Adjuvant Human Papillomavirus Vaccination in Recurrent Respiratory Papilloma Patients Older than 45.

OBJECTIVES: The primary objective was to examine the intersurgical interval (ISI) of recurrent respiratory papillomatosis (RRP) in patients older than 45 years before and after a Gardasil vaccination series. METHODS: We conducted a retrospective chart review of adult patients >45 years of age diagnosed with RRP from 2012 to 2022. Patients were excluded if they did not receive at least two doses of the Gardasil vaccine series or if they underwent two or fewer surgeries during the study period. RESULTS: Thirteen patients met the inclusion criteria, 11 males and two females. The age at initial diagnosis ranged from 46 to 80 years, with a mean of 59 years. There was a significant increase in the average ISI, from 126 ± 87 days pre-vaccination compared to 494 ± 588 days post-vaccination (p < 0.01). The average number of surgeries per patient was 6.8 ± 2.4 over an average follow-up of 49.7 ± 30.3 months. CONCLUSION: Adjuvant Gardasil use in RRP patients older than 45 years significantly increases the ISI. Current CDC recommendations include only patients ages 9 to 45, but this study provides evidence that RRP patients outside this age range may benefit from adjuvant HPV vaccination. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3226-3229, 2024.

Novel Pannexin 1 isoform is increased in cancer.

Pannexin 1 (PANX1) is upregulated in many cancers, where its activity and signalling promote tumorigenic properties. Here, we report a novel ∼25 kDa isoform of human PANX1 (hPANX1-25K) which lacks the N-terminus and was detected in several human cancer cell lines including melanoma, osteosarcoma, breast cancer and glioblastoma multiforme. This isoform was increased upon hPANX1 CRISPR/Cas9 deletion targeting the first exon near M1, suggesting a potential alternative translation initiation (ATI) site. hPANX1-25K was confirmed to be a hPANX1 isoform via mass spectrometry, can be N-linked glycosylated at N254, and can interact with both ß-catenin and full length hPANX1. A double deletion of hPANX1 and hPANX1-25K reduces cell growth and viability in cancer cells. hPANX1-25K is prevalent throughout melanoma progression, and its levels are increased in squamous cell carcinoma cells and patient-derived tumours, compared to keratinocytes and normal skin, indicating that it may be differentially regulated in normal and cancer cells.

Smoking and Carcinoma Trends in Recurrent Respiratory Papillomatosis Patients.

INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a chronic disease of the upper respiratory tract caused by human papillomavirus types 6 and 11. The disease course is characteristically unpredictable, ranging from spontaneous remission to aggressive, recurrent disease. Thus, management is often challenging and requires unique approaches tailored to each individual patient. While recent literature has described risk factors for more aggressive disease, few sources have investigated the impact of smoking on RRP disease course and risk for malignant transformation. METHODS: A retrospective chart review was conducted for adult RRP patients evaluated at an academic tertiary care center between 2005 and 2020. A total of 188 patients were identified. Demographic and clinical data were collected, including smoking and alcohol history, HPV subtype, history of dysplasia and/or carcinoma, voice handicap index scores, Derkay scores, debulkings (in office and operating room), and days to papilloma recurrence. RESULTS: Malignant degeneration in RRP occurred in 16.3% of smokers and 3.6% of nonsmokers. Smokers who developed carcinoma had less debulkings per years of evaluation than those not developing carcinoma (0.21 vs 0.92, P = .004). Additionally, patients that either presented with or developed carcinoma during their course had a higher pack-year smoking history (18.0 vs 12.21, P = .0002). No difference in days to recurrence or inter-surgical interval was demonstrated between smokers and nonsmokers. CONCLUSIONS: The report demonstrates that smoking can increase the risk of malignant transformation in RRP patients.

Recurrent respiratory papillomatosis disease course in immunosuppressed populations.

OBJECTIVE: Recurrent respiratory papillomatosis is a benign manifestation of human papillomavirus types 6 and 11 in the respiratory tract. Disease is recurrent, and factors predicting these recurrences and severity of disease are incompletely characterised. This retrospective cohort study examined the relationship of immunosuppression with recurrent respiratory papillomatosis morbidity. METHODS: A retrospective cohort of 97 adult patients with recurrent respiratory papillomatosis treated at a tertiary referral centre from 2005 to 2020 was conducted. Measures assessed included inter-surgical interval, Voice Handicap Index ('VHI-10') and anatomical Derkay scores. RESULTS: Bivariate analyses comparing average inter-surgical interval, Voice Handicap Index and Derkay scores in immunosuppressed and healthy patients were insignificant. When controlling for diabetes mellitus and comparing immunosuppressed to healthy patients, inter-surgical interval and Voice Handicap Index change were insignificant (p = 0.458 and p = 0.465, respectively). CONCLUSION: Recurrent respiratory papillomatosis morbidity for immunosuppressed patients did not significantly differ from that of immunocompetent patients.

