Stereotactic body radiotherapy is a highly effective form of radiation therapy for palliation of bone metastases, but it can also lead to rare but severe side effects, such as myonecrosis. According to the literature, the incidence of myonecrosis after stereotactic body radiotherapy is low and mostly dose dependent. It is crucial to consider the potential impact of immunotherapy and other systemic therapies in the assessment. The course of radiation myonecrosis can vary, and corticosteroids or vascular endothelial growth factor inhibitors may potentially play a role in its treatment. Herein, we report two patients presenting with myonecrosis after stereotactic body radiotherapy for bone metastasis.

Viperid snake venoms induce severe tissue damage, characterized by the direct toxic action of venom components, i.e., phospholipases A2 (PLA2s) and metalloproteinases (SVMPs), concomitantly with the onset of endogenous inflammatory processes, in an intricate scenario of tissue alterations. Understanding the expression of relevant genes in muscle tissue will provide valuable insights into the undergoing pathological and inflammatory processes. In this study, we have used the Nanostring technology to evaluate the patterns of gene expression in mouse skeletal muscle 1 h, 6 h, and 24 h after injection of the venoms of Bothrops asper and Daboia russelii, two medically relevant species in Latin America and Asia, respectively, with somewhat different clinical manifestations. The dose of venoms injected (30 µg) induced local pathological effects and inflammation in muscle tissue. We focused our analysis on genes related to extracellular matrix (ECM) metabolism, immune system, programmed cell death, and autophagy. The results revealed a complex pattern of expression of genes. Regarding ECM metabolism and regulation, up-regulated genes included proteinase inhibitor Serpine 1, thrombospondin 1, collagens 1A1 and 4A1 (at 1 h in the case of B. asper), TIMP1, MMP-3 (at 24 h), and lysil oxidase (LOX). In contrast, collagen chains 5A3 and 5A1 were down-regulated, especially at 6 h. Transforming growth factor β (TGF-β) and several genes related to myofibroblast regulation were also up-regulated, which might be related to the development of fibrosis. Several genes related to cytokine and chemokine synthesis and regulation and NFκB signaling were also up-regulated. Our observations show a variable expression of genes associated with programmed cell death and autophagy, thus revealing a hitherto unknown role of autophagy in tissue affected by snake venoms. These results provide clues to understanding the complex pattern of gene expression in tissue affected by viperid snake venoms, which likely impacts the final pathophysiology of damaged tissue in envenomings.

Inflammatory myopathies are a rare group of disorders that can cause significant disruption in the ability of an individual to adequately perform activities of daily living. In this case report, we present a case of a girl presenting with a substantial compromise of her ambulation with a muscle biopsy consistent with myonecrosis. She was subsequently diagnosed with an inflammatory myopathy and started on glucocorticoid and methotrexate therapy with minimal symptomatic improvement. Further in her clinical course, hypocalcemia and an undetectable 25-hydroxyvitamin D level were detected. Prompt institution of calcium and vitamin D supplementation significantly improved her myopathic condition. While there is evidence in the literature linking vitamin D deficiency with myopathy, there is a lack of data on the association between hypocalcemia and vitamin D deficiency with myonecrosis, which could represent comorbid states in myonecrosis. Therefore, vitamin D status should be established in all patients with myonecrosis, as vitamin D deficiency is easy to diagnose and treat, as exemplified in our patient\'s case, which shows that such treatment could lead to significant clinical improvement.

The genus Clostridium is an important group of pathogenic and nonpathogenic Gram-positive anaerobic bacteria with a sporulation capacity and wide distribution in different environments, including the gastrointestinal tracts of healthy and diseased animals and humans. Among the pathogenic species of the genus, Clostridium chauvoei stands out as a histotoxic agent. It causes significant myonecrosis such as blackleg, a disease with high lethality, especially in young cattle, and is responsible for significant livestock losses worldwide. The pathogenicity of the disease is complex and has not yet been fully elucidated. Current hypotheses cover processes from the initial absorption to the transport and deposition of the agent in the affected tissues. The virulence factors of C. chauvoei have been divided into somatic and flagellar antigens and soluble antigens/toxins, which are the main antigens used in vaccines against blackleg in Brazil and worldwide. This review provides important information on the first and current approaches to the agent C. chauvoei and its virulence factors as well as a compilation of data on Brazilian studies related to blackleg.

