Skeletal Muscle Loss Research Articles

Water-soluble dietary fiber alleviates cancer-induced muscle wasting through changes in gut microenvironment in mice.

Cancer cachexia and the associated skeletal muscle wasting are considered poor prognostic factors, although effective treatment has not yet been established. Recent studies have indicated that the pathogenesis of skeletal muscle loss may involve dysbiosis of the gut microbiota and the accompanying chronic inflammation or altered metabolism. In this study, we evaluated the possible effects of modifying the gut microenvironment with partially hydrolyzed guar gum (PHGG), a soluble dietary fiber, on cancer‐related muscle wasting and its mechanism using a colon‐26 murine cachexia model. Compared with a fiber‐free (FF) diet, PHGG contained fiber‐rich (FR) diet–attenuated skeletal muscle loss in cachectic mice by suppressing the elevation of the major muscle‐specific ubiquitin ligases Atrogin‐1 and MuRF1, as well as the autophagy markers LC3 and Bnip3. Although tight‐junction markers were partially reduced in both FR and FF diet–fed cachectic mice, the abundance of Bifidobacterium, Akkermansia, and unclassified S24‐7 family increased by FR diet, contributing to the retention of the colonic mucus layer. The reinforcement of the gut barrier function resulted in the controlled entry of pathogens into the host system and reduced circulating levels of lipopolysaccharide‐binding protein (LBP) and IL‐6, which in turn led to the suppression of proteolysis by downregulating the ubiquitin‐proteasome system and autophagy pathway. These results suggest that dietary fiber may have the potential to alleviate skeletal muscle loss in cancer cachexia, providing new insights for developing effective strategies in the future.

ASO Visual Abstract: Perioperative Ghrelin Administration Attenuates Postoperative Skeletal Muscle Loss in Patients Undergoing Esophagectomy for Esophageal Cancer—Secondary Analysis of a Randomized, Controlled Trial

ASO Visual Abstract: Perioperative Ghrelin Administration Attenuates Postoperative Skeletal Muscle Loss in Patients Undergoing Esophagectomy for Esophageal Cancer—Secondary Analysis of a Randomized, Controlled Trial

Yeast hydrolysate ameliorates dexamethasone-induced muscle atrophy by suppressing MuRF-1 expression in C2C12 cells and C57BL/6 mice

• Effect of YH on C2C12 cell and DEX-induced muscle atrophy mouse were conducted. • YH can promote muscle differentiation in C2C12 cell. • YH prevented muscle atrophy via downregulating MuRF-1, FoxO3a, Atrogin-1 in vitro . • YH prevented skeletal muscle loss and downregulates MuRF-1 in DEX-induced muscle atrophy mouse model. In this study, we evaluated the effects of yeast ( Saccharomyces cerevisiae ) hydrolysate (YH) on muscle differentiation and muscle atrophy inhibitory activity in C2C12 cells and atrophy inhibitory activity in a dexamethasone (DEX)-induced muscle atrophy mouse model. Jenner-Giemsa staining revealed that the length and area of ​​myotubes increased in the YH groups. Moreover, the gene expression of myogenic differentiation 1 and myogenin was significantly increased in the YH groups. In the DEX-induced muscle atrophy C2C12 model, the expression of muscle ring-finger protein-1 (MuRF-1), forkhead box class O3a, and Atrogin-1 were significantly reduced in the YH groups. Furthermore, in the muscle-atrophy mice model, grip strength and lean mass were increased by 1.28-fold and 3.5%, respectively compared to the control in the YH group (300 mg/kg). These results were confirmed by the downregulation of MuRF-1 in muscle. In conclusion, YH promoted muscle cell differentiation and exhibited an inhibitory effect on DEX-induced muscle atrophy.

CT-defined low-skeletal muscle mass as a prognostic marker for survival in prostate cancer: A systematic review and meta-analysis.

