Charcot-Marie-Tooth gene, SBF2, associated with taxane-induced peripheral neuropathy in African Americans.

PURPOSE: Taxane-induced peripheral neuropathy (TIPN) is one of the most important survivorship issues for cancer patients. African Americans (AA) have previously been shown to have an increased risk for this toxicity. Germline predictive biomarkers were evaluated to help identify a priori which patients might be at extraordinarily high risk for this toxicity. EXPERIMENTAL DESIGN: Whole exome sequencing was performed using germline DNA from 213 AA patients who received a standard dose and schedule of paclitaxel in the adjuvant, randomized phase III breast cancer trial, E5103. Cases were defined as those with either grade 3-4 (n=64) or grade 2-4 (n=151) TIPN and were compared to controls (n=62) that were not reported to have experienced TIPN. We retained for analysis rare variants with a minor allele frequency <3% and which were predicted to be deleterious by protein prediction programs. A gene-based, case-control analysis using SKAT was performed to identify genes that harbored an imbalance of deleterious variants associated with increased risk of TIPN. RESULTS: Five genes had a p-value < 10-4 for grade 3-4 TIPN analysis and three genes had a p-value < 10-4 for the grade 2-4 TIPN analysis. For the grade 3-4 TIPN analysis, SET binding factor 2 (SBF2) was significantly associated with TIPN (p-value=4.35 x10-6). Five variants were predicted to be deleterious in SBF2. Inherited mutations in SBF2 have previously been associated with autosomal recessive, Type 4B2 Charcot-Marie-Tooth (CMT) disease. CONCLUSION: Rare variants in SBF2, a CMT gene, predict an increased risk of TIPN in AA patients receiving paclitaxel.

Acellular dermal matrices in abdominal wall reconstruction: a systematic review of the current evidence.

BACKGROUND: Reconstruction of the anterior abdominal wall is a complex procedure that can be complicated by contamination, loss of domain, previous scarring or radiotherapy, and reduced availability of local tissues. With the introduction of acellular dermal matrices to clinical use, it was hoped that many of the problems associated with previous synthetic materials could be overcome. With their enhanced biocompatibility, acellular dermal matrices are believed to integrate with surrounding tissues while demonstrating resistance to infection, extrusion, erosion, and adhesion formation. METHODS: The MEDLINE database was reviewed, including all publications as of December 31, 2011, using the search terms "dermal matrix" or "human dermis" or "porcine dermis" or "bovine dermis," applying the limits "human" and "English language." Prospective and retrospective clinical articles were identified. RESULTS: A total of 40 eligible articles were identified and included in this review. Thirty-five of the studies were level IV; the remaining studies were level III. Acellular dermal matrix was used to reconstruct the abdominal wall in a wide range of clinical settings, including trauma, tumor resection, sepsis, and hernia repairs. The operative methods varied widely among clinical studies. While the heterogeneity of the patient populations and techniques limited interpretation of the data, concerns were identified regarding high rates of hernia recurrence with acellular dermal matrix use. CONCLUSION: High-quality data derived from level I, II, and III studies are necessary to determine the indications for acellular dermal matrix use and the optimal surgical techniques to maximize outcomes in abdominal wall reconstruction.

Microvascular anastomosis using a photochemical tissue bonding technique.

BACKGROUND AND OBJECTIVES: Photochemical tissue bonding (PTB) combines photoactive dyes with visible light to create fluid-tight seals between tissue surfaces without causing collateral thermal damage. The potential of PTB to improve outcomes over standard of care microsurgical reanastomoses of blood vessels in ex vivo and in vivo models was evaluated. STUDY DESIGN: The mechanical strength and integrity of PTB and standard microsurgical suture repairs in ex vivo porcine brachial arteries (n = 10) were compared using hydrostatic testing of leak point pressure (LPP). Femoral artery repair in vivo was measured in Sprague-Dawley rats using either standard microvascular sutures (n = 20) or PTB (n = 20). Patency was evaluated at 6 hours (n = 10) and 8 weeks post-repair (n = 10) for each group. RESULTS: PTB produced significantly higher LPPs (1,100+/- 150 mmHg) than suture repair (350+/-40 mmHg, P<0.001) in an ex vivo study. In an in vivo study all femoral arteries in both suture and PTB repair groups were patent at 6 hours post-repair. At 8 weeks post-repair the patency rate was 80% for both groups. No evidence of aneurysm formation was seen in either group and bleeding was absent from the repair site in the PTB-treated vessels, in contrast to the suture repair group. CONCLUSION: PTB is a feasible microvascular repair technique that results in an immediate, mechanically robust bond with short- and long-term patency rates equal to those for standard suture repair.

Photochemical tissue bonding: a promising technique for peripheral nerve repair.

BACKGROUND: Photochemical tissue bonding (PTB) is a novel tissue repair technique that uses visible light and a photosensitizing dye to crosslink proteins on tissue surfaces. This technique has been successfully demonstrated in a number of tissue repair models. An ideal nerve repair technique would be atraumatic and avoid placement of foreign bodies at the repair site. The epineurium is suited to photochemical repair as it is thin, translucent and has a relatively high collagen content. This study was designed to determine if PTB could be successfully applied in a peripheral nerve repair model. MATERIAL AND METHODS: Forty Sprague Dawley rats underwent transection of the sciatic nerve. Animals were then randomized to four treatment groups; epineurial suture repair, epineurial cuff with PTB, epineurial cuff alone, and no repair. Functional recovery was assessed at 10 day intervals using walking track analysis and sciatic function index calculations. At 90 days postoperatively animals were sacrificed and sciatic nerves harvested for histology and histomorphometry. RESULTS: Functional recovery in the suture repair and epineural cuff with PTB groups were not significantly different (-70.6 +/- 17.8 versus -76.9 +/- 10.3, P = 0.64) at 90 days postrepair. Histology showed good axonal regeneration with all repair techniques. Histomorphometric analysis found no significant difference between the repair groups. CONCLUSIONS: This study illustrates that peripheral nerves can be successfully repaired using a photochemical tissue bonding technique with results similar to those achieved with the current gold standard. With further development and refinement PTB may prove a useful tool in peripheral nerve repair.