Trilayered Hydrogel Scaffold for Vocal Fold Tissue Engineering.

The lamina propria within the vocal fold (VF) is a complex multilayered tissue that increases in stiffness from the superficial to deep layer, where this characteristic is crucial for VF sound production. Tissue-engineered scaffolds designed for VF repair must mimic the biophysical nature of the native vocal fold and promote cell viability, cell spreading, and vibration with air flow. In this study, we present a unique trilayered, partially degradable hydrogel scaffold that mimics the multilayered structure of the VF lamina propria. Using thiol-norbornene photochemistry, trilayered hydrogel scaffolds were fabricated via layer-by-layer stacking with increasing polymer concentration from the top to middle to deep layer. Mechanical analysis confirmed that hydrogel modulus increased with increasing polymer concentration. Partially degradable hydrogels promoted high cell viability and cell spreading in three dimensions as assessed via live/dead and cytoskeleton staining, respectively. Importantly, partially degradable hydrogels maintained some degree of the three dimensional polymer network following protease exposure, while still enabling encapsulated cells to remodel their local environment via protease secretion. Finally, the trilayered hydrogel scaffold successfully vibrated and produced sound in proof-of-concept air flow studies. This work represents a critical first step toward the design of a multilayered, hydrogel scaffold for vocal fold tissue engineering.

Mortality risk in post-operative head and neck cancer patients during the SARS-Cov2 pandemic: early experiences.

PURPOSE: The objective of this report is to outline our early experience with head and neck cancer patients in a tertiary referral center, during the SARS-Cov2 pandemic, and to describe the poor outcomes of patients who acquired the infection. METHODS: In this case series from a single-center, national tertiary referral center for head and neck cancer we describe three consecutive head and neck cancer patients who contracted SARS-Cov2 during their inpatient stay. RESULTS: Of the three patients described in our case series that contracted SARS-Cov2, two patients died from SARS-Cov2 related illness. CONCLUSION: We have demonstrated the significant implications that SARS-Cov2 has on head and neck cancer patients, with 3 patients acquiring SARS-Cov2 in hospital, and 2 deaths in our that cohort. We propose a complete separation in the location of where these patients are being managed, and also dedicated non-SARS-Cov2 staff for their peri-operative management. LEVEL OF EVIDENCE: IV.

Development of xeno-free epithelial differentiation media for adherent, non-expanded adipose stromal vascular cell cultures.

INTRODUCTION: Reconstruction of respiratory epithelium is critical for the fabrication of bioengineered airway implants. Epithelial differentiation is typically achieved using bovine pituitary extract (BPE). Due to the xenogenic nature and undefined composition of BPE, an alternative for human clinical applications, devoid of BPE, must be developed. The goal of this study was to develop two different BPE-free media, with and without select pituitary hormone (PH), which could initiate epithelial differentiation for use in human implantation. METHODS: The ability of the two BPE-free media to initiate epithelial differentiation of adherent, non-expanded stromal-vascular cells grown on porcine small intestinal submucosa was compared to traditional BPE-containing media (M1). Nanostring® was used to measure differences in gene expression of stemness (MSC), basal cell (basal), and ciliated markers (muco-cil), and staining was performed support the gene data. RESULTS: Compared to baseline, both BPE-free media upregulated epithelial and stemness genes, however this was to a lower degree than BPE-containing media. In general, the expression of basal cell markers (COL17A1, DSG3, ITGA6, KRT6A, LOXL2) and secreted mucous proteins (PLUNC, MUC5B, SCGB2A1) was upregulated. The gene expression of ciliated markers C9orf24, TUBA3 and DNCL2B but not of the key transcription factor for cilagenesis FOXJ1 were upregulated, indicating that mucus-secreting cell differentiation occurs more rapidly than ciliogenesis. The ability of the adherent stromal vascular cells to upregulate gene expression of both epithelial and stemness markers suggests maintenance of the self-renewal capacity of undifferentiated and/or basal cell-like cells contributing to proliferation and ensuring a persisting source of cells for regenerative medicine applications. CONCLUSION: This study provides the initial step to defining a BPE-free epithelial differentiation medium for clinical translation. Thus, either of the proposed BPE-free medium are viable alternatives to BPE-containing medium for partial epithelial differentiation for human translational applications.

