SummaryVinculin was identified as a component of adherens junctions 30 years ago, yet its function there remains elusive. Deletion studies are consistent with the idea that vinculin is important for the organization of cell-cell junctions. However, this approach removes vinculin from both cell-matrix and cell-cell adhesions, making it impossible to distinguish its contribution at each site. To define the role of vinculin in cell-cell junctions, we established a powerful short hairpin-RNA-based knockdown/substitution model system that perturbs vinculin preferentially at sites of cell-cell adhesion. When this system was applied to epithelial cells, cell morphology was altered, and cadherin-dependent adhesion was reduced. These defects resulted from impaired E-cadherin cell-surface expression. We have investigated the mechanism for the effects of vinculin and found that the reduced surface E-cadherin expression could be rescued by introduction of vinculin, but not of a vinculin A50I substitution mutant that is defective for -catenin binding. These findings suggest that an interaction between -catenin and vinculin is crucial for stabilizing E-cadherin at the cell surface. This was confirmed by analyzing a -catenin mutant that fails to bind vinculin. Thus, our study identifies vinculin as a novel regulator of E-cadherin function and provides important new insight into the dynamic regulation of adherens junctions.

BackgroundThe surgical treatment of end-stage tibiotalar arthritis continues to be a controversial topic. Advances in surgical technique and implant design have lead to improved outcomes after both ankle arthrodesis (AA) and total ankle arthroplasty (TAA), yet a clear consensus regarding the most ideal form of treatment is lacking. In this study, the outcomes and complications following AA and TAA are compared in order to improve our understanding and decision-making for care and treatment of symptomatic tibiotalar arthritis.MethodsStudies reporting on outcomes and complications following TAA or AA were obtained for review from the PubMed database between January 2006 and July 2016. Results from studies reporting on a minimum of 200 total ankle arthroplasties or a minimum of 80 ankle arthrodesis procedures were reviewed and pooled for analysis. All studies directly comparing outcomes and complications between TAA and AA were also included for review. Only studies including modern third-generation TAA implants approved for use in the USA (HINTEGRA, STAR, Salto, INBONE) were included.ResultsA total of six studies reporting on outcomes following TAA and five reporting on outcomes following AA met inclusion criteria and were included for pooled data analysis. The adjusted overall complication rate was higher for AA (26.9%) compared to TAA (19.7%), with similar findings in the non-revision reoperation rate (12.9% for AA compared to 9.5% for TAA). The adjusted revision reoperation rate for TAA (7.9%) was higher than AA (5.4%). Analysis of results from ten studies directly comparing TAA to AA suggests a more symmetric gait and less impairment on uneven surfaces after TAA.ConclusionsPooled data analysis demonstrated a higher overall complication rate after AA, but a higher reoperation rate for revision after TAA. Based on the existing literature, the decision to proceed with TAA or AA for end-stage ankle arthritis should be made on an individual patient basis.

OBJECT Patients with symptomatic intradural-extramedullary (ID-EM) tumors may be successfully treated with resection of the lesion and decompression of associated neural structures. Studies of patients undergoing open resection of these tumors have reported high rates of gross-total resection (GTR) with minimal long-term neurological deficit. Case reports and small case series have suggested that these patients may be successfully treated with minimally invasive surgery (MIS). These studies have been limited by small patient populations. Moreover, there are no studies directly comparing perioperative outcomes between patients treated with open resection and MIS. The objective of this study was to compare perioperative outcomes in patients with ID-EM tumors treated using open resection or MIS. METHODS A retrospective review was performed using data collected from 45 consecutive patients treated by open resection or MIS for ID-EM spine tumors. These patients were treated over a 9-year period between April 2003 and October 2012 at Northwestern University and the University of Chicago. Statistical analysis was performed to compare perioperative outcomes between the two groups. RESULTS Of the 45 patients in the study, 27 were treated with the MIS approach and 18 were treated with the open approach. Operative time was similar between the two groups: 256.3 minutes in the MIS group versus 241.1 minutes in the open group (p = 0.55). Estimated blood loss was significantly lower in the MIS group (133.7 ml) compared with the open group (558.8 ml) (p < 0.01). A GTR was achieved in 94.4% of the open cases and 92.6% of the MIS cases (p = 0.81). The mean hospital stay was significantly shorter in the MIS group (3.9 days) compared with the open group (6.1 days) (p < 0.01). There was no significant difference between the complication rates (p = 0.32) and reoperation rates (p = 0.33) between the two groups. Multivariate analysis demonstrated an increased rate of complications in cervical spine tumors (OR 15, p = 0.05). CONCLUSIONS Thoracolumbar ID-EM tumors may be safely and effectively treated with either the open approach or an MIS approach, with an equivalent rate of GTR, perioperative complication rate, and operative time. Patients treated with an MIS approach may benefit from a decrease in operative blood loss and shorter hospital stays.

Glioblastoma multiforme (GBM) is one of the most common and aggressive primary brain tumors, composing 12%–20% of all intracranial tumors in adults. Average life expectancy is merely 12–14 months following initial diagnosis. Patients with this neoplasm have one of the worst 5-year survival rates among all cancers despite aggressive multimodal treatment consisting of maximal tumor resection, radiation therapy, and adjuvant chemotherapy. With recent advancements in management strategies, there has been improvement in the overall trend in patient outcomes; however, recurrence remains nearly inevitable. While most tumors recur locally, metastases to distal locations have become more common. Specifically, the last decade has seen an increased incidence of spinal metastases, representing an emerging complication in patients with intracranial GBM. However, the literature regarding prevention strategies and the presentation of spinal metastases has remained scarce. As local control of primary lesions continues to improve, more cases of spinal metastases are likely to be seen. In this review the authors present a new case of metastatic GBM to the L-5 nerve root, and they summarize previous cases of intracranial GBM with leptomeningeal spinal metastatic disease. They also characterize key features of this disease presentation and discuss areas of future investigation necessary for enhanced prevention and treatment of this complication.