Neutrophils are essential for successful host eradication of bacterial pathogens and for survival to polymicrobial sepsis. During inflammation, the bone marrow provides a large reserve of neutrophils that are released into the peripheral circulation where they traverse to sites of infection. Although neutrophils are essential for survival, few studies have investigated the mechanisms responsible for neutrophil mobilization from the bone marrow during polymicrobial sepsis. Using a cecal ligation and puncture model of polymicrobial sepsis, we demonstrate that neutrophil mobilization from the bone marrow is not dependent on TLR4, MyD88, TRIF, IFNARα/β or CXCR2 pathway signaling during sepsis. In contrast, we observe that bone marrow CXCL12 mRNA abundance and specific CXCL12 levels are sharply reduced, while splenic CXCR4 mRNA and cell surface expression are increased during sepsis. Blocking CXCL12 activity significantly reduced the blood neutrophilia by inhibiting bone marrow release of granulocytes during sepsis. CXCL12 inhibition, however, had no impact on the expansion of bone marrow neutrophil precursors and hematopoietic progenitors. Bone marrow neutrophil retention by CXCL12 blockade prevented blood neutrophilia, inhibited peritoneal neutrophil accumulation, allowed significant peritoneal bacterial invasion and elevated polymicrobial sepsis mortality. We conclude that changes in the pattern of CXCL12 signaling during sepsis are essential for neutrophil bone marrow mobilization and host survival while having little impact on bone marrow granulopoiesis.
Cardiac surgical procedures can be performed with acceptable short-term and long-term outcomes in liver transplant recipients. Elevated preoperative and postoperative MELD scores and postoperative peak creatinine level may portend death in this cohort. There is a constant hazard of death of 10% per year.
Aortic dissection is a potentially lethal clinical entity that requires rapid diagnosis, appropriate medical management, and potential surgical intervention. Nomenclature and treatments for aortic dissection are based on the location and extent of the dissection. Aortic dissections result from an intimal tear and may occur in the ascending aorta, aortic arch, or descending aorta. Patients with aortic dissection may present with a wide variety of symptoms secondary to the pattern of dissection and end organ malperfusion. Optimal medical therapy, often using a combination of medications to achieve systolic blood pressure control is essential in management of dissection. Surgical intervention is indicated for aortic dissection of the ascending aorta and aortic arch, and in selective dissections of the descending aorta. Regardless of operative technique, the goal of surgery is to prevent progression of the dissection, restore end organ perfusion whenever possible, and prevent rapid cardiovascular collapse and death.
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