 1.054–28.158). Myopenia and myosteatosis were independently associated with an increased risk of severe complications. Statin use was associated with a higher risk of having major morbidity only in the subgroup of patients with myopenia.

Sarcobesity, but not visceral fat, is an independent risk factor for complications after radical resection of colorectal cancer.

The influence of body composition on the outcome of colorectal cancer surgery is controversial. The aim of this study was to evaluate the effects of visceral obesity and sarcobesity on the incidence of total and surgical complications after radical resection of colorectal cancer. We collected a total of 426 patients who underwent elective radical resection of colorectal cancer at Beijing Friendship Hospital, Capital Medical University from January 2017 to May 2018. According to the inclusion and exclusion criteria, 387 patients were finally included. A CT scan at the level of the L3-L4 intervertebral disk was selected to measure the values of visceral fat area and skeletal muscle area. Multivariate analysis was used to explore the independent risk/protective factors affecting postoperative complications. 128 (33.1%) patients developed complications, and 44 (11.4%) patients developed major complications. Among them, 111 patients developed surgical complications and 21 developed medical complications. Visceral fat area (Z = -3.271, p = 0.001), total fat area (Z = -2.613, p = 0.009), visceral fat area to subcutaneous fat area ratio (V/S, Z = -2.633, p = 0.008), and sarcobesity index (Z = -2.282, p = 0.023) were significantly associated with total complications. Visceral fat area (Z = -2.119, p = 0.034) and V/S (Z = -2.010, p = 0.044) were significantly associated with total surgical complications. Sarcobesity index, smoking, stoma, blood loss, surgery time, and American Society of Anesthesiology (ASA) score were selected as risk factors for total postoperative complications according to LASSO regression. Multivariate logistic regression analysis suggested that sarcobesity index was an independent risk factor for postoperative total complications and surgical complications. Subgroup analysis suggested that albumin level was an independent protective factor for postoperative total complications in male patients. Smoking, operative time, and sarcobesity index were independent risk factors, and cholesterol was an independent protective factor for total postoperative complications in female patients. Increased sarcobesity index is an independent risk factor for postoperative complications in patients with colorectal cancer, while visceral fat area is not. For female patients, smoking, operation time, and obesity index are independent risk factors for postoperative complications, while cholesterol is an independent protective factor. For male patients, serum albumin is an independent protective factor for postoperative complications.

The effects of muscle mass and quality on mortality of patients with acute kidney injury requiring continuous renal replacement therapy

This study examined the effects of muscle mass on mortality in patients with acute kidney injury requiring continuous renal replacement therapy. It was conducted in eight medical centers between 2006 and 2021. The data of 2200 patients over the age of 18 years with acute kidney injury who required continuous renal replacement therapy were retrospectively collected. Skeletal muscle areas, categorized into normal and low attenuation muscle areas, were obtained from computed tomography images at the level of the third lumbar vertebra. Cox proportional hazards models were used to investigate the association between mortality within 1, 3, and 30 days and skeletal muscle index. Sixty percent of patients were male, and the 30-day mortality rate was 52%. Increased skeletal muscle areas/body mass index was associated with decreased mortality risk. We also identified a 26% decreased risk of low attenuation muscle area/body mass index on mortality. We established that muscle mass had protective effects on the mortality of patients with acute kidney injury requiring continuous renal replacement therapy. This study showed that muscle mass is a significant determinant of mortality, even if the density is low.

Body composition and endometrial cancer outcomes.

