3 research outputs found
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The Onco-cardiologist Dilemma: to Implant, to Defer, or to Avoid Transcatheter Aortic Valve Replacement in Cancer Patients with Aortic Stenosis?
Aging is associated with an increased prevalence of both cancer and heart disease. The progression of aortic valve calcification to aortic stenosis may be accelerated by both cardiovascular risk factors and cancer treatments, such as radiotherapy with mediastinal involvement. Symptomatic aortic stenosis is occasionally diagnosed in cancer patients undergoing cardiovascular evaluation; likewise, cancer is often recognized during assessment preceding aortic valve interventions. In these complex cases, physicians face difficult treatment decisions. Due to a myriad of clinical presentations of cancer and valve disease, specific guidelines for this patient population are not currently in place. Management is currently based on clinical judgment, on an individual basis.Patients with cancer in remission or with a favorable prognosis should be treated according to current cardiovascular guidelines. In these patients, aortic valve replacement can be performed either by surgery or transcatheter. Significant challenges arise in patients with active cancer, especially those receiving anti-cancer treatment. Recent data suggests that these patients can be offered aortic valve replacement, with a trend of favoring the transcatheter route in order to minimize perioperative risk and complications associated with major surgery. Patients with advanced cancer and severe aortic stenosis should be offered palliative care and can benefit from aortic balloon valvuloplasty if indicated. Modern cancer treatments associated with improved long-term prognosis may allow the appropriate cure of aortic stenosis. We discuss the protocol, outcomes, and evolving recommendations of aortic valve replacement in cancer patients with aortic stenosis
Transcriptional Profiling and Functional Analysis of N1/N2 Neutrophils Reveal an Immunomodulatory Effect of S100A9-Blockade on the Pro-Inflammatory N1 Subpopulation
Neutrophils have been classically viewed as a homogenous population. Recently, neutrophils were phenotypically classified into pro-inflammatory N1 and anti-inflammatory N2 sub-populations, but the functional differences between the two subtypes are not completely understood. We aimed to investigate the phenotypic and functional differences between N1 and N2 neutrophils, and to identify the potential contribution of the S100A9 alarmin in neutrophil polarization. We describe distinct transcriptomic profiles and functional differences between N1 and N2 neutrophils. Compared to N2, the N1 neutrophils exhibited: i) higher levels of ROS and oxidative burst, ii) increased activity of MPO and MMP-9, and iii) enhanced chemotactic response. N1 neutrophils were also characterized by elevated expression of NADPH oxidase subunits, as well as activation of the signaling molecules ERK and the p65 subunit of NF-kB. Moreover, we found that the S100A9 alarmin promotes the chemotactic and enzymatic activity of N1 neutrophils. S100A9 inhibition with a specific small-molecule blocker, reduced CCL2, CCL3 and CCL5 chemokine expression and decreased MPO and MMP-9 activity, by interfering with the NF-kB signaling pathway. Together, these findings reveal that N1 neutrophils are pro-inflammatory effectors of the innate immune response. Pharmacological blockade of S100A9 dampens the function of the pro-inflammatory N1 phenotype, promoting the alarmin as a novel target for therapeutic intervention in inflammatory diseases