Management of Lateral Wall Insufficiency.

Lateral wall insufficiency is a commonly encountered etiology of nasal obstruction, resulting from dynamic collapse at the level of the internal or external nasal valve. Various management strategies exist to strengthen the lateral wall or stent the nasal valves to relieve nasal obstruction, and range from noninvasive devices, minimally invasive implants, or surgical reconstructive techniques. Surgical options to address the nasal valves are selected based on each patient's anatomic findings, aesthetic and functional goals, and surgeon preference. This article describes the anatomy and physiology of the nasal sidewall and nasal valves and diagnosis of lateral wall insufficiency, and provides a framework for treatment options.

Modern use of tranexamic acid in facial plastic surgery.

PURPOSE OF REVIEW: Although tranexamic acid is commonly used in surgical fields such as obstetrics, orthopedics, and trauma, its utilization in facial plastic surgery is a recently emerging concept, and studies examining its potential impact have been few. This review highlights how tranexamic acid may be employed during facial plastic procedures and the promising impact it may have. RECENT FINDINGS: Tranexamic acid is primarily being studied in rhinoplasties and rhytidectomies, with intravenous administration and local infiltration being the most common routs of application, respectively. During rhinoplasties, tranexamic acid has the potential to improve the visualization of the surgical field by decreasing blood loss and to improve postoperative edema and ecchymosis. For rhytidectomies, on the contrary, it may shorten time to attain hemostasis, lessen the rate of hematoma formation, and lead to lower surgical drain output. Its efficacy is preserved at low doses, and significant medication side effects have not been reported after facial plastic procedures. SUMMARY: Altogether, tranexamic acid may present a valuable adjuvant to facial plastic surgery, as it could increase both surgeon and patient satisfaction while exhibiting a benign safety profile.

Surgical Management of Facial Paralysis: Demographic and Socioeconomic Associations.

Objective: To determine demographic and socioeconomic variables associated with whether surgery is performed for patients with facial paralysis (FP). Background: Management of FP may include elective surgery dependent on patient goals of care and physician experience. Methods: The 2016 State Inpatient Database and State Ambulatory Surgery Services Database for six states were queried to identify patients with FP. These patients were then stratified based on receiving surgery for FP. Demographic and socioeconomic information was collected. Multivariable logistic regression modeling was used to identify predictors of undergoing FP surgery, as well as the hospital setting in which surgery was performed. Results: Of 20,218 patients with FP, 515 underwent surgery. Black patients were significantly less likely to undergo surgery (p < 0.001), as were patients with Medicaid or self-pay insurance (p < 0.001). Those living in rural areas were also less likely to receive surgery (p = 0.001). Individuals receiving surgery in the inpatient setting were more likely to have private insurance, whereas those in the ambulatory setting were more likely to have Medicare (p < 0.001). Conclusion: Several variables are correlated with whether FP is managed surgically, including insurance status, race, and type of residential area.

Perceptions of Patients with Facial Paralysis: Predicting Social Implications and Setting Goals.

The goal of this article is to better understand the social impact of facial paralysis. Patients with facial paralysis may suffer from impaired social interactions, disruption of self-concept, psychological distress, and decreased overall quality of life. Vigilance in detecting patients suffering from mental health issues may result in providing early referral for psychological evaluation and psychosocial support resources complementing facial reanimation treatment.

A Guide to Facial Trauma Triage and Precautions in the COVID-19 Pandemic.

COVID-19 is an emerging viral illness that has rapidly transmitted throughout the world. Its impact on society and the health care system has compelled hospitals to quickly adapt and innovate as new information about the disease is uncovered. During this pandemic, essential medical and surgical services must be carried out while minimizing the risk of disease transmission to health care workers. There is an elevated risk of COVID-19 viral transmission to health care workers during surgical procedures of the head and neck due to potential aerosolization of viral particles from the oral cavity/naso-oropharynx mucosa. Thus, patients with facial fractures pose unique challenges to the variety of injuries and special considerations, including triaging injuries and protective measures against infection. The proximity to the oral cavity/naso-oropharyngeal mucosa, and potential for aerosolization of secretions containing viral particles during surgical procedures make most patients undergoing operative interventions for facial fractures high risk for COVID-19 transmission. Our proposed algorithm aims to balance patient care with patient/medical personnel protection as well as judicious health care utilization. It stratifies facial trauma procedures by urgency and assigns a recommended level of personal protective equipment, extreme or enhanced, incorporating current best practices and existing data on viral transmission. As this pandemic continues to evolve and more information is obtained, the protocol can be further refined and individualized to each institution.

Ultrasonic Aspiration for Debulking Infiltrative Masses of the Orbit.