Strengthening the case for gender-neutral and the nonavalent HPV vaccine.

PURPOSE: The purpose of this review is to highlight the benefits of gender-neutral and the nonavalent human papillomavirus vaccination. Human papillomavirus infection is the most commonly sexually transmitted disease and is known to cause several types of cancers, including cervical, vulvar, vaginal, penile, oropharyngeal, anal, and rectal. 5% of cancers every year are attributable to human papillomavirus infection, with cervical cancer the most common and oropharyngeal cancer estimated to surpass the incidence of cervical cancer by 2020. METHODS: PubMed and MEDLINE were searched using the following search terms: [(human papillomavirus OR HPV) AND (vaccine OR vaccination)] AND [(gardasil OR gardasil9 OR cervarix OR quadrivalent OR nonavalent OR ninevalent) OR (gender neutral OR male)]. RESULTS: There are currently three different types of human papillomavirus vaccinations and range in cover from four to nine different strains known to cause human disease. Most countries currently only supply vaccination to females; however, recent data point towards both a personal benefit as well as a cost-effective population-based benefit with gender-neutral vaccination. Data from female vaccination only have shown the vaccine to be effective in preventing premalignant cervical lesions, and are believed to have the same effect for other human papillomavirus cancers. Male vaccination not only provides personal benefit but also has a "herd effect" for females by preventing the propagation of the virus. CONCLUSION: Gender-neutral vaccination provides significant cost-effective benefits for preventing human papillomavirus-related diseases, and this effect is further enhanced by the use of the nonavalent vaccine.

HPV overtakes smoking as the leading cause of oropharyngeal cancer in Ireland: experience of a head and neck surgery tertiary referral centre.

BACKGROUND: Worldwide, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by human papillomavirus (HPV), a sexually transmitted virus, is increasing. This increase has yet to be demonstrated in an Irish cohort. AIMS: To evaluate the number of OPSCC presentations locally, to stratify cases by HPV status and to estimate if any changes in the patient population had occurred over a 10-year period. METHODS: A STROBE-compliant, retrospective evaluation of patients with OPSCC at St James's Hospital between 2012 and 2022 was performed. Patients with non-SCC histology, undocumented HPV status and residual or recurrent tumours were excluded. RESULTS: We included 294 patients with a mean age of 60.4 years (95% CI 59.2-61.5 years) and 175 (59.5%) patients had HPV+ OPSCC. The number of new OPSCC diagnoses increased from 115 patients (39.1%) between 2012 and 2016 to 179 patients (60.9%) between 2017 and 2021. This was associated with an increased proportion of HPV-linked OPSCC (50.4% 2012-2016 vs. 65.4% 2017-2021, p = 0.011). Over time, more patients had a functionally limiting comorbidity (p = 0.011). The mean age of HPV+ OPSCC cases increased by 3.6 years (p = 0.019). Patients with HPV+ OPSCC had greater 2-year OS (83.9% vs. 54.9%; p < 0.001) and 2-year DFS (73.5% vs. 45.6%; p < 0.001). The 2-year OS and DFS did not change over time for HPV+ or HPV- patients. CONCLUSIONS: In our institution, the number of patients with OPSCC is increasing due to an escalation in cases associated with HPV. Population-level interventions such as vaccination programs may alter the current increase in the incidence of these tumours.

A multi-disciplinary team approach to pediatric malignant mandibular tumors.

