Effect of Glycyrrhiza uralensis crude water extract on the expression of Nitric Oxide Synthase 2 gene during myogenesis.

Glycyrrhiza uralensis is a traditional herbal medicine with significant bioactivity. This study investigated the effect of G. uralensis crude water extract (GU-CWE) on nitric oxide synthase 2 (NOS2) expression during myogenesis. GU-CWE treatment increased myoblast differentiation by downregulating NOS2 and upregulating myogenic regulatory factors (MYOD, MYOG, and MYH). Notably, this effect was supported by an observed decrease in NOS2 expression in the gastrocnemius tissues of mice treated with GU-CWE. In addition, GU-CWE treatment and NOS2 knockdown were associated with reductions in reactive oxygen species levels. We further elucidate the role of the NOS2 gene in myoblast differentiation, demonstrating that its role was expression dependent, being beneficial at low expression but detrimental at high expression. High NOS2 gene expression induced oxidative stress, whereas its low expression impaired myotube formation. These findings highlight that the modulation of NOS2 expression by G. uralensis can potentially be use for managing muscle wasting disorders.

The mortality burden of cachexia or weight loss in patients with colorectal or pancreatic cancer: A systematic literature review.

Cancer-associated cachexia is a multifactorial wasting disorder characterized by anorexia, unintentional weight loss (skeletal muscle mass with or without loss of fat mass), progressive functional impairment, and poor prognosis. This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with colorectal or pancreatic cancer in recent literature. The SLR was conducted following PRISMA guidelines. Embase® and PubMed were searched to identify articles published in English between 1 January 2016 and 10 October 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, defined by international consensus (IC) diagnostic criteria or a broader definition of any weight loss. Included publications were studies in ≥100 patients with colorectal or pancreatic cancer. Thirteen publications in patients with colorectal cancer and 13 with pancreatic cancer met eligibility criteria. Included studies were observational and primarily from Europe and the United States. Eleven studies (42%) reported cachexia using IC criteria and 15 (58%) reported any weight loss. An association between survival and cachexia or weight loss was assessed across studies using multivariate (n = 23) or univariate (n = 3) analyses and within each study across multiple weight loss categories. Cachexia/weight loss was associated with a statistically significantly poorer survival in at least one weight loss category in 16 of 23 studies that used multivariate analyses and in 1 of 3 studies (33%) that used univariate analyses. Of the 17 studies demonstrating a significant association, 9 were in patients with colorectal cancer and 8 were in patients with pancreatic cancer. Cachexia or weight loss was associated with significantly poorer survival in patients with colorectal or pancreatic cancer in nearly two-thirds of the studies. The classification of weight loss varied across and within studies (multiple categories were evaluated) and may have contributed to variability. Nonetheless, awareness of cachexia and routine assessment of weight change in clinical practice in patients with colorectal or pancreatic cancer could help inform prognosis and influence early disease management strategies.

Comparison between Effect of Indirect Calorimetry vs Weight-based Equation (25 kcal/kg/day)-guided Nutrition on Quadriceps Muscle Thickness as Assessed by Bedside Ultrasonography in Medical Intensive Care Unit Patients: A Randomized Clinical Trial.

