Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection.

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers.

Tumor mutational burden and somatic mutation status to predict disease recurrence in advanced melanoma.

Tumor mutational burden (TMB) has recently been identified as a biomarker of response to immune checkpoint inhibitors in many cancers, including melanoma. Co-assessment of TMB with inflammatory markers and genetic mutations may better predict disease outcomes. The goal of this study was to evaluate the potential for TMB and somatic mutations in combination to predict the recurrence of disease in advanced melanoma.

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

Objective: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma.

Summary Background Data: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization.

A Retrospective, Observational Analysis of Tumor Infiltrating Lymphocytes and Tumor Regression in Melanoma.

Background: Tumor infiltrating lymphocytes (TILs) and regression are thought to be distinct markers of the immune response to melanoma.

Objective: This study sought to analyze the relationship of TIL grade and presence of regression to each other and to other prognostic histopathologic and clinical values in melanoma.

Materials And Methods: A retrospective analysis was conducted using patients diagnosed with melanoma between 2013 and 2019 whose complete histopathologic reports were available.

RAGE interacts with the necroptotic protein RIPK3 and mediates transfusion-induced danger signal release.

RBC transfusion is associated with increased morbidity and mortality in critically ill patients. Endothelial cell necroptosis and subsequent damage-associated molecular pattern (DAMP) release has been identified as a mechanism of injury following RBC transfusion. Mounting evidence implicates the pro-inflammatory pattern recognition receptor, Receptor for Advanced Glycation End Products (RAGE), in initiating cell death programmes such as necroptosis.

Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study.

Background: Necroptosis, a form of programmed cell death mediated by receptor interacting serine/threonine-protein kinase-3 (RIPK3), is implicated in murine models of acute respiratory distress syndrome (ARDS). We hypothesized that plasma RIPK3 concentrations in sepsis and trauma would be associated with ARDS development and that plasma RIPK3 would reflect changes in lung tissue RIPK3 in a murine model of systemic inflammation.

Methods: We utilized prospective cohort studies of critically ill sepsis (n = 120) and trauma (n = 180) patients and measured plasma RIPK3 at presentation and 48 h.

Red Blood Cells Homeostatically Bind Mitochondrial DNA through TLR9 to Maintain Quiescence and to Prevent Lung Injury.

Rationale: Potentially hazardous CpG-containing cell-free mitochondrial DNA (cf-mtDNA) is routinely released into the circulation and is associated with morbidity and mortality in critically ill patients. How the body avoids inappropriate innate immune activation by cf-mtDNA remains unknown. Because red blood cells (RBCs) modulate innate immune responses by scavenging chemokines, we hypothesized that RBCs may attenuate CpG-induced lung inflammation through direct scavenging of CpG-containing DNA.

S. aureus blocks efferocytosis of neutrophils by macrophages through the activity of its virulence factor alpha toxin.

Bacterial pneumonia, such as those caused by Staphylococcus aureus, is associated with an influx of inflammatory neutrophils into the lung tissue and airways. Regulation and clearance of recruited neutrophils is essential for preventing tissue damage by "friendly fire", a responsibility of macrophages in a process called efferocytosis. We hypothesized that S.

Plasma Levels of Receptor Interacting Protein Kinase-3 (RIP3), an Essential Mediator of Necroptosis, are Associated with Acute Kidney Injury in Critically Ill Trauma Patients.

Background: Receptor interacting protein kinase-3 (RIP3) is a key mediator of necroptosis, a form of regulated cell death recently implicated in murine models of renal ischemia-reperfusion injury and transfusion-associated endothelial injury. The importance of necroptosis in human AKI is unknown. We hypothesized that plasma RIP3 concentrations would be associated with acute kidney injury (AKI) after severe trauma.