PURPOSE: To demonstrate the utility of an ultrasonic aspirator (Sonopet, Stryker Corporation; Kalamazoo, MI) for debulking firm, soft tissue masses of the orbit. METHODS: Case series. The ultrasonic aspirator was used to debulk firm, soft tissue masses in 3 cases. The initial patient had a large orbitofacial mass extending to the inferior and lateral orbital apex secondary to IgG4 disease. The second patient had a lacrimal sac adenocarcinoma extending to the medial orbital apex. The third patient had a large orbital mass extending to the apex secondary to granulomatosis with polyangiitis. RESULTS: The ultrasonic aspirator facilitated debulking of infiltrative firm soft tissue masses of the orbit. The device's ability to emulsify, irrigate, and aspirate, along with its small footprint, facilitated precise sculpting and debulking to an extent which would have been difficult otherwise due to location. CONCLUSIONS: The ultrasonic aspirator allows precise sculpting of infiltrative firm soft tissue masses in the orbit and is particularly useful in cases with challenging anatomical access.

Predicting Perceived Disfigurement from Facial Function in Patients with Unilateral Paralysis.

BACKGROUND: Clinical rating tools such as the electronic, clinician-graded facial function (eFACE) scale provide detailed information about aspects of facial functioning relevant to the assessment and treatment of facial paralysis. Past research has established that eFACE scores significantly relate to expert ratings of facial disfigurement. However, no studies have examined the extent to which eFACE scores relate to casual observers' perceptions of disfigurement in facial paralysis. METHODS: Casual observers (n = 539) were recruited at the 2016 Minnesota State Fair, and were shown short videos of facial expressions made by patients (n = 61) with unilateral facial paralysis. Observer ratings of disfigurement were recorded and related to eFACE scores (total and subscores) using mixed-effect regression models. RESULTS: Patients' eFACE scores were significantly related to observers' disfigurement ratings, such that improved function (as indicated by a higher eFACE score) corresponded to a decreased perception of disfigurement. The resting face of patients, their total movement capability, and their involuntary movement through synkinesis all played a significant role in predicting the casual observers' ratings. CONCLUSIONS: The results establish a clear connection between clinician eFACE ratings of facial function and casual observer judgments of disfigurement. In addition, the findings provide insight into which clinical aspects of facial dysfunction are most salient for casual observers' perceptions of disfigurement. Such insights can help both patients and clinicians better understand the expected social implications of different clinical aspects of facial dysfunction.

Dynamic properties of successful smiles.

Facial expression of emotion is a foundational aspect of social interaction and nonverbal communication. In this study, we use a computer-animated 3D facial tool to investigate how dynamic properties of a smile are perceived. We created smile animations where we systematically manipulated the smile's angle, extent, dental show, and dynamic symmetry. Then we asked a diverse sample of 802 participants to rate the smiles in terms of their effectiveness, genuineness, pleasantness, and perceived emotional intent. We define a "successful smile" as one that is rated effective, genuine, and pleasant in the colloquial sense of these words. We found that a successful smile can be expressed via a variety of different spatiotemporal trajectories, involving an intricate balance of mouth angle, smile extent, and dental show combined with dynamic symmetry. These findings have broad applications in a variety of areas, such as facial reanimation surgery, rehabilitation, computer graphics, and psychology.

Quantifying Labial Strength and Function in Facial Paralysis: Effect of Targeted Lip Injection Augmentation.

IMPORTANCE: Facial muscle weakness from paralysis or muscle dystrophy can significantly affect lip strength and function. Lip muscle weakness may result in articulation difficulties and spillage of food, both of which are socially and functionally disruptive for patients. There are few quantitative data on the effect of facial paralysis on lip strength. OBJECTIVES: To quantify the effect of facial paralysis and muscular dystrophy on lip strength and evaluate the effectiveness of targeted lip injection augmentation. DESIGN, SETTING, AND PARTICIPANTS: Analysis of patients at the Johns Hopkins Hospital between January 1, 2008, and July 31, 2014, presenting for treatment of lip incompetence due to facial paralysis and facial muscular dystrophy was prospectively undertaken. Patients who had undergone direct surgical lip procedures were excluded. MAIN OUTCOMES AND MEASURES: Lip pressure measurements, anterior bolus spillage, and articulation of bilabial sounds before and after treatment were assessed by a single speech pathologist. Lip pressures were measured with the Iowa Oral Performance Instrument. RESULTS: Twenty-two patients with unilateral facial paralysis were evaluated for this study. Three patients with facioscapulohumeral muscular dystrophy were also evaluated. In unilateral facial paralysis, central lip strength was reduced in all patients compared with sex-corrected normative data (mean [SD] central lip strength, 5.5 [2.5] kPa in females and 9.6 [4.6] kPa in males). Compared with the nonparalyzed side, labial strength on the paralyzed sided was reduced by 69%. After injection augmentation of the paralyzed side, labial strength improved across the entire lip. Mean lip strength improved by 0.7-fold in the central lip from 5.60 to 9.30 kPa (P = .009), by 1.4-fold on the paralyzed side from 2.2 to 5.33 kPa (P = .006), and by 0.4-fold on the unaffected side from 7.11 to 9.56 kPa (P = .12). Lip strength in the 3 patients with facioscapulohumeral muscular dystrophy were uniformly reduced across the entire lip and improved by 6- to 7-fold after injection augmentation. All patients were noted by the speech pathologist to have improved articulation of plosive sounds and decreased anterior bolus spillage after the injection. CONCLUSIONS AND RELEVANCE: Labial strength is reduced across the lip in patients with unilateral facial paralysis. The Iowa Oral Performance Instrument is an effective tool for measuring labial strength and can be use to evaluate the effectiveness of facial reanimation procedures. Injection augmentation of the lip is a simple and effective means of improving labial strength, bilabial sounds, and anterior spillage in patients with facial paralysis or facial muscular dystrophy. LEVEL OF EVIDENCE: 3.

