Loss Of Muscle Volume Research Articles

Sarcopenia as a prognostic factor in patients with hepatocellular carcinoma treated with transcatheter arterial chemoembolization plus sorafenib.

Loss of skeletal muscle volume is an important aspect of sarcopenia in hepatocellular carcinoma (HCC) patients treated by surgical resection, transcatheter arterial chemoembolization (TACE), or sorafenib. This study determined the influence of sarcopenia and other laboratory results on survival in patients with HCC treated with TACE plus sorafenib. The patients were divided into two groups based on the presence of sarcopenia. The skeletal muscle index was calculated by normalizing the cross-sectional muscle area at the L3 level on an abdominal computed tomography scan before embolization according to the patient's height. The clinical characteristics of the two groups were then compared. The progression-free survival (PFS) and overall survival (OS) rates after treatment were determined. Sarcopenia was present in 75 of the 102 (74%) patients with HCC included in this study. The albumin, prealbumin, and cholinesterase levels were lower in those with sarcopenia. The OS (P = 0.001) and PFS (P = 0.008) were significantly prolonged in the nonsarcopenia group compared to the sarcopenia group. Sarcopenia, ECOG (≥2), and prealbumin (<180 mg/L) were significantly associated with PFS. Sarcopenia, ECOG (≥2), Child-Pugh B, BCLC stage C, prealbumin (<180 mg/L), and cholinesterase (<5,320 U/L) were significantly associated with OS. The prognostic factors for OS included sarcopenia, ECOG (≥2), and cholinesterase (<5,320 U/L), whereas only ECOG (≥2) was identified as a prognostic factor for PFS. Sarcopenia may be an indicator of poor clinical outcome in patients with HCC receiving TACE plus sorafenib.

Skeletal muscle status and survival among patients with advanced biliary tract cancer

BackgroundStudies have demonstrated a prognostic role of sarcopenia (i.e., loss of skeletal muscle volume and functionality) in patients with various cancer types. In patients with biliary tract cancer, the quantity and quality of skeletal muscles and their serial changes have not been fully investigated in relation to survival outcomes.MethodsWe identified 386 patients with unresectable or recurrent biliary tract cancer and calculated skeletal muscle index (SMI) and skeletal muscle density (SMD) to estimate muscular quantity and quality, respectively, based on computed tomography images. Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) according to skeletal muscle status and its serial change.ResultsCompared to patients without sarcopenia, patients with sarcopenia were associated with shorter PFS (multivariable HR, 1.60; 95% CI, 1.15–2.22; P = 0.005), but not with OS (P = 0.027) at the adjusted α level of 0.013. SMD at baseline was associated with OS (multivariable HR comparing the extreme quartiles, 1.52; 95% CI, 1.07–2.14; Ptrend = 0.012), but not with PFS (Ptrend = 0.13). A reduction in SMI rather than that in SMD was associated with OS. Progressive disease was a risk factor for reductions in SMI and SMD.ConclusionsSkeletal muscle quantity and quality and their serial changes were associated with survival outcomes in patients with advanced biliary tract cancer. Our data highlight the importance of designing nutritional and physical interventions for improvements in skeletal muscle status.

Acceleration of sarcopenia in elderly patients who develop asymptomatic pneumonia shadow within one year after surgery for early gastric cancer

