Rate of Development of Hallucal Interphalangeal Degenerative Joint Disease After First Metatarsophalangeal Joint Arthrodesis: A Retrospective Radiographic Analysis.

The development of hallux interphalangeal joint (IPJ) arthritis after an arthrodesis of the first metatarsophalangeal joint has been established in the literature. However, the significance has not been well reported. A retrospective, radiographic review of patients who had undergone a first metatarsophalangeal joint arthrodesis was performed. The Coughlin classification for degree of arthritic degeneration, hallux abductus angle, and hallux interphalangeus angle were measured in 107 radiographs of 103 patients preoperatively and postoperatively. Postoperative angles were measured immediately following surgery at approximately 6 weeks, 3 months, 6 months, 12 months, and 24 months. We found that the hallux abductus angle had decreased in the patients postoperatively; however, the hallux abductus interphalangeus angle increased on average after first metatarsophalangeal fusion. The majority of patients started with a Coughlin classification I of the hallux IPJ, which remained unchanged over the postoperative period, with no statistically significant difference in IPJ degeneration in the patients with or without fusion of the first metatarsophalangeal joint. In addition, no patients had a symptomatic hallux IPJ postoperatively within our limited study period. Further prospective studies would be beneficial with longer follow-up times to assess IPJ degeneration following first metatarsophalangeal joint fusions. Levels of Evidence: Level III: Retrospective, comparative study.

IFN-alpha and bortezomib overcome Bcl-2 and Mcl-1 overexpression in melanoma cells by stimulating the extrinsic pathway of apoptosis.

We hypothesized that IFN-alpha would enhance the apoptotic activity of bortezomib on melanoma cells. Combined treatment with bortezomib and IFN-alpha induced synergistic apoptosis in melanoma and other solid tumor cell lines. Apoptosis was associated with processing of procaspase-3, procaspase-7, procaspase-8, and procaspase-9 and with cleavage of Bid and poly(ADP-ribose) polymerase. Bortezomib plus IFN-alpha was effective at inducing apoptosis in melanoma cells that overexpressed Bcl-2 or Mcl-1, suggesting that this treatment combination can overcome mitochondrial pathways of cell survival and resistance to apoptosis. The proapoptotic effects of this treatment combination were abrogated by a caspase-8 inhibitor, led to increased association of Fas and FADD before the onset of cell death, and were significantly reduced in cells transfected with a dominant-negative FADD construct or small interfering RNA targeting Fas. These data suggest that bortezomib and IFN-alpha act through the extrinsic pathway of apoptosis via FADD-induced caspase-8 activation to initiate cell death. Finally, bortezomib and IFN-alpha displayed statistically significant antitumor activity compared with either agent alone in both the B16 murine model of melanoma and in athymic mice bearing human A375 xenografts. These data support the future clinical development of bortezomib and IFN-alpha for malignant melanoma.