OBJECTIVE: Mandibular tumors in the pediatric population are rare. These malignancies are variable in their histology, and combined with their rarity, has made it difficult to describe their clinical course, and treatment guidelines. The aim of this paper is to describe the experience of Boston Children's Hospital, a pediatric tertiary referral center, with treating malignant mandibular malignancies, as well as provide multi-disciplinary team approach in managing this clinical entity. METHODS: A retrospective search was performed for mandibular malignancies in pediatric patients between 1995 and 2020 via the pathological database at Boston Children's Hospital. Only patients with malignant solid mandibular neoplasms were included, leaving 15 patients for final analysis. RESULTS: The median age at presentation was 10.1 ± 10.3 years. Nine of 15 patients (60%) presented with jaw mass which was the most common clinical presentation. The most commonly identified histological diagnosis was rhabdomayosarcoma and osteosarcoma (n = 4, 26% each). A mandibulectomy was performed in 12 (80%) cases. Reconstruction of the mandible was performed using a fibular free flap in 6 (40%) cases, and a plate in 3 (20%) cases. Mean follow-up was 4.6 ± 4.9 years. CONCLUSION: Malignant tumors most commonly present with a jaw mass, however asymptomatic and incidental presentations follow closely and pathologies can vary greatly. Surgical resection and reconstruction is often indicated, multidisciplinary tumor board review is required to determine when children are best treated with neo-/adjuvant treatment with chemo- and radiotherapy.

Pattern of nodal metastasis of cutaneous squamous cell carcinoma involving the temporal bone.

Objective: The objective of this study was to explore the pattern of lymph-node spread of SCCs involving the temporal bone. Methods: We retrospectively reviewed all cutaneous SCCs involving the temporal bone over a 20-year time-period. Forty-one patients were eligible. Results: Mean age was 72.8 years. The diagnosis was cutaneous SCC in all cases.All patients underwent a temporal bone resection, 70.7% had a neck-dissection and 78.0% a parotidectomy.Level 2 was the most common area of neck metastasis, and occurred in 12.2%. The parotid had disease in 34.1%. 51.2% of patients underwent free-flap reconstruction.Mean overall survival of the cohort was 4.2 years. Conclusions: Overall, the rate of cervical nodal metastasis was 22.0% and 13.5% in the occult setting. The parotid was involved in 34.1% and 10.0% in the occult setting. Results from the present study support consideration for performing a parotidectomy at the time of temporal bone resection, while a neck dissection can be performed for adequate staging of the nodal basin. Level of Evidence: 3.

The role of surgery for anaplastic thyroid carcinoma in the era of targeted therapeutics: A scoping review.

Background: Questions exist regarding patient selection for surgery in anaplastic thyroid carcinoma (ATC), particularly with the advent of neoadjuvant-targeted therapeutics. The present scoping review sought to evaluate what extent of surgical resection should be performed in ATC. Methods: A scoping review was carried out in accordance with Joanna Briggs Institute and the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) protocols. Included studies were required to provide clear description of the surgery performed for ATC. Results: The final search identified 6901 articles. Ultimately only 15 articles including 1484 patients met inclusion criteria. A total of 765 patients (51.5%) underwent attempted curative intent surgery. The approach to resection of adjacent tissues varied between studies. Eight studies considered laryngeal ± pharyngeal resection (8/15, 53.3%), eight studies (53.3%) considered tracheal resection and again eight studies (53.3%) considered esophageal resection. More extensive resections increased morbidity without improving overall survival (OS) (<9 months in the 12 studies using a combination of surgery and chemoradiotherapy). In the three studies utilizing targeted therapy in addition to surgery, OS was notably improved while surgical resection following neoadjuvant therapy was less extensive. Conclusions: There is no clear agreement in the literature regarding the limits of surgical resection in locoregionally advanced ATC. A definition of surgically resectable disease will be required to guide surgical decision making in ATC, particularly with the potential to reduce tumor burden using neoadjuvant targeted treatment in suitable patients. Level of evidence: III.

Transoral robotic surgery in Ireland: the beginning.