BackgroundAlthough early gastric cancer is curable with local treatment, the overall survival in elderly patients did not reach 80% at five years after surgery. The major cause of death in elderly patients with early gastric cancer is not cancer itself but is related to postoperative sarcopenia. Elderly patients frequently develop postoperative asymptomatic pneumonia shadow, which is associated with a poor prognosis. However, why asymptomatic pneumonia shadow worsens the prognosis remains unclear. We investigated whether sarcopenia is accelerated in patients who developed asymptomatic pneumonia shadow.MethodsWe retrospectively examined patients of > 75 years of age who underwent R0 gastrectomy for gastric cancer and were diagnosed with T1 disease at National Cancer Center Hospital between 2005 and 2012. The diagnosis of asymptomatic pneumonia shadow was defined by diagnostic findings of pneumonia (consolidation type, reticular type, and nodular type) which were newly observed on chest computed tomography performed one year after surgery in comparison to preoperative computed tomography. Postoperative muscle loss was assessed by a computed tomography-based analysis using the L3 skeletal muscle index before and two years after surgery and the rate of decrease was calculated. Patients were classified into two groups according to the rate of decrease (cut-off value: 10%).ResultsOf the 3412 patients who underwent gastrectomy in our hospital during the study period, 142 were included in this study. Asymptomatic pneumonia shadow was found in 26 patients (18%). Patients who developed asymptomatic pneumonia shadow showed a significantly greater loss of muscle volume in comparison to patients who did not develop asymptomatic pneumonia shadow. In the multivariate analysis, total gastrectomy and asymptomatic pneumonia shadow were the independent risk factors for severe muscle loss. However, there was no significant difference in prognosis between the two groups.ConclusionsSarcopenia was accelerated in elderly patients who developed asymptomatic pneumonia shadow after surgery for early gastric cancer. However, the poor prognosis in these patients may not be related to accelerated sarcopenia.

The Loss of Temporal Muscle Volume is Associated with Poor Outcome in Patients with Subarachnoid Hemorrhage: An Observational Cohort Study

BackgroundIntensive care unit (ICU) acquired weakness is a major contributor to poor functional outcome of ICU patients. Quantification of temporal muscle volume assessed on routine computed tomography (CT) scans may serve as a biomarker for muscle wasting in patients suffering from acute brain injury.MethodsThis is a retrospective analysis of prospectively collected data. Temporal muscle volume was assessed on head CT scans of consecutive patients with spontaneous subarachnoid hemorrhage within prespecified time frames (on admission, then weekly ± 2 days). Whenever possible, temporal muscle volume was assessed bilaterally and averaged for the analysis. Poor functional outcome was defined as a 3-month modified Rankin Scale Score ≥ 3. Statistical analysis was performed using generalized estimating equations to handle repeated measurements within individuals.ResultsThe analysis comprised 110 patients with a median Hunt & Hess score of 4 (interquartile range 3–5). Median age was 61 (50–70) years, 73 patients (66%) were women. Baseline temporal muscle volume was 18.5 ± 0.78 cm3 and significantly decreased over time (p < 0.001) by a mean of 7.9% per week. Higher disease severity (p = 0.002), hydrocephalus (p = 0.020), pneumonia (p = 0.032), and bloodstream infection (p = 0.015) were associated with more pronounced muscle volume loss. Patients with poor functional outcome had smaller muscle volumes 2 and 3 weeks after subarachnoid hemorrhage compared with those with good outcome (p = 0.025). The maximum muscle volume loss during ICU stay was greater in patients with poor functional outcome (− 32.2% ± 2.5% vs. − 22.7% ± 2.5%, p = 0.008). The hazard ratio for poor functional outcome was 1.027 (95% confidence interval 1.003–1.051) per percent of maximum muscle volume loss.ConclusionsTemporal muscle volume, which is easily assessable on routine head CT scans, progressively decreases during the ICU stay after spontaneous subarachnoid hemorrhage. Because of its association with disease severity and functional outcome, it may serve as a biomarker for muscle wasting and outcome prognostication.

Arthralgia of menopause - A retrospective review.

Arthralgia is a common complaint around the time of menopause in many women. It is estimated that over 50% of women experience arthralgia or arthritis at the time of menopause. The complex of symptoms has been linked to the joint and tendon response to the decline in sex hormones as well as sarcopenia, or loss of muscle volume associated with aging. The diagnosis of "arthritis of menopause" has been identified since 1925, but treatments have been symptomatic at best.1,2 Joint synovium and cartilage interaction with estrogen is well documented. This article reviews the literature regarding the current approaches to treatment of arthralgia of menopause.

Estimation of subvoxel fat infiltration in neurodegenerative muscle disorders using quantitative multi-T2 analysis.

