Facial nerve repair after operative injury: Impact of timing on hypoglossal-facial nerve graft outcomes.

PURPOSE: Reanimation of facial paralysis is a complex problem with multiple treatment options. One option is hypoglossal-facial nerve grafting, which can be performed in the immediate postoperative period after nerve transection, or in a delayed setting after skull base surgery when the nerve is anatomically intact but function is poor. The purpose of this study is to investigate the effect of timing of hypoglossal-facial grafting on functional outcome. MATERIALS AND METHODS: A retrospective case series from a single tertiary otologic referral center was performed identifying 60 patients with facial nerve injury following cerebellopontine angle tumor extirpation. Patients underwent hypoglossal-facial nerve anastomosis following facial nerve injury. Facial nerve function was measured using the House-Brackmann facial nerve grading system at a median follow-up interval of 18months. Multivariate logistic regression analysis was used determine how time to hypoglossal-facial nerve grafting affected odds of achieving House-Brackmann grade of ≤3. RESULTS: Patients who underwent acute hypoglossal-facial anastomotic repair (0-14days from injury) were more likely to achieve House-Brackmann grade ≤3 compared to those that had delayed repair (OR 4.97, 95% CI 1.5-16.9, p=0.01). CONCLUSIONS: Early hypoglossal-facial anastomotic repair after acute facial nerve injury is associated with better long-term facial function outcomes and should be considered in the management algorithm.

Carbon Dioxide Laser Rejuvenation of the Facial Skin.

This article reviews the evaluation and techniques for facial skin rejuvenation using the fractionated carbon dioxide laser. It includes a detailed overview of laser skin rejuvenation and discusses the potential complications associated with this procedure. A review of clinical outcomes in the literature is also included.

Carbon Dioxide Laser Rejuvenation of the Facial Skin.

This article reviews the evaluation and techniques for facial skin rejuvenation using the fractionated carbon dioxide laser. It includes a detailed overview of laser skin rejuvenation and discusses the potential complications associated with this procedure. A review of clinical outcomes in the literature is also included.

Septal Perfoplasty for Management of Symptomatic Nasal Septal Perforation: An Alternative to Surgical Closure.

Importance: Symptomatic septal perforations are often difficult to manage and can have a significant impact on patient quality of life. Available surgical techniques for repair have demonstrated a varying rate of success, presenting a need for reliable interventions targeting symptom control. Objectives: To describe the modified surgical technique here termed septal perfoplasty. To demonstrate that creation of favorable septal perforation characteristics is effective in managing symptoms and improving patient quality of life. Design, Setting, and Participants: A retrospective review of the medical record was performed of patients who underwent the procedure of interest between July 1, 2006 and October 1, 2019 at Vanderbilt University Medical Center. All patients with symptomatic septal perforation who underwent septal perfoplasty within the timeframe reviewed were included. Septal perfoplasty was standardly performed in combination with turbinate reduction in all cases. This was combined with other indicated procedures for chronic sinusitis, repair of vestibular stenosis or nasal deformity. Main Outcomes and Measures: Creation of a well-mucosalized septal perforation, combined with patient-reported acceptable symptom control, was the primary outcome. Secondary outcomes include time to resolution, duration of follow-up, postsurgical complications, and need for further intervention. Results: Twenty patients (70% female; mean [range] age, 45.8 [15-72] years) underwent septal perfoplasty over the course of 13 years. The most common etiology of perforation was trauma (40%), presenting symptom was crusting (95%), and size of perforation repaired was large (60%). Mean follow-up was 37.6 months (range, 1-153 months). Overall, favorable perforation characteristics were created in 95% of cases by the first postoperative appointment. Acceptable symptomatic control was achieved in 18 out of 20 patients (90%), with a median time to improvement of 66 days. Eight patients required additional surgery to address chronic sinusitis or vestibular stenosis. Two patients experienced postoperative infections, treated conservatively with antibiotics. Conclusion and Relevance: Septal perfoplasty is a safe, simple, and effective method for management of symptomatic nasal septal perforation, which provides an alternative to more complicated interventions with comparable rates of symptomatic resolution. This procedure should particularly be considered for patients in which difficult repair is anticipated.

Negative regulation of immunoglobulin E-dependent allergic responses by Lyn kinase.

