Faculty Bibliography

OBJECTIVES/OBJECTIVE:The medial sural artery perforator (MSAP) free flap is an uncommonly utilized soft tissue flap in head and neck reconstruction. It is a thin, pliable, fasciocutaneous flap that provides significant pedicle length. The donor site can be closed primarily, and its location is more aesthetically pleasing to patients. We aim to describe the MSAP flap and compare it to other commonly used free flaps in the head and neck. STUDY DESIGN/METHODS:Retrospective case series. METHODS:A retrospective review of all MSAP cases performed at New York University Langone Health was performed from July 2016 to November 2017. We examined the patients' age, diagnosis, history of prior radiation therapy, and comorbidities, as well as flap-specific information and recipient site. RESULTS:(15 cm × 8 cm). The flaps ranged from 5 to 12 mm in thickness. Venous coupler size ranged from 2.0 to 3.5 mm. Primary closure of the donor site was achieved in 18 of 21 flaps. Twenty of 21 flaps were transferred successfully. CONCLUSION/CONCLUSIONS:The MSAP flap is a highly versatile and reliable option for a thin, pliable soft tissue flap with a donor site that may be preferable over the radial forearm free flap and anterolateral thigh flap in complex head and neck reconstruction. LEVEL OF EVIDENCE/METHODS:4. Laryngoscope, 2018.

OBJECTIVE:The aim of this in vivo study is to compare the osseointegration of endosteal implants placed in atrophic mandibular alveolar ridges with alveolar ridge expansion surgical protocol via an experimental osseodensification drilling versus conventional osteotome technique. METHODS:Twelve endosteal implants, 4 mm × 13 mm, were placed in porcine models in horizontally atrophic mandibular ridges subsequent to prior extraction of premolars. Implants were placed with osseodensification drilling technique as the experimental group (n = 6) and osteotome site preparation as the control group (n = 6). After 4 weeks of healing, samples were retrieved and stained with Stevenel's Blue and Van Gieson's Picro Fuschin for histologic evaluation. Quantitative analysis via bone-to-implant contact (BIC%) and bone area fraction occupancy (BAFO%) were obtained as mean values with corresponding 95% confidence interval. A significant omnibus test, post-hoc comparison of the 2 drilling techniques' mean values was accomplished using a pooled estimate of the standard error with P-value set at 0.05. RESULTS:The mean BIC% value was approximately 62.5% in the osseodensification group, and 31.4% in the regular instrumentation group. Statistical analysis showed a significant effect of the drilling technique (P = 0.018). There was no statistical difference in BAFO as a function of drilling technique (P = 0.198). CONCLUSION/CONCLUSIONS:The combined osseodensification drilling-alveolar ridge expansion technique showed increased evidence of osseointegration and implant primary stability from a histologic and biomechanical standpoint, respectively. Future studies will focus on expanding the sample size as well as the timeline of the study to allow investigation of long-term prognosis of this novel technique.

AIM/OBJECTIVE:To evaluate the influence of brain-derived neurotrophic factor (BDNF) in combination with collagen sponges on periodontal tissue regeneration. METHODS:Unilateral, "box-type" (4x5mm), one-wall intrabony defects were surgically created at posterior mandibular teeth in 14 Beagle dogs. Animals received all experimental groups and the defects were randomly treated as follow: Emdogain® (positive control) [EMD]; HeliPlug®+BDNF [H/B]; RCP®+BDNF [R/B]; negative control [Control]; TeruPlug®+BDNF [Tp/B] and TeruPlug®+BDNF2 [Ts/B]. Periodontal wound healing was observed every 2 weeks by computed tomography. The animals were euthanized at 8 weeks post-surgery for microcomputed tomography and histomorphometric evaluation. RESULTS:All groups presented ∼1mm apical epithelial attachment relative to cementoenamel junction. Although linear measurements did not demonstrate significant differences between groups for cementum and periodontal ligament regeneration, semi-quantitative analysis depicted higher percentage of samples with mineralized cementum and functional PDL for Ts/B, R/B and H/B groups relative to EMD and Control (p<0.046). Irrespective of quantification method (2D or 3D), Ts/B, Control, Tp/B and H/B groups presented the highest mean percentage of new bone (not significantly different), followed by R/B and EMD groups. CONCLUSION/CONCLUSIONS:While no significant differences were detected in quantitative analyses, Ts/B combination results in significantly more samples with full periodontal tissue regeneration relative to control groups.