Low-skeletal muscle mass (LSMM) is defined as progressive skeletal muscle loss, which can be assessed by imaging modalities. It was shown that this parameter is predictive and prognostic of several clinically relevant factors in several tumor entities. Our aim was to establish the effect of LSMM on overall survival (OS) in prostate cancer patients based on a large patient sample. MEDLINE library, EMBASE and SCOPUS databases were screened for the associations between LSMM and mortality in prostate cancer patients up to April 2021. The primary endpoint of the systematic review was the hazard ratio of LSMM on OS. In total, five studies were suitable for the analysis and included into the present study. The included studies comprised over all 1221 patients. The identified frequency of LSMM was 61.02%. The pooled hazard ratio for the effect of LSMM on OS was 1.4 [95% CI 0.7-2.5] in univariate analysis and was 1.6 [95% CI 1.2-2.1] in multivariate analysis. CT-defined LSMM has a frequency of 61% in patients with PC and shows a positive association with the overall survival with a hazard ratio of 1.4. LSMM assessment should therefore be included into clinical routine as a relevant prognostic biomarker.

Amino acid profile of skeletal muscle loss in type 2 diabetes: Results from a 7-year longitudinal study in asians

AimsLittle is known about pathophysiology of sarcopenia in diabetes. We aimed to study amino acid profile associated with skeletal muscle mass loss longitudinally in Type 2 Diabetes Mellitus (T2DM). MethodsThis is a prospective study of 1140 patients aged 56.6 ± 10.6 years from the SMART2D cohort. Skeletal muscle mass was measured using bio-impedance analysis at baseline and follow-up. Amino acids were measured by mass spectrometry. ResultsOver a period of up to 7.9 years, 43.9% experienced skeletal muscle mass loss. Lower baseline valine, leucine and isoleucine levels were associated with decreased skeletal muscle mass index (SMI) with corresponding coefficient 0.251(95 %CI 0.009 to 0.493), 0.298(95 %CI 0.051 to 0.544)) and 0.366(95 %CI 0.131 to 0.600). Higher baseline valine, leucine, isoleucine, alanine and tryptophan levels were associated with reduced odds of muscle mass loss with corresponding odds ratio (OR)0.797 (95 %CI 0.690 to 0.921), 0.825 (95 %CI 0.713 to 0.955), 0.826 (95 %CI 0.718–0.950), 0.847 (95 %CI 0.739–0.969) and 0.835 (95 %CI 0.720–0.979). ConclusionThe branched-chain amino acids valine, leucine and isoleucine were positively associated with change in SMI and reduced odds of muscle mass loss longitudinally. Further studies should be conducted to elucidate the pathophysiological mechanisms underlying the relationship between these amino acids and muscle mass loss in T2DM.

Perioperative Ghrelin Administration Attenuates Postoperative Skeletal Muscle Loss in Patients Undergoing Esophagectomy for Esophageal Cancer: Secondary Analysis of a Randomized Controlled Trial.

Ghrelin has been reported to reduce postoperative weight loss by improving appetite and food intake in patients undergoing upper gastrointestinal surgery. We aimed to investigate whether growth hormone induction, another essential effect of ghrelin, may attenuate skeletal muscle loss in patients during postoperative starvation. Esophageal cancer patients were randomized to receive a continuous intravenous infusion of high-dose ghrelin (HD; 0.5 µg/kg/h), low-dose ghrelin (LD; 0.25 µg/kg/h), or placebo for 7 days after surgery. During this period, oral feeding was not introduced but the patients received the same parenteral and enteral nutrition. We investigated the effects of ghrelin on body weight, skeletal muscle mass, nutritional status, and hormone levels. Overall, 73 patients were enrolled in this study. The rate of weight loss on postoperative day (POD) 7 relative to that before surgery was significantly lower in the HD group than in the placebo group (HD vs. placebo: -0.61% vs. 1.8%, p=0.030). The rate of muscle loss in the erector spinae muscle on POD 7 in the HD and LD groups was significantly lower than that in the placebo group (HD vs. placebo: 2.8% vs. 8.5%, p<0.001; LD vs. placebo: 4.9% vs. 8.5%, p=0.028). The levels of growth hormone on PODs 1, 3, and 7, and insulin-like growth factor 1 on PODs 3, 7, and 14 were significantly higher in patients who received ghrelin. Continuous ghrelin administration could attenuate skeletal muscle loss in esophageal cancer patients during postoperative starvation.

Features of trunk muscle wasting during acute care and physical function recovery with aortic disease.