MRI's T2 relaxation time is a valuable biomarker for neuromuscular disorders and muscle dystrophies. One of the hallmarks of these pathologies is the infiltration of adipose tissue and a loss of muscle volume. This leads to a mixture of two signal components, from fat and from water, to appear in each imaged voxel, each having a specific T2 relaxation time. In this proof-of-concept work, we present a technique that can separate the signals from water and from fat within each voxel, measure their separate T2 values, and calculate their relative fractions. The echo modulation curve (EMC) algorithm is a dictionary-based technique that offers accurate and reproducible mapping of T2 relaxation times. We present an extension of the EMC algorithm for estimating subvoxel fat and water fractions, alongside the T2 and proton-density values of each component. To facilitate data processing, calf and thigh anatomy were automatically segmented using a fully convolutional neural network and FSLeyes software. The preprocessing included creating two signal dictionaries, for water and for fat, using Bloch simulations of the prospective protocol. Postprocessing included voxelwise fitting for two components, by matching the experimental decay curve to a linear combination of the two simulated dictionaries. Subvoxel fat and water fractions and relaxation times were generated and used to calculate a new quantitative biomarker, termed viable muscle index, and reflecting disease severity. This biomarker indicates the fraction of remaining muscle out of the entire muscle region. The results were compared with those using the conventional Dixon technique, showing high agreement (R = 0.98, p< 0.001). It was concluded that the new extension of the EMC algorithm can be used to quantify abnormal fat infiltration as well as identify early inflammatory processes corresponding to elevation in the T2 value of the water (muscle) component. This new ability may improve the diagnostic accuracy of neuromuscular diseases, help stratification of patients according to disease severity, and offer an efficient tool for tracking disease progression.

Impact of combined resection of the internal iliac artery on loss of volume of the gluteus muscles after pelvic exenteration.

To clarify the influence of additional internal iliac artery (IIA) resection on the loss of the gluteus muscle volume after pelvic exenteration (PE). The subjects of this retrospective analysis were 78 patients who underwent PE with or without IIA resection (n = 44 and n = 34, respectively) between 2006 and 2018. The areas of gluteal muscles (GMs) and psoas muscles (PSMs) were calculated using CT images before and 6months after PE, and the difference was compared. The volumes of the GMs and PSMs were significantly reduced after PE (P < 0.001 and P = 0.005, respectively). In the IIA resection group, the GMs were significantly reduced after surgery, but the PSMs were not. The maximum GM (Gmax) was the most atrophied among the GMs. Multivariable analysis revealed that complete IIA resection was an independent promotor of the loss of volume of the Gmax (P = 0.044). In 18 patients with unilateral IIA resection, the downsizing rate of the Gmax was significantly greater on the resected side than on the non-resected side (P = 0.008). The GMs and PSMs were significantly smaller after PE. Complete IIA resection reduced the Gmax area remarkably. Preservation of the superior gluteus artery is likely to help maintain Gmax size, suggesting a potential preventative measure against secondary sarcopenia.

P.32 Impact of age on muscle volume and T2-relaxation time during adulthood in mice using quantitative MRI

