OBJECTIVE: Sarcopenia is the generalized loss of muscle strength, mass, and function. The aim was to investigate whether pretherapeutic sarcopenia, as determined by the psoas muscles, affects therapy-mediated toxicity in patients with malignant melanoma undergoing immunotherapy.
METHODS: Measurement of psoas musculature was performed pretherapeutically using computed tomography at the level of the third lumbar vertebra in the axial plane in 75 patients between January 2011 and December 2020. Sarcopenia was defined using the psoas muscle index (PMI). Immune-related toxicity was retrospectively assessed.
RESULTS: Treatment-related toxicity was recorded in 33 of the 75 patients (44%). Of these, 16 patients (36.2%) experienced dose-limiting severe events (DLT). Pretherapeutic sarcopenia was identified in 25 patients (33.3%). Comparative analysis showed that the patients with a DLT had lower PMI values compared with the patient group without a DLT (4.65 ± 1.33 vs. 5.79 ± 1.67 cm2m-2, p = 0.015) (odds ratio = 0.60, 95% confidence interval 0.40-0.92, p = 0.02).
CONCLUSIONS: Pretherapeutic sarcopenia measured based on the psoas muscle is not a significant predictor of immune-mediated toxicity in patients with malignant melanoma treated with immune checkpoint inhibitors. Patients with DLT have lower values for the psoas muscle parameters PMI compared to the group of patients without DLT.
UNASSIGNED: HINTERGRUND: Sarkopenie ist die Verminderung der Muskelkraft und -masse sowie Einschränkung der Funktion. Das Ziel der vorliegenden Studie war es zu untersuchen, ob die anhand der Psoasmuskulatur bestimmte prätherapeutische Sarkopenie die therapievermittelte Toxizität bei Patienten mit malignem Melanom unter einer Immuncheckpoint-Inhibition beeinflusst.
UNASSIGNED: Die Vermessung der Psoasmuskulatur erfolgte prätherapeutisch mithilfe der Computertomographie auf der Höhe des 3. Lendenwirbelkörpers (LWK) bei 75 Patienten zwischen Januar 2011 und Dezember 2020. Die Sarkopenie wurde anhand des Psoasmuskelindex (PMI) definiert. Die immunvermittelte Toxizität wurde retrospektiv ermittelt.
UNASSIGNED: Bei 33 der 75 Patienten (44 %) wurde eine behandlungsbedingte Toxizität unter Therapie mit Immuncheckpoint-Inhibitoren registriert. Davon erlitten 16 Patienten (36,2 %) eine dosislimitierende schwere Toxizität (DLT). Eine prätherapeutische Sarkopenie wurde bei 25 Patienten (33,3 %) ermittelt. Die Vergleichsanalyse ergab, dass die Patienten mit einer DLT im Vergleich zu der Patientengruppe ohne DLT niedrigere PMI-Werte aufwiesen (4,65 ± 1,33 vs. 5,79 ± 1,67 cm2m−2, p = 0,015) (OR = 0,60, 95 %-KI: 0,40–0,92, p = 0,02).
UNASSIGNED: Die anhand der Psoasmuskulatur gemessene prätherapeutische Sarkopenie ist kein signifikanter Prädiktor für DLT bei Patienten mit malignem Melanom unter einer Immuncheckpoint-Inhibition. Patienten mit einer DLT weisen jedoch im Vergleich zu der Patientengruppe ohne DLT niedrigere Werte für die Psoasmuskelparameter PMI und Gauge auf.

Skeletal muscle atrophy is a morbidity and mortality risk factor that happens with disuse, chronic disease, and aging. The tissue remodeling that happens during recovery from atrophy or injury involves changes in different cell types such as muscle fibers, and satellite and immune cells. Here, we show that the previously uncharacterized gene and protein Zfp697 is a damage-induced regulator of muscle remodeling. Zfp697/ZNF697 expression is transiently elevated during recovery from muscle atrophy or injury in mice and humans. Sustained Zfp697 expression in mouse muscle leads to a gene expression signature of chemokine secretion, immune cell recruitment, and extracellular matrix remodeling. Notably, although Zfp697 is expressed in several cell types in skeletal muscle, myofiber-specific Zfp697 genetic ablation in mice is sufficient to hinder the inflammatory and regenerative response to muscle injury, compromising functional recovery. We show that Zfp697 is an essential mediator of the interferon gamma response in muscle cells and that it functions primarily as an RNA-interacting protein, with a very high number of miRNA targets. This work identifies Zfp697 as an integrator of cell-cell communication necessary for tissue remodeling and regeneration.

