Brian B. Hughley

The promotion of mandibular defect healing by the targeting of S1P receptors and the recruitment of alternatively activated macrophages.

Endogenous signals originating at the site of injury are involved in the paracrine recruitment, proliferation, and differentiation of circulating progenitor and diverse inflammatory cell types. Here, we investigate a strategy to exploit endogenous cell recruitment mechanisms to regenerate injured bone by local targeting and activation of sphingosine-1-phosphate (S1P) receptors. A mandibular defect model was selected for evaluating regeneration of bone following trauma or congenital disease. The particular challenges of mandibular reconstruction are inherent in the complex anatomy and function of the bone given that the area is highly vascularized and in close proximity to muscle. Nanofibers composed of poly(DL-lactide-co-glycolide) (PLAGA) and polycaprolactone (PCL) were used to delivery FTY720, a targeted agonist of S1P receptors 1 and 3. In vitro culture of bone progenitor cells on drug-loaded constructs significantly enhanced SDF1α mediated chemotaxis of bone marrow mononuclear cells. In vivo results show that local delivery of FTY720 from composite nanofibers enhanced blood vessel ingrowth and increased recruitment of M2 alternatively activated macrophages, leading to significant osseous tissue ingrowth into critical sized defects after 12 weeks of treatment. These results demonstrate that local activation of S1P receptors is a regenerative cue resulting in recruitment of wound healing or anti-inflammatory macrophages and bone healing. Use of such small molecule therapy can provide an alternative to biological factors for the clinical treatment of critical size craniofacial defects.

Complications With Forehead Flaps in Nasal Reconstruction

To determine what characteristics and comorbidities are associated with a higher rate of complications in patients undergoing nasal reconstruction with a forehead flap.

Construct validity of a simulator for myringotomy with ventilation tube insertion

Objectives: To establish construct validity of an anatomic model as a simulator for myringotomy with ventilation tube insertion and to assess its subjective appeal. Study Design: Cross-sectional, repeated-measures comparative evaluation of simulator. Setting: University academic otolaryngology residency program. Subjects and Methods: Using an anatomic model of the human auricle, ear canal, eardrum, and middle ear space, 18 otolaryngologists of various levels of training performed 10 timed procedures: myringotomy with ventilation tube insertion. Errors were recorded, and participants reported the quality of their experience. Results: Both time-to-completion and errors per trial discriminated novices from non-novice participants; novices (02:23, 95% confidence interval [CI], 01:42-03:04) were 3.6 times slower than non-novices (00:39, 95% CI, 00:35-00:43) and 6.5 times more error prone (novices 2.16 errors/trial, 95% CI, 1.68-2.64; non-novices 0.33 errors/trial, 95% CI, 0.21-0.45). Errors were strongly correlated with prior surgical experience. All participants required more time to complete the first trial, and their performance stabilized thereafter. Overall, the simulation was perceived as a valuable experience. Conclusion: Our model is a valid platform for simulating myringotomy with ventilation tube insertion. The model discriminates novices from non-novices, has a learning curve, and is perceived to be a valuable and realistic teaching tool by users.

Revision aural atresia surgery: indications and outcomes.

Objective: To determine the most common indications for revision congenital aural atresia (CAA) surgery and the postoperative healing and hearing outcomes of revision surgery. Study Design: Retrospective case review. Setting: Tertiary care academic otologic practice. Patients: Patients undergoing revision surgery for CAA. Intervention: Revision surgery for CAA. Main Outcome Measures: Indications for revision atresiaplasty, time to revision surgery, postoperative external auditory canal (EAC) patency, incidence of chronic drainage and/or infection, and postoperative speech reception thresholds (SRTs), and air-bone gaps. Results: Indications for 75 ears (69 patients) undergoing 107 revision operations for CAA included 58% for EAC stenosis, 19% for chronic drainage and/or infection, and 20% for conductive hearing loss (CHL) alone. Fifty ears (67%) required a single revision. Twenty-five ears (33%) required more than 1 revision. With follow-up longer than 3 months (mean, 41 mo), 69% of ears revised for EAC stenosis achieved a patent canal (29% required >1 revision); 75% of ears revised for chronic drainage and/or infection (mean follow-up, 53 mo) realized a dry canal (22% required >1 revision). For all revision surgeries with adequate follow-up (n = 80), the mean postoperative short-term SRT of 24 dB HL was a significant improvement from the mean preoperative SRT of 39 dB HL (p < 0.01, paired t test). Conclusion: EAC stenosis is the most common indication for revision atresiaplasty. Despite the challenges of revision surgery, improvement in canal patency, epithelialization, and hearing utcomes can be achieved.