BackgroundLow skeletal muscle area or density, such as myosteatosis, identified on computed tomography (CT) is associated with poor prognosis in patients with cardiovascular diseases. However, there is a lack of evidence regarding the clinical process of skeletal muscle decline as a short‐term change during acute care settings. This study focused on the use of routine CT imaging for aortic disease management and investigated the changes in skeletal muscle before and after acute care.MethodsThis prospective study included 123 patients who underwent abdominal CT before and after acute care. The all‐abdominal and each abdominal muscle areas were divided into eight parts (e.g. rectus abdominis, psoas, and erector spine), and their areas and densities were measured at the third lumbar vertebra level after the patients were discharged and de‐identified with blinding to avoid measurement bias. Short physical performance battery (SPPB) was measured at the start and end of in‐hospital cardiac rehabilitation. A generalized linear model with patients as random effects was made to investigate skeletal muscle loss during acute care. Multivariate linear regression analysis was also used to assess the relationship between the change in skeletal muscle during acute care and SPPB during in‐hospital cardiac rehabilitation.ResultsThe median age of the patients was 70 (interquartile: 58–77) years, and 69.9% (86/123) were men. The median day between acute care from the day of surgery or hospital admission and follow‐up CT was 7 (interquartile: 3–8) days. Overall muscle density declined after acute care (estimate value: −3.640, 95% confidence interval [CI]: −4.538 to −2.741), and each abdominal muscle density consistently declined (interaction: F value = 0.099, P = 0.998). In contrast, there was no significant change in the overall muscle area (estimate value: −0.863, 95% CI: −2.925 to 1.200). Changes in the muscle area were different for each skeletal muscle (interaction: F value = 2.142, P = 0.037), and only the erector spine muscle significantly declined (estimate value: −1.836, 95% CI: −2.507 to −1.165). After adjusting for confounding factors, a greater decline in muscle density was associated with lower recovery score on SPPB (β = 0.296, 95% CI: 0.066 to 0.400).ConclusionsMuscle density consistently declined after acute care, especially the erector spine muscles, which also significantly decreased in size. A higher decline in muscle density was associated with a slower recovery of physical function during in‐hospital cardiac rehabilitation in patients with aortic diseases.

Billroth II anastomosis maintains SMI and BMI better than Roux-en-Y anastomosis following totally laparoscopic distal gastrectomy: a propensity score-matched study.

Gastric cancer is a major public health problem around the globe. With the standardization of tumor treatment, surgery continues to be the most important treatment method for gastric cancer. However, changes in body composition and nutrition index parameters in patients with Billroth II and Roux-en-Y anastomosis following totally laparoscopic distal gastrectomy (TLDG) remain unclear. This was a single-center retrospective study. A total of 369 patients who underwent TLDG at the First Affiliated Hospital of Soochow University (Suzhou, China) between January 2016 and February 2019 were included and assigned to the Billroth II group or Roux-en-Y group according to the anastomosis method. After propensity score matching, body composition and relevant clinical data were compared between the two groups. The operation time for the Billroth II group was significantly shorter than for the Roux-en-Y group (174.12 ± 39.33min vs. 229.19 ± 28.12min, P < 0.001). In addition, the Billroth II group showed lower skeletal muscle loss. Specifically, the Billroth II group showed a - 4.77 ± 4.88% change in the skeletal muscle index (SMI), whereas the Roux-en-Y group showed a - 11.89 ± 8.68% change (P = 0.001). The Billroth II group also showed a smaller decrease in BMI than the Roux-en-Y group (- 6.67 ± 7.76% vs. - 13.12 ± 10.79%, P = 0.018). These results suggest that Billroth II anastomosis after TLDG has advantages over Roux-en-Y for maintaining patient body composition, especially in terms of SMI, and may serve as a useful reference when choosing an anastomosis method.

Effect of Epicatechin on Skeletal Muscle.

Loss of skeletal muscle (SkM) quality is associated with different clinical conditions such as aging, diabetes, obesity, cancer, and heart failure. Nutritional research has focused on identifying naturally occurring molecules that mitigate the loss of SkM quality induced by pathology or syndrome. In this context, although few human studies have been conducted, epicatechin (Epi) is a prime candidate that may positively affect SkM quality by its potential ability to mitigate muscle mass loss. This seems to be a consequence of its antioxidant and anti-inflammatory properties and its stimulation of mitochondrial biogenesis to increase myogenic differentiation, as well as its modulation of key proteins involved in SkM structure, function, metabolism, and growth. In conclusion, the Epi could prevent, mitigate, delay, and even treat muscle-related disorders caused by aging and diseases. However, studies in humans are needed.

Is the amino acid pattern in medical nutrition therapy crucial for successfully attenuating muscle mass loss in adult ICU patients? Secondary analysis of a RCT.