BACKGROUND: Dysferlin-deficient limb-girdle muscular dystrophy type 2B (Dysf) mice are notorious for their mild phenotype. Raising plasma total cholesterol (CHOL) via apolipoprotein E (ApoE) knockout (KO) drastically exacerbates muscle wasting in Dysf mice. However, dysferlinopathic patients have abnormally reduced plasma high-density lipoprotein cholesterol (HDL-C) levels. The current study aimed to determine whether HDL-C lowering can exacerbate the mild phenotype of dysferlin-null mice.
METHODS: Human cholesteryl ester transfer protein (CETP), a plasma lipid transfer protein not found in mice that reduces HDL-C, and/or its optimal adapter protein human apolipoprotein B (ApoB), were overexpressed in Dysf mice. Mice received a 2% cholesterol diet from 2 months of age and characterized through ambulatory and hanging functional tests, plasma analyses, and muscle histology.
RESULTS: CETP/ApoB expression in Dysf mice caused reduced HDL-C (54.5%) and elevated ratio of CHOL/HDL-C (181.3%) compared to control Dysf mice in plasma, but without raising CHOL. Compared to the severe muscle pathology found in high CHOL Dysf/ApoE double knockout mice, Dysf/CETP/ApoB mice did not show significant changes in ambulation, hanging capacity, increases in damaged area, collagen deposition, or decreases in cross-sectional area and healthy myofibre coverage.
CONCLUSIONS: CETP/ApoB over-expression in Dysf mice decreases HDL-C without increasing CHOL or exacerbating muscle pathology. High CHOL or nonHDL-C caused by ApoE KO, rather than low HDL-C, likely lead to rodent muscular dystrophy phenotype humanization.

This study aimed to evaluate the influence of combined intermittent fasting (IF) and high-intensity interval training (HIIT) on morphology, caspase-independent apoptosis signaling pathway, and myostatin expression in soleus and gastrocnemius (white portion) muscles from healthy rats. Sixty-day-old male Wistar rats (n = 60) were divided into four groups: control (C), IF, high-intensity-interval training (T), and high-intensity-interval training and intermittent fasting (T-IF). The C and T groups received ad libitum chow daily; IF and T-IF received the same standard chow every other day. Animals from T and T-IF underwent a HIIT protocol five times a week for 12 weeks. IF reduced gastrocnemius mass and increased pro-apoptotic proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in soleus and cleaved-to-non-cleaved PARP-1 ratio and myostatin expression in gastrocnemius white portion. HIIT increased AIF and apoptosis repressor with caspase recruitment domain expression in soleus and cleaved-to-total PARP-1 ratio in gastrocnemius muscle white portion. The combination of IF and HIIT reduced fiber cross-sectional area in both muscles, increased EndoG and AIF expression, and decreased cleaved-to-non-cleaved PARP-1 ratio in gastrocnemius muscle white portion. Muscle responses to IF and HIIT are directly impacted by the muscle fiber type composition and are modulated, at least in part, by myostatin and caspase-independent apoptosis signaling.

Skeletal muscle atrophy, characterized by diminished muscle strength and mass, arises from various causes, including malnutrition, aging, nerve damage, and disease-related secondary atrophy. Aging markedly escalates the prevalence of sarcopenia. Concurrently, the incidence of muscle atrophy significantly rises among patients with chronic ailments such as heart failure, diabetes, and chronic obstructive pulmonary disease (COPD). Epigenetics plays a pivotal role in skeletal muscle atrophy. Aging elevates methylation levels in the promoter regions of specific genes within muscle tissues. This aberrant methylation is similarly observed in conditions like diabetes, neurological disorders, and cardiovascular diseases. This study aims to explore the relationship between epigenetics and skeletal muscle atrophy, thereby enhancing the understanding of its pathogenesis and uncovering novel therapeutic strategies.

