Background: Ankle syndesmotic ligament injury is an important factor affecting clinical outcome after lower extremity injury with as little as 2 mm of syndesmotic displacement leading to worse clinical outcome. One important factor is the appropriate placement of clamps and fixation across the syndesmosis. When not ideally aligned, these can result in malalignment of the fibula in the incisura. This study sought to provide computer validation of using the center-center technique to identify an ideal centroid axis for placement of syndesmotic implants. Methods: Thirty computed tomography (CT) scans of patients from July 1, 2016, to June 30, 2018, with normal syndesmoses were evaluated. Center-center and centroid measurements were drawn and compared on the axial CT images at 10, 20, and 30 mm superior to the tibial plafond. Three observers recorded measurements for the same 50 patients in order to compare interobserver reliability. Results: The difference between the centroid and center-center axis at each height level was a mean 0.4 degrees (range, 0.3-0.5 degrees). The center-center and centroid axis change by externally rotating as the height increases away from the tibial plafond with mean, 3 degrees (range, 0-6.1 degrees). Intraclass correlation coefficients (ICCs) were measured at 0.98, thus demonstrating excellent intraobserver and interobserver reliability on these measurements. Conclusion: The center-center technique can be used to identify the centroid axis within an acceptable degree of rotation at heights above the tibial plafond that are relevant to an operating surgeon placing syndesmotic fixation. Clinical Relevance: Theoretically, this aligns the centroids of the fibula and tibia, which achieves the same ideal patient-specific alignment and raises the question as to the extent to which the centroid and center-center axes correlate in the general population. If present, a strong correlation has potentially high clinical importance when planning syndesmotic fixation.

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Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL) and is characterized by epidermotrophism of malignant CD4+ T-lymphocytes. When MF advances to a recurrent stage, patients require treatment with systemic therapies such as vorinostat, a histone deacetylase inhibitor. While vorinostat has been shown to exhibit anti-tumor activity in MF, its exact molecular mechanism has yet to be fully discerned. In the present study, we examined the transcriptomic and proteomic profiles of vorinostat treatment in two MF cell lines, Myla 2059 and HH. We find that vorinostat downregulates CTLA-4, CXCR4, and CCR7 in both cell lines, but its effect on several key pathways differs between the two MF cell lines. For example, vorinostat upregulates CCL5, CCR5, and CXCL10 expression in Myla cells but downregulates CCL5 and CXCL10 expression in HH cells. Furthermore, vorinostat upregulates IFN-γ and IL-23 signaling and downregulates IL-6, IL-7, and IL-15 signaling in Myla cells but does not affect these pathways in HH cells. Although Myla and HH represent established MF cell lines, their distinct tumor origin from separate patients demonstrates that inherent phenotypic variations within the disease persist, underscoring the importance of using a variety of MF cells in the preclinical development of MF therapeutics.

Background: When intraoperative computed tomography (CT) is unavailable, open syndesmosis assessment is a universally available, safe alternative that is more accurate than radiographic assessment. However, it has a documented malreduction rate of up to 16%. This may be improved upon with a validated technique for assessing the accuracy of open syndesmosis reductions. The “tibiofibular line” (TFL) is a CT-based technique found to be sensitive for malreduction. The purpose of this study was to assess the feasibility of adapting the CT-TFL method into a reliable intraoperative open technique by refining the methodology of previous work exploring the clinical TFL technique. Methods: Three observers were instructed to clinically simulate the TFL on cadaveric lower limbs. For each specimen, observers repeated and recorded 3 clinical TFL measurements for each of 4 measurement series representing different degrees of fibula reduction. Intraclass correlation was used to assess intra- and interobserver reliabilities. Results: Mean intraobserver reliability was .88. Mean interobserver reliability was .75. Both intra- and interobserver reliabilities were highest for anatomic syndesmosis reduction. Conclusion: The findings of excellent to near perfect intraobserver and good to excellent interobserver reliability indicate the feasibility of translating the CT-TFL into a reliable open technique. Levels of Evidence: Level III: Diagnostic study