Obesity is a known risk factor for developing endometrial cancer. However, the association of obesity with endometrial cancer (EC) outcomes has not been clearly established. This study examined how outcomes in women with early stage EC vary with body composition measured via computed tomography (CT). In this retrospective study, patients diagnosed with EC international Federation of Gynecology and Obstetrics stages I-III and available CT scans were included. Automatica software was used to assess the areas of visceral adipose tissue, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) and skeletal muscle area. Of 293 patient charts assessed, 199 met eligibility criteria. Median body mass index (BMI) was 32.8 kg/m2 (interquartile range [IQ] = 26.8-38.9); 61.8% had histologic subtype endometrioid carcinoma. Adjusted for age, international Federation of Gynecology and Obstetrics stage, and histologic subtype, a BMI of at least 30 vs less than 30 kg/m2 was associated with lower endometrial cancer-specific survival (ECSS) (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.27 to 4.25) and overall survival (OS) (HR = 2.7, 95% CI = 1.35 to 5.39). Higher IMAT 75th vs 25th percentile and SAT of at least 225.6 vs less than 225.6 cm2 were associated with lower ECSS (HR = 1.53, 95% CI = 1.1 to 2.13, and HR = 2.57, 95% CI = 1.13 to 5.88) and OS (HR = 1.50, 95% CI = 1.11 to 2.02, and HR = 2.46, 95% CI = 1.2 to 5.01), respectively. The association of visceral adipose tissue (75th vs 25th percentile) with ECSS and OS was not statistically significant (HR = 1.42, 95% CI = 0.91 to 2.22, and HR = 1.24, 95% CI = 0.81 to 1.89). Higher BMI, IMAT, and SAT were associated with higher mortality from EC and lower OS. A better understanding of the mechanisms underlying these relationships could inform strategies to improve patient outcomes.

Sarcopenia provides extra value outside the PULP score for predicting mortality in older patients with perforated peptic ulcers

BackgroundPerforated peptic ulcer (PPU) remains challenging surgically due to its high mortality, especially in older individuals. Computed tomography (CT)-measured skeletal muscle mass is a effective predictor of the surgical outcomes in older patients with abdominal emergencies. The purpose of this study is to assess whether a low CT-measured skeletal muscle mass can provide extra value in predicting PPU mortality.MethodsThis retrospective study enrolled older (aged ≥ 65 years) patients who underwent PPU surgery. Cross-sectional skeletal muscle areas and densities were measured by CT at L3 and patient-height adjusted to obtain the L3 skeletal muscle gauge (SMG). Thirty-day mortality was determined with univariate, multivariate and Kaplan–Meier analysis.ResultsFrom 2011 to 2016, 141 older patients were included; 54.8% had sarcopenia. They were further categorized into the PULP score ≤ 7 (n=64) or PULP score > 7 group (n=82). In the former, there was no significant difference in 30-day mortality between sarcopenic (2.9%) and nonsarcopenic patients (0%; p=1.000). However, in the PULP score > 7 group, sarcopenic patients had a significantly higher 30-day mortality (25.5% vs. 3.2%, p=0.009) and serious complication rate (37.3% vs. 12.9%, p=0.017) than nonsarcopenic patients. Multivariate analysis showed that sarcopenia was an independent risk factor for 30-day mortality in patients in the PULP score > 7 group (OR: 11.05, CI: 1.03-118.7).ConclusionCT scans can diagnose PPU and provide physiological measurements. Sarcopenia, defined as a low CT-measured SMG, provides extra value in predicting mortality in older PPU patients.

Muscle loss during cancer therapy is associated with poor outcomes in advanced ovarian cancer.

Data evaluating change in body composition during treatment of advanced cancer are limited. Here we evaluated computed tomography (CT)-based changes in muscle mass during treatment for advanced ovarian cancer (OC) and association with outcomes. We analyzed the preoperative and posttreatment skeletal muscle index (SMI), skeletal muscle area normalized for height of 109 patients with advanced OC who underwent primary surgery and platinum-based chemotherapy from 2006 to 2016. Based on an SMI less than 39 cm2/m2, 54.1% of patients were never sarcopenic, 24.8% were sarcopenic on both CT scans, and 21.1% were newly sarcopenic upon treatment completion. Patients who lost muscle during treatment had the worst survival of the 3 groups identified: median survival 2.6 years vs 4.6 years if sarcopenic on both CT scans and 4.8 years if never sarcopenic. Loss of muscle portends a poor prognosis among patients with OC. Additional research is needed to better understand and best mitigate these changes.

Decreased Expression of Mitochondrial Calcium Uptake Protein 1 Leads to Skeletal Muscle Dysfunction in Septic Mice

