Although the role of systemic activation of the nuclear factor kappaB (NF-kappaB) pathway in septic coagulation has been well documented, little is known about the contribution of endothelial-specific NF-kappaB signaling in this pathologic process. Here, we used transgenic mice that conditionally overexpress a mutant I-kappaBalpha, an inhibitor of NF-kappaB, selectively on endothelium, and their wild-type littermates to define the role of endothelial-specific NF-kappaB in septic coagulation. In wild-type mice, lipopolysaccharide (LPS) challenge (5 mg/kg intraperitoneally) caused markedly increased plasma markers of coagulation, decreased plasma fibrinogen level, and widespread tissue fibrin deposition, which were abrogated by endothelial NF-kappaB blockade in transgenic mice. Endothelial NF-kappaB blockade inhibited tissue factor expression in endothelial cells, but not in leukocytes. Endothelial NF-kappaB blockade did not inhibit LPS-induced tissue factor expression in heart, kidney, and liver. Endothelial NF-kappaB blockade prevented LPS down-regulation of endothelial protein C receptor (EPCR) and thrombomodulin protein expressions, inhibited tissue tumor necrosis factor-alpha converting enzyme activity, reduced EPCR shedding, and restored plasma protein C level. Our data demonstrate that endothelial intrinsic NF-kappaB signaling plays a pivotal role in septic coagulation and suggests a link between endothelial-specific NF-kappaB activation and the impairment of the thrombomodulin-protein C-EPCR anticoagulation pathway.

Segmental pedicle screw fixation is rapidly becoming a popular method of spinal instrumentation. Few studies have investigated the rates of adjacent superior segment facet joint violation. The purpose of our study were to investigate the incidence of superior segment facet joint violation after pedicle screw instrumentation in the lumbar spine and to evaluate technical factors related to the incidence. A prospective study including 96 patients who underwent lumbar and lumbosacral fusion was conducted between March 2006 and December 2007. All patients had bilateral or unilateral posterior pedicle screw-rod instrumentation with either CD-Horizon (top-loading screw) or TSRH (side-connecting screw) implants. Pedicle screws were instrumented according to the methods advocated by Roy-Camille (Group 1, 20 cases) or Weinstein (Group 2, 76 cases). All patients had computed tomography scan at 1 week post operation. CT scans were reviewed blind by an experienced spine research fellow and a consultant radiologist to determine violation of the adjacent superior segment facet joint. Superior segment facet joint violation occurred in all of the 20 patients (100%) and all of the top-level screws (100%) in Group 1. The spinal research fellow noted the incidence of facet joint violation to be present in 23.8% of the screws and 32.9% of the patients in Group 2, whereas the consultant radiologist noted this to be the case in 25.2 and 35.5%, respectively. The incidence of facet joint violation in patients with CD-Horizon screws was far lower than patients with TSRH screws (P < 0.001). In conclusion, it seems that meticulous surgical dissection without injuring the top-level facet joints, proper instrumentation of pedicle screws with the appropriate entry site (Weinstein's method), trajectory, and use of top-loading screw heads are some ways that surgeons could minimize the risk of top-level facet joint violation.

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