-
BioRxiv : the Preprint Server For... Jun 2024Cachexia is a wasting syndrome comprised of adipose, muscle, and weight loss observed in cancer patients. Tumor loss-of-function mutations in , a regulator of the...
Cachexia is a wasting syndrome comprised of adipose, muscle, and weight loss observed in cancer patients. Tumor loss-of-function mutations in , a regulator of the energy sensor AMP-activated protein kinase, induce cancer cachexia (CC) in preclinical models and are associated with cancer-related weight loss in NSCLC patients. Here we characterized the relevance of the NSCLC-associated cachexia factor growth differentiation factor 15 (GDF15) in several patient-derived and genetically engineered -mutant NSCLC cachexia lines. Both tumor mRNA expression and serum concentrations of tumor-derived GDF15 were significantly elevated in multiple mice transplanted with patient-derived -mutated NSCLC lines. GDF15 neutralizing antibody administered to mice transplanted with patient- or mouse-derived -mutated NSCLC lines suppressed cachexia-associated adipose loss, muscle atrophy, and changes in body weight. The silencing of in multiple human NSCLC lines was also sufficient to eliminate circulating GDF15 levels and abrogate cachexia induction, suggesting that tumor and not host tissues represent a key source of GDF15 production in these cancer models. Finally, reconstitution of wild-type in a human loss-of-function NSCLC line that normally induces cachexia correlated with the absence of tumor-secreted GDF15 and rescue from the cachexia phenotype. The current data provide evidence for tumor-secreted GDF15 as a conduit and a therapeutic target through which NSCLCs with loss-of-function mutations promote cachexia-associated wasting.
PubMed: 38948776
DOI: 10.1101/2024.06.14.598891 -
Indian Journal of Orthopaedics Jul 2024Recently the peroneus longus tendon (PLT) gained popularity in anterior cruciate ligament (ACL) reconstruction and has been utilized with satisfactory outcomes. However,...
BACKGROUND
Recently the peroneus longus tendon (PLT) gained popularity in anterior cruciate ligament (ACL) reconstruction and has been utilized with satisfactory outcomes. However, there are concerns regarding donor site morbidity. This study aims to compare the functional outcome of ACL reconstruction using hamstring (HT) and PLT autografts and evaluate the donor site morbidity.
METHODS
Patients who underwent ACL reconstruction were allocated to two groups (HT and PLT). Graft diameter was measured intraoperatively. Knee functional outcome was evaluated with IKDC and Tegner-Lysholm scores preoperatively, and postoperatively after 3 months, 6 months, and 1 year. Donor site morbidities were assessed with thigh circumference measurements, subjective evaluation of sensory disturbances, and ankle scoring with AOFAS and FADI scores.
RESULTS
At 1-year follow-up, the PLT group showed comparable IKDC ( = 0.925) and Tegner-Lysholm ( = 0.600) scores with those of the HT group. The mean graft diameter in the PLT group (7.93 ± 0.52 mm) was larger compared with the HT group (7.43 ± 0.50 mm) ( < 0.001). The incidence of thigh atrophy (HT-16.7%, PLT-10%) and sensory disturbances (HT-73.3%, PLT-10%) was greater in the HT group. There was no significant ankle donor site morbidity in the PLT group (AOFAS-98.67 ± 3.45, FADI-99.23 ± 1.69).
CONCLUSION
ACL reconstruction with PLT had comparable functional outcome with that of HT at 1 year. However, PLT demonstrated larger graft diameter, less donor site morbidity, and enhanced muscle recovery without significantly affecting the ankle function. PLT can be safely used as an acceptable alternative graft choice harvested from outside the knee for ACL reconstruction.
PubMed: 38948366
DOI: 10.1007/s43465-024-01185-5 -
Journal of Experimental Zoology. Part... Jul 2024Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most...
Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most or all distal limb muscle. We previously showed that nascent muscles are present in the jerboa hindfoot at birth and that these myofibers are rapidly and completely lost soon after by a process that shares features with pathological skeletal muscle atrophy. Here, we apply an intra- and interspecies differential RNA-Seq approach, comparing jerboa and mouse muscles, to identify gene expression differences associated with the initiation and progression of jerboa hindfoot muscle loss. We show evidence for reduced hepatocyte growth factor and fibroblast growth factor signaling and an imbalance in nitric oxide signaling; all are pathways that are necessary for skeletal muscle development and regeneration. We also find evidence for phagosome formation, which hints at how myofibers may be removed by autophagy or by nonprofessional phagocytes without evidence for cell death or immune cell activation. Last, we show significant overlap between genes associated with jerboa hindfoot muscle loss and genes that are differentially expressed in a variety of human muscle pathologies and rodent models of muscle loss disorders. All together, these data provide molecular insight into the process of evolutionary and developmental muscle loss in jerboa hindfeet.
