Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis.

Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in muscle disease remains unclear. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six clusters and unexpectedly found that none corresponded to traditional definitions of M1 or M2 macrophages. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 (gal-3) and osteopontin (Spp1). Spatial transcriptomics, computational inferences of intercellular communication, and in vitro assays indicated that macrophage-derived Spp1 regulates stromal progenitor differentiation. Gal-3+ macrophages were chronically activated in dystrophic muscle, and adoptive transfer assays showed that the gal-3+ phenotype was the dominant molecular program induced within the dystrophic milieu. Gal-3+ macrophages were also elevated in multiple human myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining their transcriptional programs and reveal Spp1 as a major regulator of macrophage and stromal progenitor interactions.

How Tasmanian Emergency Departments 'Choose Wisely' When Investigating Suspected Pulmonary Embolism.

Overuse of computed tomography pulmonary angiograms (CTPAs) for diagnosis of pulmonary embolism (PE) has been recognised as an issue for over ten years, with Choosing Wisely Australia recommending that CTPAs only be ordered if indicated by a clinical practice guideline (CPG). This study aimed to explore the use of evidence-based practice within regional Tasmanian emergency departments in relation to CTPA orders by determining whether CTPAs were ordered in accordance with validated CPGs. We conducted a retrospective medical record review of all patients who underwent CTPA across all public emergency departments in Tasmania between 1 August 2018 and 31 December 2019 inclusive. Data from 2758 CTPAs across four emergency departments were included. PE was reported in 343 (12.4%) of CTPAs conducted, with yield ranging from 8.2% to 16.1% between the four sites. Overall, 52.1% of participants had neither a CPG documented, nor a D-dimer conducted before their scan. A CPG was documented before 11.8% of scans, while D-dimer was conducted before 43% of CTPAs. The findings presented in this study indicate that Tasmanian emergency departments are not consistently 'Choosing Wisely' when investigating PE. Further research is required to identify explanations for these findings.

Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis.

The monocytic/macrophage system is essential for skeletal muscle homeostasis, but its dysregulation contributes to the pathogenesis of muscle degenerative disorders. Despite our increasing knowledge of the role of macrophages in degenerative disease, it still remains unclear how macrophages contribute to muscle fibrosis. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six novel clusters. Unexpectedly, none corresponded to traditional definitions of M1 or M2 macrophage activation. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 and spp1. Spatial transcriptomics and computational inferences of intercellular communication indicated that spp1 regulates stromal progenitor and macrophage interactions during muscular dystrophy. Galectin-3 + macrophages were chronically activated in dystrophic muscle and adoptive transfer assays showed that the galectin-3 + phenotype was the dominant molecular program induced within the dystrophic milieu. Histological examination of human muscle biopsies revealed that galectin-3 + macrophages were also elevated in multiple myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining the transcriptional programs induced in muscle macrophages, and reveal spp1 as a major regulator of macrophage and stromal progenitor interactions.

Use of Computed Tomography Pulmonary Angiography in Emergency Departments: A Literature Review.

Computed tomography pulmonary angiography (CTPA) has become the most widely used technique for diagnosis or exclusion of a pulmonary embolism (PE). It has been suggested that overuse of this imaging type may be prevalent, especially in emergency departments (EDs). The purpose of this literature review was to explore the use of CTPAs in EDs worldwide. A review following PRISMA guidelines was completed, with research published between September 2010 and August 2020 included. Five key topics emerged: use of CTPAs; explanations for overuse; use of D-dimer; variability in ordering practices between clinicians; and strategies to reduce overuse. This review found that CTPAs continue to be overused in EDs, leading to superfluous risks to patients. Published studies identify that while clinical practice guidelines (CPGs) have a strong effect on reducing unnecessary CTPAs with no significantly increased risk of missed diagnosis, the adoption of these tools by ED clinicians has remained low. This literature review highlights the need for further research into why CTPAs continue to be overused within EDs and why clinicians are hesitant to use CPGs in the clinical setting. Moreover, investigations into other potential strategies that may combat the overuse of this diagnostic tool are essential to reduce potential harm.