We hypothesized that in long-term immobilized intensive care unit (ICU) patients, both the quantity and quality of protein nutrition are vital in supporting muscle mass maintenance. Hence, the aim of this secondary analysis of our recently performed RCT was to calculate the intake of individual amino acids and to evaluate the potential associations of amino acid patterns with muscle mass loss during the ICU stay. Clinical and nutritional data were collected from a recent RCT conducted in long-term immobilized, critically ill patients receiving medical nutrition therapy with either 1.8g (interventional group) or 1.2g (standard group) of protein/amino acids per kg body weight per day over 4 weeks. Intake of the individual amino acids as well as the sum scores of the indispensable, conditionally indispensable, and dispensable amino acids were calculated for all patients, both group specific (n=21 in each group) and in total (n=42), based on the detailed nutrition protocols; inter-group differences were analyzed by t-tests. Linear regression models were used to test the effects of individual amino acids and the sum scores on the extent of skeletal muscle loss by measuring the quadriceps muscle layer thickness during the study period. The significance level was adjusted for multiple testing according to the Bonferroni procedure (α=0.002). In both groups, the proportion of indispensable amino acids was approximately 41% of the total exogenous protein supply, with the proportion of enteral administration slightly over 50%. The intake of conditionally indispensable amino acids (glutamine, tyrosine, cysteine, histidine, and arginine) accounted for 17% and 18% of the total amino acids in the interventional and standard groups, respectively; glutamine (5% of total amino acids) was exclusively administered enterally. The intake of dispensable amino acid varied widely, with glutamic acid, proline, and asparagine/aspartic acid representing the highest proportions (10%, 8%, and 8% of total amino acids, respectively). For all amino acids, no statistically significant association was observed between the quantitative intake and the skeletal muscle changes after terminating the intervention phase. This secondary analysis of the RCT conducted in routine clinical practice did not support our working hypothesis that the amino acid patterns of medical nutrition therapy have a statistically significant impact on the skeletal muscle loss in long-term immobilized ICU patients. Due to the limited variety of enteral/parenteral products used in this single-center study, the calculated amino acid patterns showed only small differences. Larger multi-center trials with adequate power are needed to evaluate the potential effects of the individual amino acids or defined amino acid patterns on the muscle protein metabolism in further detail. German Clinical Trials Register (http://www.drks.de); DRKS-ID: DRKS00013594.

Cathepsin K activity controls cachexia-induced muscle atrophy via the modulation of IRS1 ubiquitination.

BackgroundCachexia is a complicated metabolic disorder that is characterize by progressive atrophy of skeletal muscle. Cathepsin K (CTSK) is a widely expressed cysteine protease that has garnered attention because of its enzymatic and non‐enzymatic functions in signalling in various pathological conditions. Here, we examined whether CTSK participates in cancer‐induced skeletal muscle loss and dysfunction, focusing on protein metabolic imbalance.MethodsMale 9‐week‐old wild‐type (CTSK+/+, n = 10) and CTSK‐knockout (CTSK−/−, n = 10) mice were injected subcutaneously with Lewis lung carcinoma cells (LLC; 5 × 105) or saline, respectively. The mice were then subjected to muscle mass and muscle function measurements. HE staining, immunostaining, quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, and western blotting were used to explore the CTSK expression and IRS1/Akt pathway in the gastrocnemius muscle at various time points. In vitro measurements included CTSK expression, IRS1/Akt pathway‐related target molecule expressions, and the diameter of C2C12 myotubes with or without LLC‐conditioned medium (LCM). An IRS1 ubiquitin assay, and truncation, co‐immunoprecipitation, and co‐localization experiments were also performed.ResultsCTSK+/+ cachectic animals exhibited loss of skeletal muscle mass (muscle weight loss of 15%, n = 10, P < 0.01), muscle dysfunction (grip strength loss > 15%, n = 10, P < 0.01), and fibre area (average area reduction > 30%, n = 5, P < 0.01). Compared with that of non‐cachectic CTSK+/+ mice, the skeletal muscle of cachectic CTSK+/+ mice exhibited greater degradation of insulin receptor substrate 1 (IRS1, P < 0.01). In this setting, cachectic muscles exhibited decreases in the phosphorylation levels of protein kinase B (Akt308, P < 0.01; Akt473, P < 0.05) and anabolic‐related proteins (the mammalian target of rapamycin, P < 0.01) and increased levels of catabolism‐related proteins (muscle RING‐finger protein‐1, P < 0.01; MAFbx1, P < 0.01) in CTSK+/+ mice (n = 3). Although there was no difference in LLC tumour growth (n = 10, P = 0.44), CTSK deletion mitigated the IRS1 degradation, loss of the skeletal muscle mass (n = 10, P < 0.01), and dysfunction (n = 10, P < 0.01). In vitro, CTSK silencing prevented the IRS1 ubiquitination and loss of the myotube myosin heavy chain content (P < 0.01) induced by LCM, and these changes were accelerated by CTSK overexpression even without LCM. Immunoprecipitation showed that CTSK selectively acted on IRS1 in the region of amino acids 268 to 574. The results of co‐transfection of IRS1‐N‐FLAG or IRS1‐C‐FLAG with CTSK suggested that CTSK selectively cleaves IRS1 and causes ubiquitination‐related degradation of IRS1.ConclusionsThese results demonstrate that CTSK plays a novel role in IRS1 ubiquitination in LLC‐induced muscle wasting, and suggest that CTSK could be an effective therapeutic target for cancer‐related cachexia.

