Reimplantation of an extruded osteoarticular segment of the femur: Case series and in vitro study in a rat model.

BACKGROUND: The treatment of open femur fractures with reimplantation of large extruded segments remains one of the most difficult clinical management scenarios. The situation is even complicated when the extruded segments contains a large osteoarticular segment and no consensus exist about the efficient sterilization. We successfully managed five cases of open femur fracture by reimplantation of a large osteoarticular segment. While the outcomes were favourable, we performed an in vitro investigation in a rat model to determine whether the bone segment preparation strategy was optimal. MATERIALS AND METHODS: After meticulous debridement and sterilization with povidone-iodine scrub/orthopaedic antibiotic solution, osteoarticular segments of the femur were reimplanted successfully in five patients with Gustilo-Anderson IIIa-IIIb fractures. Furthermore, in vitro study performed to assess the relative efficacy of various methods of sterilization employed osteoarticular segments of rat femurs. After contamination, osteoarticular segments were treated via one of the following protocols: (1) saline rinse; (2) povidone-iodine scrub and saline rinse; (3) povidone-iodine scrub and autoclaving; (4) povidone-iodine scrub and immersion in antibiotic solution; (5) povidone-iodine scrub and immersion in povidone-iodine solution; or (6) povidone-iodine scrub and gamma-irradiation. The osteoarticular segments were then cultured and finally evaluated for infection and morphological changes. RESULTS: At the mean 40 month follow-up, there were no infection in the patients and the fractures achieved completed union. For the basic research, only approaches involving povidone-iodine scrub with autoclaving or antibiotic solution immersion were 100% effective in eliminating bacterial growth. Furthermore, povidone-iodine scrub with antibiotic solution immersion preserved the articular surface morphology. CONCLUSION: Our study suggests that reimplantation of extruded osteoarticular segments of long bone may represent a feasible alternative to amputation. This is the first description of such a technique and its long-term outcomes in the clinical setting, which were corroborated with the outcomes of in vitro investigation in a rat model, concluding that contaminated extruded osteoarticular segments can be adequately sterilized for reimplantation by cleaning with povidone-iodine scrub followed by brief soaking in antibiotic solution. However, it remains unclear whether the antibacterial efficacy of different sterilizations noted in vitro is reflected in vivo, warranting further research.

RUNX1 prevents oestrogen-mediated AXIN1 suppression and ß-catenin activation in ER-positive breast cancer.

Recent high-throughput studies revealed recurrent RUNX1 mutations in breast cancer, specifically in oestrogen receptor-positive (ER(+)) tumours. However, mechanisms underlying the implied RUNX1-mediated tumour suppression remain elusive. Here, by depleting mammary epithelial cells of RUNX1 in vivo and in vitro, we demonstrate combinatorial regulation of AXIN1 by RUNX1 and oestrogen. RUNX1 and ER occupy adjacent elements in AXIN1's second intron, and RUNX1 antagonizes oestrogen-mediated AXIN1 suppression. Accordingly, RNA-seq and immunohistochemical analyses demonstrate an ER-dependent correlation between RUNX1 and AXIN1 in tumour biopsies. RUNX1 loss in ER(+) mammary epithelial cells increases ß-catenin, deregulates mitosis and stimulates cell proliferation and expression of stem cell markers. However, it does not stimulate LEF/TCF, c-Myc or CCND1, and it does not accelerate G1/S cell cycle phase transition. Finally, RUNX1 loss-mediated deregulation of ß-catenin and mitosis is ameliorated by AXIN1 stabilization in vitro, highlighting AXIN1 as a potential target for the management of ER(+) breast cancer.