Although this study was limited by a paucity of randomized control trials, these results demonstrate superior durability for open bypass, although with longer LOS and increased risk for complications and mortality, when compared to the endovascular approach.

Risk, II.

Therapeutic, V.

Background The fibula free flap (FFF) remains the criterion standard for complex mandibular reconstruction. Surgeons have incorporated virtual surgical planning (VSP) into the reconstructive algorithm with the assertion that VSP increases operative efficiency and may improve clinical outcomes. To date, no large-scale studies have analyzed these claims. This study examines the literature and tests the hypothesis that VSP improves operative efficiency, clinical outcomes, and accuracy when compared with traditional techniques. Methods A systematic review was performed to identify articles utilizing VSP and traditional techniques for FFF-based mandibular reconstruction. Two reviewers independently assessed all articles for methodological quality using a validated instrument (weighted Cohen κ for interrater reliability = 0.70). Outcomes included operative time, length of stay, complications, and accuracy. Meta-analytic comparisons were performed using data from comparative studies using a random-effects model and differences of means analysis for outcomes measured on identical scales. Results One hundred thirty-one articles were identified, and 25 met the inclusion criteria: 12 were VSP only, whereas 13 were comparative. There were 241 VSP patients and 214 traditional patients available for meta-analysis. Patients undergoing reconstruction with VSP had a significant reduction in operative time by 44.64 minutes (95% confidence interval [CI], −74.69 to −14.58 minutes; P < 0.01) and demonstrated a mean trend toward shorter hospital admission (mean difference, −1.24 days; 95% CI, −4.00 to 1.52 days; P = 0.38). There was no statistical difference between cohorts for major (odds ratio, 1.03; 95% CI, 0.46–2.31; P = 0.95) or minor complications (odds ratio, 0.97; 95% CI, 0.54–1.71; P = 0.90). Insufficient data were available for cost analysis and accuracy. Conclusions Virtual surgical planning–guided mandibular reconstruction with FFF is associated with significantly decreased operative time and a mean trend toward shorter hospital admission. While multiple studies reported a high degree of accuracy, no standard measurement was available for meta-analysis.

Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper craniofacial development. A gain-of-function mutation in the 2c splice variant of the receptor’s gene is associated with Crouzon syndrome, which is characterized by craniosynostosis, the premature fusion of one or more of the cranial vault sutures, leading to craniofacial maldevelopment. Insight into the molecular mechanism of craniosynostosis has identified the ERK-MAPK signaling cascade as a critical regulator of suture patency. The aim of this study is to investigate the role of FGFR2c-induced ERK-MAPK activation in the regulation of coronal suture development. Loss-of-function and gain-of-function Fgfr2c mutant mice have overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia. In vivo analysis of coronal sutures in loss-of-function and gain-of-function models demonstrated fundamentally different pathogenesis underlying coronal suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated enhanced osteoblastic function and maturation with concomitant increase in ERK-MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126 mitigated ERK protein activation levels with a concomitant reduction in alkaline phosphatase activity. This study identifies FGFR2c-mediated ERK-MAPK signaling as a key mediator of craniofacial growth and coronal suture development. Furthermore, our results solve the apparent paradox between loss-of-function and gain-of-function FGFR2c mutants with respect to coronal suture synostosis.

Risk, II.

Therapeutic, III.

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .