Staged distraction osteogenesis followed by arthrodesis using internal fixation as a form of surgical treatment for complex conditions of the ankle.

Aims: The aim of this study was to describe the technique of distraction osteogenesis followed by arthrodesis using internal fixation to manage complex conditions of the ankle, and to present the results of this technique. Patients and Methods: Between 2008 and 2014, distraction osteogenesis followed by arthrodesis using internal fixation was performed in 12 patients with complex conditions of the ankle due to trauma or infection. There were eight men and four women: their mean age was 35 years (23 to 51) at the time of surgery. Bone healing and functional recovery were evaluated according to the criteria described by Paley. Function was assessed using the ankle-hindfoot scale of the American Orthopedic Foot and Ankle Society (AOFAS). Results: A solid fusion of the ankle and eradication of infection was achieved in all patients. A mean lengthening of 6.1 cm (2.5 to 14) was achieved at a mean follow-up of 25.2 months (14 to 37). The mean external fixation index (EFI) was 42 days/cm (33.3 to 58). The function was judged to be excellent in six patients and good in six patients. Bone results were graded as excellent in ten patients and good in two patients. The mean AOFAS score was 37.3 (5 to 77) preoperatively and 75.3 (61 to 82) at the final follow-up. Minor complications, which were treated conservatively, included pain, pin-tract infection, loosening of wires, and midfoot stiffness. Major complications, which were treated surgically included grade V pin-tract infection with inflammation and osteolysis, poor consolidation of the regenerate bone, and soft-tissue invagination. The reoperations required to treat the major complications included the exchange of pins and wires, bone grafting and invagination split surgery. Conclusion: The technique of distraction osteogenesis followed by arthrodesis using internal fixation is an effective form of treatment for the management of complex conditions of the ankle. It offers a high rate of union, an opportunity to remove the frame early, and a reduced EFI without infection or wound dehiscence. Cite this article: Bone Joint J 2018;100-B:755-60.

Erk pathway inhibitor U0126 induces gamma-globin expression in erythroid cells.

Fetal hemoglobin (HbF) induction is an effective approach to improve clinical symptoms in sickle cell disease. Understanding molecular mechanisms for gamma-gene re-activation will aid efforts to design lead compounds. A potential inhibitory role for the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway in gamma-gene expression has been suggested recently. Therefore, we determined the ability of U0126, a selective inhibitor of MEK1/2 the upstream activators of ERK, to re-activate gamma-globin expression. K562 stable lines over-expressing constitutively active MEK1 were established. A significant increase in ERK phosphorylation was observed and gamma-gene expression was silenced concomitantly, however U0126 attenuated this effect. Studies in human erythroid progenitors confirmed the ability of U0126 to induce HbF. Cellular mechanisms for the inhibitory role of ERK signaling in drug-mediated HbF induction will be discussed.