Overall ageing is associated with a loss of muscle volume and function over time; nevertheless, detailed changes of muscle tissue are incompletely understood. In this preliminary study, magnetic resonance imaging (MRI) was used to assess the effect of age on muscle volume and T2. A cohort of 13 C57Bl/6J Rj male mice was followed from 2.5 to 17 months of age. MRI acquisitions were done at 7 Tesla using a 1H surface cryoprobe. Muscle volume and T2 of the anterior compartment (TA+EDL: tibialis anterior + extensor digitorum longus) were assessed by cross sectional area (CSA) from high-resolution gradient-echo axial images and from a multi-slice multi echo MRI sequence, respectively. Student's paired t test and ANOVA were used for statistical analysis (p < 0.05). Body weight increased up to 12 months and stayed constant until 17 months of age. Muscle volume reached its maximum at 9 months of age. The maximum CSA of TA+EDL muscles, measured on a single slice, decreased significantly from 9 to 17 months of age (8±0.5 mm² at 9 m/o vs 7.1±0.4 mm² at 17 m/o). In parallel, muscle T2 increased significantly from 2.5 to 17 months of age (T2 at 2.5 m/o = 21.5 ±0.2 ms vs T2 at 17 m/o = 22.6±0.3 ms) and from 2.5 to 6 months of age (T2 at 6 m/o = 22.3±0.4 ms). A similar tendency was also observed between 9 and 17 months of age (T2 at 9 m/o = 22± 0.5; p = 0.054). Repeated acquisitions of high-resolution images allowed for longitudinal follow-up of muscle volume from 2.5 up to 17 months of age in mice. The onset of muscle ageing seems to be around 9 months whereas body weight still increases up to 12 months. Muscle T2 increased significantly with age over the timespan of the study. In young ages (2.5 to 6 m/o), T2 increase probably reflects slight changes of histological water compartmentation related to tissue maturation. Ongoing experiments will refine this longitudinal follow-up and provide data at older ages.

Diagnosis of sarcopenia and nutritional intervention in the elderly: literature review

Sarcopenia is a skeletal muscle disorder that affects the elderly, characterized by loss of muscle volume associated with loss of strength and performance, increasing the risk of fractures, falls, physical disability and mortality. The diagnosis includes DEXA, physical performance tests, anthropometric measurements as calf circumference and strength test using handgrip strenght that check muscle volume, it’s quality and the elderly mobility and balance hability. Nutritional intervention is an essential strategy in the control of sarcopenia and comprises the adequate energy and protein intake, in addition to vitamin D, primarily. In this context, this narrative review aimed to collect current information about the characteristics of sarcopenia, diagnosis methods and nutritional strategies for the treatment. Updates were searched in BVS, PubMed and SciELO databases, technical books, and Brazilian and international consensus. The structured content makes consultation and updating on sarcopenia easier, from diagnosis to the most relevant dietary recommendations for the treatment of the disease.

462. IMPACT OF THE RATIO OF THE VISCERAL FAT AREA TO PSOAS MUSCLE AREA ON SURVIVAL FOR SURGICALLY RESECTED ESOPHAGEAL CANCER

Abstract Sarcopenia (the loss of skeletal muscle volume and/or quality) and obesity have received increasing attention in many malignancies because they are associated with postoperative complications and poor surgical outcomes. The synergic effects of muscle mass reduction with excess body adiposity in surgically resected esophageal cancer (EC) patients remains controversial, especially in non-obese patients. One hundred and six patients with EC who underwent surgery between 2006 and 2014 were included in this study. Reduction in muscle mass and excess body adiposity were defined as the ratio of the visceral fat area (VFA) to psoas muscle area (PMA) (V/P ratio) on the same axial computed tomography (CT) slice at the third lumbar vertebra (L3). A high V/P ratio was associated with higher age (p = 0.03), higher body mass index (BMI) (p&amp;lt;0.001), higher VFA (p&amp;lt;0.001), and increased age-adjusted Charlson comorbidity index (ACCI) (p = 0.005). Multivariate analysis revealed a high V/P ratio to be an independent prognostic factor for poor overall survival (OS) in EC patients who underwent surgery (p = 0.003). The prognostic value of the V/P ratio was still significant in EC patients with a BMI &amp;lt; 25. A high V/P ratio was associated with poor survival in surgically resected EC patients, even in non-obese patients. The V/P ratio as a surrogate marker of relative muscle mass reduction and fat accumulation may have prognostic value in EC patients regardless of body composition differences.