Aim and background: Sarcopenia is a substantial contributor to intensive care unit (ICU)-acquired weakness and is associated with significant short- and long-term outcomes. It can, however, be mitigated by providing appropriate nutrition. Indirect calorimetry (IC) is believed to be the gold standard in determining caloric targets in the dynamic environment of critical illness. We conducted this study to compare the effect of IC vs weight-based (25 kcal/kg/day) feeding on quadriceps muscle thickness (QMT) by ultrasound in critically ill patients. Materials and methods: A prospective study was conducted on 60 mechanically ventilated patients randomized to two groups [weight-based equation (WBE) group or the IC group] in medical ICU after obtaining institutional ethics committee approval, and fed accordingly. The right QMT measurement using ultrasound and caloric targets were documented on day 1, 3 and 7 and analyzed statistically. The IC readings were obtained from the metabolic cart E-COVX ModuleTM. Results: The baseline demographics, APACHE-II, NUTRIC score, and SOFA scores on day 1, 3, and 7 were comparable between the two groups. The resting energy expenditure (REE) obtained in the IC group was significantly less than the WBE energy targets and the former were fed with significantly less calories. A significantly less percent reduction of QMT in the IC group compared with the WBE group was observed from day 1 to day 3, day 3 to day 7, and day 1 to day 7. Conclusion: From our study, we conclude that IC-REE-based nutrition is associated with lesser reduction in QMT and lesser calories fed in critically ill mechanically ventilated patients compared from WBE. CTRI registration-CTRI/2023/01/049119. How to cite this article: Chandrasekaran A, Pal D, Harne R, Patel SJ, Jagadeesh KN, Pachisia AV, et al. Comparison between Effect of Indirect Calorimetry vs Weight-based Equation (25 kcal/kg/day)-guided Nutrition on Quadriceps Muscle Thickness as Assessed by Bedside Ultrasonography in Medical Intensive Care Unit Patients: A Randomized Clinical Trial. Indian J Crit Care Med 2024;28(6):587-594.

Decreased skeletal muscle intramyocellular lipid droplet-mitochondrial contact contributes to myosteatosis in cancer cachexia.

Cancer cachexia, the unintentional loss of lean mass, contributes to functional dependency, poor treatment outcomes, and decreased survival. Although its pathogenicity is multifactorial, metabolic dysfunction remains a hallmark of cachexia. However, significant knowledge gaps exist in understanding the role of skeletal muscle lipid metabolism and dynamics in this condition. We examined skeletal muscle metabolic dysfunction, intramyocellular lipid droplet (LD) content, LD morphology and subcellular distribution, and LD-mitochondrial interactions using the Lewis lung carcinoma (LLC) murine model of cachexia. C57/BL6 male mice (n = 20) were implanted with LLC cells (106) in the right flank or underwent PBS sham injections. Skeletal muscle was excised for transmission electron microscopy (TEM; soleus), oil red O/lipid staining [tibialis anterior (TA)], and protein (gastrocnemius). LLC mice had a greater number (232%; P = 0.006) and size (130%; P = 0.023) of intramyocellular LDs further supported by increased oil-red O positive (87%; P = 0.0109) and "very high" oil-red O positive (178%; P = 0.0002) fibers compared with controls and this was inversely correlated with fiber size (R2 = 0.5294; P < 0.0001). Morphological analyses of LDs show increased elongation and complexity [aspect ratio: intermyofibrillar (IMF) = 9%, P = 0.046) with decreases in circularity [circularity: subsarcolemmal (SS) = 6%, P = 0.042] or roundness (roundness: whole = 10%, P = 0.033; IMF = 8%, P = 0.038) as well as decreased LD-mitochondria touch (-15%; P = 0.006), contact length (-38%; P = 0.036), and relative contact (86%; P = 0.004). Furthermore, dysregulation in lipid metabolism (adiponectin, CPT1b) and LD-associated proteins, perilipin-2 and perilipin-5, in cachectic muscle (P < 0.05) were observed. Collectively, we provide evidence that skeletal muscle myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in a preclinical model of cancer cachexia.NEW & NOTEWORTHY We sought to advance our understanding of skeletal muscle lipid metabolism and dynamics in cancer cachexia. Cachexia increased the number and size of intramyocellular lipid droplets (LDs). Furthermore, decreases in LD-mitochondrial touch, contact length, and relative contact along with increased LD shape complexity with decreases in circularity and roundness. Dysregulation in lipid metabolism and LD-associated proteins was also documented. Collectively, we show that myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in cancer cachexia.

Physical performance and plasma metabolic profile as potential prognostic factors in metastatic lung cancer patients.

BACKGROUND: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells. METHODS: This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis. RESULTS: We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance. CONCLUSION: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.

Nexus Between Sarcopenia and Microbiome Research: A Bibliometric Exploration.

