Faculty Bibliography

OBJECTIVE: This study evaluated the osseointegration of commercially pure titanium (Ti) grade-2 (G2) and Ti-6Al-4V alloy (G5) implants with the same geometry and surface treatment. MATERIALS AND METHODS: Thirty-six dental implants with a grit-blasted acid-etched surface were used (n = 18, each). Two implants, one per group, were installed in each subject, in the radius diaphysis (n = 18 beagle dogs), with interchanged fixture position (proximal-distal) between animals for a balanced number of devices per group and time in vivo (1, 3, and 6 weeks). RESULTS: Similar topographical parameters between G2 and G5 were observed for average surface roughness, root mean square, developed surface ratio, maximum height of surface, and density of summits. Removal torque was significantly higher for G5 than for G2. No differences were observed for bone-to-implant contact and bone-area-fraction occupancy. Removal torque significantly increased with time for both groups. At 1 week, new bone formation in direct contact with the implant surface and osteogenic tissue migration was observed with an increase in woven bone formation at 3 weeks followed by the onset of lamellar bone formation at 6 weeks. CONCLUSION: Although both surfaces were biocompatible and osteoconductive, increased removal torque was observed for Ti-6Al-4V compared with commercially pure Ti implants.

Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.

PURPOSE: Reduction mammoplasty (RM) during breast-conserving surgery is popular among women with large-volume breasts because it reduces redundant breast folds and may decrease skin-related morbidity from radiation therapy. However, RM may obscure the lumpectomy cavity (LC) and pose challenges to administering an LC boost, potentially affecting local control. We investigated the impact of RM on acute side effects and use of LC boosts. METHODS AND MATERIALS: The records of 645 consecutive women treated with whole-breast irradiation at an urban university and 2 community practices between January 2012 and December 2014 were reviewed on an institutional review board-approved study. The primary endpoint was grade >/=3 radiation dermatitis; the secondary endpoint was use of LC boost. Student 2-sample t tests, Pearson chi2 tests, Fisher exact tests, and univariate and multivariable logistic regression analyses were performed. RESULTS: Forty-three (7%) RMs were performed in 650 treated breasts. No significant differences in grade 3 toxicities were identified among RM and non-RM patients. LC boost was delivered to 474 breasts. Fewer (16/43) RM patients received LC boosts compared with non-RM patients (458/607), P = .0001. RM patients were more likely to have neoadjuvant chemotherapy, stage III or multifocal disease, higher body mass index, larger planning treatment volumes, and conventional fractionation (P < .05). CONCLUSIONS: RM was associated with decreased use of LC boost without significant differences in acute toxicities. Further investigation to delineate LCs in patients undergoing RM or identify alternative strategies for delivering LC dose is needed.

BACKGROUND: Nipple-areola complex (NAC) malposition after nipple-sparing mastectomy (NSM) can be a challenging issue to correct. The current literature is largely limited to smaller series and implant-based reconstructions. METHODS: A retrospective review of all NSMs from 2006 to 2016 at a single institution was performed. Incidence, risk factors and corrective techniques of NAC malposition were analyzed. RESULTS: 1037 cases of NSM were identified, of which 77 (7.4%) underwent NAC repositioning. All were performed in a delayed fashion. The most common techniques included crescentic periareolar excision (25; 32.5%) and directional skin excision (10; 13.0%).Cases requiring NAC repositioning were significantly more likely to have preoperative radiation (p=0.0008), a vertical or Wise pattern incision (p=0.0157), autologous reconstruction (p=0.0219), and minor mastectomy flap necrosis (p=0.0462) (Table 1). Previous radiation (OR=3.6827, p=0.0028), vertical radial mastectomy incisions (OR=1.8218, p=0.0202), and autologous reconstruction (OR=1.77, p=0.0053) were positive independent predictors of NAC repositioning, whereas implant-based reconstruction (OR=0.5552, p<0.0001) was a negative independent predictor of repositioning. BMI (p=0.7104) and adjuvant radiation (p=0.9536), among other variables, were not predictors of NAC repositioning. CONCLUSIONS: NAC malposition after NSM can be successfully corrected with various techniques. Previous radiation, vertical mastectomy incisions, and autologous reconstruction are independently predictive of NAC malposition.