Algorithmic approach to lower lid blepharoplasty.

The debate continues around transconjunctival versus transcutaneous approaches. Despite the perceived safety of the former, many experienced surgeons continue to advocate the latter. This review aims to present a balanced view of each approach. It will first address the anatomic basis of lower lid aging and then organize recent literature and associated discussion into the transconjunctival and transcutaneous approaches. The integrated algorithm employed by the senior author will be presented. Finally this review will describe less mainstream suture techniques for lower lid rejuvenation and lower lid blepharoplasty complications with a focus upon lower lid malposition.

Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma.

Human papillomavirus-associated head and neck squamous cell carcinomas (HPV-HNSCC) originate in the tonsils, the major lymphoid organ that orchestrates immunity to oral infections. Despite its location, the virus escapes immune elimination during malignant transformation and progression. Here, we provide evidence for the role of the PD-1:PD-L1 pathway in HPV-HNSCC immune resistance. We show membranous expression of PD-L1 in the tonsillar crypts, the site of initial HPV infection. In HPV-HNSCCs that are highly infiltrated with lymphocytes, PD-L1 expression on both tumor cells and CD68+ tumor-associated macrophages is geographically localized to sites of lymphocyte fronts, whereas the majority of CD8+ tumor-infiltrating lymphocytes express high levels of PD-1, the inhibitory PD-L1 receptor. Significant levels of mRNA for IFN-γ, a major cytokine inducer of PD-L1 expression, were found in HPV+ PD-L1(+) tumors. Our findings support the role of the PD-1:PD-L1 interaction in creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance once tumors are established and suggest a rationale for therapeutic blockade of this pathway in patients with HPV-HNSCC.

Molecular etiology of second primary tumors in contralateral tonsils of human papillomavirus-associated index tonsillar carcinomas.

OBJECTIVES: For patients with tobacco-related head and neck squamous cell carcinoma (HNSCC), the occurrence of a second primary tumor (SPT) is an ominous development that is attributed to a field cancerization effect and portends a poor clinical outcome. The goal of this study was to determine whether patients with human papillomavirus (HPV)-related index tonsillar carcinomas can also develop SPTs in the contralateral tonsil, and to discern the molecular etiology of HPV-related tumor multifocality. MATERIALS AND METHODS: The surgical pathology archives of The Johns Hopkins Hospital were searched for all patients with primary HPV-related tonsillar squamous cell carcinoma who developed a synchronous or metachronous carcinoma in the contralateral tonsil. The HPV-16 E6 exon was sequenced from each independent cancer site to determine whether the tumor pairs harbored the same or a different HPV-16 variant. RESULTS: Four patients with bilateral HPV-related tonsillar carcinomas were identified. In every case, the HPV DNA sequences derived from the index tumor and corresponding SPT were 100% concordant, indicating that the index and SPTs were caused by the same HPV-16 variant. CONCLUSION: For the small subset of patients with tonsillar carcinomas who develop SPTs in the contralateral tonsil, the index case and the SPT consistently harbored the same HPV variant. This finding suggests that HPV-related tumor multi-focality can be attributed either to independent inoculation events by the same virus, or by migration of HPV-infected cells from a single inoculation site to other regions of Waldeyer's ring.

Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine.

Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8(+) T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8(+) T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8(+) T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic antitumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8(+) T cells, which led to higher ratios of CD8(+)/Treg and CD8(+)/CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8(+) T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells.

Otolaryngologic manifestations of skeletal dysplasias in children.

