Diabetic myonecrosis complicated by emphysematous pyomyositis and abscess caused by Escherichia coli: a case report.

BACKGROUND: Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging. CASE PRESENTATION: We describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3-4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case. CONCLUSIONS: Identifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.

Myonecrosis as a rare side effect of stereotactic body radiotherapy for bone metastases: Report of two cases and a comprehensive literature review.

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.

Gemcitabine-Induced Myonecrosis Following Hypofractionated Radiation.

Palliative radiation is often used to abate pain and prevent bone fractures in patients with metastatic cancer. Hypofractionation, meaning delivery of larger doses of radiation in each treatment session (fraction), has become the standard of care in most cases. It not only reduces the burden on the medical system and facilitates the relief of symptoms but also enables the maintenance of the continuity of systemic therapy. Radiation recall phenomenon (RRP) is an acute inflammatory reaction in previously irradiated tissues that is provoked by chemotherapeutic drug administration. The incidence, severity, and prognosis of RRP following hypofractionated radiation therapy have not been studied. The symptoms of RRP depend on the radiation field, with the greatest concern associated with mucosal and dermal damage, though other symptoms have also been reported. Here, we describe a case of a 41-year-old woman with metastatic breast cancer (hormone receptor-positive, HER2/neu negative), who received palliative radiation to four other fields along the course of her disease, before her presentation with isolated myonecrosis of the thigh muscles. This RRP occurred four months following the last of two fractions of 8 Gy radiation to this region, given three months apart, and after six courses of cisplatin + gemcitabine. The symptoms improved with cessation of gemcitabine and prolonged administration of non-steroidal anti-inflammatory medications.

Development of recombinase amplification assays for the rapid detection of infectious myonecrosis virus.

Infectious myonecrosis virus (IMNV) has affected shrimp farming in many countries, such as northeastern Brazil and southeast Asia, and poses a serious threat to the global shrimp industry. Reverse transcription enzymatic recombinant amplification technology (RT-ERA) is a rapid DNA amplification assay with high specificity in isothermal conditions and has been widely applied to the pathogen's detection. In this study, two novel ERA assays of IMNV, real-time RT-ERA and an RT-ERA combined with lateral flow dipsticks assay (RT-ERA-LFD), were developed and evaluated. The real-time RT-ERA assay could be carried out at 38-42 °C and had the highest end-point fluorescence value and the smallest Ct value at 41 °C. The brightness and width of the detection line were at a maximum at 39 °C and 30 min, and these conditions were selected in RT-ERA-LFD. Both real-time RT-ERA and RT-ERA-LFD produced positive results with IMNV standard plasmids only and showed no cross-reaction with Vibrio parahaemolyticus, which causes acute hepatopancreatic necrosis disease (VpAHPND); white spot syndrome virus (WSSV); infectious hypodermal and hematopoietic necrosis virus (IHHNV); or Ecytonucleospora hepatopenaei (EHP). Meanwhile, we compared the sensitivities of nested RT-PCR, real-time RT-PCR, real-time RT-ERA, and RT-ERA-LFD. The sensitivities of real-time RT-ERA and RT-ERA-LFD were both 101 copies/µL. The detection sensitivities of nested RT-PCR and real-time RT-PCR were 100 and 102 copies/µL, respectively. As a result, two ERA assays were determined to be specific, sensitive, and economical methods for the on-site diagnosis of IMNV infection, showing great potential for the control of IMNV infections.

Radiation-Induced Myonecrosis: A Case Report of a Cervical Cancer Patient With a History of Systemic Lupus Erythematosus.

Radiation-induced myonecrosis is a rare but serious complication of radiation therapy. We present a case of a 49-year-old woman with systemic lupus erythematosus who developed radiation-induced myonecrosis after concurrent chemoradiation for cervical cancer. She underwent external-beam radiation therapy, weekly cisplatin chemotherapy (40 mg/m2), and intracavitary brachytherapy. One month later, she received one cycle of nedaplatin (80 mg/m2) and irinotecan (60 mg/m2). Two months after treatment, she experienced pain in the left inguinal region. An MRI revealed a mass in the left obturator externus muscle and right pectineus muscle suggestive of myonecrosis. A biopsy confirmed the diagnosis. She received hyperbaric oxygen therapy, and her symptoms improved. The masses resolved completely.

Aeromonas hydrophila induced necrotizing fasciitis following laparoscopic cholecystectomy.

