Unilateral hindlimb ischaemia-induced systemic inflammation is associated with non-ischaemic skeletal muscle inflammation.

Skeletal muscle atrophy and dysfunction commonly accompany cardiovascular diseases such as peripheral arterial disease and may be partially attributable to systemic inflammation. We sought to determine whether acute systemic inflammation in a model of hindlimb ischaemia (HLI) could affect skeletal muscle macrophage infiltration, fibre size, or capillarization, independent of the ischaemia. Eight-week-old C57BL/6 male mice underwent either Sham or HLI surgery, and were killed 1, 3, or 7 days post-surgery. Circulating inflammatory cytokine concentrations were measured, as well as immune cell infiltration and morphology of skeletal muscle from both limbs of HLI and Sham mice. In HLI compared with Sham mice at day 1, plasma interleukin-1ß levels were 216% higher (0.48 ± 0.10 vs. 0.15 ± 0.01 pg/µL, P = 0.005) and decreased by day 3. This was followed by increased macrophage presence in muscle from both ischaemic and non-ischaemic limbs of HLI mice by day 7 (7.3- and 2.3-fold greater than Sham, respectively, P < 0.0001). In HLI mice, muscle from the ischaemic limb had 21% lower fibre cross-sectional area than the non-ischaemic limb (724 ± 28 vs. 916 ± 46 µm2, P = 0.01), but the non-ischaemic limb of HLI mice was no different from Sham. This shows that HLI induces acute systemic inflammation accompanied by immune infiltration in both ischaemic and remote skeletal muscle; however, this did not induce skeletal muscle atrophy in remote muscle within the 7-day time course of this study. This effect of local skeletal muscle ischaemia on the inflammatory status of remote skeletal muscle may signal a priming of muscle for subsequent atrophy over a longer time course. HIGHLIGHTS: What is the central question of this study? Does hindlimb ischaemia-induced inflammation cause acute immune, inflammatory and morphological alterations in remote non-ischaemic skeletal muscle? What is the main finding and its importance? Hindlimb ischaemia induced systemic inflammation with subsequent neutrophil and macrophage infiltration in both ischaemic and non-ischaemic skeletal muscle; however, morphological changes did not occur in non-ischaemic muscle within 7 days. These immune alterations may have functional implications that take longer than 7 days to manifest, and subsequent or prolonged systemic inflammation and immune infiltration of muscle could lead to morphological changes and functional decline.

Melanoma Brain Metastases: A Systematic Review of Opportunities for Earlier Detection, Diagnosis, and Treatment.

Introduction: Melanoma continues to represent the most serious skin cancer worldwide. However, few attempts have been made to connect the body of research on advanced melanoma. In the present review, we report on strides made in the diagnosis and treatment of intracranial metastatic melanoma. Methods: Relevant Cochrane reviews and randomized-controlled trials published by November 2022 were systematically retrieved from the Cochrane Library, EMBASE, and PubMed databases (N = 27). Search and screening methods adhered to the 2020 revision of the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Results: Although the research surrounding the earlier detection of melanoma brain metastasis is scarce, several studies have highlighted specific markers associated with MBM. Such factors include elevated BRAFV600 mutant ctDNA, high LDH concentration, and high IGF-1R. The approach to treating MBM is moving away from surgery and toward nonsurgical management, namely, a combination of stereotactic radiosurgery (SRS) and immunotherapeutic agents. There is an abundance of emerging research seeking to identify and improve both novel and established treatment options and diagnostic approaches for MBM, however, more research is still needed to maximize the clinical efficacy, especially for new immunotherapeutics. Conclusions: Early detection is optimal for the efficacy of treatment and MBM prognosis. Current treatment utilizes chemotherapies and targeted therapies. Emerging approaches emphasize biomarkers and joint treatments. Further exploration toward preliminary identification, the timing of therapies, and methods to ameliorate adverse treatment effects are needed to advance MBM patient care.