Effect of Blood Flow Restriction Therapy Following Achilles Rupture and Repair: A Randomized Controlled Trial

Category:Sports; OtherIntroduction/Purpose:Blood flow restriction (BFR) therapy involves the use of a tourniquet to partially occlude blood flow to the affected limb, creating an anaerobic environment during exercise. This is thought to stimulate growth and recovery by increasing the body's anabolic response. BFR therapy can be initiated shortly after surgery since it allows for significant muscle activation with limited load bearing. To date, no existing study has evaluated the effect of using BFR therapy for recovery following Achilles tendon rupture and repair, after which patients often experience significant losses in calf strength and girth. This is a randomized controlled trial designed to study whether BFR can minimize loss of calf strength and muscle volume after Achilles rupture compared to a conventional physical therapy protocol.Methods:Patients presenting with an acute Achilles tendon rupture were randomized into the BFR or control group. Patients in the control group performed at-home exercises and began in-person physical therapy at 6 weeks postoperatively, as is the standard of care in our practice. The exercises were standardized across groups with BFR the isolated variable. The primary outcome studied was ankle plantarflexion strength as measured during isokinetic strength testing 3 months after surgical repair. We also tested knee strength during flexion and extension. All strength tests were performed at two rotational speeds. Calf atrophy was assessed by measuring the circumference of both calves 15 cm below the joint line at the time of operation and at 2 weeks, 6 weeks, 3 months, and 6 months postoperatively. Finally, Patient-Reported Outcome Measurement Information System (PROMIS) scores were collected pre- and postoperatively.Results:The study enrolled 43 patients, 24 of whom were assigned to the BFR group. 30 patients completed strength testing at 3 months and 26 at 6 months. Calf measurements through 3 months were completed for 39 patients and 6 month measurements were completed for 32 patients. Results for ankle plantarflexion strength at 3 months are displayed in Table 1, showing that patients in the BFR group demonstrated greater absolute strength in the operative calf compared to the control group, but no significant advantage in strength relative to the uninvolved calf. We failed to detect a significant difference in strength between groups for ankle dorsiflexion, knee extension, or knee flexion. Our model of calf circumference over time showed that BFR had a positive but insignificant correlation to calf circumference (p = 0.59). The only factors that demonstrated a significant (p<0.05) positive relationship to calf circumference were male sex and BMI.Conclusion:We have observed significant advantages in the BFR group when analyzing absolute calf strength metrics when compared to a randomized control group. This indicates that, when used during rehabilitation following Achilles rupture, BFR therapy may increase the strength of the operative leg and may facilitate recovery and outcome.

Superior capsule reconstruction: anatomy, biomechanics, indications, and graft treatment.

Superior capsule reconstruction: anatomy, biomechanics, indications, and graft treatment.

Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging.

During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function impacting mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs); however, the relationship between MuSCs and innervation has not been established. Herein, we administered severe neuromuscular trauma to a transgenic murine model that permits MuSC lineage tracing. We show that a subset of MuSCs specifically engraft in a position proximal to the neuromuscular junction (NMJ), the synapse between myofibers and motor neurons, in healthy young adult muscles. In aging and in a mouse model of neuromuscular degeneration (Cu/Zn superoxide dismutase knockout - Sod1-/-), this localized engraftment behavior was reduced. Genetic rescue of motor neurons in Sod1-/- mice reestablished integrity of the NMJ in a manner akin to young muscle and partially restored MuSC ability to engraft into positions proximal to the NMJ. Using single cell RNA-sequencing of MuSCs isolated from aged muscle, we demonstrate that a subset of MuSCs are molecularly distinguishable from MuSCs responding to myofiber injury and share similarity to synaptic myonuclei. Collectively, these data reveal unique features of MuSCs that respond to synaptic perturbations caused by aging and other stressors.

Real-Time Functional Assay of Volumetric Muscle Loss Injured Mouse Masseter Muscles via Nanomembrane Electronics.

Skeletal muscle has a remarkable regeneration capacity to recover its structure and function after injury, except for the traumatic loss of critical muscle volume, called volumetric muscle loss (VML). Although many extremity VML models have been conducted, craniofacial VML has not been well‐studied due to unavailable in vivo assay tools. Here, this paper reports a wireless, noninvasive nanomembrane system that integrates skin‐wearable printed sensors and electronics for real‐time, continuous monitoring of VML on craniofacial muscles. The craniofacial VML model, using biopsy punch‐induced masseter muscle injury, shows impaired muscle regeneration. To measure the electrophysiology of small and round masseter muscles of active mice during mastication, a wearable nanomembrane system with stretchable graphene sensors that can be laminated to the skin over target muscles is utilized. The noninvasive system provides highly sensitive electromyogram detection on masseter muscles with or without VML injury. Furthermore, it is demonstrated that the wireless sensor can monitor the recovery after transplantation surgery for craniofacial VML. Overall, the presented study shows the enormous potential of the masseter muscle VML injury model and wearable assay tool for the mechanism study and the therapeutic development of craniofacial VML.

