Ex Vivo Patient-Derived Explant Model for Neurofibromatosis Type 1-Related Cutaneous Neurofibromas.

Cutaneous neurofibromas (CNFs) are benign tumors that occur in the dermis of individuals with the inherited tumor predisposition disorder, neurofibromatosis type 1. CNFs cause disfigurement, pain, burning, and itching, resulting in substantially reduced QOL in patients with neurofibromatosis type 1. CNFs are benign tumors that exhibit cellular and molecular heterogeneity, making it difficult to develop tractable in vitro or in vivo models. As a result, CNF research and drug discovery efforts have been limited. To address this need, we developed a reproducible patient-derived explant (PDE) ex vivo culture model using CNF tumors from patients with neurofibromatosis type 1. CNF PDEs remain viable in culture for over 9 days and recapitulate the cellular composition and molecular signaling of CNFs. Using CNF PDEs as a model system, we found that proliferation was associated with increased T-cell infiltration. Furthermore, we identified a pattern of reciprocal inflammatory signaling in CNF PDEs in which tumors rely on prostaglandin or leukotriene-mediated signaling pathways. As proof of principle, we show that ex vivo glucocorticoid treatment reduced the expression of proinflammatory genes, confirming that CNF PDEs are a useful model for both mechanistic studies and preclinical drug testing.

Hip Strength Before and After Arthroscopic Femoroacetabular Impingement Surgery.

Femoroacetabular impingement (FAI) and labral pathology are associated with pain, decreased function, and hip strength deficits. Existing data are in conflict regarding when hip strength normalizes following arthroscopic treatment of FAI. The objective of this study was to identify preoperative hip strength relative to the contralateral hip not undergoing surgery as well as when postoperative strength in 4 functional muscle groups normalizes following arthroscopic treatment of FAI. Ninety-eight individuals with radiographic evidence of FAI and labral pathology underwent arthroscopic labral repair. Pre-surgical hip strength testing was performed in the symptomatic "surgical hip" and the contralateral "non-surgical hip." Hip strength measurements were repeated at 8 and 16 weeks postoperatively. Significant preoperative hip strength deficits were noted in the surgical hip compared with the non-surgical hip in flexion, extension, and adduction. At 8 weeks postoperatively, hip strength in the surgical hip improved to being equivalent to that in the non-surgical hip in adduction and extension, remained equivalent to that of the non-surgical hip in abduction, and decreased in flexion relative to the non-surgical hip. At 16 weeks, hip strength remained equivalent in the surgical hip and the non-surgical hip in abduction and adduction, but the surgical hip exceeded the non-surgical hip in extension. While flexion strength improved between 8 and 16 weeks postoperatively for the surgical hip, it had not fully recovered to that of the non-surgical hip. Using a structured postoperative rehabilitation protocol, abduction strength was maintained at 8 weeks postoperatively, while adduction and extension strength had improved to those of the non-surgical hip. At 16 weeks postoperatively, hip abduction and adduction had strength equivalent to those of the non-surgical hip. Despite preoperative improvement, flexion of the surgical hip lagged behind that of the non-surgical hip 16 weeks postoperatively. [Orthopedics. 2021;44(3):148-153.].