Progressive Skeletal Muscle Loss After Surgery and Adjuvant Radiotherapy Impact Survival Outcomes in Patients With Early Stage Cervical Cancer.

The effect of skeletal muscle loss associated with surgery and adjuvant radiotherapy on survival outcomes in patients with early-stage cervical cancer remains unclear. We analyzed the data of 133 patients with early-stage cervical cancer who underwent surgery and adjuvant radiotherapy between 2013 and 2018 at two tertiary centers. Skeletal muscle changes were measured using computed tomography scans at baseline, at simulation for radiotherapy, and at 3 months post-treatment. A decrease of ≥5% in the skeletal muscle was defined as “muscle loss.” The Patient-Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was used to assess gastrointestinal toxicity. The Patient-Generated Subjective Global Assessment (PG-SGA) was used for nutritional assessment. Predictors of overall survival were identified using the Cox regression models. The median follow-up period was 3.7 years. After treatment, 32 patients (24.1%) experienced muscle loss. The rate of muscle loss was higher in patients with PRO-CTCAE score ≥3 or PG-SGA score ≥4 at the end of radiotherapy than in patients with PRO-CTCAE score ≤2 or PG-SGA score 0–3 (75.0 vs. 10.5%, p < 0.001; 71.4 vs. 2.2%, p < 0.001). The 3-year overall survival was significantly lower in patients with muscle loss than in those with muscle preserved (65.6 vs. 93.9%, p < 0.001). Multivariate analysis showed that muscle loss was independently associated with poor overall survival (hazard ratio, 4.55; 95% confidence interval: 1.63–12.72; p < 0.001). Muscle loss after surgery and adjuvant radiotherapy was associated with poor overall survival in patients with early-stage cervical cancer. Muscle loss is associated with patient-reported gastrointestinal toxicity and deterioration in nutritional status.

Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223

ObjectiveAndrogen deprivation therapy alters body composition promoting a significant loss in skeletal muscle (SM) mass through inflammation and oxidative damage. We verified whether SM anthropometric composition and metabolism are associated with unfavourable overall survival (OS) in a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients submitted to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) imaging before receiving Radium-223.Patients and methodsLow-dose CT were opportunistically analysed using a cross-sectional approach to calculate SM and adipose tissue areas at the third lumbar vertebra level. Moreover, a 3D computational method was used to extract psoas muscles to evaluate their volume, Hounsfield Units (HU) and FDG retention estimated by the standardized uptake value (SUV). Baseline established clinical, lab and imaging prognosticators were also recorded.ResultsSM area predicted OS at univariate analysis. However, this capability was not additive to the power of mean HU and maximum SUV of psoas muscles volume. These factors were thus combined in the Attenuation Metabolic Index (AMI) whose power was tested in a novel uni- and multivariable model. While Prostate-Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase and Hemoglobin, Metabolic Tumor Volume, Total Lesion Glycolysis and AMI were associated with long-term OS at the univariate analyses, only PSA, ALP and AMI resulted in independent prognosticator at the multivariate analysis.ConclusionThe present data suggest that assessing individual 'patients' SM metrics through an opportunistic operator-independent computational analysis of FDG PET/CT imaging provides prognostic insights in mCRPC patients candidates to receive Radium-223.Graphical abstract