Despite over 30 years of microbiome and skeletal muscle research, no quantitative analysis of sarcopenia and the microbiome literature had been conducted. Our bibliometric study examined research status, hotspots, and future trends. We utilized bibliometric techniques to search the Science Citation Index Extended Database on February 27, 2023, using the Bibliometrix package in R to create a map displaying scientific production and subject categories. Collaborative network maps between countries/regions were visualized using Scimago Graphica, while VOSviewer explored collaboration modes among individuals and institutions. We analyzed the top 25 emerging keywords, top co-occurring keyword networks, and co-occurring keyword clusters using CiteSpace. A total of 997 articles were retrieved for sarcopenia and microbiome, of which 633 papers were analyzed. Both the number of publications and total citation frequency had been continuously increasing. The United States had the highest total citation frequency, while China had the highest number of publications. Research on the impact of the microbiome on sarcopenia was in its nascent stage and spans multiple disciplines, including nutrition, microbiology, geriatrics, immunology, endocrinology and metabolism, molecular biology, and sports medicine. The University of Copenhagen contributed the most to the number of publications (n=16), with Tibbett M (n=7) and Hulver MW (n=7) among the top authors. The most published journal was "Nutrients" (n=24). Analysis of keywords and clusters revealed new research hotspots in microbes and sarcopenia, such as malnutrition, dietary fiber, signaling pathways, frailty, and intestinal permeability. Research on the impact of the microbiome on sarcopenia is in its infancy and spans multiple disciplines. Malnutrition, dietary fiber, signaling pathways, frailty, and intestinal microbes are currently research hotspots. Furthermore, the visual atlas analysis of research on microbes and sarcopenia helps to track the knowledge structure in research fields related to sarcopenia and microbes, providing direction for future research.

C-C chemokine ligand 2 signaling promotes skeletal muscle wasting in non-tumor and breast tumor mouse models.

Despite advancements in treatment, approximately 25% of breast cancer patients experience long-term skeletal muscle wasting (SMW), which limits mobility, reduces drug tolerance and adversely impacts survival. By understanding the underlying molecular mechanisms of SMW, we may develop new strategies to alleviate this condition and improve the lives of breast cancer patients. Chemokines are small soluble factors that regulate homing of immune cells to tissues during inflammation. In breast cancers, overexpression of the C-C chemokine ligand 2 (CCL2) correlates with unfavorable prognosis. Elevated levels of CCL2 in peripheral blood indicate possible systemic effects of this chemokine in breast cancer patients. Here, we investigated the role of CCL2 signaling on SMW in a tumor and non-tumor context. In vitro, increasing concentrations of CCL2 inhibits myoblast and myotube function through C-C chemokine receptor 2 (CCR2) dependent mechanisms involving JNK, SMAD3 and AMPK signaling. In healthy mice, delivery of recombinant CCL2 protein promotes SMW in a dose dependent manner. In vivo knockdown of breast tumor derived CCL2 partially protects against SMW. Overall, chronic, upregulated CCL2/CCR2 signaling positively regulates SMW, with implications on therapeutic targeting.

Gracilaria chorda attenuates obesity-related muscle wasting through activation of SIRT1/PGC1α in skeletal muscle of mice.

Gracilaria chorda (GC) is a red algal species that is primarily consumed in Asia. Here, we investigated the effect of GC on obesity-related skeletal muscle wasting. Furthermore, elucidating its impact on the activation of sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) constituted a critical aspect in understanding the underlying mechanism of action. In this study, 6-week-old male C57BL/6 mice were fed a high-fat diet (HFD) for 8 weeks to induce obesity, then continued on the HFD for another 8 weeks while orally administered GC. GC decreased ectopic fat accumulation in skeletal muscle and increased muscle weight, size, and function in obese mice. Furthermore, GC reduced skeletal muscle atrophy and increased hypertrophy in mice. We hypothesized that the activation of SIRT1/PGC1α by GC regulates skeletal muscle atrophy and hypertrophy. We observed that GC increased the expression of SIRT1 and PGC1α in skeletal muscle of mice and in C2C12 cells, which increased mitochondrial function and biogenesis. In addition, when C2C12 cells were treated with the SIRT1-specific inhibitor EX-527, no changes were observed in the protein levels of SIRT1 and PGC1α in the GC-treated C2C12 cells. Therefore, GC attenuated obesity-related muscle wasting by improving mitochondrial function and biogenesis through the activation of SIRT1/PGC1α in the skeletal muscle of mice.