Necrotizi ng fasciit is [NF] i s a m ultifaceted disease of the muscle fascia and body tissues which demands the earliest intervention. Past reviews have documented ver y few cases of Aeromonas Hydroph ila [AH] induced N F fol lo wing abdominal surgery. AH can cause fatal NF as seen in a 72 year old female patient reported at Liaquat National Hospital &Medical College; a ter tiary care center in Karachi, Pakistan on 2nd April, 2022. She had a k nown comorbidity of hypertension and presented with the chief complaint of symptomatic gallstones for which she unde rwent Laparoscopic Cholecystectomy (LAPCHOL). She developed NF of the lower ab domen post- oper atively. Following uneventful Laparoscopic Cholecystectomy our pati ent presented to the ER two days later with severe lower abdo minal pain and overlyi ng celluliti s. Fasc io to my revealed extensive myonecrosis with necrotizing soft tissue in fe ction. Despite u ndergoing extensive surgical debr idement and broad spectr um antibi ot ic administration; the patient died in the ICU on the fifth postoperat ive day followi ng septic complications. Histopathologica l an alysis, confirmed i nflammat ion and necrosis. Culture sensitivity of the debrided tissue revealed AH. Approach should lie towards analyzing the behaviour of such microbes in high risk patients through collective case studies. This is the first clinical case showcasing such parameters e ncountered in the General Surger y Department.

Naja nigricincta nigricincta venom, a murine model. Evaluation of skeletal and cardio-myonecrosis, kidney injury and inflammatory response along with neutralisation efficacy by the SAIMR/SAVP - And EchiTAb-Plus-ICP polyvalent antivenoms.

African spitting cobra, Naja nigricincta nigricincta (Zebra snake), envenomation is an important cause of snakebite morbidity and mortality in Namibia. The snake is endemic to central and northern Namibia as well as southern Angola. The venom is mainly cytotoxic, resulting in aggressive dermo-necrosis and often accompanied by severe systemic complications. No specific antivenom exists. Rhabdomyolysis, systemic inflammatory response, haemostatic abnormalities, infective necrotising fasciitis as well as acute kidney failure have been documented. Based on murine models, this study assessed SAVP/SAIMR - and EchiTAb-Plus-ICP polyvalent antivenom neutralisation as well as subdermal necrosis. Additional muscle, cardiac, kidney and lung histology, creatine kinase measurements and post-mortems were performed. An intravenous median lethal dose (LD50) of Naja nigricincta nigricincta venom was determined at 18.4 (CI: 16.3; 20.52) µg and a subdermal lethal dose at 15.3(CI: 12.96; 17.74)µg. The SAIMR/SAVP polyvalent antivenom median effective dose (ED50) was 1.2 ml antivenom/1 mg venom equating to a potency (WHO) of 1 ml antivenom neutralising 0.63 mg venom and approximately 240 ml (24 vials) needed for initial treatment. The ED50 of the EchiTAb-Plus-ICP was 1 ml antivenom/1 mg venom and a potency of 65 mg venom/ml antivenom (3.3 x LD50), estimating 230 ml (23 vials) for treatment. Histology and serology (creatine kinase) evidenced venom induced skeletal myotoxicity, which was not prevented by the antivenoms tested. Cardiac myonecrosis, an inflammatory response, direct venom kidney tubular necrosis and cardio-pulmonary failure were documented.

A Complex Pattern of Gene Expression in Tissue Affected by Viperid Snake Envenoming: The Emerging Role of Autophagy-Related Genes.

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 ß (TGF-ß) 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.

Case Report: Severe vitamin D deficiency in a girl with inflammatory myopathy and myonecrosis.

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.

Blackleg: A Review of the Agent and Management of the Disease in Brazil.

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.

Alterations of the skeletal muscle contractile apparatus in necrosis induced by myotoxic snake venom phospholipases A2: a mini-review.

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.

Diabetic Muscle Infarction: An Uncommon Diabetic Complication With a Lack of Standardized Treatment.

Diabetic muscle infarction (DMI) is a rare yet serious complication that has been strongly associated with uncontrolled diabetes, although other risk factors are unclear. DMI is an uncommon complication of diabetes with a lack of structured guidelines for evaluation or management. End-stage renal disease (ESRD) could have further implications in patients with DMI in terms of management given that nonsteroidal anti-inflammatory drugs (NSAIDs), which have been shown to reduce the recovery times and recurrence of DMI, could be contraindicated. We present a rare case of DMI in an African American man with ESRD who presented for new-onset right lower-extremity pain and swelling. We discuss the challenges involved with the diagnosis and treatment of this rare condition. This case adds to the knowledge of DMI, which is limited because of the low incidence of this condition, and it helps us understand how this condition affects the African American population and patients with ESRD.

