In this study, a surgical delay of more than twelve hours significantly increased the adjusted risk of thirty-day mortality and a surgical delay of more than twenty-four hours significantly increased the adjusted risk of ninety-day mortality. The adjusted risk of both thirty-day and ninety-day mortality increased significantly when the education level of the surgeon was below that of an attending surgeon. The study findings challenge orthopaedic departments to facilitate fast surgical treatment supported by attending orthopaedic surgeons.

BackgroundMicro RNAs (miRs) have emerged as key regulators during oncogenesis. They have been found to regulate cell proliferation, differentiation, and apoptosis. Mir-125b has been identified as an oncomir in various forms of tumours, but we have previously proposed that miR-125b is a suppressor of lymph node metastasis in cutaneous malignant melanoma. Our goal was therefore to further examine this theory.MethodsWe used in-situ-hybridization to visualise miR-125b expression in primary tumours and in lymph node metastasis. Then using a miRVector plasmid containing a miR-125b-1 insert we transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and β-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further examined with in-situ-hybridization.ResultsIn primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki67 than the control tumours.ConclusionsOur results confirm the theory that miR-125b functions as a tumour supressor in cutaneous malignant melanoma by regulating cellular senescence, which is one of the central mechanisms protecting against the development and progression of malignant melanoma.

Background: The purpose of this study was to estimate the incidence of reoperation and the effect of implant position on the risk of reoperation within 12 months following osteosynthesis with use of parallel implants for femoral neck fractures. Methods: From cases registered in the Danish Fracture Database, 1,206 consecutive surgeries for a primary femoral neck fracture treated with use of parallel implants during the period of December 2011 to November 2015, and having available radiographs and follow-up data, were reviewed. Data included age, sex, time to surgery, fracture classification, and American Society of Anesthesiologists (ASA) score. Fracture displacement, posterior tilt, the number of implants, posterior distance, calcar distance, tip-cartilage distance, and angulation of implants were measured on pre- and postoperative radiographs. Data on secondary surgeries were collected from the Danish Civil Registration System. The effects of the included variables on the risk of reoperation were evaluated using Cox regression analysis. Results: The median age was 73 years (range, 21 to 102 years); in 69% of the cases, the patient was female. Two implants were used in 997 cases and 3 implants were used in 209. In 157 cases, the patient underwent reoperation within 1 year; in 228 cases, the patient died within 1 year. The median time to reoperation was 116 days. Patients <70 years of age were more likely to undergo reoperation (18.0% compared with 9.8%) but less likely to die (7.4% compared with 26.3%) than were patients ≥70 years of age. Female sex, higher ASA score, and displaced fractures were associated with increased risk of reoperation. Time to surgery was associated with increased risk of reoperation for displaced fractures only. Of the variables pertaining to the osteosynthesis, only insufficient fracture reduction, placement of the implants with an angle to the shaft of ≤125°, and femoral head perforation significantly increased the risk of reoperation. We found no effect of the posterior distance, the calcar distance, the tip-caput distance, or whether or not the implants were parallel. Conclusions: Insufficient reduction, varus position of the implants, and perforation of the femoral head cartilage were the only surgical factors influencing the risk of reoperation. Sufficient fracture reduction is perhaps more important than focusing on an optimal position of the implants. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.