ABSTRACT
Sinonasal mucosal melanoma (SNMM) is a rare malignancy with poor prognosis and high recurrence rate. In those with recurrence, survival is dismal. Immunotherapy is an emerging area of investigation; however, there is a scarcity of data on immunotherapy outcomes in SNMM patients with recurrence. We report outcomes of immunotherapy in recurrent SNMM patients with distant versus nondistant recurrence. Fifty-four patients with recurrent SNMM were identified, and 31 (57.4%) had distant recurrence. One-year overall survival (OS) following recurrence was 47.5% (95% confidence interval [CI]: 34.0%-60.9%), with a median survival of 2.8 years (95% CI: 2.0-5.3). In those with distant recurrence, receipt of immunotherapy was associated with better OS compared to those without immunotherapy (hazard ratio [HR] = 0.29 [95% CI: 0.12-0.68], P = .004). While patients with nondistant recurrence (n = 23), who received immunotherapy (n = 6) had worse OS compared to those who did not receive immunotherapy (HR = 4.76 [95% CI: 1.36, 15.89], P = .02). LEVEL OF EVIDENCE: Level IV.
ABSTRACT
Orthopedic injuries, particularly those involving tendons and ligaments, are some of the most commonly treated musculoskeletal ailments, but are associated with high costs and poor outcomes. A significant barrier in the design of biomaterials for tendon tissue engineering is the rapid de-differentiation observed for primary tenocytes once removed from the tendon body. Herein, we evaluate the use of an anisotropic collagen-glycosaminoglycan (CG) scaffold as a tendon regeneration platform. We report the effects of structural properties of the scaffold (pore size, collagen fiber crosslinking density) on resultant tenocyte bioactivity, viability, and gene expression. In doing so we address a standing hypothesis that scaffold anisotropy and strut flexural rigidity (stiffness) co-regulate long-term maintenance of a tenocyte phenotype. We report changes in equine tenocyte specific gene expression profiles and bioactivity across a homologous series of anisotropic collagen scaffolds with defined changes in pore size and crosslinking density. Anisotropic scaffolds with higher crosslinking densities and smaller pore sizes were more able to resist cell-mediated contraction forces, promote increased tenocyte metabolic activity, and maintain and increase expression of tenogenic gene expression profiles. These results suggest that control over scaffold strut flexural rigidity via crosslinking and porosity provides an ideal framework to resolve structure-function maps relating the influence of scaffold anisotropy, stiffness, and nutrient biotransport on tenocyte-mediated scaffold remodeling and long-term phenotype maintenance.