OBJECTIVE:is associated with one or more particular comorbidities. STUDY DESIGN/METHODS:or DH lesion to a control patient who had a history of dentoalveolar surgery with uneventful healing and no history of antiresorptive therapy. Comorbidity data included medical conditions and smoking. RESULTS:and DH than in controls [M(SD) = 1.94 (1.2) and 2.0 (1.3) vs 1.26 (0.89); both P < .001]. CONCLUSIONS:and DH.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Various animal models have been employed to investigate vocal fold (VF) and phonatory function. However, biomechanical testing techniques to characterize vocal fold structural properties vary and have not compared critical properties across species. We adapted a nondestructive, automated indentation mapping technique to simultaneously quantify VF structural properties (VF cover layer and intact VF) in commonly used species based on the hypothesis that VF biomechanical properties are largely preserved across species. STUDY DESIGN/METHODS:Ex vivo animal model. METHODS:Canine, leporine, and swine larynges (n = 4 each) were sagittally bisected, measured, and subjected to normal indentation mapping (indentation at 0.3 mm; 1.2 mm/s) with a 2-mm spherical indenter to quantify normal force along the VF cover layer, structural stiffness, and displacement at 0.8 mN; two-dimensional maps of the free VF edge through the conus elasticus were created for these characterizations. RESULTS:Structural stiffness was 7.79 gf/mm (0.15-74.55) for leporine, 2.48 gf/mm (0.20-41.75) for canine, and 1.45 gf (0.56-4.56) for swine. For each species, the lowest values were along the free VF edge (mean ± standard deviation; leporine: 0.40 ± 0.21 gf/mm, canine: 1.14 ± 0.49 gf/mm, swine: 0.89 ± 0.28 gf/mm). Similar results were obtained for the cover layer normal force at 0.3 mm. On the free VF edge, mean (standard deviation) displacement at 0.08 gf was 0.14 mm (0.05) in leporine, 0.11 mm (0.03) in canine, and 0.10 mm (0.02) in swine. CONCLUSIONS:Automated indentation mapping yielded reproducible biomechanical property measurement of the VF cover and intact VF. Divergent VF structural properties across canine, swine, and leporine species were observed. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2018.

Bone cancer metastasis is extremely painful and decreases the quality of life of the affected patients. Available pharmacological treatments are not able to sufficiently ameliorate the pain and as cancer patients are living longer new treatments for pain management are needed. Decitabine (5-aza-2'-deoxycytidine), a DNA methyltransferases inhibitor, has analgesic properties in pre-clinical models of post-surgical and soft tissue oral cancer pain by inducing an up-regulation of endogenous opioids. In this study, we report that daily treatment with decitabine (2µg/g, i.p.) attenuated nociceptive behavior in the 4T1-luc2 mouse model of bone cancer pain. We hypothesized that the analgesic mechanism of decitabine involved activation of the endogenous opioid system through demethylation and reexpression of the transcriptionally silenced endothelin B receptor gene, Ednrb. Indeed, Ednrb was hypermethylated and transcriptionally silenced in the mouse model of bone cancer pain. We demonstrated that expression of Ednrb in the cancer cells lead to release of β-endorphin in the cell supernatant which reduced the number of responsive DRG neurons in an opioid-dependent manner. Our study supports a role of demethylating drugs, such as decitabine, as unique pharmacological agents targeting the pain in the cancer microenvironment.

PURPOSE/OBJECTIVE:Conflicting data exist regarding the incidence, demographics, and abnormalities associated with microtia. Using a large national cohort database, a comprehensive evaluation of microtia in the United States was performed. METHODS:The Kids' Inpatient Database was reviewed over a 15-year consecutive period. Information regarding patient demographics, comorbidities, postoperative complications, and hospital setting was collected. Statistical tests were analyzed using independent t tests and χ analysis. RESULTS:A total of 23,479,792 births over 15 consecutive years from 1997 to 2012 were included in the study. Microtia was identified in 1563 births. Incidence of microtia was higher in males (P<0.01) and patients of Asian or Hispanic race (P<0.01). Patients with microtia had significantly more congenital anomalies relative to the rest of the population (P<0.01). Specifically, cardiac and genitourinary anomalies were 51 and 19 times, respectively, more likely in microtia patients. Risk of associated congenital anomalies with microtia was highest in female and Black patients. 12.6% of all microtia patients had an associated craniofacial syndrome with a comparable postsurgical course to the nonsyndromic population. CONCLUSION/CONCLUSIONS:This study represents the largest national, longitudinal study of microtia allowing for demographic, socioeconomic, and comorbidity commentary. By quantifying relative risk of associated congenital anomalies, it can help inform the type and utility of screening modalities when evaluating microtia patients.