Multilayer Cell-Seeded Polymer Nanofiber Constructs for Soft-Tissue Reconstruction

IMPORTANCE Cell seeding throughout the thickness of a nanofiber construct allows for patient-specific implant alternatives with long-lasting effects, earlier integration, and reduced inflammation when compared with traditional implants. Cell seeding may improve implant integration with host tissue; however, the effect of cell seeding on thick nanofiber constructs has not been studied. OBJECTIVE To use a novel cell-preseeded nanofiber tissue engineering technique to create a 3-dimensional biocompatible implant alternative to decellularized extracellular matrix. DESIGN Animal study with mammalian cell culture to study tissue engineered scaffolds. SETTING Academic research laboratory. PARTICIPANTS Thirty-six Sprague-Dawley rats. INTERVENTIONS The rats each received 4 implant types. The grafts included rat primary (enhanced green fluorescent protein-positive [eGFP+]) fibroblast-seeded polycaprolactone (PCL)/collagen nanofiber scaffold, PCL/collagen cell-free nanofiber scaffold, acellular human cadaveric dermis (AlloDerm), and acellular porcine dermis (ENDURAGen). Rats were monitored postoperatively and received enrofloxacin in the drinking water for 4 days prophylactically and buprenorphine (0.2-0.5 mg/kg administered subcutaneously twice a day postoperatively for pain for 48 hours). MAIN OUTCOMES AND MEASURES The viability of NIH/3T3 fibroblasts cultured on PCL electrospun nanofibers was evaluated using fluorescence microscopy. Soft-tissue remodeling was examined histologically and with novel ex vivo volume determinations of implants using micro-computed tomography of cell-seeded implants relative to nanofibers without cells and commonly used dermal grafts of porcine and human origin (ENDURAGen and AlloDerm, respectively). The fate and distribution of eGFP+ seeded donor fibroblasts were assessed using immunohistochemistry. RESULTS Fibroblasts migrated across nanofiber layers within 12 hours and remained viable on a single layer for up to 14 days. Scanning electron microscopy confirmed a nanoscale structure with a mean (SD) diameter of 158 (72) nm. Low extrusion rates demonstrated the excellent biocompatibility in vivo. Histological examination of the scaffolds demonstrated minimal inflammation. Cell seeding encouraged rapid vascularization of the nanofiber implants. Cells of donor origin (eGFP+) declined with the duration of implantation. Implant volume was not significantly affected for up to 8 weeks by the preseeding of cells (P > .05). CONCLUSIONS AND RELEVANCE Polymer nanofiber-based scaffolds mimic natural extracellular matrix. Preseeding the nanofiber construct with cells improved vascularization without notable effects on volume. An effect of cell preseeding on scaffold vascularization was evident beyond the presence of preseeded cells. This 3-dimensional, multilayer method of cell seeding throughout a 1-mm-thick construct is simple and feasible for clinical application. Further development of this technique may affect the clinical practice of facial plastic and reconstructive surgeons.

Survival outcomes in elderly patients with untreated upper aerodigestive tract cancer

This study is an evaluation of survival in patients with upper aerodigestive tract (UADT) cancer who did not receive guideline‐directed therapy.

Revision of the functionally devastated nasal airway.

Functional rhinoplasty can be especially challenging in a patient who has had previous surgery, trauma, anatomic abnormalities, or systemic disease affecting the nasal mucosa. A thorough analysis of the type and location of the obstruction is critical, and only after identifying the precise anatomic cause of the problem can surgical planning begin. Scarring, altered anatomy, and disrupted tissue planes all complicate this process. Structural support and nasal mucosa often require augmentation with autogenous grafts from the ear, rib, or other portions of the nasal cavity. Attention to nasal support mechanisms, the internal and external nasal valves, and internal lining during primary surgery may help to avoid future complications. Through careful analysis and planning, proper function may be restored to a functionally devastated nasal airway.

Antiangiogenic antibody improves melanoma detection by fluorescently labeled therapeutic antibodies

Evaluate if vascular normalization with an antiangiogenic monoclonal antibody improves detection of melanoma using fluorescently labeled antibody‐based imaging.

Cutaneous Head and Neck Malignancies in the Elderly

Cutaneous malignancy of the head and neck affects a large proportion of elderly patients. The severity ranges from small, easily treatable lesions to large, invasive, potentially metastatic tumors. Surgical treatment is the primary treatment of most skin cancers; however, geriatric patients are more likely to have multiple comorbidities that increase the risk of surgery. Multiple treatment modalities exist, including surgical, radiation, and medical therapy. Recommendations and treatment options for basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and melanoma are outlined and reviewed.

Effects of Neoadjuvant Chemotherapy and Radiotherapy on Flap Perfusion in a Novel Mouse Model Using Standard Clinical Assessment and Near-Infrared Fluorescence Angiography

Purpose: Minimizing surgical morbidity after local fl ap reconstruction is important in the management of cutaneous defects. Controversy exists in current literature regarding the effects of radiation and chemotherapy on fl ap perfusion. Neoadjuvant treatments can damage the microvasculature of the surgical bed through fi brosis, endothelial cell damage, and reduced cell proliferation, which collectively increase the likelihood of postoperative fl ap failure.