Skeletal muscle necrosis is a common clinical manifestation of snakebite envenoming. The predominant myotoxic components in snake venoms are catalytically-active phospholipases A2 (PLA2) and PLA2 homologs devoid of enzymatic activity, which have been used as models to investigate various aspects of muscle degeneration. This review addresses the changes in the contractile apparatus of skeletal muscle induced by these toxins. Myotoxic components initially disrupt the integrity of sarcolemma, generating a calcium influx that causes various degenerative events, including hypercontraction of myofilaments. There is removal of specific sarcomeric proteins, owing to the hydrolytic action of muscle calpains and proteinases from invading inflammatory cells, causing an initial redistribution followed by widespread degradation of myofibrillar material. Experiments using skinned cardiomyocytes and skeletal muscle fibers show that these myotoxins do not directly affect the contractile apparatus, implying that hypercontraction is due to cytosolic calcium increase secondary to sarcolemmal damage. Such drastic hypercontraction may contribute to muscle damage by generating mechanical stress and further sarcolemmal damage.

Snake bite is a neglected disease that affects millions of people worldwide. WHO reported approximately 5 million people are bitten by various species of snakes each year, resulting in nearly 1 million deaths and an additional three times cases of permanent disability. Snakes utilize the venom mainly for immobilization and digestion of their prey. Snake venom is a composition of proteins and enzymes which is responsible for its diverse pharmacological action. Snake venom phospholipase A2 (SvPLA2) is an enzyme that is present in every snake species in different quantities and is known to produce remarkable functional diversity and pharmacological action like inflammation, necrosis, myonecrosis, hemorrhage, etc. Arachidonic acid, a precursor to eicosanoids, such as prostaglandins and leukotrienes, is released when SvPLA2 catalyzes the hydrolysis of the sn-2 positions of membrane glycerophospholipids, which is responsible for its actions. Polyvalent antivenom produced from horses or lambs is the standard treatment for snake envenomation, although it has many drawbacks. Traditional medical practitioners treat snake bites using plants and other remedies as a sustainable alternative. More than 500 plant species from more than 100 families reported having venom-neutralizing abilities. Plant-derived secondary metabolites have the ability to reduce the venom\'s adverse consequences. Numerous studies have documented the ability of plant chemicals to inhibit the enzymes found in snake venom. Research in recent years has shown that various small molecules, such as varespladib and methyl varespladib, effectively inhibit the PLA2 toxin. In the present article, we have overviewed the knowledge of snake venom phospholipase A2, its classification, and the mechanism involved in the pathophysiology of cytotoxicity, myonecrosis, anticoagulation, and inflammation clinical application and inhibitors of SvPLA2, along with the list of studies carried out to evaluate the potency of small molecules like varespladib and secondary metabolites from the traditional medicine for their anti-PLA2 effect.

Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder, culminating in a complete loss of ambulation, hypertrophic cardiomyopathy and a fatal cardiorespiratory failure. Necroptosis is the form of necrosis that is dependent upon the receptor-interacting protein kinase (RIPK) 3; it is involved in several inflammatory and neurodegenerative conditions. We previously identified RIPK3 as a key player in the acute myonecrosis affecting the hindlimb muscles of the mdx dystrophic mouse model. Whether necroptosis also mediates respiratory and heart disorders in DMD is currently unknown.
Evidence of activation of the necroptotic axis was examined in dystrophic tissues from Golden retriever muscular dystrophy (GRMD) dogs and R-DMDdel52 rats. A functional assessment of the involvement of necroptosis in dystrophic animals was performed on mdx mice that were genetically depleted for RIPK3. Dystrophic mice aged from 12 to 18 months were analysed by histology and molecular biology to compare the phenotype of muscles from mdxRipk3+/+ and mdxRipk3-/- mice. Heart function was also examined by echocardiography in 40-week-old mice.
RIPK3 expression in sartorius and biceps femoris muscles from GRMD dogs positively correlated to myonecrosis levels (r = 0.81; P = 0.0076). RIPK3 was also found elevated in the diaphragm (P ≤ 0.05). In the slow-progressing heart phenotype of GRMD dogs, the phosphorylated form of RIPK1 at the Serine 161 site was dramatically increased in cardiomyocytes. A similar p-RIPK1 upregulation characterized the cardiomyocytes of the severe DMDdel52 rat model, associated with a marked overexpression of Ripk1 (P = 0.007) and Ripk3 (P = 0.008), indicating primed activation of the necroptotic pathway in the dystrophic heart. MdxRipk3-/- mice displayed decreased compensatory hypertrophy of the heart (P = 0.014), and echocardiography showed a 19% increase in the relative wall thickness (P < 0.05) and 29% reduction in the left ventricle mass (P = 0.0144). Besides, mdxRipk3-/- mice presented no evidence of a regenerative default or sarcopenia in skeletal muscles, moreover around 50% less affected by fibrosis (P < 0.05).
Our data highlight molecular and histological evidence that the necroptotic pathway is activated in degenerative tissues from dystrophic animal models, including the diaphragm and the heart. We also provide the genetic proof of concept that selective inhibition of necroptosis in dystrophic condition improves both histological features of muscles and cardiac function, suggesting that prevention of necroptosis is susceptible to providing multiorgan beneficial effects for DMD.