To observe the effect of sepsis on skeletal muscle function and to explore the role of skeletal muscle mitochondrial calcium uptake protein 1 (MICU1). A total of 40 specific-pathogen-free (SPF) healthy male C57BL/6J mice were randomly assigned to 4 groups, a sham operation group (Sham group, n=8), a sepsis modeling 6 h group (cecal ligation and puncture [CLP]-6 h group, n=10), a sepsis modeling 12 h group (CLP-12 h group, n=10), and a sepsis modeling 24 h group (CLP-24 h, n=12). The sepsis model was established by CLP. Mice in the Sham group only underwent laparotomic exploration of the cecum. Another 20 SPF mice were selected. The tibialis anterior muscle on one side was empty-transfected with adeno-associated virus (AAV) as controls (AAV-C), and the tibialis anterior muscle on the other side was transfected with AAV to enhance MICU1 expression (AAV-M). The mice were randomly assigned to two groups, a sham operation group (AAV-C-Sham and AAV-M-Sham, n=8) and a sepsis model 24 h group (AAV-C-CLP and AAV-M-CLP, n=12). The grip strength and compound muscle action potential (CMAP) of the tibialis anterior muscle were measured in each group at the corresponding time points. The levels of inflammatory factors, including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), in the skeletal muscle were measured by ELISA. The morphological changes of skeletal muscle cells were observed through H&E staining. The expression levels of MICU1 and muscle atrophy-related proteins, including muscle RING-finger containing protein 1 (MuRF1) and muscle atrophy Fbox protein (MAFbx), were determined by Western blot. The expression levels of MICU1 mRNA in skeletal muscle were determined by RT-qPCR. Compared with mice in the Sham group, mice in the CLP group showed decreased body weight ( P<0.05); their grip strength decreased with the prolongation of CLP modeling time ( P<0.05); the amplitude of CMAP decreased, showing prolonged duration and latency ( P<0.05); the expression levels of inflammatory factors, including TNF-α and IL-6, in skeletal muscle increased gradually ( P<0.05); the fiber diameter and cross-sectional area of skeletal muscle decreased gradually with the prolongation of modeling time ( P<0.05); the protein expression levels of MuRF1and MAFbx proteins increased gradually ( P<0.05); the expression levels of MICU1 protein and mRNA decreased gradually ( P<0.05). There was no significant difference in all indices between AAV-M-Sham and AAV-C-Sham groups ( P>0.05). Compared with mice in the AAV-C-CLP group, mice in the AAV-M-CLP group showed increased grip strength ( P<0.05); the amplitude of CMAP increased, showing shortened duration and latency ( P <0.05); the fiber diameter and cross-sectional area of skeletal muscle increased ( P<0.05); the expression levels of MuRF1and MAFbx decreased ( P<0.05). Sepsis leads to skeletal muscle dysfunction, which is related to the decrease in mitochondrial MICU1 expression.

Morphology of neuromuscular junction in patients with peripheral artery disease

Peripheral artery disease (PAD) is primarily caused by occlusion of arteries that supply blood to the lower limbs and presents significantly pathological changes of calf muscles, include degenerating and regenerating fibers, reduction of the skeletal muscle area, connective tissue proliferation and fibrosis, fat accumulation, and abnormal mitochondria, all of which are predictors of muscle functional decline. Additionally, skeletal muscles also require the motor nerve innervation for the signal transmission through the neuromuscular junction (NMJ) to induce skeletal muscle contraction. To observe whether the NMJ is changed in the PAD patients, gastrocnemius muscles were collected from 2 health subjects and 6 PAD stage III/IV patients. The motor nerve terminals were labeled with anti-neurofilament 200 and anti-synaptophysin antibodies, the nicotinic acetylcholine receptors (nAChRs) were labeled with α-Bungarotoxin. Labeled NMJs were imaged using a laser scanning confocal microscope with Z-stack. The image was captured in 65 NMJs from health subjects and 140 NMJs from PAD patients, respectively. The total nAChR area and the number of discrete fragments of each nAChR cluster, the area per fragment, the percentage of fragmented nAChR clusters, the nerve innervation and the nerve terminal occupancy were calculated. The results were represented with mean ± standard error (SE). The nAChR area was 354.9 ± 12.7 and 209.4 ± 8.2, the average number of fragment/ nAChR cluster was 2.6 ± 0.2 and 3.1 ± 0.2, 6.2% and 19.3% of the nAChR clusters were fragmented, and the nerve terminal occupancy was 61.5 ± 1.4 % and 52.0 61.5 ± 1.8 in the health subjects and PAD patients, respectively. All nAChR clusters were innervated by the motor nerve terminal in the health subjects, whereas 8.6% of nAChR clusters were denervated in PAD Patients. These data indicate that the total nAChR area per nAChR cluster and the area of each discrete fragment are reduced and fragmented nAChR clusters are increased in PAD patients. Additionally, the denervation of nAChR clusters is increased in PAD patients. These results suggest that the neuromuscular transmission is compromised in PAD patients, which limits patients’ physical activities. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