BACKGROUND: Transoral robotic surgery (TORS) has shown promising results in the treatment of myriad head and neck pathologies but is now most commonly used in the investigation and management of oropharyngeal squamous cell carcinoma. AIMS: The aim of this study was to report our cases of the newly introduced TORS, particularly its role in identifying primary of unknown origin and the potential implications for patients. A literature review and our early experience should begin to debunk some of the criticisms of TORS including setup times and cost. METHODS: Prospective data was collected from all patients undergoing transoral robotic surgery including demographics, indication, histology results in primary of unknown origin and complications. RESULTS: We have performed 36 TORS procedures in total ranging from intermediate to major complex. Our complication rate is low, and this has improved with the passage of time. Haemorrhage rates remain at 5.6% (n = 2), and the average length of stay is 1 day. Successful identification of a primary tumour in cancer of unknown primary was 80% (n = 8). CONCLUSIONS: We anticipate the integration of TORS into routine practice in the investigation and management of a number of ENT pathologies following robust clinical trials.

Differences in patient satisfaction with virtual telephone clinics in a tertiary referral centre for otolaryngology during and after lockdown measures during the SARS-Cov2 pandemic.

INTRODUCTION: The SARS-Cov2 pandemic has caused considerable disruption to provision of routine outpatient care. This pandemic has necessitated a more modern and innovative approach to clinics, which could potentially change outpatient organisation and improve efficiency in the long term. Telephone clinics are the most practical way to deliver healthcare at a distance. AIM: The purpose of the present study was to assess patient satisfaction with a virtual telephone clinic in a tertiary referral centre for otolaryngology first during the height of the SARS-Cov2 pandemic, and subsequently at a physical follow-up appointment after easing of "lockdown" measures. METHODS: Patients were enrolled prospectively via a telephone interview over a 1-week period during the height of the "lockdown" measures, and subsequently at a physical appointment when measures eased. RESULTS: Overall, patients responded very positively in the anonymised questionnaire at the time of their virtual appointment. However, at a subsequent physical appointment, there was a reduction in overall favourable responses from patients. While patients still thought virtual clinics were a good idea and convenient in the context of SARS-Cov2, we noted a reduction in satisfaction in other key aspects of their care. Notably, patients were less likely to think that virtual clinics were able to properly address their condition. CONCLUSION: While virtual clinics remain a useful tool during the height of lockdown measures during the SARS-Cov2 pandemic, we did note a significant reduction in favourable responses to virtual appointments over physical ones upon easing of lockdown measures. Patients remained cautious in suggesting that outpatient appointments may be replaced by virtual clinics.

Impact of the COVID-19 Pandemic on Pelvic and Acetabular Trauma: Experiences From a National Tertiary Referral Centre.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on daily life. Restrictions imposed to help minimise virus transmission have limited both population movement and employment, as well as altering the potential mechanisms of high-energy trauma. The objective of this study was to assess the impact of the COVID-19 pandemic on pelvic and acetabular trauma. Materials and methods A retrospective observational study of the incidence, causality, patient profile, fracture morphology, and treatment strategy of pelvic and acetabular trauma managed in a national tertiary referral specialist pelvic and acetabular centre between the 1st of March and 1st of August 2020 was undertaken and compared to corresponding time periods in the two preceding years. Results A total of 78 patients were referred for management following pelvic and acetabular trauma during the study period with a mean age of 52 years (SD +/- 24.2). Overall, 45% and 42% of patients were referred following isolated pelvic or acetabular fractures respectively. The most frequent mechanism of injury was a fall from height (>1m) (42%), with 53% of patients suffering from concomitant injuries and 32% requiring surgical management. While there was a statistically significant difference in mechanism of injury (P=0.026), there was no significant difference in overall incidence, fracture types, incidence of concomitant injuries, or overall proportion requiring surgical intervention during the study period when compared to previous years. Conclusion While some variation in the mechanisms of injury have been observed, the overall incidence, patient, fracture, and injury profiles associated with pelvic and acetabular trauma appear to have remained consistent during the COVID-19 pandemic. Additionally, the number and proportion of those requiring surgical treatment of these fractures have remained stable. Understanding the continued burden of these potentially severe injuries may help guide injury prevention, treatment, and resource allocation as the pandemic continues.

Supporting the use of adjuvant radiotherapy in recurrent pleomorphic adenoma of the parotid.