BACKGROUND: The authors present their grading scale and the outcomes of the largest cohort of top surgery published to date. Application of this grading system can help determine which patients will benefit from a subcutaneous mastectomy with free nipple graft versus a circumareolar technique, with the primary endpoint being need for aesthetic revisions. METHODS: The authors reviewed their database of transgender males who underwent bilateral mastectomy between 2006 and 2015. Data collected included age, body mass index, American Society of Anesthesiologists class, smoking, diabetes, testosterone use, months of social transition, technique used, postoperative complications, and need for revision. Two techniques were used, circumareolar incision and free nipple graft technique. RESULTS: Between 2006 and 2015, 1686 consecutive mastectomies were performed on 843 patients. Of those, 548 patients were excluded because of inadequate follow-up. Of the 295 included, 109 were treated using a circumareolar incision and 186 were treated using a free nipple graft technique. There was no statistically significant difference in complications between the two groups; however, there was a statistically significant difference in the rate of aesthetic revisions in the grade 2B circumareolar incision group (34 percent versus 8.8 percent). CONCLUSIONS: The authors' outcomes are comparable to the literature, and demonstrate that these procedures can safely be performed in an outpatient setting. The authors' grading scale classifies patients and helps the surgeon select a surgical technique. The authors show a statistical difference in rates of aesthetic revisions in Fischer grade 2B patients when a circumareolar incision is selected over a free nipple graft technique. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PURPOSE: To assess the probability of survival (reliability) and failure modes of narrow implants with different diameters. MATERIALS AND METHODS: For fatigue testing, 42 implants with the same macrogeometry and internal conical connection were divided, according to diameter, as follows: narrow (O3.3x10mm) and extra-narrow (O2.9x10mm) (21 per group). Identical abutments were torqued to the implants and standardized maxillary incisor crowns were cemented and subjected to step-stress accelerated life testing (SSALT) in water. The use-level probability Weibull curves, and reliability for a mission of 50,000 and 100,000 cycles at 50N, 100, 150 and 180N were calculated. For the finite element analysis (FEA), two virtual models, simulating the samples tested in fatigue, were constructed. Loading at 50N and 100N were applied 30 degrees off-axis at the crown. The von-Mises stress was calculated for implant and abutment. RESULTS: The beta (beta) values were: 0.67 for narrow and 1.32 for extra-narrow implants, indicating that failure rates did not increase with fatigue in the former, but more likely were associated with damage accumulation and wear-out failures in the latter. Both groups showed high reliability (up to 97.5%) at 50 and 100N. A decreased reliability was observed for both groups at 150 and 180N (ranging from 0 to 82.3%), but no significant difference was observed between groups. Failure predominantly involved abutment fracture for both groups. FEA at 50N-load, O3.3mm showed higher von-Mises stress for abutment (7.75%) and implant (2%) when compared to the O2.9mm. CONCLUSIONS: There was no significant difference between narrow and extra-narrow implants regarding probability of survival. The failure mode was similar for both groups, restricted to abutment fracture.

Loss-of-function mutations in stromal interaction molecule 1 (STIM1) impair the activation of Ca2+ release-activated Ca2+ (CRAC) channels and store-operated Ca2+ entry (SOCE), resulting in a disease syndrome called CRAC channelopathy that is characterized by severe dental enamel defects. The cause of these enamel defects has remained unclear given a lack of animal models. We generated Stim1/2K14cre mice to delete STIM1 and its homolog STIM2 in enamel cells. These mice showed impaired SOCE in enamel cells. Enamel in Stim1/2K14cre mice was hypomineralized with decreased Ca content, mechanically weak, and thinner. The morphology of SOCE-deficient ameloblasts was altered, showing loss of the typical ruffled border, resulting in mislocalized mitochondria. Global gene expression analysis of SOCE-deficient ameloblasts revealed strong dysregulation of several pathways. ER stress genes associated with the unfolded protein response were increased in Stim1/2-deficient cells, whereas the expression of components of the glutathione system were decreased. Consistent with increased oxidative stress, we found increased ROS production, decreased mitochondrial function, and abnormal mitochondrial morphology in ameloblasts of Stim1/2K14cre mice. Collectively, these data show that loss of SOCE in enamel cells has substantial detrimental effects on gene expression, cell function, and the mineralization of dental enamel.