CT-defined pectoralis muscle mass and muscle density are associated with mortality in acute pulmonary embolism. A multicenter analysis

Computed tomography (CT) defined muscle mass can be used as a surrogate parameter for sarcopenia. The present study used thoracic CT to assess pectoralis muscle area and density as an imaging biomarker for prognosis of 30-day mortality in patients with acute pulmonary embolism (PE) METHODS: The clinical database was retrospectively screened for patients with thoracic CT in 3 centers. Pectoralis musculature was measured on axial slices of the thoracic CT at the level of T4 of contrast enhanced pulmonary angiography CT. Skeletal muscle area (SMA), skeletal muscle index (SMI), muscle density and gauge were calculated. Overall, 981 patients (440 female, 44.9%) with a mean age of 63.5±15.9 years were included into the study and 144 patients (14.6%) died within the 30-days period. Every pectoral muscle value was higher in survivors compared to non-survivors (exemplarily for SMI 9.9±3.5cm2/m2 versus 7.8±2.6cm2/m2, p<0.001). Moreover, 91 patients were defined as hemodynamically instable (9.3%). Comparable, every pectoral muscle parameter was higher in patients with hemodynamically stable course compared to instable course. Different muscle variables are related to 30-day mortality: SMA, OR=0.94 (95%CI= (0.92; 0.96), p<0.001); SMI, OR=0.78 (95%CI= (0.72; 0.84), p<0.001); muscle density, OR=0.96 (95%CI= (0.94; 0.97), p<0.001); muscle gauge OR=0.96 (95%CI= (0.94; 0.99), p<0.001). SMI and muscle density were independently associated with 30-days mortality: SMI, OR=0.81 (95%CI= (0.75; 0.88), p<0.001); muscle density: OR=0.96 (95%CI= (0.95; 0.98), p<0.001). Parameters of the pectoralis musculature are associated with 30-day mortality in patients with acute PE. These findings should lead to an independent validation study and ultimately to the inclusion into clinical routine as a prognostic factor.

Post-transjugular Intrahepatic Portosystemic Shunt Hepatic Encephalopathy: Sarcopenia Adds Insult to Injury.

Hepatic encephalopathy, which is a serious complication, and sarcopenia are undesirable consequences in cirrhosis. Transjugular intrahepatic portosystemic shunt increases the risk of hepatic encephalopathy. We investigated the effect of sarcopenia on the incidence of post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy. Clinical data of patients who underwent transjugular intrahepatic portosystemic shunt were extracted retrospectively. Computed tomography images at L3 level of scans performed prior to transjugular intrahepatic portosystemic shunt were analyzed to assess skeletal muscle index-expressed as skeletal muscle area (cm2)/ height (m2). Of 210 patients who underwent transjugular intrahepatic portosystemic shunt, complete information was available in 79 [male: 68 (86%); age: 50.5 ± 11.2 years; Child-Turcotte-Pugh score: 8.81 ± 1.23; etiology-alcohol: 44 (56%), non-alcoholic steatohepatitis: 16 (20%), others: 19 (24%); transjugular intrahepatic portosystemic shunt indication-ascites: 56 (71%); bleed: 23 (29%); sarcopenics: 42 (53%)]. Post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy developed in 29 (37%) patients. In patients who developed hepatic encephalopathy, both serum ammonia [177.6 ± 82.5 vs. 115.5 ± 40.5 µg/dL, P =.008] and prevalence of sarcopenia [69% vs. 44%; P =.02; odds ratio (95% CI): 2.8 (1.08-7.4), P =.02] were higher, with sarcopenics having 3 times higher risk of hepatic encephalopathy and 8 times higher risk of multiple episode of hepatic encephalopathy [31% vs. 5.4%; odds ratio (95% CI): 8.2 (1.68- 40.5), P =.009]. In multivariate analysis, age [odds ratio (95% CI): 1.05 (1.001-1.11), P =.047], serum albumin [odds ratio (95% CI): 0.162 (0.05-0.56), P =.004], and skeletal muscle index [odds ratio (95% CI): 0.925 (0.89-0.99), P =.017] were independently associated with post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy. Sarcopenia is present in nearly half of the cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt, which increases the risk of a single episode of hepatic encephalopathy by 3-fold and that of multiple episodes of hepatic encephalopathy by 8-fold after transjugular intrahepatic portosystemic shunt procedure. Increased skeletal muscle index is associated with decreased risk of hepatic encephalopathy.

