No standard criteria exist for diagnosing fracture nonunion, and studies suggest that assessment of fracture healing varies among orthopaedic surgeons. This variability can be problematic in both clinical and orthopaedic trauma research settings. An understanding of risk factors for nonunion and of diagnostic tests used to assess fracture healing can facilitate a systematic approach to evaluation and management. Risk factors for nonunion include medical comorbidities, age, and the characteristics of the injury. The method of fracture management also influences healing. Comprehensive evaluation includes an assessment of the patient's symptoms, signs, and immune and endocrine status as well as the biologic capacity of the fracture, presence of infection, and quality of reduction and fixation. Diagnostic tests include plain radiography, CT, ultrasonography, fluoroscopy, bone scan, MRI, and several laboratory tests, including assays for bone turnover markers in the peripheral circulation. A systematic approach to evaluating fracture union can help surgeons determine the timing and nature of interventions.

Brahma-related gene 1 (BRG1) is a catalytic subunit of the switch in mating type/sucrose nonfermentation complex and plays an important role in cancer development. Mouse homozygous knockout experiments testing the role of BRG1 in tumorigenesis have been hampered because BRG1 inactivation is embryonic lethal. To bypass this constraint, we developed a lung-specific conditional knockout of BRG1 and examined the effect of BRG1 inactivation in an ethyl carbamate lung carcinogenesis mouse model. We found that the heterozygous loss of BRG1 resulted in increases in both the number and size of tumors when compared with controls. In contrast, when both BRG1 alleles were inactivated, neither the number nor the size of tumors increased compared with controls. In mouse lung tissue where BRG1 was homozygously inactivated, immunostaining for apoptotic markers showed significant increase in Apo-BrdUrd and cleaved caspase-3. These data indicate that a loss of cell viability underlies why biallelic inactivation of BRG1 does not increase tumorigenesis. We also examined mice when exposed to the carcinogen ethyl carbamate and then subjected to BRG1 inactivation. In these cells, loss of BRG1 after carcinogen exposure potentiated tumor development. A subset of tumors retained BRG1 expression, whereas others showed either partial or complete loss of BRG1 expression. Tumors completely devoid of BRG1 expression were significantly larger and expressed higher levels of two markers of proliferation, proliferating cell nuclear antigen and Ki67. Although biallelic inactivation of BRG1 could not initiate tumor development in untransformed cells, our results indicate that transformation and tumor progression are greatly affected by loss of BRG1. [Cancer Res 2008;68(10):3689-96]

The design of total ankle arthroplasty systems is evolving as a result of findings from longer-term studies. Our understanding of modes of failure has increased, and surgical techniques have become more refined. Currently, five total ankle arthroplasty systems are used in the United States. The landscape has changed considerably in the decade since the latest article reviewing total ankle design was published. Some implants with acceptable intermediate results had much poorer outcomes at 7- to 10-year follow-up. As more research showing mid- to long-term outcomes is published, the design rationale and current outcomes data for each of these implants must be considered.