Delay in weight bearing in surgically treated tibial shaft fractures is associated with impaired healing: a cohort analysis of 166 tibial fractures.

BACKGROUND: The relation between timing of weight bearing after a fracture and the healing outcome is yet to be established, thereby limiting the implementation of a possibly beneficial effect for our patients. The current study was undertaken to determine the effect of timing of weight bearing after a surgically treated tibial shaft fracture. MATERIALS AND METHODS: Surgically treated diaphyseal tibial fractures were retrospectively studied between 2007 and 2015. The timing of initial weight bearing (IWB) was analysed as a predictor for impaired healing in a multivariate regression. RESULTS: Totally, 166 diaphyseal tibial fractures were included, 86 cases with impaired healing and 80 with normal healing. The mean age was 38.7 years (range 16-89). The mean time until IWB was significantly shorter in the normal fracture healing group (2.6 vs 7.4 weeks, p < 0.001). Correlation analysis yielded four possible confounders: infection requiring surgical intervention, fracture type, fasciotomy and open fractures. Logistic regression identified IWB as an independent predictor for impaired healing with an odds ratio of 1.13 per week delay (95% CI 1.03-1.25). CONCLUSIONS: Delay in initial weight bearing is independently associated with impaired fracture healing in surgically treated tibial shaft fractures. Unlike other factors such as fracture type or soft tissue condition, early resumption of weight bearing can be influenced by the treating physician and this factor therefore has a direct clinical relevance. This study indicates that early resumption of weight bearing should be the treatment goal in fracture fixation. LEVEL OF EVIDENCE: 3b.

Targeting non-human coronaviruses to human cancer cells using a bispecific single-chain antibody.

To explore the potential of using non-human coronaviruses for cancer therapy, we first established their ability to kill human tumor cells. We found that the feline infectious peritonitis virus (FIPV) and a felinized murine hepatitis virus (fMHV), both normally incapable of infecting human cells, could rapidly and effectively kill human cancer cells artificially expressing the feline coronavirus receptor aminopeptidase N. Also 3-D multilayer tumor spheroids established from such cells were effectively eradicated. Next, we investigated whether FIPV and fMHV could be targeted to human cancer cells by constructing a bispecific single-chain antibody directed on the one hand against the feline coronavirus spike protein--responsible for receptor binding and subsequent cell entry through virus-cell membrane fusion--and on the other hand against the human epidermal growth factor receptor (EGFR). The targeting antibody mediated specific infection of EGFR-expressing human cancer cells by both coronaviruses. Furthermore, in the presence of the targeting antibody, infected cancer cells formed syncytia typical of productive coronavirus infection. By their potent cytotoxicity, the selective targeting of non-human coronaviruses to human cancer cells provides a rationale for further investigations into the use of these viruses as anticancer agents.