Association of Sarcopenia With Mortality in Patients With Chronic Limb-Threatening Ischemia Undergoing Endovascular Revascularization

IntroductionChronic limb-threatening ischemia (CLTI) is the most severe form of peripheral artery disease and leads high mortality. Sarcopenia, characterized by the loss of muscle mass or poor muscle quality, is associated with adverse clinical outcomes. This study aimed to investigate the association between sarcopenia and the long-term outcomes in patients with CLTI after endovascular revascularization. MethodsWe retrospectively reviewed the medical records of all patients with CLTI who underwent endovascular revascularization between January 2015, and December 2021. The skeletal muscle area was calculated at the third lumbar vertebra from computed tomography images using the manual trace method and normalized to patient height. Sarcopenia was defined as a third lumbar skeletal muscle index of <40.8 cm2/m2 in males and <34.9 cm2/m2 in females. The Kaplan–Meier and Cox proportional hazards regression analyses were used for survival analysis and to evaluate the association between sarcopenia and mortality. ResultsA total of 137 patients (90 men; mean age 71.7 ± 9.6 y) were enrolled for the study, of whom 56 (40.8%) had sarcopenia. The 3-year overall survival rate in patients with CLTI who underwent endovascular revascularization was 71.2%. The sarcopenic group had a significantly worse 3-year overall survival rate than the nonsarcopenic group (55.3% versus 78.6%, P = 0.001). Multivariate Cox proportional hazard regression analyses revealed that sarcopenia (hazard ratio, 2.262; 95% confidence interval, 1.132-4.518; P = 0.021) and dialysis (hazard ratio, 3.021; 95% confidence interval, 1.337-6.823; P = 0.008) were independently associated with increased risk of all-cause mortality, whereas technical success had significantly opposing correlation with mortality. (hazard ratio, 0.400, 95% confidence interval, 0.194-0.826, P = 0.013). ConclusionsSarcopenia can be highly prevalent in patients with CLTI who undergo endovascular revascularization, and is independently associated with long-term mortality. These results may help risk stratification to assist in personalized assessment and clinical decision-making.

Impact of sarcopenia indexes on survival and severe immune acute toxicity in metastatic non-small cell lung cancer patients treated with PD-1 immune checkpoint inhibitors

Sarcopenia has long been associated with higher toxicity induced by anti-cancer treatments and shorter survival in patients with solid tumors. The creatinine-to-cystatin ratio (CC ratio, serum creatinine/cystatin C×100) and the sarcopenia index (SI, serum creatinine×cystatin C (CysC)-based glomerular filtration rate (eGFRCysC)) are have been reported to be correlated with skeletal muscle mass. The aim of this study is to assess primarily whether the CC ratio and the SI could predict mortality in metastatic non-small cell lung cancer (NSCLC) patients treated with PD-1 inhibitors, and secondarily their impact on severe immune-related adverse effects (irAEs). From the prospective CERTIM cohort, we analyzed retrospectively stage IV NSCLC patients, who received PD-1 inhibitors between June 2015 and November 2020 in Cochin Hospital (Paris, France). We assessed sarcopenia measuring skeletal muscle area (SMA) by computed tomography and handgrip strength (HGS) by a hand dynamometer. In total, 200 patients were analyzed. The CC ratio and the IS were significantly correlated with SMA and HGS: rCC/SMA=0.360, rSI/SMA=0.407, rCC/HGS=0.331, rSI/HGS=0.370. In multivariate analysis of overall survival, a lower CC ratio (HR 1.73, P=0.033) and a lower SI (HR 1.89, P=0.019) were independent predictors of poor prognosis. In univariate analysis of severe irAEs, CC ratio (OR 1.01, P=0.628) and SI (OR 0.99, P=0.595) were not associated with a higher risk of severe irAEs. In metastatic NSCLC patients treated with PD-1 inhibitors, a lower CC ratio and a lower SI are independent predictors of mortality. However, they are not associated with severe irAEs.

Surrogates of Muscle Mass on Cardiac MRI Correlate with Exercise Capacity in Patients with Fontan Circulation.