Restoring Skeletal Muscle Health through Exercise in Breast Cancer Patients and after Receiving Chemotherapy.

Breast cancer (BC) stands out as the most commonly type of cancer diagnosed in women worldwide, and chemotherapy, a key component of treatment, exacerbates cancer-induced skeletal muscle wasting, contributing to adverse health outcomes. Notably, the impact of chemotherapy on skeletal muscle seems to surpass that of the cancer itself, with inflammation identified as a common trigger for muscle wasting in both contexts. In skeletal muscle, pro-inflammatory cytokines modulate pathways crucial for the delicate balance between protein synthesis and breakdown, as well as satellite cell activation and myonuclear accretion. Physical exercise consistently emerges as a crucial therapeutic strategy to counteract cancer and chemotherapy-induced muscle wasting, ultimately enhancing patients' quality of life. However, a "one size fits all" approach does not apply to the prescription of exercise for BC patients, with factors such as age, menopause and comorbidities influencing the response to exercise. Hence, tailored exercise regimens, considering factors such as duration, frequency, intensity, and type, are essential to maximize efficacy in mitigating muscle wasting and improving disease outcomes. Despite the well-established anti-inflammatory role of aerobic exercise, resistance exercise proves equally or more beneficial in terms of mass and strength gain, as well as enhancing quality of life. This review comprehensively explores the molecular pathways affected by distinct exercise regimens in the skeletal muscle of cancer patients during chemotherapy, providing critical insights for precise exercise implementation to prevent skeletal muscle wasting.

Unveiling the detrimental vicious cycle linking skeletal muscle and COVID-19: A systematic review and meta-analysis.

OBJECTIVE: Skeletal muscle catabolism supports multiple organs and systems during severe trauma and infection, but its role in COVID-19 remains unclear. This study investigates the interactions between skeletal muscle and COVID-19. METHODS: The PubMed, EMbase, and The Cochrane Library databases were systematically searched from January 2020 to August 2023 for cohort studies focusing on the impact of skeletal muscle on COVID-19 prevalence and outcomes, and longitudinal studies examining skeletal muscle changes caused by COVID-19. Skeletal muscle quantity (SMQN) and quality (SMQL) were assessed separately. The random-effect model was predominantly utilized for statistical analysis. RESULTS: Seventy studies with moderate to high quality were included. Low SMQN/SMQL was associated with an increased risk of COVID-19 infection (OR = 1.62, p < 0.001). Both the low SMQN and SMQL predicted COVID-19-related mortality (OR = 1.53, p = 0.016; OR = 2.18, p = 0.001, respectively). Mortality risk decreased with increasing SMQN (OR = 0.979, p = 0.009) and SMQL (OR = 0.972, p = 0.034). Low SMQN and SMQL were also linked to the need for intensive care unit/mechanical ventilation, increased COVID-19 severity, and longer hospital stays. Significant skeletal muscle wasting, characterized by reduced volume and strength, was observed during COVID-19 infection and the pandemic. CONCLUSIONS: This study reveals a detrimental vicious circle between skeletal muscle and COVID-19. Effective management of skeletal muscle could be beneficial for treating COVID-19 infections and addressing the broader pandemic. These findings have important implications for the management of future virus pandemics. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023395476.

Targeted nutritional intervention attenuates experimental lung cancer cachexia.