A role for Lyn kinase as a positive regulator of immunoglobulin (Ig)E-dependent allergy has long been accepted. Contrary to this belief, Lyn kinase was found to have an important role as a negative regulator of the allergic response. This became apparent from the hyperresponsive degranulation of lyn-/- bone marrow-derived mast cells, which is driven by hyperactivation of Fyn kinase that occurs, in part, through the loss of negative regulation by COOH-terminal Src kinase (Csk) and the adaptor, Csk-binding protein. This phenotype is recapitulated in vivo as young lyn-/- mice showed an enhanced anaphylactic response. In vivo studies also demonstrated that as lyn-/- mice aged, their serum IgE increased as well as occupancy of the high affinity IgE receptor (FcepsilonRI). This was mirrored by increased circulating histamine, increased mast cell numbers, increased cell surface expression of the high affinity IgE receptor (FcepsilonRI), and eosinophilia. The increased IgE production was not a consequence of increased Fyn kinase activity in lyn-/- mice because both lyn-/- and lyn-/- fyn-/- mice showed high IgE levels. Thus, lyn-/- mice and mast cells thereof show multiple allergy-associated traits, causing reconsideration of the possible efficacy in therapeutic targeting of Lyn in allergic disease.

Incorporating Postoperative Debriefing Into Surgical Education.

PURPOSE: We investigated the feasibility and utility of a postoperative "debriefing" process to improve the educational value of surgical procedures. METHODS: Residents provided a baseline preintervention assessment of personal and attending surgeon current practice for seeking and receiving feedback on performance after an operative case. Surgeons subsequently were educated (the intervention) about the purpose and content of the postoperative debriefing initiative. Each resident completed 8 surgical cases (minimum) in which the debriefing process occurred. A survey was completed after each debriefing and at study completion that inquired about utility, educational value, and feasibility. Descriptive results are reported and comparisons made with Fisher's exact tests, when appropriate. RESULTS: In all, 69% of residents felt the attending surgeon "sometimes or always" identified aspects of the case that they performed competently preintervention compared with 93% postintervention. Overall, 56% of residents were aware of the attending surgeon's impression of their performance preintervention compared with 93% postintervention. Nearly all residents planned on making postoperative debriefing a routine part of self-assessment (93%). Most felt that the duration of time required for debriefing was "just right" (93%) and felt that the process to be "easy and effective" (86%). CONCLUSION: Resident respondents indicated the postoperative debriefing process was educational, desirable, and feasible. We have made the postoperative debriefing a routine practice in the surgical education of Vanderbilt Otolaryngology residents.

Stat5: an essential regulator of mast cell biology.

Interleukin-3 (IL-3) and stem cell factor (SCF) are important mast cell growth and differentiation factors. Since both cytokines activate the transcription factor Stat5, a known regulator of proliferation and survival, we investigated the effects of Stat5 deficiency on mast cell development and survival. This article will review data presented at The Fourth International Workshop on Signal Transduction in the Activation and Development of Mast Cells and Basophils. The full set of data is now in preparation for publication. We find that the absence of Stat5 A and B results in a total loss of in vivo mast cell development. Bone marrow-derived mast cell (BMMC) populations can be cultured and maintained from Stat5-deficient mice in IL-3+SCF, but not in either cytokine alone. The absence of Stat5 resulted in aberrant control of Bcl-2, Bcl-x(L) and cyclin A2, with increased apoptosis and delayed cell cycle progression after IL-3 or SCF stimulation. These results indicate that Stat5 A and B are critical regulators of in vitro and in vivo mast cell biology.

Costimulation with interleukin-4 and interleukin-10 induces mast cell apoptosis and cell-cycle arrest: the role of p53 and the mitochondrion.