Diabetic myonecrosis is a rare and poorly understood complication of long-standing, inadequately controlled diabetes mellitus. Theoretical mechanisms contributing to the pathophysiology of diabetic myonecrosis include microvascular complications due to advanced glycation end-products, ischemia-reperfusion injuries, and dysregulated coagulation-fibrinolysis activity. Case reports of diabetic myonecrosis most commonly describe diabetic patients with chronically poor glycemic control who experience isolated swelling and severe pain in a unilateral lower limb with no signs of infection or systemic toxicity. Due to the rarity of this condition, there are currently no treatment guidelines. This case describes a 58-year-old male with a history of uncontrolled diabetes who presented with diabetic ketoacidosis with mixed hypovolemic and septic shock. Diabetic myonecrosis was incidentally discovered in the patient\'s right latissimus dorsi with CT imaging and subsequent surgical exploration. Spontaneous diabetic myonecrosis may mimic several other serious conditions and elicit suboptimal management strategies, particularly in the context of atypical presentations.

Sodium monensin is the most frequently used ionophore as a growth promoter in ruminant diets. It has numerous benefits; however its toxic effects have also been observed in several animal species. Naturally occurring cases have not yet been reported in goats. This study describes an outbreak of accidental poisoning, characterizing its clinical, laboratory and pathological findings. Thirty-seven of 40 Anglo Nubian goat kids became intoxicated after receiving a diet that was erroneously supplemented with sodium monensin. They ingested an estimated toxic dose between 25 and 39 mg/kg BW. Clinical evolution was monitored (n = 27), followed by serum creatine kinase (CK) and aspartate aminotransferase (AST) activities measurements, and blood gas analysis. Postmortem examinations were performed between 1 and 8 days of evolution (n = 14). Clinical signs began 5 h after ingestion and included reticuloruminal hypomotility, lethargy, anorexia, tachycardia, cardiac arrhythmia, wet cough, pulmonary and tracheal crackles, and serous nasal discharge. The morbidity and lethality rates were 92.5 and 62.1%, respectively. CK and AST activities increased, reaching median values of 10,860 and 1596 U/L, respectively; the hyperchloremic metabolic acidosis was mild. The lesions were characterized by degeneration and necrosis of the cardiac and skeletal muscles, pulmonary congestion and edema, and passive liver congestion. The kids essentially developed cardiomyopathy with left and right congestive heart failures. Unlike in other ruminant species, skeletal muscle functional disability was infrequent. It can be concluded that monensin is toxic to goats and should be used with caution in their diet.

Clostridium septicum is a very rare cause of severe spontaneous pediatric enterocolitis and is often associated with underlying malignancy or immunocompromise. Likewise, cyclic neutropenia is a rare congenital immunodeficiency that is characterized by cyclical periods of neutropenia, often with more severe symptoms in the pediatric population. Here, we present a unique case of spontaneous C. septicum enterocolitis, sepsis, and myonecrosis in a child with undiagnosed cyclic neutropenia. Early recognition of pediatric sepsis, frequent reevaluation and identification of rapidly progressive infection, and early surgical intervention are critical for the effective management of a rare and severe infection.