Surgery
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Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide. Greater than 90% of SCCHN of the oropharynx overexpress the epidermal growth factor receptor (EGFR or HER1). Cetuximab (Erbitux-TM) is a humanized anti-HER1 monoclonal antibody (mAb) that binds to HER1 overexpressing tumor cells. Cetuximab has a direct effect on HER1-positive cancer cells, but it also can activate immune cells that bear receptors for the Fc (constant portion) of IgG such as natural killer (NK) cells. NK cells have an activating Fc receptor for IgG (FcγRIIIa), which mediates Ab dependent cellular cytotoxicity (ADCC) and enhances production of interferon-γ (IFN-γ) in response to Ab-coated targets. Interleukin-12 (IL-12) is a cytokine produced by antigen-presenting cells that stimulates IFN-γ production from NK cells. We hypothesized that IL-12 would enhance the anti-tumor activity of cetuximab by activating the FcR effector mechanisms of NK cells. ⋯ Cytokine stimulation of NK cells in the presence of cetuximab-coated head and neck cancer cells leads to enhanced NK cell mediated ADCC and cytokine secretion independent of tumor cell HPV-status. Cytokine administration could be a useful adjuvant in the cetuximab treatment of HER1-positive head and neck cancer.
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High-dose perioperative corticosteroids are the standard of care for steroid-treated patients undergoing surgery. There is little evidence, however, to support this practice. We investigated the safety of perioperative low-dose steroids in patients with inflammatory bowel disease (IBD) undergoing major colorectal surgery. ⋯ In steroid-treated IBD patients undergoing major colorectal surgery, the use of low-dose perioperative corticosteroids seems safe. A prospective study assessing perioperative corticosteroid dosing is in progress.
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Acute lung injury (ALI) is a complication of hemorrhagic shock (HS). Histone deacetylase inhibitors, such as valproic acid (VPA), can improve survival after HS; however, their effects on late organ injury are unknown. Herein, we have investigated the effects of HS and VPA treatment on ALI and circulating cytokines that may serve as biomarkers for the development of organ injury. ⋯ Hemorrhage resulted in the development of ALI, which was prevented with VPA treatment. Circulating CINC-1 levels rose rapidly after hemorrhage, and serum CINC-1 levels correlated with lung CINC-1 and MPO levels. This suggests that circulating CINC-1 levels could be used as an early marker for the subsequent development of organ inflammation and injury.
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Growing evidence suggests platelets are essential in posttraumatic, acute lung injury (ALI). Halogenated ethers interfere with the formation of platelet-granulocyte aggregates. The potential benefit of halogenated ethers has not been investigated in models of trauma/hemorrhagic shock (T/HS). Therefore, we hypothesized that isoflurane decreases T/HS-mediated ALI through platelet inhibition. ⋯ Isoflurane attenuates ALI through an antiplatelet mechanism, in part, through inhibition of the platelet ADP pathway. Isoflurane given postinjury also protects against ALI, and highlights the potential applications of this therapy in various clinical scenarios of ischemia/reperfusion.
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Disparities in access to services across genders have been reported in many healthcare settings. The extent to which this occurs in the case of emergency surgical care is unknown. We set out to evaluate whether gender is a determinant of access to trauma center care, particularly in the setting where trauma triage guidelines are strong facilitators to ensure that access is determined by physiologic status and injury characteristics. ⋯ Severely injured women were less likely to be directed to a trauma center across 2 types of providers. The reasons for this differential in access might be related to perceived difference in injury severity, likelihood of benefiting from trauma center care, or subconscious gender bias.