PubMed: 38946691
DOI: 10.1002/jez.b.23268 -
Physiological Reports Jul 2024Cancer cachexia is a multifactorial syndrome associated with advanced cancer that contributes to mortality. Cachexia is characterized by loss of body weight and muscle...
Cancer cachexia is a multifactorial syndrome associated with advanced cancer that contributes to mortality. Cachexia is characterized by loss of body weight and muscle atrophy. Increased skeletal muscle mitochondrial reactive oxygen species (ROS) is a contributing factor to loss of muscle mass in cachectic patients. Mice inoculated with Lewis lung carcinoma (LLC) cells lose weight, muscle mass, and have lower muscle sirtuin-1 (sirt1) expression. Nicotinic acid (NA) is a precursor to nicotinamide dinucleotide (NAD+) which is exhausted in cachectic muscle and is a direct activator of sirt1. Mice lost body and muscle weight and exhibited reduced skeletal muscle sirt1 expression after inoculation with LLC cells. C2C12 myotubes treated with LLC-conditioned media (LCM) had lower myotube diameter. We treated C2C12 myotubes with LCM for 24 h with or without NA for 24 h. C2C12 myotubes treated with NA maintained myotube diameter, sirt1 expression, and had lower mitochondrial superoxide. We then used a sirt1-specific small molecule activator SRT1720 to increase sirt1 activity. C2C12 myotubes treated with SRT1720 maintained myotube diameter, prevented loss of sirt1 expression, and attenuated mitochondrial superoxide production. Our data provides evidence that NA may be beneficial in combating cancer cachexia by maintaining sirt1 expression and decreasing mitochondrial superoxide production.
Topics: Animals; Cachexia; Sirtuin 1; Muscle Fibers, Skeletal; Mice; Oxidative Stress; Mice, Inbred C57BL; Carcinoma, Lewis Lung; Male; Heterocyclic Compounds, 4 or More Rings; Mitochondria, Muscle; Cell Line; Niacin; Mitochondria; Reactive Oxygen Species
PubMed: 38946587
DOI: 10.14814/phy2.16103 -
European Review For Medical and... Jun 2024Sarcopenia is a condition characterized by muscle mass loss. Skeletal muscle is capable of producing and secreting different molecules called myokines, and apelin is one...
OBJECTIVE
Sarcopenia is a condition characterized by muscle mass loss. Skeletal muscle is capable of producing and secreting different molecules called myokines, and apelin is one of them. The literature contains contradictory data on the relationship between apelin and sarcopenia. We decided to investigate the role of apelin in sarcopenia in subjects with disease-related malnutrition (DRM), a group of patients with a high rate of sarcopenia.
PATIENTS AND METHODS
83 elderly patients with DRM assessed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria were included in the study, with a mean age of 69.9±3.8 years. Anthropometric data, muscle mass by ultrasound at the rectus femoris quadriceps (RFQ) level, bioimpedance [skeletal muscle mass (SMM), appendicular SMM (aSMM) and aSMM index (aSMMI)], dynamometry, biochemical parameters, dietary intake, circulating apelin levels were determined in all patients.
RESULTS
a total of 33 patients (37.9%) were diagnosed with sarcopenia, while 54 patients did not present sarcopenia (60.1%). Body weight (-5.5±2.0 kg, p=0.01), calf circumference (-1.9±0.2 cm, p=0.02), phase angle (-0.6±0.2º, p=0.01), reactance (-6.8±2.3 Ohms, p=0.03), resistance (-38.8±12.3 Ohms, p=0.04), SMM (-2.2±0.3 kg, p=0.04), aSMM (-2.2±0.2 kg, p=0.03) and aSMMI (-0.6±0.2 kg, p=0.02), dominant muscle area (-0.6±0.2 cm2, p=0.04), dominant Y axis (-0.4±0.1 cm, p=0.03), dominant X/Y axis (1.1±0.3 cm, p=0.04), strength (-5.1±1.3 kg, p=0.01), albumin (-0.9±0.1 g/dl, p=0.02) and prealbumin (-4.6±0.7 mg/dl, p=0.02) were worse in patients with sarcopenia than non-sarcopenic patients. Circulating apelin levels were similar in both groups. No significant correlation of apelin levels was detected, either with bioimpedance data or with muscle ultrasonography data. The multivariant analysis did not detect a significant association of apelin with the presence of sarcopenia.