BACKGROUND: In healthy individuals, blood flow restriction training (BFRT) has shown positive effects on muscle mass, strength, fatigue resistance, as well as tendon and bone metabolism. BFRT reduces blood flow in the extremities using inflatable cuffs, creating local muscular hypoxia, which produces an anabolic metabolic environment. This promotes significant muscular and cardiovascular adaptations even at low mechanical training loads.
UNASSIGNED: BFRT also shows promising initial results in pre- and postoperative applications for knee endoprostheses (KTEP). Both preoperative and postoperative BFRT can improve muscle strength and joint function, accelerate recovery, and alleviate pain. Although the method is generally safe, potential risks such as discomfort and rare side effects must be considered. Clear application protocols are still lacking, necessitating further research and individualized programs to achieve optimal training effects. BFRT thus offers an innovative way to effectively rehabilitate patients despite their low load tolerance.
UNASSIGNED: HINTERGRUND: Bei der Anwendung an Gesunden werden positiven Effekte des Blutflussrestriktionstrainings (BFRT) auf Muskelmasse, -kraft, Ermüdungsresistenz sowie Sehnen- und Knochenstoffwechsel beschrieben. BFRT reduziert den Blutfluss in den Extremitäten durch aufblasbare Manschetten, wodurch eine lokale muskuläre Hypoxie entsteht, welche ein anaboles Stoffwechselmilieu erzeugt. Dieses fördert auch bei geringen mechanischen Trainingsbelastungen signifikante muskuläre und kardiovaskuläre Anpassungen.
UNASSIGNED: Auch bei Knieendoprothesen (KTEP) zeigt BFRT vielversprechende erste Ergebnisse in der prä- und postoperativen Anwendung. Präoperatives und postoperatives BFRT kann die Muskelkraft und Gelenkfunktion im Bereich des Kniegelenkes verbessern, die Genesung beschleunigen und Schmerzen lindern. Obwohl die Methode meist sicher ist, müssen potenzielle Risiken wie Unbehagen und seltene Nebenwirkungen berücksichtigt werden. Klare Anwendungsprotokolle fehlen noch, weshalb weitere Forschung und individuell angepasste Programme notwendig sind, um die optimalen Trainingseffekte zu erzielen. BFRT bietet somit eine innovative Möglichkeit, Patienten trotz geringer Belastbarkeit effektiv zu rehabilitieren.

OBJECTIVE: The umami taste receptor (TAS1R1/TAS1R3) is endogenously expressed in skeletal muscle and is involved in myogenesis; however, there is a lack of evidence about whether the expression of the umami taste receptor is involved in muscular diseases. This study aimed to elucidate the effects of the umami taste receptor and its mechanism on muscle wasting in cancer cachexia using in vivo and in vitro models.
METHODS: The Lewis lung carcinoma-induced cancer cachexia model was used in vivo and in vitro, and the expressions of umami taste receptor and muscle atrophy-related markers, muscle atrophy F-box protein, and muscle RING-finger protein-1 were analyzed.
RESULTS: Results showed that TAS1R1 was significantly downregulated in vivo and in vitro under the muscle wasting condition. Moreover, overexpression of TAS1R1 in vitro in the human primary cell model protected the cells from muscle atrophy, and knockdown of TAS1R1 using siRNA exacerbated muscle atrophy.
CONCLUSIONS: Taken together, the umami taste receptor exerts protective effects on muscle-wasting conditions by restoring dysregulated muscle atrophy in cancer cachexia. In conclusion, this result provided evidence that the umami taste receptor exerts a therapeutic anti-cancer cachexia effect by restoring muscle atrophy.