Receptor interacting protein kinase-3 mediates both myopathy and cardiomyopathy in preclinical animal models of Duchenne muscular dystrophy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors.

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.

Bilateral Lower Extremity Calcific Myonecrosis: A Case Report.

Introduction: Calcific myonecrosis is a rare soft-tissue disease where a single muscle or muscle compartment is replaced with central liquefaction and peripheral calcification. This disease usually occurs in a single limb after trauma. Until now, bilateral muscle involvement has not been previously reported. Case Report: A 73-year-old woman presented with symptomatic masses in the soft tissues of bilateral anterior thighs. She had no known history of trauma but recalled a specific tearing sensation episode in both her legs while squatting when weightlifting in the distant past. The patient had calcified masses that had replaced the rectus femoris muscle bilaterally with associated effects on hip and knee range of motion. The patient underwent excision of a portion of calcific myonecrosis and two locations of rectus femoris tenotomies in one leg and only a simple rectus femoris tenotomy on the contralateral leg. The patient subsequently experienced a significant improvement in hip and knee motion and a reduction in associated pain on both sides. Conclusion: Historical and radiographic information are key in making the diagnosis of calcific myonecrosis. Treatment decisions should be based on the patient's symptoms balanced with the morbidity of the expected procedures. Symptomatic patients should be considered for excision of the symptomatic involved areas. A tenotomy may be a viable option if a limitation in motion is the primary complaint. Asymptomatic patients with a stable lesion and imaging should undergo conservative management due to the high risk of infection and wound healing problems.

Diabetic Myonecrosis of the Axilla: A Novel Case With Severe Clinical Features.

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.

Accidental monensin poisoning in goats.

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.

A distinct case of an 8-year-old female with cyclic neutropenia presenting with C. septicum abdominal sepsis and myonecrosis requiring a bowel resection and leg fasciotomy.

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.

A Hidden Complication of Poorly Managed Diabetic Control: A Case of Diabetic Myonecrosis.

Diabetic myonecrosis is an infrequently encountered complication of poorly managed type 2 diabetes. Despite its relative rarity, early detection and appropriate management can yield favorable outcomes. This case report details the presentation, diagnosis, and management of a 53-year-old male patient with a history of type 2 diabetes who presented with acute-onset pain, swelling of the muscles, and weakness. Following a battery of laboratory investigations, radiological imaging, and a muscle biopsy, the patient was diagnosed with diabetic myonecrosis. The patient was treated conservatively with analgesics, physiotherapy, and optimization of glycemic control, significantly improving muscle strength and function. This case highlights the necessity of considering diabetic myonecrosis as a potential differential diagnosis in diabetic patients who present with sudden muscle weakness and discomfort.

The Adiponectin Receptor Agonist, ALY688: A Promising Therapeutic for Fibrosis in the Dystrophic Muscle.

Duchenne muscular dystrophy (DMD) is one of the most devastating myopathies, where severe inflammation exacerbates disease progression. Previously, we demonstrated that adiponectin (ApN), a hormone with powerful pleiotropic effects, can efficiently improve the dystrophic phenotype. However, its practical therapeutic application is limited. In this study, we investigated ALY688, a small peptide ApN receptor agonist, as a potential novel treatment for DMD. Four-week-old mdx mice were subcutaneously treated for two months with ALY688 and then compared to untreated mdx and wild-type mice. In vivo and ex vivo tests were performed to assess muscle function and pathophysiology. Additionally, in vitro tests were conducted on human DMD myotubes. Our results showed that ALY688 significantly improved the physical performance of mice and exerted potent anti-inflammatory, anti-oxidative and anti-fibrotic actions on the dystrophic muscle. Additionally, ALY688 hampered myonecrosis, partly mediated by necroptosis, and enhanced the myogenic program. Some of these effects were also recapitulated in human DMD myotubes. ALY688's protective and beneficial properties were mainly mediated by the AMPK-PGC-1α axis, which led to suppression of NF-κß and TGF-ß. Our results demonstrate that an ApN mimic may be a promising and effective therapeutic prospect for a better management of DMD.