OBJECTIVE: The aim of this study was to determine the mechanism by which interleukin (IL)-4 + IL-10 costimulation regulates mast cell numbers to maintain immune homeostasis. MATERIALS AND METHODS: We employed mouse bone marrow-derived mast cells (BMMC) to measure the effects of IL-4 + IL-10 on survival and cell-cycle progression. p53-Deficient, bax-deficient, and bcl-2 transgenic BMMC were compared to wild-type cells to determine the role of these proteins in apoptosis. The molecular regulation of apoptosis and cell-cycle progression was investigated using flow cytometric analysis, RNase protection, and Western blotting. RESULTS: IL-4 + IL-10 induced BMMC apoptosis and arrest. Apoptosis was p53-dependent. Cell death was accompanied by loss of mitochondrial membrane potential, the importance of which was demonstrated by resistance to IL-4 + IL-10-mediated cell death when Bax was deleted or Bcl-2 was overexpressed. Those cells not killed by apoptosis demonstrated a p53-independent G1 cell-cycle arrest. Apoptosis and arrest may be explained by reduced IL-3 receptor signaling. CONCLUSION: Costimulation with IL-4 + IL-10 partly controls mast cell homeostasis through a delayed apoptosis and arrest program that is induced by a blockade of IL-3 receptor signaling. The delay in these negative effects would allow the protective effects of mast cell activation to occur for several days.

Techniques for rejuvenation of the neck platysma.

This article reviews evaluation and techniques for neck rejuvenation. It includes a detailed overview of cervical rhytidectomy and discusses the potential complications associated with surgical correction. A review of clinical outcomes in the literature is also included.

Integra Bilayer Matrix Wound Dressing closure of large periorbital traumatic wound.

We report the first use of the Integra Bilayer Matrix Wound Dressing (Integra LifeSciences Corp), a collagen sheet with glycosaminoglycans and a silicone layer, in an innovative reconstruction approach to devastating traumatic tissue loss in the periocular area. A 36-year-old woman was involved in a motor vehicle crash with a resultant large defect from the medial canthus to the temporal fossa and from the pretarsal skin to the brow. There was denudation of skin and soft tissue to the bone at the superolateral orbital apex. The severity of tissue loss precluded placement of an autograft or allograft; thus, a skin substitute was instead used, with a successful reconstructive outcome. Application of the newer bioengineered skin products for full-thickness skin wounds should be considered for reconstruction of the periocular area.

Genes involved in radiation therapy response in head and neck cancers.

OBJECTIVES: This is a pilot study designed to identify gene expression profiles able to stratify head and neck squamous cell carcinoma (HNSCC) tumors that may or may not respond to chemoradiation or radiation therapy. STUDY DESIGN: We prospectively evaluated 14 HNSCC specimens, arising from patients undergoing chemoradiotherapy or radiotherapy alone with curative intent. A complete response was assessed by clinical evaluation with no evidence of gross tumor after a 2-year follow-up period. METHODS: Residual biopsy samples from eight complete responders (CR) and six nonresponders (NR) were evaluated by genome-wide gene expression profiling using HG-U133A 2.0 arrays. Univariate parametric t-tests with proportion of false discoveries controlled by multivariate permutation tests were used to identify genes with significantly different gene expression levels between CR and NR cases. Six different prediction algorithms were used to build gene predictor lists. Three representative genes showing 100% crossvalidation support after leave-one-out crossvalidation (LOOCV) were further validated using real-time QRT-PCR. RESULTS: We identified 167 significant probe sets that discriminate between the two classes, which were used to build gene predictor lists. Thus, 142 probe sets showed an accuracy of prediction ranging from 93% to 100% across all six prediction algorithms. The genes represented by these 142 probe sets were further classified into different functional networks that included cellular development, cellular movement, and cancer. CONCLUSIONS: The results presented herein offer encouraging preliminary data that may provide a basis for a more precise prognosis of HNSCC, as well as a molecular-based therapy decision for the management of these cancers.

IL-3-mediated TNF production is necessary for mast cell development.

Mouse mast cell development and survival are largely controlled by the cytokines IL-3 and stem cell factor (SCF). We have found that IL-3 stimulation of bone marrow cells induces the production of TNF via a PI3K- and MAPK kinase/ERK-dependent pathway. Specifically, Mac-1-positive cells were responsible for TNF production, which peaked on days 7-10 of culture and decreased rapidly thereafter. The importance of IL-3-induced TNF secretion was demonstrated by the failure of TNF-deficient bone marrow cells to survive for >3 wk when cultured in IL-3 and SCF, a defect that was reversed by the addition of soluble TNF. The development of human mast cells from bone marrow progenitors was similarly hampered by the addition of TNF-blocking Abs. Cell death was due to apoptosis, which occurred with changes in mitochondrial membrane potential and caspase activation. Apoptosis appeared to be due to loss of IL-3 signaling, because TNF-deficient cells were less responsive than their wild-type counterparts to IL-3-mediated survival. In vitro cultured mast cells from TNF-deficient mice also demonstrated reduced expression of the high affinity IgE receptor, which was restored to normal levels by the addition of soluble TNF. Finally, TNF-deficient mice demonstrated a 50% reduction in peritoneal mast cell numbers, indicating that TNF is an important mast cell survival factor both in vitro and in vivo.

