A major concern in therapy of acute liver failure is protection of hepatocytes to prevent apoptosis and maintain liver function. Small interfering RNA (siRNA) is a powerful tool to silence gene expression in mammalian cells. To evaluate the therapeutic efficacy of siRNA in vivo we used different mouse models of acute liver failure. We directed 21-nt siRNAs against caspase 8, which is a key enzyme in death receptor-mediated apoptosis. Systemic application of caspase 8 siRNA results in inhibition of caspase 8 gene expression in the liver, thereby preventing Fas (CD95)-mediated apoptosis. Protection of hepatocytes by caspase 8 siRNA significantly attenuated acute liver damage induced by agonistic Fas (CD95) antibody (Jo2) or by adenovirus expressing Fas ligand (AdFasL). However, in a clinical situation the siRNAs most likely would be applied after the onset of acute liver failure. Therefore we injected caspase 8 siRNA at a time point during AdFasL-and adenovirus wild type (Adwt)-mediated liver failure with already elevated liver transaminases. Improvement of survival due to RNA interference was significant even when caspase 8 siRNA was applied during ongoing acute liver failure. In addition, it is of particular interest that caspase 8 siRNA treatment was successful not only in acute liver failure mediated by specific Fas agonistic agents (Jo2 and AdFasL) but also in acute liver failure mediated by Adwt, which is an animal model reflecting multiple molecular mechanisms involved in human acute viral hepatitis. Consequently, our data raise hope for future successful application of siRNA in patients with acute liver failure.

We prospectively followed a case series of 68 patients with 69 AO/ASIF 41-C-type fractures treated with the Less Invasive Stabilization System for the proximal lateral tibia. We assessed malreduction, secondary loss of reduction, and infection rates in patients with a locked screw plate for unilateral fixation of bicondylar fractures. Sixty-two (91%) patients returned for final followup (range, 11-13 months). Malreduction and malalignment were defined as an intraarticular step-off of 2 mm or greater, or as a malalignment in the frontal or sagittal plane greater than 5 degrees . Fourteen fractures were open. Primary bone grafting was done in 13 patients. Significant malreduction was seen in 16 patients. There were four superficial infections and one deep infection. One fracture did not heal, and nine patients had substantial loss of reduction. Unilateral locked screw plating is a good alternative for treatment of problematic fractures of the tibial plateau that are associated with soft tissue damage and metaphyseal comminution. The reduction technique for exact alignment is demanding.

Rupture of the patellar tendon is a rare injury requiring acute repair to reestablish knee extensor continuity and to allow early motion. Different pathomechanisms have been postulated, and multiple techniques for repair have been described in the literature. Firstly, the current study reviews the epidemiology, pathomechanism, and risk factors. Secondly, we compare the outcome of two augmentation techniques after end-to-end sutures: reinforcement with either a wire cerclage or a PDS cord. In the first part of the study, the medical records of 66 patients with 68 ruptures were reviewed. For the second part, 33 patients were included who had no prior injury to the extensor mechanism of the knee and had suffered an indirect, low-velocity injury followed by immediate repair. Twenty-seven patients with 29 ruptures of the patellar tendon returned for follow-up. Follow-up averaged 8.1 years (range 1-16 years). In the follow-up group, 22 ruptures had augmentation with a wire cerclage (group A), and 7 ruptures had augmentation with a 2-mm PDS cord (group B). Follow-up evaluation consisted of a subjective questionnaire, a physical and radiographic examination, the Hospital for Special Surgery Knee Score, and the Insall-Salvati ratio. Nineteen patients underwent Cybex isokinetic strength testing of the quadriceps. Indirect, low-velocity injuries occurred most often in the 30-40 year age group, whereas complex knee traumas or knee luxations were more evenly distributed. In 10 of 46 patients with an indirect, low-velocity injury, there was a history of prior injury and illness to the extensor mechanism of the knee, compared with 1 of 22 patients with a high-velocity complex knee trauma. In the follow-up group, no patient sustained a rerupture. Two of 22 patients had an extension lag in group A compared with no extension lag in group B. Average flexion in group A was 130 degrees (SD 29 degrees) compared with 137 degrees (SD 12 degrees ) in group B. The average Hospital for Special Surgery Knee Score was 92 (SD 17) in group A and 96 (SD 12) in group B. Three patients were dissatisfied. All had radiographic signs of retropatellar osteoarthritis. In contrast, 9 of 26 patients who were satisfied with their result had radiographic signs of retropatellar osteoarthritis. A postoperative difference in the Insall-Salvati ratio did not correlate with the development of osteoarthritis. Both augmentation techniques are reliable and demostrate good intermediate to long-term results. The outcome did not show significant differences. To avoid reoperation for removal of the cerclage wire, a PDS cord can be used. The infection rate seems to be higher in the PDS group. A larger prospective study group is necessary to determine whether this phenomenon can be reproduced.

From these preliminary results we conclude that the comfort of limb lengthening with the ISKD is increased by the elimination of fixator-associated complications and by the simple distraction mechanism, which is well tolerated by the patients. Further advantages of the ISKD are early full weight bearing and excellent limb function.

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