ASP2409, A Next-Generation CTLA4-Ig, Versus Belatacept in Renal Allograft Survival in Cynomolgus Monkeys.

Belatacept is the first costimulatory blockade agent approved for maintenance immunosuppression in kidney transplant recipients. Clinical results have indicated that belatacept is associated with superior renal function and improved metabolic profile; however, higher incidence of acute rejection and posttransplant lymphoproliferative disorder are the shortcomings of this agent. In this study, ASP2409, a new cytotoxic T-lymphocyte associated protein 4-immunoglobulin possessing 14-fold higher in vitro CD86 binding affinity than belatacept, was tested for renal allograft survival in cynomolgus monkeys. ASP2409 monotherapy dose-dependently prolonged renal allograft survival. Low-dose ASP2409 in combination with a subtherapeutic dose of tacrolimus showed much longer median survival time than monotherapy. Similar allograft survival results were observed in regimens based on high-dose ASP2409, belatacept, and therapeutic-dose tacrolimus. The results of renal allograft histopathology with high-dose ASP2409-based regimens were not inferior to the belatacept-based regimen. Moreover, higher frequencies of FoxP3-positive regulatory T cells in renal allografts were observed in ASP2409- and belatacept-based regimens compared with tacrolimus-based regimens. No serious side effects related to ASP2409 administration were found during the study. These data suggest that ASP2409 is a promising candidate for calcineurin inhibitor-sparing or -avoidance regimens.

Extracranial radial forearm free flap closure of refractory cerebrospinal fluid leaks: a novel hybrid transantral-endoscopic approach.

BACKGROUND: Although rare, recalcitrant cerebrospinal fluid (CSF) leak after skull base tumor resection or major head trauma is a difficult therapeutic challenge, often complicated by lack of local vascularized tissue in a scarred, radiated field. Craniotomy with a free tissue transfer has been described for CSF leak repair from these complicated skull base defects. OBJECTIVE: : We present our experience with a novel extracranial approach to manage refractory CSF leaks with a radial forearm free flap set in through a transantral and ethmoid sinus approach. METHODS: Five patients with recalcitrant CSF leaks in the anterior skull base underwent radial forearm free tissue transfer via a hybrid transantral-endoscopic approach. RESULTS: There were 4 female patients and 1 male patient. Average age was 58 years (range, 30-72 years). Four patients had previous neurosurgical anterior skull base tumor resections, and 1 patient had significant head trauma leading to a recalcitrant CSF leak. All 5 patients had undergone multiple prior endoscopic and/or open repairs. All 5 patients had successful resolution of their leak after undergoing radial forearm free tissue transfer. Two of 5 patients required a second minor endoscopic procedure. No patients required a craniotomy. CONCLUSION: An extracranial transantral-endoscopic approach for the inset of radial forearm free flap is a safe treatment technique that precludes the need for a craniotomy and promotes effective repair of CSF leaks refractory to traditional endoscopic procedures. ABBREVIATION: RFFF, radial forearm free flap.

[Characterization of slowly-growing mycobacteria species by capillary gas chromatography].

A method for the characterization of mycobacteria species by capillary gas chromatography is described. After strains of mycobacteria being hydrolyzed, saponified in an acidic solution, various methyl esters resulted from mycobacteria were studied on an OV-101 column at optimum chromatographic conditions. The constituents of 9 slowly-growing mycobacteria species were analyzed and the results showed that there were obvious differences between different mycobacteria species, but same characteristics were observed between strains of the same species. The 9 species can be identified by the ratio of peak height of C18:1, C18:0 and TBSA. They are C18:1>TBSA>C18:0 for M. tuberculosis, C18:0>C18:1>TBSA for M. triviale, TBSA>C18:1>C18:0 for M. intracellulare, TBSA>C18:0>C18:1 for M. avium and C18:1>C18:0>TBSA for M. bovis, M. kansasii, M. gordonae, M. nonchromogenicum and M. terrae respectively. The 5 latter species can be distinguished by the presence of characteristic peaks of iC16:1 and C19:0. 75 strains of clinical isolated mycobacteria were analysed at the same chromatographic conditions. The results showed that they belonged to 9 different species. The accuracy of the proposed method was examined according to biological analysis.