Large-bowel disease presenting as small-bowel obstruction is associated with a poor prognosis.

INTRODUCTION: Small-bowel obstruction (SBO) is a common cause of admission to the surgical service. On rare occasions, a diagnosed SBO is actually due to large-bowel pathology combined with an incompetent ileocecal valve. The purpose of this study was to investigate this phenomenon. METHODS: We performed a retrospective medical record review of patients that were admitted with a diagnosis of SBO at University of Louisville hospital and the Veterans Affairs hospitals in Louisville, KY, from 2006 until 2014. RESULTS: A total of 498 patients were admitted with SBO during this time period. Forty-one patients were found to have an underlying large-bowel disease. The most common large-bowel pathologies included malignancy (51%), inflammation (15%), and infection (15%). Fifteen (43%) of these patients died during admission; 93% of these were due to either their bowel obstruction or the underlying disease state. This was significantly higher than the general population (9.4% mortality, 6% due to underlying disease). CONCLUSIONS: Patients that present with SBO due to a large-bowel source have a much higher mortality rate than those that present with other causes. Rapid identification of these patients will allow for more timely and appropriate treatment.

Anti-inflammatory effects of miR-21 in the macrophage response to peritonitis.

We investigated the role of microRNA-21 in the macrophage response to peritonitis; microRNA-21 expression increases in peritoneal macrophages after lipopolysaccharide stimulation but is delayed until 48 hours after cecal ligation and puncture. MicroRNA-21-null mice and bone marrow-derived cell lines were exposed to cecal ligation and puncture or lipopolysaccharide, and survival, microRNA-21 levels, target messenger RNAs and proteins, and cytokines were assayed. Macrophages were also transfected with microRNA-21 mimics and antagomirs, and similar endpoints were measured. Survival in microRNA-21-null mice was significantly decreased after lipopolysaccharide-induced peritonitis but unchanged after cecal ligation and puncture compared with similarly treated wild-type mice. MicroRNA-21 expression, tumor necrosis factor-α, interleukin 6, and programmed cell death protein 4 levels were increased after lipopolysaccharide addition in peritoneal cells. Pelino1 and sprouty (SPRY) messenger RNAs were similarly increased early, whereas programmed cell death protein 4 messenger RNA was decreased after lipopolysaccharide, and all microR-21 target messenger RNAs were subsequently decreased by 24 hours after lipopolysaccharide. Transfection with mimics and antagomirs led to appropriate responses in microRNA-21 and tumor necrosis factor-α. Knockdown of microRNA-21 in bone marrow-derived cells showed increased tumor necrosis factor-α and decreased interleukin 10 in response to lipopolysaccharide. Target proteins were unaffected by knockdown as was extracellular signal-regulated kinase; however, the nuclear factor κB p65 subunit was increased after lipopolysaccharide in the microRNA-21 knockout cells. In contrast, there was little change in these parameters after cecal ligation and puncture induction between null and wild-type mice. MicroRNA-21 is beneficial to survival in mice following lipopolysaccharide peritonitis. Overexpression of microRNA-21 decreased tumor necrosis factor-α secretion, whereas suppression of microRNA-21 expression increased tumor necrosis factor-α and interleukin 6, and decreased interleukin 10 levels after lipopolysaccharide. Protein targets of microRNA-21 were not different following suppression of microRNA-21. Nuclear factor κB was increased by suppression of microRNA-21. These findings demonstrate microRNA-21 is beneficial in modulating the macrophage response to lipopolysaccharide peritonitis and an improved understanding of the anti-inflammatory effects of microRNA-21 may result in novel, targeted therapy against peritonitis and sepsis.