Nutritional Approach to Cancer Cachexia: A Proposal for Dietitians

Cachexia is one of the most common, related factors of malnutrition in cancer patients. Cancer cachexia is a multifactorial syndrome characterized by persistent loss of skeletal muscle mass and fat mass, resulting in irreversible and progressive functional impairment. The skeletal muscle loss cannot be reversed by conventional nutritional support, and a combination of anti-inflammatory agents and other nutrients is recommended. In this review, we reviewed the effects of nutrients that are expected to combat muscle loss caused by cancer cachexia (eicosapentaenoic acid, β-hydroxy-β-methylbutyrate, creatine, and carnitine) to propose nutritional approaches that can be taken at present. Current evidence is based on the intake of nutrients as supplements; however, the long-term and continuous intake of nutrients as food has the potential to be useful for the body. Therefore, in addition to conventional nutritional support, we believe that it is important for the dietitian to work with the clinical team to first fully assess the patient’s condition and then to safely incorporate nutrients that are expected to have specific functions for cancer cachexia from foods and supplements.

Dietary patterns, skeletal muscle mass loss, and cardiovascular risk among elderly men: A preliminary cross-sectional study in Sichuan province

The present study investigated the correlation between dietary patterns (DPs) with skeletal muscle mass (SMM) and cardiovascular risks in Sichuan males aged ≥65-years-old. Three major DPs were extracted by principal component analysis: animal-based and processed food, traditional food, and ovo-lacto vegetarian food, which accounted for 14.83%, 14.36%, and 11.86% of the variance, respectively. Adjusted logistic regression analysis showed that animal-based and processed food DP was positively associated with overweight/obesity(OR: 3.25, 95% CI: 1.94–5.46) and dyslipidemia(OR: 3.53, 95% CI: 2.00–6.22). Traditional DP was negatively associated with overweight/obesity(OR: 0.51, 95% CI: 0.36–0.72), dyslipidemia(OR: 0.50, 95% CI: 0.35–0.75), and high blood pressure(OR: 0.54, 95% CI: 0.38–0.77), but positively associated with decreased SMM (OR: 2.21, 95% CI: 1.36–3.16). Ovo-lacto vegetarian DP was negatively associated with dyslipidemia (OR: 0.56, 95% CI: 0.39–0.81) and hyperuricemia (OR: 0.56, 95% CI: 0.39–0.79), but positively associated with decreased SMM (OR: 1.57, 95% CI: 0.74–2.32). How to choose the best DP to control the cardiovascular risks and fight skeletal muscle loss needs further investigation in the future.

Low muscle mass and early hospital readmission post-kidney transplantation.

Patients exhibiting features of frailty and sarcopenia increasingly are presenting for kidney transplantation (KT) assessment. Sarcopenia, when ascertained by radiological measures, is associated with a higher transplant waiting list mortality; but studies on post-operative outcomes are lacking. We aimed to determine the clinical significance of low muscle mass in chronic kidney disease (CKD) patients subsequently receiving KT. We retrospectively analyzed 63 patients with Stage 4-5 CKD who, between 2012 and 2020, had undergone abdominal computed tomography (CT) scanning up to 2years before KT. The degree of skeletal muscle loss was assessed using the total cross-sectional skeletal muscle area at the third lumbar vertebral level (L3). Cox proportional-hazards regression and Frailty models were used to identify risk factors for early hospital readmission post KT. Thirty-four patients (54%) displayed low muscle mass, which was independently associated with a lower serum creatinine and phosphate, lower body mass index, lower mean muscle attenuation of the L3 cross-sectional area, and higher serum parathyroid hormone (for all p < 0.05). Deceased donor transplant recipients (n = 45) with low muscle mass demonstrated greater hospital readmissions within 30days of KT [adjusted hazard ratio (HR) = 4.24, 95% CI 1.40-12.90, p = 0.01]. Low muscle mass is highly prevalent in the pre-transplant CKD population and is associated with increased hospital readmission in the early post-transplant period.

