ABSTRACT
Sepsis is a major cause of death worldwide. It triggers systemic inflammation, the role of which remains unclear. In the current study, we investigated the induction of microRNA (miRNA) during sepsis and their role in the regulation of inflammation. Patients, on days 1 and 5 following sepsis diagnosis, had reduced T cells but elevated monocytes. Plasma levels of IL-6, IL-8, IL-10 and MCP-1 dramatically increased in sepsis patients on day 1. T cells from sepsis patients differentiated primarily into Th2 cells, whereas regulatory T cells decreased. Analysis of 1163 miRNAs from PBMCs revealed that miR-182, miR-143, miR-145, miR-146a, miR-150, and miR-155 were dysregulated in sepsis patients. miR-146a downregulation correlated with increased IL-6 expression and monocyte proliferation. Bioinformatics analysis uncovered the immunological associations of dysregulated miRNAs with clinical disease. The current study demonstrates that miRNA dysregulation correlates with clinical manifestations and inflammation, and therefore remains a potential therapeutic target against sepsis.
Subject(s)
Cytokines/blood , Inflammation/pathology , Interleukin-6/genetics , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , MicroRNAs/genetics , Sepsis/immunology , Aged , Cell Differentiation , Chemokines/blood , Chemokines/genetics , Chemokines/immunology , Computational Biology , Cytokines/genetics , Cytokines/immunology , Down-Regulation , Female , Gene Expression Regulation , Humans , Inflammation/genetics , Inflammation/immunology , Interleukin-6/blood , Interleukin-6/immunology , Male , Metabolic Networks and Pathways , Middle Aged , Monocytes/immunology , Monocytes/metabolism , Oligonucleotide Array Sequence Analysis , Sepsis/diagnosis , Sepsis/genetics , T-Lymphocytes/classification , T-Lymphocytes/immunologyABSTRACT
Hereditary spherocytosis is a common form of hemolytic anemia sometimes requiring splenectomy in recalcitrant cases. The complications of splenectomy include an increased risk of thrombosis, usually presenting with deep vein thrombosis or pulmonary embolism. However, common complaints such as headache should warn clinicians of involvement in less common sites, primarily the dural venous system. The case of dural venous thrombosis in a patient with hereditary spherocytosis and splenectomy is discussed. The potential mechanisms associated with thrombosis formation in this population and its treatment are discussed.
Subject(s)
Spherocytosis, Hereditary/complications , Splenectomy/adverse effects , Subarachnoid Hemorrhage/etiology , Venous Thrombosis/etiology , Cerebral Angiography , Female , Fibrinolytic Agents/administration & dosage , Heparin/administration & dosage , Humans , Infusions, Intravenous , Spherocytosis, Hereditary/surgery , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/drug therapy , Tomography, X-Ray Computed , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy , Young AdultABSTRACT
Though uncommon, right-to-left shunt through a patent foramen ovale with normal right-side pressure and with a normal interatrial pressure gradient has been reported. The speculated pathophysiology is attributed to directional blood flow streaming from the vena cava to the left atrium. Hypoxemia secondary to right-to-left shunt with normal pulmonary artery pressure has been extensively documented after right pneumonectomy. Five prior cases have documented hypoxemia secondary to a right-to-left shunt through a patent foramen ovale in the presence of an elevated right hemidiaphragm. This is the sixth documented case of right-to-left shunt through a patent foramen ovale in the presence of an elevated right hemidiaphragm with a similar presentation in which closure of the patent foramen ovale resulted in resolution of hypoxemia.