UNASSIGNED: The clinical implications of structural integrity have been a subject of long debate. The oversimplified binary categorization of structural integrity into either healing or retear, along with faulty preoperative baselines for comparison, may contribute to the controversy.
UNASSIGNED: To determine how the quality of structural integrity in a repaired cuff tendon affects both clinical and structural outcomes by dividing the patients into groups based on integrity and using the immediate postoperative baseline (time zero).
UNASSIGNED: Cohort study; Level of evidence, 3.
UNASSIGNED: A total of 504 patients with a full-thickness rotator cuff tear who underwent arthroscopic rotator cuff repair and were followed up for at least a year with magnetic resonance imaging (MRI) were included. The quality of structural integrity was graded using the Sugaya classification. To evaluate clinical outcomes, pain, range of motion, strength, functional scores, and overall satisfaction and function were used for within- and between-group analyses at the last follow-up. For the assessment of structural outcomes, the Goutallier classification for fatty infiltration (FI) and the tangent sign, occupation ratio, and normalized cross-sectional area for muscle atrophy (MA) were used. The baselines for these structural measurements were both the preoperative and the time-zero MRI scans.
UNASSIGNED: The mean clinical follow-up period was 31.8 ± 27.5 months, and the MRI follow-up period was 10.9 ± 5.3 months. There were 178 (35.3%), 228 (45.2%), 58 (11.5%), 14 (2.8%), and 26 (5.2%) shoulders with Sugaya grades 1, 2, 3, 4, and 5, respectively. Regardless of structural integrity, all clinical outcomes at a mean follow-up of 31.8 months after repair significantly improved compared with those before repair. Only in shoulders with Sugaya grade 1 did the FI of the supraspinatus muscle improve significantly from baseline. FI of the infraspinatus muscle did not change significantly in those with grades 1 and 2 but worsened in those with grades 3 and 5. MA measured using the occupation ratio improved significantly in shoulders with Sugaya grades 1 and 2 but declined in those with grade 5.
UNASSIGNED: This study established a correlation between improved structural integrity of the repaired cuff tendon and enhanced structural outcomes in rotator cuff muscles. Furthermore, the findings revealed that both FI and MA could be reversed in patients exhibiting high-quality structural integrity. However, these structural improvements were not mirrored in the clinical outcomes.

The deltoid muscle and rotator cuff tissue are structural components that maintain the dynamic stability of the shoulder joint. However, atrophy of the deltoid muscle may affect the stability of the shoulder joint, which in turn alters the mechanical distribution of rotator cuff tissue. Currently, the effect of muscle volume changes in the deltoid muscle on reducing the load on the rotator cuff tissue is still unknown. Therefore, this paper intends to analyze the mechanical changes of rotator cuff tissue by deltoid muscle atrophy through finite elements. Based on previously published finite element shoulder models, the deltoid muscle was modeled by constructing deltoid muscle models with different degrees of atrophy as, 100% deltoid muscle (Group 1), 80% deltoid muscle (Group 2), and 50% deltoid muscle (Group 3), respectively. The three models were given the same external load to simulate glenohumeral joint abduction, and the stress changes in the rotator cuff tissue were analyzed and recorded. In all three models, the stress in the rotator cuff tissue showed different degrees of increase with the increase of abduction angle, especially in the supraspinatus muscle. At 90° of glenohumeral abduction, supraspinatus stress increased by 58% and 118% in Group 2 and Group 3, respectively, compared with Group 1; In the subscapularis, the stress in Group 3 increased by 59% and 25% compared with Group 1 and Group 2, respectively. In addition, the stress of the infraspinatus muscle and teres minor muscle in Group 2 and Group 3 were higher than that in Group 1 during the abduction angle from 30° to 90°. Deltoid atrophy alters the abduction movement pattern of the glenohumeral joint. During glenohumeral abduction activity, deltoid atrophy significantly increases the stress on the rotator cuff tissue, whereas normal deltoid volume helps maintain the mechanical balance of the rotator cuff tissue.

BACKGROUND: Sarcopenia, characterized by degenerative skeletal muscle loss, is increasingly linked to poor surgical outcomes. Glutamine, an immune-modulating formula, may stimulate muscle protein synthesis and inhibit degradation. We used the psoas major muscle area (PMMA) at the third lumbar vertebra, normalized for height (PMMA index), as a skeletal muscle indicator. This study investigates whether perioperative glutamine supplementation mitigates psoas muscle atrophy.
METHODS: We enrolled gastric adenocarcinoma (GA) patients undergoing gastrectomy. Computed tomography assessed the psoas muscle short axis. Muscle atrophy was estimated by changes between preoperative and three-month post-gastrectomy scans. Perioperative glutamine supplementation (PGS) comprised five-day parenteral plus one-month oral use. Propensity score matching minimized potential bias. A linear regression model predicted the association.
RESULTS: Of 516 patients analyzed (2016-2019), 100 (19.4%) received PGS. After propensity score matching, each group contained 97 cases. The PGS group showed a significantly higher median PMMA index change than the non-PGS group (0.3 vs. -0.3 cm2/m2, p = 0.004). Multivariate analysis revealed that PGS was significantly associated with increased PMMA index (coefficient = 0.60; 95% CI: 0.19-1.01; p = 0.005).
CONCLUSIONS: PGS may help restore psoas muscle atrophy in GA patients undergoing gastrectomy. The underlying mechanisms likely relate to glutamine\'s role in protein metabolism and immune function. Further studies are needed to elucidate these mechanisms fully.