Assessment of muscle volume using magnetic resonance imaging (MRI) in football players after hamstring injuries

ABSTRACT Muscle injuries of the hamstrings are among the most frequent in football and a main cause for significant time away from training and competition. The purpose of this study was to prospectively evaluate the loss of muscle volume in recreational football players three and six weeks after initial trauma. We hypothesized that significant muscle volume loss occurs within 6 weeks after the initial injury event. Twenty recreational football players (mean-age=25 ± 4years; mean-height=181 ± 8cm; mean-weight=81 ± 10kg) with type3a (minor partial muscle tear) and type3b (moderate partial muscle tear) injuries were included. Muscle volume was determined using established methods for the hamstrings and the quadriceps femoris muscle within 3 days and after 3 and 6 weeks following the initial injury. The injured hamstrings lost 6.5% (mean=64 cm3(95%CI=31–98 cm3), p<0.001), the healthy hamstrings lost 2.1% (mean=21 cm3(3–44 cm3),p=0.096) of muscle volume after six weeks. The quadriceps in the injured leg lost 3.8% (mean=78 cm3(51–104 cm3), p<0.001) and 4.5% (83 cm3 (45–121 cm3), p<0.001) in the healthy leg. Muscle volume loss inversely correlated with activity levels in the healthy leg for the quadriceps (r=0.96 (0.90–0.98); R 2=0.92; p<0.001) and the hamstrings (r=0.72 (0.40–0.88); R 2=0.51; p<0.001), as well as the quadriceps in the injured leg (r=0.70 (0.37–0.87); R 2=0.49; p<0.001), but not the injured hamstrings. Muscle volume ratio of hamstrings to quadriceps in the control limb was 0.52 ± 0.06 and 0.53 ± 0.06 in the injured leg. The rehabilitation period of six weeks did not have a relevant negative or a positive effect on ratios. Significant muscle volume loss in the upper thigh occurs in recreational soccer players within three, and within six weeks after a hamstring injury and lies between 2% and 7%.

The association between TP53 rs1625895 polymorphism and the risk of sarcopenic obesity in Iranian older adults: a case-control study

BackgroundAging and obesity are the two major global health concerns. Sarcopenia, an age-linked disease, wherein a progressive loss of muscle volume, muscle strength, and physical activity occurs. In this study we evaluated the association of TP53 rs1625895 polymorphism with the susceptibility to sarcopenic obesity in Iranian old-age subjects.MethodsTotal of 176 old individuals (45 sarcopenic and 131 healthy) were recruited in this research and genotyped by PCR–RFLP. BMI, Skeletal Muscle Mass Index, body composition, Handgrip Strength, Gait Speed (GS), and biochemical parameters were measured. Chi-square test was done for genotypes and alleles frequency. Linear regression was applied to find the correlation between TP53 rs1625895 polymorphism, and biochemical and anthropometric parameters. The correlation between TP53 rs1625895 and the risk of sarcopenia and sarcopenic obesity was investigated by logistic regression.ResultsG allele was significantly higher in sarcopenic obesity group [P = 0.037, OR (CI 95%) = 1.9 (1.03–3.5)] compared to A allele. BMI (P = 0.049) and LDL (P = 0.04) were significantly differed between genotypes when GG was compared to AA/AG genotype. The results revealed when GG genotype compared to AA/AG genotype in adjusted model for age, the risk of sarcopenic obesity [P value = 0.011, OR (CI 95%); 2.72 (1.25–5.91)] increased. Similarly, GG/AG genotype increased the risk of sarcopenic obesity [P value = 0.028, OR (CI 95%); 2.43 (1.10–5.36)] in adjusted model for age compared to AA genotype.ConclusionsWe suggested that TP53 rs1625895 polymorphism may increase the risk of sarcopenic obesity in Iranian population.