BACKGROUND: Cachexia, a syndrome with high prevalence in non-small cell lung cancer patients, impairs quality of life and reduces tolerance and responsiveness to cancer therapy resulting in decreased survival. Optimal nutritional care is pivotal in the treatment of cachexia and a recommended cornerstone of multimodal therapy. Here, we investigated the therapeutic effect of an intervention diet consisting of a specific combination of high protein, leucine, fish oil, vitamin D, galacto-oligosaccharides, and fructo-oligosaccharides on the development and progression of cachexia in an orthotopic lung cancer mouse model. METHODS: Eleven-week-old male 129S2/Sv mice were orthotopically implanted with 344P lung epithelial tumour cells or vehicle (control). Seven days post-implantation tumour-bearing (TB) mice were allocated to either intervention- or isocaloric control diet. Cachexia was defined as 5 days of consecutive body weight loss, after which mice were euthanized for tissue analyses. RESULTS: TB mice developed cachexia accompanied by significant loss of skeletal muscle mass and epididymal fat mass compared with sham operated mice. The cachectic endpoint was significantly delayed (46.0 ± 15.2 vs. 34.7 ± 11.4 days), and the amount (-1.57 ± 0.62 vs. -2.13 ± 0.57 g) and progression (-0.26 ± 0.14 vs. -0.39 ± 0.11 g/day) of body weight loss were significantly reduced by the intervention compared with control diet. Moreover, systemic inflammation (pentraxin-2 plasma levels) and alterations in molecular markers for proteolysis and protein synthesis, indicative of muscle atrophy signalling in TB-mice, were suppressed in skeletal muscle by the intervention diet. CONCLUSIONS: Together, these data demonstrate the potential of this multinutrient intervention, targeting multiple components of cachexia, as integral part of lung cancer management.

The therapeutic effect of NRF2 activator, ezetimibe, in cardiac cachexia.

INTRODUCTION: Heart failure (HF) is caused by functional and structural irregularity leading to impaired ejection or filling capacity of the heart. HF leads to chronic inflammatory conditions in the heart leads to weight loss, anorexia, and muscle atrophy known as cachexia. The present study was carried out to investigate the role of Ezetimibe, an NRF2 activator, in cardiac cachexia and to develop a treatment strategy for cardiac cachexia. METHOD: Balb/c mice of either sex at 6-8 weeks of age were given 2 mg/kg of doxorubicin in 0.9% sodium chloride solution intraperitoneally (i.p.) for the alternate days for the first week and then once a week for the next 4 weeks. After induction of cardiac atrophy, treatment with Ezetimibe (1.5 mg/kg, p.o) was given for the next 4 weeks. RESULT: In the cardiac cachectic animals, a significant decrease in body weight, food, and water intake was observed. Cardiac cachectic animals showed a significant increase in serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH, and CRP levels. Cardiac atrophic index, heart weight to body weight ratios (HW/BW), right ventricular weight to heart weight ratios (RV/HW), and left ventricular weight to heart weight ratios (LV/HW), were significantly decreased in cardiac cachectic animals. The weights of the skeletal muscles such as EDL, gastrocnemius, soleus, tibialis anterior, and quadriceps muscles, and the weight of adipose tissue such as subcutaneous, visceral, perirenal, and brown adipose tissue were significantly decreased in the cardiac cachectic group relative to the normal group. Treatment with ezetimibe improves body weight, food intake, and water intake. Ezetimibe decreases serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH and CRP levels. Cardiac atrophic markers such as HW/BW, RV/HW, and LV/HW were improved. The weight of skeletal muscles and adipose tissue was increased after treatment with ezetimibe. CONCLUSION: Our data showed that the NRF2 activator, Ezetimibe produces a beneficial effect on cardiac cachexia in the doxorubicin-induced cardiac cachexia model. Ezetimibe was successful to reduce the levels of inflammatory cytokines, ameliorate the effects on cardiac muscle wasting, lipid levels, fat tissues, and skeletal muscles.

Incorporating ultrasonography to the nutritional assessment process in intensive care settings to improve the prescription of enteral and parenteral nutrition: Benefits, practicality, and challenges.

The validity of the traditional nutritional assessment tools in intensive care settings might be compromised when the patient has conditions such as oedema and inflammation. Ultrasound (US) is considered a non-invasive, bedside tool that can be utilized to assess changes in muscle mass. Hence, US could guide healthcare practitioners in identifying the varying degrees of malnutrition and adjusting the nutritional prescription accordingly. This review discusses the currently available data regarding the feasibility and practicality of using US measurements in intensive care settings. Overall, the data suggest that using US as part of the standard anthropometric assessment for critically ill patients is a promising tool to track variations in muscle mass. This has the potential to enhance nutritional prescription and tailor the provision of protein and energy to critically ill patients based on their lean body mass measurements. Therefore, it is recommended to train dietitians on utilizing US for body composition measurements.

