ABSTRACT
Shortening of the first ray is a potential complication associated with first metatarsal procedures. Correction of this deformity conventionally has required the use of a tricortical bone graft to lengthen the bone. Graft complications, including donor site morbidity, poor graft stability, and graft resorption, have revealed a need for an alternative procedure. The present report shows that titanium cage scaffolding has lower extremity applications beyond its previous uses in the ankle and spine. Two patients underwent surgical correction for failed first ray procedures using a titanium cage apparatus with a calcaneal autograft and other biologic agents. The scaffolds were appropriately sized to fill the defect. Patients remained non-weightbearing until radiographic evidence of healing appeared. Success was determined by diminished pain, a return to activity, ambulation, and patient satisfaction. Patients exhibited faster-than-anticipated healing, including a return to protected weightbearing activities and increased stability within 6 weeks. Titanium cage implants provide long-term stability and resistance to stress and strain in the forefoot. The implant we have described, newly applied to the first ray, is analogous to a system used in salvage of failed ankle replacements. In addition to reducing reliance on the iliac crest bone graft, the titanium cage apparatus is advantageous because it is customized to fill a defect using computed tomography scanning, thereby reducing graft failure secondary to an improper shape. These cases demonstrate the potential beneficial applications for titanium cages in failed first ray reconstruction.
Subject(s)
Arthroplasty/adverse effects , Bone Transplantation/methods , Hallux Valgus/surgery , Metatarsophalangeal Joint/surgery , Tissue Scaffolds , Arthroplasty/methods , Calcaneus/surgery , Calcaneus/transplantation , Female , Hallux Valgus/diagnostic imaging , Humans , Male , Metatarsophalangeal Joint/diagnostic imaging , Middle Aged , Prognosis , Prostheses and Implants , Prosthesis Implantation , Reoperation , Risk Assessment , Sampling Studies , Titanium , Transplantation, Autologous/methods , Treatment OutcomeABSTRACT
Rasgrf-1 is a guanine exchange factor (GEF) that catalyzes the exchange of GDP for GTP. In a RNA microarray analysis of chronic lymphocytic leukemia (CLL) specimens (n = 5), this gene was found to be overexpressed in CLL as compared to normal peripheral blood mononuclear cell (PBMC) CD19 + B cells (n = 3). CLL specimens (n = 29) expressed Rasgrf-1 RNA at levels 5-300-fold higher as compared to normal B cells. CLL specimens expressed a 75 kDa isoform that was smaller than the expected full-length protein (140 kDa) and the truncated variant had higher GEF activity. Knockdown of Rasgrf-1 in CLL specimens inhibited active GTP-bound Ras and the Ras/Erk/mitogen-activated protein kinase (MAPK) pathway. Rasgrf-1 was phosphorylated and activated by B cell receptor (BCR) signaling that increased its GEF function, and this phosphorylation was blocked by Src and Bruton's tyrosine kinase (BTK) inhibitors. Rasgrf-1 is a novel GEF protein that has a role in BCR signaling and its overexpression further activates the Ras/Erk/MAPK pathway in CLL specimens.