BACKGROUND: The use of adjuvant radiotherapy remains controversial in the treatment of recurrent pleomorphic adenomas. AIMS/OBJECTIVES: The aim of this study was to provide the highest level of evidence possible by performing a systematic review and meta-analysis of the literature. MATERIAL AND METHODS: We searched the English-language literature between 1985 and 2019.Inclusion criteria included any study on the treatment and outcome of recurrent pleomorphic adenomas. Exclusion criteria included the use of radiotherapy for residual tumors, case reports, and pleomorphic adenomas not arising from the parotid. RESULTS: A total of 522 abstracts were studied, data analyzed from 14 studies, on a total of 697 patients. When the data werepooled, the overall risk of further recurrence was 21%. In studies where surgery alone was undertaken this increased to 26% and decreased to 10% in those receiving adjuvant radiotherapy (p = .000). There were 21 recurrences in 159 patients in the radiotherapy group, and 151 recurrences out of 538 patients in the surgery group (p < .0001). CONCLUSIONS: These data support the use of radiotherapy to decrease the risk of re-recurrence in recurrent pleomorphic adenoma. SIGNIFICANCE: This study is the highest level of evidence currently available in guiding management of recurrent pleomorphic adenoma.

The impact of repetitive hyperbaric exposure during SCUBA diving on cochlear implants.

OBJECTIVES/HYPOTHESIS: Complications during or after cochlear implantation are relatively rare. They occur more frequently in patients who partake in activities that can potentially lead to local trauma. No formal recommendations exist for participation in self-contained underwater breathing apparatus (SCUBA) activities. We describe three patients with a combined five cochlear implants and extensive diving experience, the largest case series to date, and highlight some of the difficulties faced. We also review the literature on previously described SCUBA-diving patients with cochlear implants. STUDY DESIGN: Retrospective case series and literature review. METHODS: A review of the known SCUBA divers in the National Hearing Implant and Research Centre in Ireland was conducted, and a review of the literature was carried out using PubMed and Google Scholar. RESULTS: Of the three SCUBA divers with cochlear implants, two required reimplantation, the first due to nonauditory stimulation, and the second due to extrusion of the electrode through the tympanic membrane following repetitive SCUBA dives. The third patient remains without complications after 80 dives. CONCLUSIONS: Patients with cochlear implants can have complications relating to the implant itself, with device failure a theoretical risk. The cochleostomy can lead to perilymphatic extravasation, as well as inner ear barotrauma, decompression sickness, and formation of air bubbles along the electrode. A combination of deafness, vestibulopathy with abrupt perilymph leak, and loss of proprioception can lead to disorientation and blue dome syndrome. Based on our experience with cochlear implants in SCUBA divers, along with those reported in the literature, we recommend caution in patients with cochlear implants who SCUBA dive regularly and strict adherence to the recommended safety limits. LEVEL OF EVIDENCE: 4 129:2760-2764, 2019.

Computed Tomography Data to Generate a Reproducible, Anatomically Accurate Hemilaryngeal Model.

OBJECTIVE: The study aims to demonstrate the reproducibility and feasibility of creating a hemilaryngeal model with a medialized vocal fold (VF) using 3-dimensional (3D) modeling techniques in both healthy larynges and those affected by cancer. STUDY DESIGN: Three-dimensional modeling of human larynges. SETTING: Tertiary academic referral center and regenerative medicine laboratory. SUBJECTS AND METHODS: Computed tomography (CT) scans from 10 healthy control and 10 patients with laryngeal cancer were segmented and imported into 3D modeling software. The larynx was cut sagittally to create a hemilaryngeal model and the vocal fold medialized. Measurements were taken from the CT and 3D model data and compared. RESULTS: All control modeling data closely matched the CT data and were not statistically different from each other. There was a significant correlation between subglottic anteroposterior diameter and VF length (r2 = 0.78, P = .0008), and it may be a valuable tool to infer true VF dimension in cases where disruption has occurred. The modeling data from patients with cancer did not show statistical difference to the control data, showing that accurate modeling can also be achieved in patients with laryngeal cancer. CONCLUSION: CT scan-based 3D modeling of the larynx and VF is possible and reproducible. The results closely match those previously reported in the literature and can also be replicated in cases with laryngeal cancer. This study paves the way for future de novo fabricated laryngeal scaffolds that can be synthesized using 3D printers and tailored to meet surgical demands.