Nocturnal Hypoxemia Is Associated with Sarcopenia in Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Our previous studies have identified that nocturnal hypoxemia causes skeletal muscle loss (i.e., sarcopenia) in in vitro models of COPD. Objectives: We aimed to extend our preclinical mechanistic findings by analyzing a large sleep registry to determine whether nocturnal hypoxemia is associated with sarcopenia in patients with COPD. Methods: Sleep studies from patients with COPD (n = 479) and control subjects without COPD (n = 275) were analyzed. Patients with obstructive sleep apnea, as defined by apnea-hypopnea index ⩾ 5, were excluded. Pectoralis muscle cross-sectional area (PMcsa) was quantified using computed tomography scans performed within 1 year of the sleep study. We defined sarcopenia as less than the lowest 20% residuals for PMcsa of control subjects, which was adjusted for age and body mass index (BMI) and stratified by sex. Youden's optimal cut-point criteria were used to predict sarcopenia based on mean oxygen saturation during sleep. Additional measures of nocturnal hypoxemia were analyzed. The pectoralis muscle index (PMI) was defined as PMcsa normalized to BMI. Results: On average, males with COPD had a 16.6% lower PMI than control males (1.41 ± 0.44 vs. 1.69 ± 0.56 cm2/BMI; P < 0.001), whereas females with COPD had a 9.4% lower PMI than control females (0.96 ± 0.27 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). Males with COPD with nocturnal hypoxemia had a 9.5% decrease in PMI versus COPD with normal O2 (1.33 ± 0.39 vs. 1.47 ± 0.46 cm2/BMI; P < 0.05) and a 23.6% decrease compared with control subjects (1.33 ± 0.39 vs. 1.74 ± 0.56 cm2/BMI; P < 0.001). Females with COPD with nocturnal hypoxemia had an 11.2% decrease versus COPD with normal O2 (0.87 ± 0.26 vs. 0.98 ± 0.28 cm2/BMI; P < 0.05) and a 17.9% decrease compared with control subjects (0.87 ± 0.26 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). These findings were largely replicated using multiple measures of nocturnal hypoxemia. Conclusions: We defined sarcopenia in the pectoralis muscle using residuals that take into account age, BMI, and sex. We found that patients with COPD have a lower PMI than patients without COPD and that nocturnal hypoxemia was associated with an additional decrease in the PMI of patients with COPD. Additional prospective analyses are needed to determine a protective threshold of oxygen saturation to prevent or reverse sarcopenia due to nocturnal hypoxemia in COPD.

Acute Skeletal Muscle Wasting is Associated with Prolonged Hospital Stay in Critical Illness with Brain Injury.

BACKGROUND: Acute muscle wasting is common in critically ill patients, and this can lead to unfavorable clinical outcomes. The aim of this study was to identify factors associated with muscle wasting and to investigate the association between skeletal muscle wasting and prolonged hospital stay in critically ill patients with acute brain injury. METHODS: This single-center prospective observational study was conducted in critically ill patients with acute brain injury who stayed in the intensive care unit for at least 1 week. The rectus femoris cross-sectional area was measured via ultrasound at baseline and a week after the first assessment. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted prolonged hospital stay. RESULTS: A total of 86 patients were included in the study. Their mean age was 49.4 ± 16.9 years, 57% were male, and 46.5% had an admission diagnosis of subarachnoid hemorrhage. The percentage change in the rectus femoris cross-sectional area was 15.8% (95% confidence interval [CI] - 19.8% to - 12.0%; p < 0.001), and 57% of all patients had acute muscle wasting. According to the univariate analysis, there was a significant association between prolonged hospital stay and acute muscle wasting (odds ratio [OR] 3.677; 95% CI 1.487-9.043; p = 0.005), mechanical ventilation status (OR 3.600; 95% CI 1.455-8.904; p = 0.006), and Glasgow Coma Scale score (OR 0.888; 95% CI 0.808-0.976; p = 0.014) at intensive care unit admission. The multivariate analysis demonstrated that acute muscle wasting (OR 3.449; 95% CI 1.344-8.853; p = 0.010) was an independent risk factor for prolonged hospital stay. CONCLUSIONS: There was considerable muscle wasting in critically ill patients with brain injuries over a 1-week period. Acute muscle wasting was associated with prolonged hospital stay in critically ill patients with acute brain injury.

