Antibody surface mobility amplifies FcγR signaling via Arp2/3 during phagocytosis.

We report herein that the anti-CD20 therapeutic antibody, rituximab, is rearranged into microclusters within the phagocytic synapse by macrophage Fcγ receptors (FcγR) during antibody-dependent cellular phagocytosis. These microclusters were observed to potently recruit Syk and to undergo rearrangements that were limited by the cytoskeleton of the target cell, with depolymerization of target-cell actin filaments leading to modest increases in phagocytic efficiency. Total internal reflection fluorescence analysis revealed that FcγR total phosphorylation, Syk phosphorylation, and Syk recruitment were enhanced when IgG-FcγR microclustering was enabled on fluid bilayers relative to immobile bilayers in a process that required Arp2/3. We conclude that on fluid surfaces, IgG-FcγR microclustering promotes signaling through Syk that is amplified by Arp2/3-driven actin rearrangements. Thus, the surface mobility of antigens bound by IgG shapes the signaling of FcγR with an unrecognized complexity beyond the zipper and trigger models of phagocytosis.

Managing Hallux Rigidus in the Elite Athlete.

Hallux rigidus can present a difficult problem to both competitive and elite athletic populations. Once an appropriate diagnostic workup has been performed, nonoperative management strategies, including anti-inflammatory medications, injection therapies, shoewear modifications, and orthotic devices, represent the mainstay conservative management options. Surgical management can be considered where an athlete's athletic performance is limited. A joint-sparing cheilectomy can provide a predictable return to sport at the most elite levels. The addition of a proximal phalangeal osteotomy can be considered when necessary. Arthroplasty or arthrodesis techniques can be used for persistent symptoms or progressive disease, but with less predictable outcomes.

Distal Tibiofibular Syndesmosis Injuries in the National Football League (NFL): A Spectrum of Pathology That Correlates With Time to Return to Full Participation.

BACKGROUND: Studies routinely evaluate high ankle sprains in isolation, but recent data suggest that these injuries are often associated with concomitant pathology, potentially influencing return to full participation. HYPOTHESIS: In National Football League (NFL) players, isolated high ankle sprains are rare and syndesmosis injuries with concomitant pathology will result in increased time to return to full participation. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: Distal tibiofibular syndesmosis injuries sustained by NFL players between 2017 and 2019 were identified through NFL Injury Surveillance Database queries and verified with video analysis. Each injury underwent a comprehensive magnetic resonance imaging (MRI) review. Regression modeling was utilized to explore the influence of numerous imaging findings on time to return to full participation. RESULTS: There were 83 external rotation ankle injuries involving the syndesmosis. Isolated distal tibiofibular syndesmosis injuries were rare (n = 11; 13%) and more often associated with other ligamentous injury (deltoid ligament and lateral ligamentous complex) and/or fractures. Regression modeling resulted in clustering of 3 injury pattern groups for time to return to full participation across numerous imaging findings: syndesmosis injury-fracture combinations (250 days [interquartile range [IQR,] 142-266 days]), syndesmosis injury with complete deep deltoid tear or acute diastasis (175 days [IQR, 20-248 days]), and all other syndesmosis injuries (27 days [IQR, 18-46 days]). CONCLUSION: In NFL athletes with external rotation ankle injuries, isolated distal tibiofibular syndesmosis injuries were rare and more often associated with concomitant pathology. Time to return to full participation was affected by an associated fracture and complete deep deltoid ligament tear or diastasis but no other relevant MRI variables such as lateral ligament complex involvement or the presence of osteochondral lesions or bone contusions.