Preparation of Stretchable Nanofibrous Sheets with Sacrificial Coaxial Electrospinning for Treatment of Traumatic Muscle Injury.

Traumatic muscle injury with massive loss of muscle volume requires intramuscular implantation of proper scaffolds for fast and successful recovery. Although many artificial scaffolds effectively accelerate formation and maturation of myotubes, limited studies are showing the therapeutic effect of artificial scaffolds in animal models with massive muscle injury. In this study, improved myotube differentiation is approved on stepwise stretched gelatin nanofibers and applied to damaged muscle recovery in an animal model. The gelatin nanofibers are fabricated by a two-step process composed of co-axial electrospinning of poly(ɛ-caprolactone) and gelatin and subsequent removal of the outer shells. When stepwise stretching is applied to the myoblasts on gelatin nanofibers for five days, enhanced myotube formation and polarized elongation are observed. Animal models with volumetric loss at quadriceps femoris muscles (>50%) are transplanted with the myotubes cultivated on thin and flexible gelatin nanofiber. Treated animals more efficiently recover exercising functions of the leg when myotubes and the gelatin nanofiber are co-implanted at the injury sites. This result suggests that mechanically stimulated myotubes on gelatin nanofiber is therapeutically feasible for the robust recovery of volumetric muscle loss.

Matricaria chamomilla (Chamomile) Ameliorates Muscle Atrophy in Mice by Targeting Protein Catalytic Pathways, Myogenesis, and Mitochondrial Dysfunction.

Muscle atrophy, or loss of skeletal muscle, is caused by aging, malnutrition, immobility through injury, or diseases such as cancer. Chamomile (Matricaria chamomilla L.) contains various active components, including flavonoids, sesquiterpenes, polyacetylenes, and coumarins, and is used in various herbal medicines in the European Pharmacopoeia. In this study, we investigated the effects of ethanol extract of chamomile [Formula: see text](MC) on muscle wasting and its mechanism of action. Mice with dexamethasone (DEX)-induced muscle atrophy were orally administered MC (100, 200, and 300 mg/kg) for 4 weeks. Micro-computed tomography analysis showed that MC (200 and 300 mg/kg) significantly recovered DEX-induced loss of muscle volume, density, and weight and MC-treated DEX-induced mice also showed increased moving distance and grip strength. MC suppressed the mRNA level of muscle RING finger 1 (MuRF1) while increasing the expression of mitochondrial transcription factor A (TFAM), MyoD, and Myogenin-1. We found 25 peaks in MC samples through HPLC analysis and identified 6 peaks by comparison with a profile of standard compounds: chlorogenic acid (CGA), luteolin-7-O-glucoside (L7G), patulitrin, apigenin-7-O-glucoside (A7G), herniarin, and (E)-tonghaosu. Of these components, the gene expression of MyoD was significantly augmented by patulitrin, herniarin, CGA, and L7G in C2C12 cells, while Myogenin-1 gene expression was increased by A7G, patulitrin, herniarin, CGA, and L7G. Moreover, TFAM gene expression and phosphorylation of AKT were increased by all six ingredients. Based on our results, we suggest MC for use as a supplement or remedy for muscle wasting, including cachexia and sarcopenia.

