What Does Minimally Invasive Mitral Valve Surgery Really Mean? Defining Totally Endoscopic Mitral Valve Surgery Through Meta Analysis.

INTRODUCTION: Minimally invasive approaches to mitral valve surgery are being performed with increasing frequency; however, many of these procedures still involve rib spreading and large incisions. The heterogeneity of self-reported "minimally invasive" approaches limits analysis of outcomes. This review aims to formally define totally endoscopic mitral valve surgery (TEMVS) and assess outcomes. MATERIALS AND METHODS: A comprehensive literature search in Pub-Med, Cochrane Library, and EMBASE was used to find studies reporting outcomes on totally endoscopic mitral valve surgery. "Totally endoscopic" was defined as incisions less than 3cm and the avoidance of rib spreading. The primary outcome was 30-day mortality and secondary endpoints included postoperative myocardial infarction (MI), stroke, early reoperation, wound infection, renal failure, and prolonged ventilation. Perioperative patient characteristics were also recorded and analyzed. RESULTS: Thirty-three studies (6031 patients) were included in our meta-analysis. The 30-day mortality rate was 0.33%, p=0.88. The most frequent complications were early reoperation (2.12%, p=0.44) and prolonged ventilation (1.46% p=<0.01). Rates of MI, stroke, and renal failure were each less than 1%. Patient characteristics including age, body mass index (BMI), and ejection fractions were also analyzed. CONCLUSIONS: We propose a formal definition of TEMVS, which is performed through incisions less than 3cm and without rib spreading. Thirty-day mortality and other adverse sequelae of TEMVS are uncommon.

Melanocortin 5 Receptor Expression and Recovery of Ocular Immune Privilege after Uveitis.

PURPOSE: The therapeutic use of the RPE-neuropeptide α-MSH suppresses experimental autoimmune uveitis (EAU). This suppression is partially through the α-MSH melanocortin 5 receptor (MC5r). Therefore, we examined the possible role of MC5r-expression in the recovery of RPE suppression of phagolysosome-activation in macrophages following α-MSH-treatment of EAU. METHODS: The conditioned media of cultured in situ RPE-eyecup from α-MSH-treated EAU wild-type and MC5r(-/-) mice were used to treat macrophages to assay for phagolysosome activation. RESULTS: MC5r(-/-) mice treated with α-MSH recovered from EAU, but with greater retinal damage, and the RPE suppressed phagolysosome activation in wild type but not in MC5r(-/-) macrophages. In addition, α-MSH did not suppress phagolysosome activation in MC5r(-/-) macrophages, and resting-MC5r(-/-) macrophages had augmented phagocytic activity. CONCLUSION: α-MSH treatment of EAU mediates a MC5r-dependent recovery of RPE suppression of phagolysosome activation in macrophages possibly altering antigen processing and presentation. Also, MC5r-expression helps protect the retina from inflammatory damage. In addition, MC5r-expression is important in the homeostatic maintenance of phagosome-maturation within macrophages.

Retinal Pigment Epithelial Cells Suppress Phagolysosome Activation in Macrophages.

Purpose: The eye is an immune-privileged microenvironment that has adapted several mechanisms of immune regulation to prevent inflammation. One of these potential mechanisms is retinal pigment epithelial cells (RPE) altering phagocytosis in macrophages. Methods: The conditioned media of RPE eyecups from eyes of healthy mice and mice with experimental autoimmune uveitis (EAU) were used to treat primary macrophage phagocytizing pHrodo bacterial bioparticles. In addition, the neuropeptides were depleted from the conditioned media of healthy RPE eyecups and used to treat phagocytizing macrophages. The conditioned media from healthy and EAU RPE eyecups were assayed for IL-6, and IL-6 was added to the healthy conditioned media, and neutralized in the EAU conditioned media. The macrophages were treated with the conditioned media and assayed for fluorescence. The macrophages were imaged, and the fluorescence intensity, relative to active phagolysosomes, was measured. Also, the macrophages were assayed using fluorescent viability dye staining. Results: The conditioned media from healthy, but not from EAU RPE eyecups suppressed phagolysosome activation. Depletion of the neuropeptides alpha-melanocyte-stimulating hormone and neuropeptide Y from the healthy RPE eyecup conditioned media resulted in macrophage death. In the EAU RPE eyecup conditioned media was 0.96 ± 0.18 ng/mL of IL-6, and when neutralized the conditioned media suppressed phagolysosome activation. Conclusions: The healthy RPE through soluble molecules, including alpha-melanocyte-stimulating hormone and neuropeptide Y, suppresses the activation of the phagolysosome in macrophages. In EAU, the IL-6 produced by the RPE promotes the activation of phagolysosomes in macrophages. These results demonstrate that under healthy conditions, RPE promotes an altered pathway of phagocytized material in macrophages with implications on antigen processing and clearance.