Clinical evaluation of AI-assisted muscle ultrasound for monitoring muscle wasting in ICU patients.

Muscle ultrasound has been shown to be a valid and safe imaging modality to assess muscle wasting in critically ill patients in the intensive care unit (ICU). This typically involves manual delineation to measure the rectus femoris cross-sectional area (RFCSA), which is a subjective, time-consuming, and laborious task that requires significant expertise. We aimed to develop and evaluate an AI tool that performs automated recognition and measurement of RFCSA to support non-expert operators in measurement of the RFCSA using muscle ultrasound. Twenty patients were recruited between Feb 2023 and July 2023 and were randomized sequentially to operators using AI (n = 10) or non-AI (n = 10). Muscle loss during ICU stay was similar for both methods: 26 ± 15% for AI and 23 ± 11% for the non-AI, respectively (p = 0.13). In total 59 ultrasound examinations were carried out (30 without AI and 29 with AI). When assisted by our AI tool, the operators showed less variability between measurements with higher intraclass correlation coefficients (ICCs 0.999 95% CI 0.998-0.999 vs. 0.982 95% CI 0.962-0.993) and lower Bland Altman limits of agreement (± 1.9% vs. ± 6.6%) compared to not using the AI tool. The time spent on scans reduced significantly from a median of 19.6 min (IQR 16.9-21.7) to 9.4 min (IQR 7.2-11.7) compared to when using the AI tool (p < 0.001). AI-assisted muscle ultrasound removes the need for manual tracing, increases reproducibility and saves time. This system may aid monitoring muscle size in ICU patients assisting rehabilitation programmes.

Unveiling the Intricate Dance: How Cancer Orchestrates Muscle Wasting and Sarcopenia.

Sarcopenia is a prevalent and clinically significant condition, particularly among older age groups and those with chronic disease. Patients with cancer frequently suffer from sarcopenia and progressive loss of muscle mass, strength, and function. The complex interplay between cancer and its treatment, including medical therapy, radiotherapy, and surgery, significantly contributes to the onset and worsening of sarcopenia. Cancer induces muscle wasting through inflammatory processes, metabolic alterations, and hormonal imbalance. Moreover, medical and radiation therapies exert direct toxic effects on muscles, contributing to the impairment of physical function. Loss of appetite, malnutrition, and physical inactivity further exacerbate muscle wasting in cancer patients. Imaging techniques are the cornerstones for sarcopenia diagnosis. Magnetic resonance imaging, computed tomography, and dual-energy X-ray absorptiometry provide valuable insights into muscle structure and quality. Although each modality has advantages and limitations, magnetic resonance imaging produces high-resolution images and provides dynamic information about muscle function. Despite these challenges, addressing sarcopenia is essential for optimizing treatment outcomes and improving survival rates in patients with cancer. This review explored the factors contributing to sarcopenia in oncologic patients, emphasizing the importance of early detection and comprehensive management strategies.

Exploring the Gut Microbiota-Muscle Axis in Duchenne Muscular Dystrophy.