The molecular and cellular level reaches of the metabolic dysregulations that characterize diabetes are yet to be fully discovered. As mechanisms underlying management of reactive oxygen species (ROS) gain interest as crucial factors in cell integrity, questions arise about the role of redox cues in regulation and maintenance of bone marrow-derived multipotent stromal cells (BMSCs) that contribute to wound healing, particularly in diabetes. Through comparison of BMSCs from wild type and diabetic mice, with a known redox and metabolic disorder, we found that the cytoprotective Nrf2/Keap1 pathway is dysregulated and functionally insufficient in diabetic BMSCs. Nrf2 is basally active, but in chronic ROS we found irregular inhibition of Nrf2 by Keap1, altered metabolism and limited BMSC multipotency. Forced upregulation of Nrf2-directed transcription, through knockdown of Keap1, restores redox homeostasis. Normalized Nrf2/Keap1 signaling restores multipotent cell properties in diabetic BMSCs through Sox2 expression. These restored BMSCs can resume their role in regenerative tissue repair and promote healing of diabetic wounds. Knowledge of diabetes and hyperglycemia-induced deficits in BMSC regulation, and strategies to reverse them offers translational promise. Our study establishes Nrf2/Keap1 as a cytoprotective pathway, as well as a metabolic rheostat that affects cell maintenance and differentiation switches in BMSCs.

PURPOSE/OBJECTIVE: Limb-sparing treatment of extremity soft tissue sarcomas requires wide resections and radiation therapy. The resulting complex composite defects necessitate reconstructions using either muscle or fasciocutaneous flaps, often in irradiated wound beds. METHODS: A retrospective chart review was performed of all limb-sparing soft tissue sarcoma resections requiring immediate flap reconstruction from 2012 through 2016. RESULTS:< 0.048). At time of follow-up, Musculoskeletal Tumor Society scores for fasciocutaneous and muscle-based reconstructions, with or without radiation, showed no significant differences between groups (mean [SD]: 91% [8%] vs. 89% [13%]). CONCLUSIONS: The similar complication rates and functional outcomes in this study support the safety and efficacy of both fasciocutaneous flaps and muscle-based flaps in reconstructing limb-sparing sarcoma resection defects, with or without radiotherapy.

Complicated craniofacial malformations interfacing with multiple intracellular regulatory mechanisms, lead to ambiguous growth patterns in Apert syndrome. This study aims to explore the chronology and pathogenesis of the development of craniofacial anatomic relationships and to verify the positional correlates between skull and facial structures in Apert syndrome. Fifty-four computed tomography scans (Apert, n = 18; control, n = 36) were included and divided into 3 age subgroups. Craniofacial 3-dimensional cephalometries were analyzed by Materialize software. The angle between sella-nasion plane and maxillary plane widens 7.74° (P = 0.003) prior to 6 months of age; thereafter, this widening increases by 10.36° (P < 0.001) in 6 months to 2 years of age, and remains increased by 8.9° (P = 0.046) throughout childhood. The angle between Frankfort horizontal plane and maxillary plane widens 5.17° (P = 0.022) before 6 months. Angles SNA, SNB, and ANB showed decreases, averaging 12.23° (P < 0.001), 5.19° (P = 0.004), and 6.72° (P = 0.001), respectively. The linear measurements showed synchronicity and continuing deformity into adulthood. Between 6 months to 2 years of age, the distance from sella to nasion (S-N), anterior nasal spine (S-ANS), and posterior nasal spine (S-PNS) decreased 8% (P = 0.006), 16% (P < 0.001), and 19% (P = 0.002), respectively, and remained shortened into adulthood. The angulation changes occur earlier in development than linear distance reduction in Apert syndrome patients compared with controls. Angular adjustments were not sufficient to maintain normal cranial base length. Facial deformity of Apert syndrome temporally begins with the midface, and affects orbit and mandible later in life.