CONCLUSIONS
Our study shows a lack of association between apelin and sarcopenia in elderly malnourished patients.
Topics: Humans; Sarcopenia; Apelin; Aged; Malnutrition; Male; Female; Muscle, Skeletal
PubMed: 38946382
DOI: 10.26355/eurrev_202406_36461 -
Muscle-Protective Effect of Carnosine against Dexamethasone-Induced Muscle Atrophy in C2C12 Myotube.Journal of Nutritional Science and... 2024This study investigated the protective effect of carnosine and its components (L-histidine and β-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in...
This study investigated the protective effect of carnosine and its components (L-histidine and β-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Myotubes were treated with Dex (10 μM) to induce muscle atrophy manifested by decreased myotube diameter, low myosin heavy chain content, and increased expression of muscle atrophy-associated ubiquitin ligases (Atrogin-1, MuRF-1, and Cbl-b). Carnosine (20 mM) treatment significantly improved the myotube diameter and MyHC protein expression level in Dex-treated C2C12 myotubes. It also downregulated the expression of Atrogin-1, MuRF-1, and Cbl-b and suppressed the expression of forkhead box O3 (FoxO3a) mediated by Dex. Furthermore, reactive oxygen species production was increased by Dex but was ameliorated by carnosine treatment. However, HA (20 mM), the component of carnosine, treatment was found ineffective in preventing Dex-induced protein damage. Therefore, based on above results it can be suggested that carnosine could be a potential therapeutic agent to prevent Dex-induced muscle atrophy compared to its components HA.
Topics: Carnosine; Dexamethasone; Muscular Atrophy; Muscle Fibers, Skeletal; Animals; Mice; Muscle Proteins; Cell Line; Reactive Oxygen Species; SKP Cullin F-Box Protein Ligases; Ubiquitin-Protein Ligases; Forkhead Box Protein O3; Tripartite Motif Proteins; Myosin Heavy Chains
PubMed: 38945887
DOI: 10.3177/jnsv.70.219 -
Clinical Radiology Jun 2024Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease caused by the degeneration of the α-motor neurons in the anterior horn of the spinal cord. SMA... (Review)
Review
Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease caused by the degeneration of the α-motor neurons in the anterior horn of the spinal cord. SMA is clinically characterized by progressive and symmetrical muscle weakness and muscle atrophy and ends up with systemic multisystem abnormalities. Quantitative MRI (qMRI) has the advantages of non-invasiveness, objective sensitivity, and high reproducibility, and has important clinical value in evaluating the severity of neuromuscular diseases and monitoring the efficacy of treatment. This article summarizes the clinical use of muscular MRI and magnetic resonance neurography in assessing the progress of SMA.
PubMed: 38945793
DOI: 10.1016/j.crad.2024.06.004 -
Advances in Gerontology = Uspekhi... 2024The foundation of healthy aging is the prevention of disability. In modern medical usage, a syndrome refers to a collection of symptoms and signs with a single... (Review)
Review
The foundation of healthy aging is the prevention of disability. In modern medical usage, a syndrome refers to a collection of symptoms and signs with a single underlying cause that may not yet be known. Geriatric syndromes, on the other hand, refer to multifactorial health conditions and occur when the accumulated effects of impairments in multiple systems make an older person vulnerable to situational changes. The use of the term "syndrome" in geriatrics emphasizes the multiple causes of a single manifestation involving an abundance of factors involving multiple organs and systems and is characterized by unique features of common health problems in older adults. It is the geriatric syndromes that can have a significant impact on quality of life and disability. Therefore, early detection of these medical conditions using targeted geriatric assessment is essential in geriatrics. Understanding the essence and feminology of geriatric syndromes, their correct positioning and interpretation is an extremely urgent problem. The main purpose of the presented review is precisely to try to answer these questions. In addition, it has not yet been determined whether geriatric syndromes should be included in the diagnosis (the only exception is sarcopenia syndrome, which was officially included in the 10th International Classification of Diseases in 2016).
Topics: Humans; Aged; Terminology as Topic; Geriatric Assessment; Syndrome; Quality of Life; Geriatrics; Sarcopenia; Aging
PubMed: 38944774
DOI: No ID Found -
Journal of Shoulder and Elbow Surgery Jun 2024The degree of atrophy and fatty infiltration of rotator cuff muscle belly is a key predictor for cuff repairability. Traditionally, Goutallier grading of fatty...
