Citations

ABSTRACT Death receptors are members of the tumor necrosis factor receptor superfamily characterized by a cytoplasmic region known as the “death domain” that enables the receptors to initiate cytotoxic signals when engaged by cognate ligands. Binding to the ligand results in receptor aggregation and recruitment of adaptor proteins, which, in turn, initiates a proteolytic cascade by recruiting and activating initiator caspases 8 and 10. Death receptors were once thought to primarily induce cytotoxic signaling cascades. However, recent data indicate that they initiate multiple signaling pathways, unveiling a number of nonapoptosis‐related functions, including regulation of cell proliferation and differentiation, chemokine production, inflammatory responses, and tumor‐promoting activities. These noncytotoxic cascades are not simply a manifestation of inhibiting proapoptotic pathways but are intrinsically regulated by adaptor protein and receptor internalization processes. Insights into these various death receptor signaling pathways provide new therapeutic strategies targeting these receptors in pathophysiological processes.—Guicciardi, M.E., Gores, G.J. Life and death by death receptors. FASEB J. 23, 1625–1637 (2009)

Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤ .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma.

ABSTRACT In a retrospective review of 24 patients with histoplasmosis, blastomycosis, or coccidioidomycosis treated with voriconazole (most for salvage therapy), the outcome was favorable (improved or stable) for 22 (95.8%) within 2 months of starting voriconazole and for 20 (83.3%) at the last follow-up. Prospective studies are required to determine its role in the treatment of endemic mycoses.

Background: Subtalar arthrodesis is a common procedure for treating subtalar arthrosis. An isolated lateral incision can be used as an approach to subtalar fusion alone. However, it can be a difficult approach for correction of varus or valgus hindfoot deformities through the subtalar joint; especially if it involves distraction to correct calcaneal alignment. Less commonly, two-incision or single-incision medial approaches also have been described, but distraction and angular correction can still be difficult. We present an alternative method, using a posterior Achilles tendon-splitting procedure, that gives excellent subtalar exposure and the ability to obtain distraction with angular correction and bone grafting. Materials and Methods: Six consecutive patients underwent subtalar fusion with a posterior approach. Both varus and valgus deformities secondary to trauma, tendon insufficiency, or congenital deformities were corrected. Distraction was accomplished with laminar spreaders, and fixation was obtained with two 7.3-mm partially threaded cannulated screws. All patients were followed until fusion, and clinical and radiographic results were recorded. No other concomitant procedures were performed. Results: Fusion was observed radiographically in all patients by 3 months postoperatively. No serious wound complications occurred. Correction to slightly valgus alignment (for varus deformity) or neutral alignment (for valgus deformity) was obtained without collapse of autologous bone graft. Talocalcaneal height and all angular measurements were significantly increased (all p < 0.05). Conclusion: The posterior approach for distraction arthrodesis is an alternative to the standard lateral approach technique. It allows safe exposure with the ability to distract while also correcting varus or valgus deformity of the subtalar joint.

The universally accepted concept of delay-loaded dental implants has recently been challenged. This study hypothesizes that early loading (decreased implant healing time) leads to increased bone formation and decreased crestal bone loss. We used 17 minipigs to study implants under a controlled load, with non-loaded implants for comparison. Radiographic and histological assessments were made of the osseointegrated bone changes for 3 healing times (between implant insertion and loading), following 5 months of loading. The effect of loading on crestal bone loss depended on the healing time. Early loading preserved the most crestal bone. Delayed loading had significantly more crestal bone loss compared with the non-loaded controls (2.4 mm vs. 0.64 mm; P < 0.05). The histological assessment and biomechanical analyses of the healing bone suggested that loading and bioactivities of osteoblasts exert a synergistic effect on osseointegration that is likely to support the hypothesis that early loading produces more favorable osseointegration.