Muscle fibrosis is a major driver of progression in diverse myopathies, yet the conserved molecular mediators of this process in humans remain poorly defined. Here, we identify collagen VI as a common regeneration-impairing extracellular matrix (ECM) component across three distinct human myopathies: Duchenne Muscular Dystrophy (DMD), Oculopharyngeal Muscular Dystrophy (OPMD), and Inclusion Body Myositis (IBM). Proteomic profiling of fibrotic biopsies reveals consistent upregulation of collagen VI and laminin γ1, alongside disease-specific alterations. Fibroadipogenic progenitors (FAPs) are the predominant source of these ECM components, including collagen VI and laminin γ1. Functionally, xenotransplantation of patient-derived FAPs into regenerating mouse muscle induces localized collagen deposition, myofiber atrophy, and depletion of Pax7⁺ muscle stem cells. Mechanistic assays demonstrate that FAP-derived collagen VI is sufficient to impair myogenic fusion, while silencing COL6 in patient FAPs restores fusion capacity, directly linking pathological collagen VI deposition to regeneration failure. Our findings uncover collagen VI as a conserved effector of fibrosis and stem cell niche disruption in human myopathies, positioning it as a potential therapeutic target across genetically and clinically distinct muscle diseases.

Cemiplimab is a fully human PD-1 inhibitor approved for cutaneous squamous cell carcinoma, basal cell carcinoma, and non-small cell lung cancer. Post-market safety surveillance is essential given the broad and evolving indications for immune checkpoint inhibitors. All FAERS reports with cemiplimab as the primary suspect drug were extracted. Proportional Reporting Ratios (PRR), Reporting Odds Ratios (ROR), and chi-squared statistics were calculated for each adverse event. Disproportionality signals were defined by PRR ≥ 2, chi-squared ≥ 3.841, and a minimum of 15 reports. A total of 1,460 cemiplimab reports were identified in the FAERS database. Twenty-two adverse events met all signal detection criteria. The strongest signals were observed for myocarditis (PRR 54.35, n = 40), myositis (PRR 46.10, n = 25), pemphigoid (PRR 36.06, n = 16), and pneumonitis (PRR 19.37, n = 31). Immune-mediated adverse events predominated, consistent with the mechanism of PD-1 blockade. FAERS disproportionality analysis identifies a signal profile for cemiplimab dominated by immune-related adverse events across cardiac, pulmonary, dermatologic, and endocrine systems. These findings are consistent with the known immunotoxicity of PD-1 inhibitors and support heightened clinical vigilance for myocarditis and immune-mediated pneumonitis.

Skeletal myositis is a disabling complication of Chagas disease for which the first-choice antiparasitic chemotherapy has limited efficacy. Therefore, we synthesized and investigated the potential of the novel nitroimidazole-based drug 1-(2-(2-methoxy-6-nitro-4-propylphenoxy)-ethyl)-2-methyl-5-nitro-1H-imidazole (ME) administered alone or combined with benznidazole (BZ) to control myocytes parasitism and skeletal myositis in Chagas disease. ME antiparasitic efficacy was investigated in vitro and in vivo in C2C12 skeletal myocytes and mice challenged with Trypanosoma cruzi Y strain. Physicochemical modeling indicated that ME presented characteristics compatible with orally bioactive drugs. Similar to BZ, our results indicated that ME showed a marked antiparasitic effect in vitro, attenuating T. cruzi viability, infection rate, and parasite load in C2C12 myocytes in a dose-dependent manner. In vivo, T. cruzi infection induced intense parasitemia, muscle parasitism, oxidative stress, and inflammation, features associated with pathological microstructural remodeling of the skeletal muscle. ME administered alone and mainly in combination with BZ significantly reduced parasitemia, parasite load, production of reactive oxygen species (ROS) and nitrogen species (RNS), oxidation of lipids and cellular proteins, inflammation (e.g., inflammatory infiltrate, NAG and MPO activity, IFN-γ, TNF, IL-6, and IL-10 levels), and microstructural damage in skeletal muscle of T. cruzi-infected animals. Our findings provide evidence that ME has direct antiparasitic effects in vitro and in vivo, showing potential efficacy for use as monotherapy and mainly in combination with BZ. This combination may be relevant to improve the etiological treatment of Chagas disease, simultaneously attenuating parasitism, oxidative stress, and skeletal myositis more efficiently than monotherapy with these drugs.

Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs), including life-threatening myositis and myocarditis. Characterizing the immunopathological features of these conditions is essential for improving clinical recognition and management. We report a case of a 76-year-old man with metastatic renal cell carcinoma who developed fatigue, elevated creatine kinase, and complete atrioventricular block after receiving nivolumab. Despite pacemaker implantation and plasmapheresis, the patient died of respiratory failure. Notably, serum tests were positive for anti-Kv1.4 and anti-titin antibodies, although typical myasthenia gravis features were absent. Autopsy revealed CD8-positive T-cell and CD163-positive macrophage infiltration in the myocardium and skeletal muscles, while also confirming a pathological complete response of the carcinoma. Spatial analysis using digital pathology demonstrated that Human leukocyte antigen (HLA) class I expression in cardiomyocytes was closely apposed to infiltrating CD8-positiveT cells in a patchy distribution. This observation suggests a potential local feedback loop where activated T cells may induce HLA class I upregulation in adjacent muscle fibers, sustaining focal inflammation. This case provides important insights into the complex pathophysiology of fatal irAEs and underscores the value of postmortem examination in irAEs.

We report the case of a previously healthy, 6-year-old boy who presented with 2 days of generalized body aches. Given a recent viral illness with cough and congestion, the emergency department's initial diagnosis of the condition was viral myositis. He was admitted for pain treatment. During his hospitalization, he developed worsening pain, decreased mobility, and intermittent nocturnal desaturations. The team elicited additional history of snoring and witnessed apneas, which raised concern for obstructive sleep apnea. They consulted pulmonology who was concerned for central sleep apnea and respiratory depression and recommended consulting neurology. Neurology recommended a lumbar puncture, the results of which led to the eventual diagnosis. This case highlights the importance of critical reasoning and knowledge of the pediatric presentation of diseases that affect both adults and children.

Sarcocystis species are highly prevalent in bovine intermediate hosts, represent an important veterinary and economic concern. The most documented losses are related to condemnation of Sarcocystis infected carcasses because of macroscopic sarcocysts or infection associated BEM (Bovine eosinophilic myositis) lesions. Previous studies have indicated some similarities between Sarcocystis species in cattle and water buffaloes. Differentiation of morphologically or genetically similar species in related hosts, remains a key diagnostic challenge. Most of the current distinguishing methods are complicated or expensive. Moreover, sanger sequencing of PCR amplicons alone not suitable for species identification in mixed infections. Although different loci such as 28SrDNA, ITS or cox1 are widely used for phylogenetic analyses, the 18 S rRNA gene remains a reliable marker due to its conserved and variable regions. So, this study aimed to develop a rapid and cost-effective allele-specific PCR (AS-PCR) method based on polymorphic sites within the 18 S rRNA gene to differentiate between species in cattle and water buffalo. Specific primers were designed based on differences found at the proper position as SNPs (single nucleotide polymorphisms). SNPs were identified based on multiple sequence alignment of GenBank published 18 S rRNA gene sequences of 65 isolates and clones of 12 recognized Sarcocystis species in cattle and water buffalos. The method uses one forward and two reverse primers, allowing clear molecular separation between macrocyst-forming species in both cattle and water buffalo. Notably, this AS-PCR enables molecular differentiation of these macrocyst-forming species from at least eight microsarcocyst-forming species without the need for sequencing. The assay successfully distinguished S. hirsuta and S. fusiformis in their respective hosts. Interestingly, a sequence closely related to S. fusiformis was also detected in some cattle samples. Phylogenetic analysis revealed that this isolate clustered closely with S. fusiformis but in a distinct clade, leading to its identification as S. fusiformis-like. This is the first molecular report of such an isolate in cattle in Iran.