Sarcopenia is an increasingly recognized marker of frailty in cardiac patients. Patients with a history of congenital heart disease and Fontan procedure have a higher risk of developing progressive muscle wasting. Our objective was to determine if we could use routine cardiac MRI (CMR) for the surveillance of muscle wasting. A retrospective study of all Fontan patients (n = 75) was conducted at our institution, with CMR performed from 2010 to 2022 and exercise stress testing performed within 12 months (4.3 ± 4.2 months). The skeletal muscle area (SMA) for the posterior paraspinal and anterior thoracic muscles were traced and indexed for body surface area (BSA). Patients were stratified by percentile into the upper and lower quartiles, and the two groups were compared. Multivariable regression was performed to control for sex and age. There was a significant positive association of both anterior (r = 0.34, p = 0.039) and paraspinal (r = 0.43, p = 0.007) SMA to peak VO2. Similarly, paraspinal but not anterior SMA was negatively associated with the VE/VCO2 (r = -0.45, p = 0.006). The upper quartile group had significantly more males (18/19 vs. 8/20; p = 0.0003) and demonstrated a significantly higher peak VO2 (32.2 ± 8.5 vs. 23.8 ± 4.7, p = 0.009), a higher peak RER (1.2 ± 0.1 vs. 1.1 ± 0.04, p = 0.007), and a significantly lower VE/VCO2 (32.9 ± 3.6 vs. 40.2 ± 6.2, p = 0.006) compared to the lowest quartile. The association of SMA to VO2 peak and VE/VCO2 was redemonstrated after controlling for sex and age. Thoracic skeletal muscle area may be an effective surrogate of muscle mass and is correlated to several measures of cardiorespiratory fitness post-Fontan. CMR would be an effective tool for the surveillance of sarcopenia in post-Fontan patients given its accessibility and routine use in these patients.

Abstract 733: Relationship between pre-diagnostic biomarkers and sarcopenia in colorectal cancer patients

Abstract To gain further understanding of why some colorectal cancer patients develop sarcopenia (loss of skeletal muscle mass) we conducted a study of metabolic and inflammatory markers in pre-diagnostic samples from a well-defined patient cohort. The study population included 755 colorectal cancer patients from population-based prospective cohorts in northern Sweden. Eleven markers were measured in plasma samples collected prior to diagnosis (median 10.1 years), and their relation to sarcopenia at diagnosis (median 7 days before surgery) was assessed. The markers included were adiponectin, total cholesterol, C-peptide, CRP, acyl ghrelin, insulin, leptin, PYY, triglycerides and plasma glucose (both fasting and 2 hours after oral glucose tolerance test). Patients were classified as either sarcopenic or non-sarcopenic based on skeletal muscle index from peri-diagnostic CT scans. Skeletal muscle index was calculated by segmentation of skeletal muscle area at the transaxial level of the third lumbar vertebrae, adjusted to body height. Due to sex differences in muscle mass, all calculations were performed separately in men and women. Multivariable logistic regression was used to estimate associations between pre-diagnostic biomarker concentrations and the risk of sarcopenia. We made adjustment for plausible confounders including age at sampling, smoking, alcohol consumption, energy intake, physical activity, and pre-diagnostic body mass index (BMI). Our preliminary results indicate an association between higher pre-diagnostic cholesterol levels and increased risk of sarcopenia in men (age-adjusted odds ratio 1.30 95% CI 1.06 - 1.59), but not women. This association remained after adjusting for potential confounders. In women, higher levels of adiponectin were associated with an increased sarcopenia risk (age-adjusted OR 1.57 95% CI 1.02 - 2.41). This association remained when adjusting for most potential confounders and was attenuated and no longer statistically significant when BMI was added. Among the other biomarkers no clear associations with sarcopenia risk were observed. In conclusion, we performed a hypothesis-generating study of pre-diagnostic, circulating metabolic and inflammatory markers in relation to radiologically estimated sarcopenia at diagnosis in colorectal cancer patients. Positive associations between cholesterol and sarcopenia in men and between adiponectin and sarcopenia in women were shown. These results need to be validated in future studies. Citation Format: Johannes Färdeman, Björn Gylling, Richard Palmqvist, Jan Axelsson, Katrine Riklund, Sophia Harlid, Bethany Van Guelpen. Relationship between pre-diagnostic biomarkers and sarcopenia in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 733.