Medial Scapular Body (MSB) Goutallier Classification - MRI based reliability and validity of evaluation of the Goutallier classification for grading fatty infiltration of the rotator cuff.
INTRODUCTION
The degree of atrophy and fatty infiltration of rotator cuff muscle belly is a key predictor for cuff repairability. Traditionally, Goutallier grading of fatty infiltration is assessed at sagittal scapular Y-view. Massive rotator cuff tears are associated with tendon retraction and medial retraction of cuff musculature, resulting in medialization of the muscle bulk. Thus, standard Y-view can misrepresent the region of interest and may misguide clinicians when assessing repairability. It is hypothesized that by assessing the muscle belly with multiple medial sagittal MRI sections at medial scapular body, the Medial Scapular Body - Goutallier Classification (MSB-GC) will improve reliability and repeatability giving a more representative approximation to the degree of fatty infiltration, as compared with original Y-view.
METHODS
Fatty infiltration of the rotator cuff muscles were classified based on the Goutallier grade (0 to 4) at three defined sections section 1: original Y-view; section 2: level of suprascapular notch; section 3: three cm medial to suprascapular notch on MRI scans. Six sub-specialist fellowship trained shoulder surgeons, and three musculoskeletal radiologists independently evaluated deidentified MRI scans of included patients.
RESULTS
Out of 80 scans, 78% (n=62) were massive cuff tears involving supraspinatus, infraspinatus and subscapularis tendon. Inter-observer reliability (consistency between observers) for Goutallier grade was excellent for all three predefined sections (range:0.87-0.95). Intra-observer reliability (repeatability) for Goutallier grade was excellent for all three sections and four rotator cuff muscles (range:0.83-0.97). There was a moderate to strong positive correlation of Goutallier grades between sections 1 and 3 and between sections 2 and 3 and these were statistically significant (p<0.001). There was a reduction in the severity of fatty infiltration on the Goutallier classification from sections 1 to 3 across all muscles. 42.5% of both supraspinatus and infraspinatus were downgraded by one, 20% of supraspinatus and 3.8% of infraspinatus were downgraded by 2 and 2.5% of supraspinatus were downgraded by 3.
CONCLUSION
This study found that applying the Goutallier classification to more medial MRI sections (MSB-GC) resulted in assignment of lower grades for all rotator cuff muscles. Additionally, this method demonstrated excellent test-retest reliability and repeatability. Inclusion of a more medial view or whole scapula on MRI, especially in advanced levels of tear retraction, could be more reliable and representative for assessment of the degree of fatty infiltration within the muscle bulk that could help predict tear repairability and therefore improve clinical decision-making which should be studied further in clinical studies.
PubMed: 38944373
DOI: 10.1016/j.jse.2024.05.013 -
Archives of Gerontology and Geriatrics Jun 2024There is growing interest in the association of CT-assessed sarcopenia with adverse outcomes in non-oncological settings.
BACKGROUND
There is growing interest in the association of CT-assessed sarcopenia with adverse outcomes in non-oncological settings.
PURPOSE
The aim of this systematic review is to summarize existing literature on the prognostic implications of CT-assessed sarcopenia in non-oncological patients.
MATERIALS AND METHODS
Three independent authors searched Medline/PubMed, Embase and Cochrane Library up to 30 December 2023 for observational studies that reported the presence of sarcopenia defined on CT head and neck in association with mortality estimates and other adverse outcomes, in non-oncological patients. The quality of included studies were assessed using the Quality of Prognostic Studies tool.
RESULTS
Overall, 15 studies (3829 participants) were included. Nine studies were at low risk of bias, and six were at moderate risk of bias. Patient populations included those admitted for trauma or treatment of intracranial aneurysms, ischemic stroke, transient ischemic attack, and intracranial stenosis. Sarcopenia was associated with increased 30-day to 2-year mortality in inpatients and patients undergoing carotid endarterectomy or mechanical thrombectomy for acute ischemic stroke. Sarcopenia was also associated with poorer neurological and functional outcomes, increased likelihood of admission to long-term care facilities, and longer duration of hospital stays. The observed associations of sarcopenia with adverse outcomes remained similar across different imaging modalities and methods for quantifying sarcopenia.
CONCLUSION
CT-assessed sarcopenia was associated with increased mortality and poorer outcomes across diverse patient populations. Measurement and early identification of sarcopenia in vulnerable patients allows for enhanced prognostication, and focused allocation of resources to mitigate adverse outcomes.
PubMed: 38944005
DOI: 10.1016/j.archger.2024.105549