IFN-gamma induces apoptosis in developing mast cells.

Mast cells are critical effectors of allergic disease, and are now implicated in immune responses observed in arthritis, multiple sclerosis, and heart disease. Because of their role in inflammation, understanding how mast cells develop is of clinical importance. In this study we determined the effects of IFN-gamma on mast cell survival. Using in vitro culture of bone marrow cells in IL-3 plus stem cell factor, we found that the addition of IFN-gamma induced apoptosis, as exhibited by the presence of subdiploid DNA and caspase activation. IFN-gamma-mediated apoptosis was Stat1-dependent, and was accompanied by loss of mitochondrial membrane potential. Apoptosis was reduced in cultures of bone marrow cells derived from p53- or Bax-deficient mice, as well as H2K-Bcl-2 transgenic mice. IFN-gamma hyperresponsiveness has been shown to result in inflammatory disease and death in mice lacking the regulatory protein suppressor of cytokine signaling (SOCS)-1. Bone marrow cells from SOCS-1 knockout (KO) mice failed to give rise to viable mast cells after culture in IL-3 plus stem cell factor, with profound apoptosis occurring as the cultures matured. However, bone marrow cells lacking both SOCS-1 and IFN-gamma survived normally. This in vitro defect in mast cell development was recapitulated in vivo. SOCS-1 KO mice demonstrated a 67% decrease in peritoneal mast cell numbers relative to wild-type mice, a deficiency that was reversed in SOCS-1/IFN-gamma KO mice. These data demonstrate the potent regulatory effects of IFN-gamma on mast cell survival and show that this cytokine can elicit mast cell death in vitro and in vivo.

TGF-beta 1 inhibits mast cell Fc epsilon RI expression.

Mast cell activation through the high affinity IgE receptor (FcepsilonRI) is a critical component of atopic inflammation. The cytokine TGF-beta1 has been shown to inhibit IgE-dependent mast cell activation, possibly serving to dampen mast cell-mediated inflammatory responses. We present proof that TGF-beta1 inhibits mast cell FcepsilonRI expression through a reversible pathway that diminishes protein, but not mRNA, expression of the FcepsilonRI subunit proteins alpha, beta, and gamma. The stability of the expressed proteins and the assembled cell surface complex was unaltered by TGF-beta1 treatment. However, TGF-beta1 decreased the rate of FcepsilonRI beta-chain synthesis, arguing that this inhibitory cytokine exerts its effects at the level of mRNA translation. TGF-beta1 consistently diminished FcepsilonRI expression on cultured human or mouse mast cells as well as freshly isolated peritoneal mast cells. The related cytokines, TGF-beta2 and TGF-beta3, had similar effects. We propose that TGF-beta1 acts as a negative regulator of mast cell function, in part by decreasing FcepsilonRI expression.

Stat5 expression is critical for mast cell development and survival.

Interleukin-3 (IL-3) and stem cell factor (SCF) are important mast cell growth and differentiation factors. Since both cytokines activate the transcription factor signal transducer and activator of transcription 5 (Stat5), a known regulator of proliferation and survival, we investigated the effects of Stat5 deficiency on mast cell development and survival. Bone marrow-derived mast cell (BMMC) populations cultured from Stat5A/B-deficient mice survived in IL-3 + SCF, but not in either cytokine alone. These cells demonstrated reduced expression of Bcl-2, Bcl-x(L), cyclin A2, and cyclin B1, with increased apoptosis and delayed cell cycle progression during IL-3 or SCF culture. Finally, the absence of Stat5 resulted in loss of in vivo mast cell development, as judged by assessments of Stat5-deficient mice and transplantation of Stat5-deficient bone marrow cells to mast cell-deficient recipient mice. These results indicate that Stat5A and Stat5B are critical regulators of in vitro and in vivo mast cell development and survival.