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Introduction/Purpose: Fifth metatarsal fractures are the most commonly encountered metatarsal fractures. It is often inferred that fifth metatarsal fractures occur at an increased frequency in patients with cavovarus foot position. In particular, zone 2 and zone 3 fractures are thought to be associated with cavovarus feet. However, limited data exists in the literature to support this claim. The hypothesis of this study is that a cavovarus foot alignment is positively correlated with the incidence of fifth metatarsal fractures.

Main protease (MPro) of SARS-CoV-2, the viral pathogen of COVID-19, is a crucial nonstructural protein that plays a vital role in the replication and pathogenesis of the virus. Its protease function relies on three active site pockets to recognize P1, P2, and P4 amino acid residues in a substrate and a catalytic cysteine residue for catalysis. By converting the P1 C(alpha) atom in an MPro substrate to nitrogen, we showed that a large variety of azapeptide inhibitors with covalent warheads targeting the MPro catalytic cysteine could be easily synthesized. Through the characterization of these inhibitors, we identified several highly potent MPro inhibitors. Specifically, one inhibitor, MPI89 that contained an aza-2,2-dichloroacetyl warhead, displayed a 10 nM EC50 value in inhibiting SARS-CoV-2 from infecting ACE2+ A549 cells and a selectivity index of 875. The crystallography analyses of MPro bound with 6 inhibitors, including MPI89, revealed that inhibitors used their covalent warheads to covalently engage the catalytic cysteine and the aza-amide carbonyl oxygen to bind to the oxyanion hole. MPI89 represents one of the most potent MPro inhibitors developed so far, suggesting that further exploration of the azapeptide platform and the aza-2,2-dichloroacetyl warhead is needed for the development of potent inhibitors for the SARS-CoV-2 MPro as therapeutics for COVID-19.

Category: Midfoot/Forefoot Introduction/Purpose: Cartiva (Wright Medical Group N.V.) was developed as an implantable interposition device for the treatment of hallux rigidus. It is performed along with a limited cheilectomy and serves as a joint preserving alternative to arthrodesis. In some patients, we have noticed gradual decreases in the joint space after surgery with Cartiva, presumably representing subsidence of the implant. The aim of this study is to report a radiographic analysis of visible joint space in surgical cases of hallux rigidus where dorsal cheilectomy and Cartiva were used. Methods: A prospectively collected patient database was queried for CPT code 28291 and those patients in which Cartiva was implanted were determined. The pre-operative and post-operative radiographs were analyzed for hallux rigidus grade, and measurements of visible joint space prior to and after Cartiva was implanted were performed at two weeks, one month, three months, and six months post-operatively. The percentage of visible joint space increase or decrease after implantation of Cartiva was calculated for each post-operative time point. Results: A total of 79 Cartiva were implanted in 74 patients between April 2017 and Sept 2018. The procedure was performed for Grade I hallux rigidus in 11% of patients (n=9), 66% grade II (n=52), 23% grade III (n=18). Mean pre-operative visible joint space measured 1.1 mm (n=79). Visible joint space measured at two weeks post-surgery was 2.2 mm (n=74); one month, 1.6 mm (n=65); three months, 1.2 mm (n=64); six months, 1.0 mm (n=30). Implantation of Cartiva resulted in 100% increase in visible joint space compared to pre-operative measurements at two weeks post-surgery, 45% increase at one month, 9% at three months, and a 9% decrease in visible joint space at six months. Conclusion: Cartiva implantation and limited cheilectomy for patients with symptomatic hallux rigidus provided a 100% increase in visible joint space on radiographs taken two weeks post operatively. However at six months post-surgery there was an overall 9% decrease in visible joint space presumably representing a subsidence of the Cartiva implant with time.