Sarcoidosis Presenting as Bilateral Vocal Fold Immobility.

Bilateral true vocal fold paralysis is rarely attributable to inflammatory diseases. Sarcoidosis is a rare but important etiology of bilateral true vocal fold paralysis by compressive lymphadenopathy, granulomatous infiltration, and neural involvement. We describe the first reported case of sarcoidosis presenting as bilateral vocal fold immobility caused by direct fixation by granulomatous infiltration severe enough to necessitate tracheostomy insertion. In addition, we discuss the presentation, the pathophysiology, and the treatment of this disease with a review of the literature of previously reported cases of sarcoidosis-related vocal fold immobility. Sarcoidosis should therefore be an important consideration for the otolaryngologist's differential diagnosis of true vocal fold immobility.

Paratesticular myositis ossificans of the spermatic cord.

A 56-year-old man presented with a painless scrotal lump, enlarging over the preceding 1 month. The lump was roughly 1 cm in size, and located in his left hemiscrotum and separate from the testis. An ultrasound revealed an echogenic focus with dystrophic tissue calcification. Subsequent surgical excision and histopathological analysis revealed it to be late-stage myositis ossificans, a benign, extraosseous formation of the bone or cartilage. We report of only the second described case of myositis ossificans of the spermatic cord in the literature to date.

Tracheal decellularization using a combination of chemical, physical and bioreactor methods.

INTRODUCTION: The purpose of this study was to compare different decellularization protocols with the conventional detergent enzymatic method (DEM) using continuous agitation. METHODS: The first experiment compared conventional DEM with sonication and lyophilization+freeze-thaw cycles. A second experiment was carried out to compare time-adjusted DEM (2-hour instead of 4-hour incubations with 4% deoxycholate) to decellularization in a bioreactor. Cellularity was determined by DNA-quantitation, H&E-staining and immunostaining for major histocompatibility complex-1 (MHC-1). RESULTS: Compared to untreated trachea, DNA content significantly decreased after 2 cycles in all groups in the first experiment and dropped below the minimal criteria for efficient decellularization (<50 ng dsDNA/mg dry weight) after 4 cycles. However, nuclei were seen in the cartilage and MCH-1 staining was detected in some submucosal areas, indicating presence of chondrocytes and cellular residues that may render the scaffold immunogenic. In the second experiment DNA content significantly decreased after 1 cycle in both groups; however, even after 4 cycles, DNA content was above the minimal criteria for efficient decellularization. While collagen-levels remained stable, glycosaminoglycans diminished significantly after the initial cycles. CONCLUSIONS: Efficient decellularization can be achieved after only 4 cycles of DEM compared to the 17 cycles previously reported. The use of a bioreactor can preserve the integrity of the extracellular matrix.

Distant melanoma causing small bowel obstruction.

Small bowel obstructions (SBOs) are common. Adhesions make up the majority of cases at 84.9%, followed by abdominal herniae and malignancies. A 71-year-old female presented with total constipation, abdominal distension, on a background of resected cutaneous melanoma nine years prior. A CT-scan showed small bowel intussusception and disseminated mucosal-enhancing lesions consistent with metastases. She was brought to the operating theatre where six areas of intussusception were identified and manually reduced. Biopsies confirmed the diagnosis of melanoma. Melanoma of the gastrointestinal tract (GIT) is rare, with most cases occurring as metastasis from cutaneous lesions. Melanomas of the GIT are usually asymptomatic in their early stages, and are often diagnosed when complications, such as obstruction or perforation occur. Management of such cases consists mainly of surgical intervention to resolve the complication. In people who present with SBO without previous surgeries or herniae, a malignant cause must be considered.