Effects of feeding level and sexual maturation on expression of genes regulating growth mechanisms in rainbow trout (Oncorhynchus mykiss)

The energy and nutrient demands of sexual maturation in salmonids requires a shift from somatic growth to gonadal development, although a loss of skeletal muscle can be avoided with adequate nutrition. How nutrient availability or ration affects the endocrine and growth factor systems that integrate nutrient partitioning, muscle metabolism, and growth during sexual maturation is poorly understood. Primary objectives of the current study were to determine how sexual maturation and ration affect expression of estrogen receptors, components of the GH/IGF axis and TGFβ superfamily system, and muscle specific regulatory factors during gonadal development in female rainbow trout (Oncorhynchus mykiss). Female diploid rainbow trout approaching ovulation were fed for 12 weeks at 0.25% and 0.50% tank biomass, and to apparent satiation. Controls for the effects of gonadal development included sterile triploid trout and two diploid females that failed to undergo gonadal development. Expression of era1 was increased in muscle of maturing diploids suggesting an increase in the catabolic effects of 17β-estradiol (E2) on muscle. In the liver, expression of era2 increased with maturation, but expression of all estrogen receptors were increased with higher rations suggesting improved E2 sensitivity for vitellogenin production. Hepatic expression of ghrs and igfs were generally reduced with maturation suggesting a reduction in systemic growth promotion. Increased ration improved capacity for IGF signaling in muscle via increased igf1 and igfr1b expression, potentially lessening effects of reduced circulating IGF-I on muscle growth. The primary carrier of IGFs, hepatic igfbp2b1, increased with maturation likely reducing systemic IGF activity, and was also elevated with higher rations. All other hepatic IGF binding proteins, except igfbp1, showed some reduction with maturation and several increased with increased ration. Increased muscle igfbp6b1 suggests restricted myogenesis with maturation. Reductions in expression of muscle regulatory factors with maturation including pax7a, myog and myf5, support reduced myogenesis with maturation but were unaffected by ration. In addition, although mstn2a was the only myostatin gene affected by maturation or ration, altered expression of components of the TGFβ superfamily suggest increased ration may inhibit myostatin signaling. In summary, moderate feeding appears to counter many changes in endocrine and growth factor system gene expression associated with growth reduction during maturation, perhaps altering endocrine and growth factor regulation to spare muscle atrophy and better prepare the fish for post-spawning recovery.

This Month in Anesthesiology

This Month in Anesthesiology

Ileal FXR-FGF15/19 signaling activation improves skeletal muscle loss in aged mice

Sarcopenia is the age-related decrease in skeletal muscle mass, and current therapies for this disease are ineffective. We previously showed that ileal farnesoid X receptor (FXR)-fibroblast growth factor 15/19 (FGF15/19) signaling acts as a regulator of gut microbiota to mediate host skeletal muscle. However, the therapeutic potential of this pathway for sarcopenia is unknown. This study showed that ileal FXR-FGF15/19 signaling was downregulated in older men and aged male mice due to changes in the gut microbiota and microbial bile acid metabolism during aging. In addition, the intestine-specific FXR agonist fexaramine increased skeletal muscle mass and improve muscle performance in aged mice. Ileal FXR activation increased skeletal muscle protein synthesis in a FGF15/19-dependent way, indicating that ileal FXR-FGF15/19 signaling is a potential therapeutic target for sarcopenia.

Effectiveness of early exercise on reducing skeletal muscle loss during preoperative neoadjuvant chemotherapy for esophageal cancer.

To investigate if early exercise can help prevent skeletal muscle loss and improve the clinical outcomes of esophageal cancer patients receiving preoperative neoadjuvant chemotherapy (NAC). This was a single-center, retrospective observational cohort study of 110 patients with advanced esophageal cancer. We analyzed the effect of early exercise on the risk of skeletal muscle loss (defined as > 2.98%) during NAC and the subsequent clinical outcomes. Patients in the early exercise group (n = 71) started exercise therapy 8days earlier than those the late exercise group (n = 39). The median age of the patients was 65.4years, the mean BMI was 21.1kg/m2, and 92 (84%) of the 110 patients were men. Skeletal muscle loss occurred in 34% and 67% of the early and late exercise groups, respectively (p < 0.001). There was a lower risk of surgical site infection in the early exercise group (1% vs 16%, p = 0.021). Multivariate analysis revealed that early exercise reduced the risk of skeletal muscle loss (OR = 0.25, 95% CI 0.09-0.65, p = 0.006). Our results suggest that early exercise reduces the risk of both skeletal muscle loss during NAC and subsequent surgical site infection in patients with esophageal cancer.