Hemorrhagic shock is caused by rapid loss of a significant blood volume, which leads to insufficient blood flow and oxygen delivery to organs and tissues, resulting in severe physiological derangements, organ failure, and death. Physiologic derangements after hemorrhage are due in a large part to the body's strong inflammatory response, which leads to severe immune dysfunction, and secondary complications such as chronic immunosuppression, increased susceptibility to infection, coagulopathy, multiple organ failure, and unregulated inflammation. Immediate management of hemorrhagic shock includes timely control of the source of bleeding, restoring intravascular volume, preferably with whole blood, and prevention of ischemia and organ failure by optimizing tissue oxygenation.
View Article and Find Full Text PDFTotal pancreatectomy is a complex procedure used in the management of pancreatic cancer. While minimally invasive techniques have been increasingly adopted, limited data exist comparing robotic total pancreatectomy (RTP) and laparoscopic total pancreatectomy (LTP). This study evaluates the utilization, short- and long-term outcomes of RTP and LTP using the National Cancer Database.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma cancer (PDAC) is projected to become the second leading cause of cancer-related death in the United States by 2030. Patients are often diagnosed with advanced disease, which explains the dismal 5-year median overall survival rate of ~12%. Immunotherapy has been successful in improving outcomes in the past decade for a variety of malignancies, including gastrointestinal cancers.
View Article and Find Full Text PDFGenetically engineered, cytotoxic, adoptively transferred T cells localize to antigen-positive cancer cells inside patients, but tumor heterogeneity and multiple immune escape mechanisms have prevented the eradication of most solid tumor types. More effective, multifunctional engineered T cells are in development to overcome the barriers to the treatment of solid tumors, but the interactions of these highly modified cells with the host are poorly understood. We previously engineered prodrug-activating enzymatic functions into chimeric antigen receptor (CAR) T cells, endowing them with a killing mechanism orthogonal to conventional T-cell cytotoxicity.
View Article and Find Full Text PDFGenetically engineered, cytotoxic, adoptive T cells localize to antigen positive cancer cells inside patients, but tumor heterogeneity and multiple immune escape mechanisms have prevented the eradication of most solid tumor types. More effective, multifunctional engineered T cells are in development to overcome the barriers to the treatment of solid tumors, but the interactions of these highly modified cells with the host are poorly understood. We previously engineered prodrug-activating enzymatic functions into chimeric antigen receptor (CAR) T cells, endowing them with an orthogonal killing mechanism to conventional T-cell cytotoxicity.
View Article and Find Full Text PDFCancer remains a leading cause of death despite many advances in medical and surgical therapy. In recent decades, the investigation for novel therapeutic strategies with greater efficacy and reduced side effects has led to a deeper understanding of the relationship between the microbiome and the immune system in the context of cancer. The ability of the immune system to detect and kill cancer is now recognized to be greatly influenced by the microbial ecosystem of the host.
View Article and Find Full Text PDFBackground: Cancelled healthcare appointments, especially in patients with complex cancers, such as esophageal cancer, risk delayed treatment and adverse outcomes. We hypothesized that patients with greater rates of healthcare appointment cancellations would have decreased survival after esophagectomy for esophageal cancer.
Methods: A retrospective analysis of patients from a single institution who underwent esophagectomy for esophageal cancer between 2004 and 2020 was performed.
Cyclin dependent kinase 4/6 inhibitors (CDK4/6i) lead to cell-cycle arrest but also trigger T cell-mediated immunity, which might be mediated by changes in human leukocyte antigen (HLA) ligands. We investigated the effects of CDK4/6i, abemaciclib and palbociclib, on the immunopeptidome at nontoxic levels in breast cancer cell lines by biochemical identification of HLA ligands followed by network analyses. This treatment led to upregulation of HLA and revealed hundreds of induced HLA ligands in breast cancer cell lines.
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