This article reviews some of the otolaryngologic manifestations of skeletal dysplasias. Achondroplasia is discussed most comprehensively. Skeletal dysplasias are bone and cartilage disorders that disrupt the development of the long bones, craniofacial skeleton, and vertebral column, with the most notable characteristic being short stature. Children with skeletal dysplasias have various medical problems. These children often develop head and neck manifestations of their disorders. Hearing loss, middle ear disease, and respiratory difficulties are seen in these children. Otolaryngologists must be knowledgeable about these disorders to diagnose, treat, and appropriately refer children with skeletal dysplasias.

Characterization of the methylation patterns in human papillomavirus type 16 viral DNA in head and neck cancers.

Human papillomavirus (HPV) type 16 can integrate into the host genome, thereby rendering the viral coding genes susceptible to epigenetic modification. Using bisulfite genomic sequencing, we determined the methylation status of all 110 CpG sites within the viral epigenome in advanced stage III/IV HPV-16-associated head and neck cancers. We found that the viral genome was hypomethylated in the majority of head and neck cancers, in particular within the viral regulatory region, long control region (LCR), which controls transcription of the E6 and E7 oncogenes. The hypomethylation status of LCR correlated with detectable levels of E6 and E7 expression, which suggests that the tumors may still be dependent on these viral oncogenes to maintain the malignant phenotype. In addition to the methylation status of LCR, we report other potential factors which may influence intratumoral E6 and E7 expression including viral copy number and integration site. We were able to detect the viral epigenetic alterations in sampled body fluids, such as serum and saliva, which correlated with the changes observed in the primary tumors. Because viral epigenetic changes occur in the setting of viral integration into the human genome, the detection of methylated HPV genes in the serum and/or saliva may have diagnostic potential for early detection strategies of viral integration and assessment of risk for cancer development in high-risk individuals. Our findings also support continued targeting of the E6 and/or E7 antigens through various vaccine strategies against HPV-associated cancers.

Characterization of human papillomavirus type 11-specific immune responses in a preclinical model.

OBJECTIVES/HYPOTHESIS: Human papillomavirus (HPV) types 6 and 11 are associated with recurrent respiratory papillomatosis (RRP). Although a prophylactic vaccine has been developed that protects against HPV infection, a therapeutic vaccine is still needed for those patients infected with and/or suffering from persistent disease. Therefore, we developed a novel, therapeutic DNA vaccine targeting HPV-11 and characterized the in vivo immunologic responses generated against HPV-11 E6 and E7 after DNA vaccination in a preclinical model. METHODS: We generated a DNA vaccine that encodes the HPV-11 E6 and E7 genes in a pcDNA3 backbone plasmid. We then vaccinated C57BL/6 mice with the pcDNA3-HPV11-E6E7 DNA plasmid. Splenocytes were harvested from these vaccinated animals and were incubated with overlapping peptides spanning either the HPV-11 E6 or E7 protein. The frequency of interferon-gamma-releasing CD8(+) T cell responses was then analyzed by flow cytometry. RESULTS: Vaccinated mice with the HPV11-E6E7 DNA generated strong CD8(+) T cell responses against the E6(aa44-51) peptide. We determined that the epitope is presented by the MHC class I H2-K(b) molecule. No significant E7 peptide-specific T cell responses were observed. CONCLUSIONS: We developed a novel DNA vaccine that targets the E6 gene of HPV-11. Characterization of the immunologic responses elicited by this DNA vaccine reveals that the E6(aa44-51) peptide contains the most immunogenic region for the HPV-11 viral type. Knowledge of this specific T cell epitope and generation of a RRP preclinical model will allow for the development and evaluation of novel vaccine strategies targeting the RRP patient population.

Limitations of PET/CT in determining need for neck dissection after primary chemoradiation for advanced head and neck squamous cell carcinoma.

OBJECTIVE: The purpose of our study was to evaluate PET/CT in predicting residual nodal disease after primary chemoradiation (CRT) for head and neck cancer (HNSCC) with N2 disease or greater. DESIGN: A retrospective cohort analysis was conducted. Thirty-eight patients received primary CRT for HNSCC with N2 or greater disease, PET/CT after treatment and neck dissection from January 2003 to December 2006. PET/CT results were correlated with pathology results from neck dissection specimens for each respective side. RESULTS: Forty-six neck regions were analyzed. Nine were determined to have either PET/CT result reports (n = 5) or pathology reports (n = 4) that were indeterminate. PET/CT demonstrated a sensitivity and specificity of 57.1 and 73.9%, respectively, an accuracy of 67.5%, a positive predictive value of 57.1% and a negative predictive value of 73.9% when compared to the final pathology. CONCLUSION: PET/CT is neither highly sensitive nor highly specific for identifying residual nodal metastases after CRT for advanced-stage HNSCC. Physicians should not rely solely on PET/CT to determine interventions on the neck after CRT. A standardization of language for reporting findings and risk of residual disease is needed.