BACKGROUND: There is controversy regarding the treatment of young patients with unilateral craniofacial microsomia and moderate dysmorphism. The relative indication for mandibular distraction in such patients poses several questions: Is it deleterious in the context of craniofacial growth and appearance? This study was designed to address these questions. METHODS: A retrospective review of patients undergoing mandibular distraction by a single surgeon between 1989 and 2010 was conducted. Patients with "moderate" unilateral craniofacial microsomia (as defined by Pruzansky type I or IIa mandibles) and follow-up until craniofacial skeletal maturity were included for analysis. Patients were divided into two cohorts: satisfactory and unsatisfactory results based on photographic aesthetic evaluation by independent blinded observers at the initial presentation and at the age of skeletal maturity. Clinical variables were analyzed to detect predictors for satisfactory distraction. RESULTS: Nineteen patients were included for analysis. The average age at distraction was 68.2 months and the average age at follow-up was 19.55 years. Thirteen patients (68.4 percent) had Pruzansky type IIA and six patients (31.6 percent) had Pruzansky type I mandibles. Twelve patients (63.2 percent) had satisfactory outcomes, whereas seven patients (36.8 percent) had unsatisfactory outcomes. Comparing the two cohorts, patients with satisfactory outcomes had distraction at an earlier age (56.4 months versus 89.8 months; p = 0.07) and a greater percentage overcorrection from craniofacial midline (41.7 percent versus 1.8 percent; p = 0.003). CONCLUSION: Mandibular distraction is successful in patients with mild to moderate dysmorphism, provided that there is a comprehensive clinical program emphasizing adequate mandibular bone stock, proper vector selection, planned overcorrection, and comprehensive orthodontic management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

INTRODUCTION: In this study we evaluated how the timing of chemotherapy for breast cancer affects post-reconstruction complications to determine whether there is an optimal time for breast reconstruction after chemotherapy. PATIENTS AND METHODS: A retrospective review identified 344 breast cancer patients who underwent chemotherapy with mastectomy and autologous/prosthetic reconstruction from 2011 to 2014. A control group of 127 breast cancer patients who underwent mastectomy and autologous/prosthetic reconstruction without chemotherapy was also identified from the same period. The 2 groups were compared and analyzed for differences in demographic characteristics, treatment, and postoperative complication rates. The chemotherapy group was subsequently stratified into 3 subgroups on the basis of the number of days between chemotherapy treatment and reconstructive surgery ( 60 days) for further analysis. RESULTS: Patients who received chemotherapy were followed for an average of 803.4 days (26.4 months) from the time of initial reconstruction (mean time to complication, 43.3 +/- 82.7 days), and experienced an overall greater complication rate compared with control subjects (32.8% vs. 24.4%; P = .078). When complications were divided into minor, major, and reconstructive failure categories, analysis revealed that the chemotherapy group experienced more minor complications than the control group (18% vs. 11%; P = .067). However, there were no statistically significant differences in major complication rates (10.5% vs. 9.4%) and reconstructive failure complication rates (3.8% vs. 2.4%) between the chemotherapy group and control group. Sixty-eight patients (19.8%) underwent surgery within 30 days of chemotherapy, 210 patients (61%) within 30 to 60 days, and 66 patients (19.2%) after 60 days. Of note, patients in the 60 days), time to complication, complication severity, or complication type. Whereas patients who underwent surgery 30 to 60 days from the time of chemotherapy had lower rates of skin necrosis (3.8%) and infection (15.7%) compared with the