The gut microbiota plays a pivotal role in maintaining the dynamic balance of intestinal epithelial and immune cells, crucial for overall organ homeostasis. Dysfunctions in these intricate relationships can lead to inflammation and contribute to the pathogenesis of various diseases. Recent findings uncovered the existence of a gut-muscle axis, revealing how alterations in the gut microbiota can disrupt regulatory mechanisms in muscular and adipose tissues, triggering immune-mediated inflammation. In the context of Duchenne muscular dystrophy (DMD), alterations in intestinal permeability stand as a potential origin of molecules that could trigger muscle degeneration via various pathways. Metabolites produced by gut bacteria, or fragments of bacteria themselves, may have the ability to migrate from the gut into the bloodstream and ultimately infiltrate distant muscle tissues, exacerbating localized pathologies. These insights highlight alternative pathological pathways in DMD beyond the musculoskeletal system, paving the way for nutraceutical supplementation as a potential adjuvant therapy. Understanding the complex interplay between the gut microbiota, immune system, and muscular health offers new perspectives for therapeutic interventions beyond conventional approaches to efficiently counteract the multifaceted nature of DMD.

Lacticaseibacillus paracasei LC86 mitigates age-related muscle wasting and cognitive impairment in SAMP8 mice through gut microbiota modulation and the regulation of serum inflammatory factors.

Purpose: Chronic inflammation contributes to the decline in muscle strength and cognitive abilities associated with aging. This study aims to clarify the effects of oral administration of Lacticaseibacillus paracasei LC86 on these age-related declines, as well as its impact on the composition of gut microbiota. Methods: Senescence-accelerated mouse prone 8 (SAMP8) mice received a 12 week regimen of LC86 (1 × 109 CFU/day). Muscle strength was assessed through forelimb grip strength and four-limb hanging tests. Cognitive function was evaluated through behavioral performance tests, and changes in gut microbiota were analyzed. Results: Administration of LC86 significantly enhanced muscle strength, demonstrated by increased grip strength and higher glycogen content in the gastrocnemius muscle (p = 0.041, p = 0.017, and p = 0.000, respectively). Behavioral tests suggested that LC86 mitigated age-related cognitive decline. Furthermore, there was a significant decrease in serum pro-inflammatory cytokines, such as IL-6, TNF-α, and MCP-1 (p = 0.002, p = 0.000, and p = 0.005, respectively), and an elevation in the anti-inflammatory cytokine IL-10 level (p = 0.000). An increase in hepatic antioxidant capacity was observed. Significant changes in the gut microbiota composition were noted, including increased populations of Bifidobacterium and Lactobacillus and decreased levels of Escherichia/Shigella and Bacteroides. Conclusion: The findings suggest that LC86 supplementation mitigates muscle weakness and cognitive impairment in aging SAMP8 mice, potentially through the modulation of inflammation and gut microbiota composition. LC86 emerges as a promising candidate for ameliorating the decline of muscular and cognitive functions associated with aging.

Superoxide is an Intrinsic Signaling Molecule Triggering Muscle Hypertrophy.

Aims: Redox signaling plays a key role in skeletal muscle remodeling induced by exercise and prolonged inactivity, but it is unclear which oxidant triggers myofiber hypertrophy due to the lack of strategies to precisely regulate individual oxidants in vivo. In this study, we used tetrathiomolybdate (TM) to dissociate the link between superoxide (O2•-) and hydrogen peroxide and thereby to specifically explore the role of O2•- in muscle hypertrophy in C2C12 cells and mice. Results: TM can linearly regulate intracellular O2•- levels by inhibition of superoxide dismutase 1 (SOD1). A 70% increase in O2•- levels in C2C12 myoblast cells and mice is necessary and sufficient for triggering hypertrophy of differentiated myotubes and can enhance exercise performance by more than 50% in mice. SOD1 knockout blocks TM-induced O2•- increments and thereby prevents hypertrophy, whereas SOD1 restoration rescues all these effects. Scavenging O2•- with antioxidants abolishes TM-induced hypertrophy and the enhancement of exercise performance, whereas the restoration of O2•- levels with a O2•- generator promotes muscle hypertrophy independent of SOD1 activity. Innovation and Conclusion: These findings suggest that O2•- is an endogenous initiator of myofiber hypertrophy and that TM may be used to treat muscle wasting diseases. Our work not only suggests a novel druggable mechanism to increase muscle mass but also provides a tool for precisely regulating O2•- levels in vivo.