Abstract 15517: Sarcopenia in Heart Failure Patients Without Dementia is Associated With Local Brain Atrophy and Predicts Poor Prognosis

Background: Sarcopenia is age-related loss of skeletal muscle volume and strength. Aged Heart failure (HF) patients without dementia may have potential risk of cognitive impairment (CI) that attenuates the effect of treatment. Patients with CI have severe brain atrophy in parahippocampal gyrus (PHG). However, it is not clear whether sarcopenia is associated with local brain atrophy and predicts prognosis. Hypothesis: Sarcopenia in HF patients without dementia is associated with local brain atrophy of PHG, a potential risk of CI, and predicts prognosis. Methods: Fifty-four HF patients (age 78+/-8 years, NYHA class II, EF47+/-18 %) were enrolled. We excluded patients with dementia using mini-mental state examination. We took 3D-T1 weighted sagittal images of whole brain using 1.5T magnetic resonance imaging. Image analysis was performed to evaluate the severity of local brain atrophy of gray matter using 2mm voxel-based morphometry by the statistical parametric mapping software. The Z-score value was calculated to evaluate the severity of atrophy in PHG. The cross-sectional area of the erector spinae muscles (CSA), an index of sarcopenia, were measured at the 12th thoracic vertebra using computed tomography. Results: Patients were divided into sarcopenia HF group (n=27) and Non-sarcopenia HF group (n=27) according to median of CSA. The severity of total brain atrophy was similar between sarcopenia HF group (8.1 +/-3.8%) and Non-sarcopenia HF group (8.9+/-3.5%). However, as shown in the representative cases (Figure A), the Z-score value in PHG (pink circle), reflecting the severity of atrophy, was prominent in sarcopenia HF group (1.57+/-0.80) (white arrows) in comparison with Non-sarcopenia HF group (0.94+/-0.63, P=0.002). Although age, gender, BNP and hemodynamic factors were similar between groups, sarcopenia HF group had a lower survival rate (Figure B). Conclusions: HF patients with sarcopenia without dementia have potential risk of CI and poor prognosis.

The Effects of Engineered Skeletal Muscle on Volumetric Muscle Loss in The Tibialis Anterior Of Rat After Three Months In Vivo.

Volumetric muscle loss (VML) is traumatic, degenerative, or surgical loss of skeletal muscle that exceeds the regenerative capacity of the remaining muscle, thus resulting in impaired muscle function. In humans, the loss of 30% or more mass of any one muscle will result in permanent structural and functional loss. Current VML repair treatments are limited by donor site morbidity and graft tissue availability, necessitating alternative muscle graft sources. To address this need, our lab has fabricated tissue-engineered skeletal muscle units (SMUs) for implantation into a 30 % VML model in the tibialis anterior (TA) muscle of rat. Previous results showed that after 28 days in vivo, muscle with a 30% VML repaired with our SMUs produced significantly more force than muscle with acute VML. But repair with our SMU did not fully restore muscle force production to that of native muscle. Thus, we hypothesized that more time for in vivo tissue regeneration would allow for greater force recovery. Therefore, the purpose of this study was to examine the long-term (3-month) effects of our SMUs on a 30% VML repair. We also assessed the effects of reinnervation by redirecting a branch of the peroneal nerve to the repair site. Thirty-nine, 2-month old female F344 rats were separated into a nonsurgical control group (n=5) and four surgical experimental groups (VML Only, n=5; VML+Nerve Redirect, n=6; VML+SMU, n=5; VML+SMU+ Nerve Redirect, n=8). Experimental rats were allowed a 3-month recovery period post-surgery before undergoing in situ force testing of the surgical (left) TA. The left TA of the control animals also underwent in situ force testing. Finally, the surgical (left) and contralateral (right) TAs of the experimental animals, as well as the left TA of the control animals, were explanted for histological analysis. Results for specific force showed that while all groups recovered specific forces similar to that of native muscle, the two SMU groups had significantly higher specific forces, on average, compared to the uninjured control group. Histological staining showed small muscle fibers in the repair site in animals that received an SMU. The average cross-sectional area of the native fibers just outside the area of repair (or the equivalent area in control animals) was not significantly different between groups, indicating that hypertrophy of remaining fibers did not contribute to the recovery of force following the VML. Our results suggest that following a 30% VML of the TA muscle, all surgical groups were able to recover TA mass, maximum tetanic and specific force production. Thus, creating a 30% VML in the TA in a rat model is not enough a sufficient VML to produce the sustained VML seen in humans following similar 30% loss of muscle volume.