Outcomes with culture-directed antibiotics following microvascular free tissue reconstruction for osteonecrosis of the jaw.

OBJECTIVES: Radiation (ORNJ) and bisphosphonate-related (BRONJ) osteonecrosis of the jaw represent challenging entities to treat, with many patients requiring segmental resection and reconstruction with microvascular free tissue transfer (MFTT) in the setting of failed conservative therapy. Microvascular reconstruction is associated with higher post-operative complication rates when performed for advanced osteonecrosis versus oncologic defects. We hypothesize that basing antibiotic therapy on cultures obtained from the healthy bone marrow following resection during MFTT for ORNJ or BRONJ reduces rates of post-operative wound and surgical complications. MATERIALS AND METHODS: In a retrospective cohort study spanning January 2016 to October 2018, 44 patients undergoing MFTT for ORNJ or BRONJ were identified. Patients were categorized into two cohorts: residual healthy marrow culture (n = 11; RHM), treated with antibiotics guided by cultures from healthy appearing mandible, and all others (n = 33; AO), treated with antibiotics guided by cultures from resected necrotic bone or purulent drainage. Patient, reconstruction, and outcome variables were compared via appropriate statistical tools. RESULTS: 81.8% of the RHM cohort versus 24.2% of the AO cohort received long-term IV antibiotics. Rates of post-operative wound complications, including those necessitating operative management, were significantly lower in the RHM cohort. Rates of flap failure were similar across both groups. CONCLUSION: Administration of long-term IV antibiotics directed by native mandible cultures may decrease complication rates following MFTT for ORNJ or BRONJ by treating residual, smoldering infection. Concurrently, transplantation of well-vascularized free tissue likely improves antibiotic delivery. Findings are crucial for the development of a standardized treatment algorithm following microvascular reconstruction for advanced osteonecrosis.

Patient-Directed Home Drain Removal in Head and Neck Surgery.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to evaluate the efficacy and safety of at home drain removal in head and neck surgery patients. METHODS: The study population included patients who underwent head and neck surgery at an academic tertiary care center between February 2020 and November 2020 and were discharged with one to four drains with instructions for home removal. Prior to discharge, patients received thorough drain removal education. Patients were prospectively followed to evaluate for associated outcomes. RESULTS: One hundred patients were evaluated in the study. There was record for ninety-seven patients receiving education at discharge. The most common methods of education were face-to-face education and written instructions with educational video link provided. Of 123 drains upon discharge, 110 drains (89.4%) were removed at home while 13 (10.6%) were removed in office. Most drains were located in the neck (86.4%). There was one seroma, two hematomas, two drain site infections, and five ED visits; however, none of these complications were directly associated with the action of drain removal at home. Calculated cost savings for travel and lost wages was $259.82 per round trip saved. CONCLUSIONS: The results demonstrate that home drain removal can provide a safe and efficacious option for patients following head and neck surgery. This approach was safe and associated with patient cost savings and better utilization of provider's time. Furthermore, patients and healthcare providers avoided additional in-person encounters and exposures during the COVID-19 pandemic. Our findings warrant further investigation into cost savings and formal patient satisfaction associated with home drain removal. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2471-2477, 2021.

ADHD, depression, and substance abuse risk among beginning college students.

Objective: This study examined differences in substance use, depression, and academic functioning among ADHD and non-ADHD college students. Participants: Included 1,748 students (ages 18-25; women 68.4%; Caucasian 71.3%) with and without history of ADHD. Methods: We assessed the relationship of ADHD to substance use variables, controlling for depressive symptoms and examined relationships with GPA. Results: ADHD students were more likely to have engaged in frequent alcohol use, binge drinking, regular marijuana use and to have used other drugs in the last year. They reported higher depression symptoms than non-ADHD students, although substance abuse risk remained high even when controlling for depressive symptoms. ADHD students had lower overall GPA than those without ADHD. However, this difference was no longer significant when controlling for depression and marijuana use. Conclusions: College campuses should consider programing aimed at identifying ADHD students at risk for developing substance abuse problems and emotional difficulties.

The Use of Vasopressor Agents in Free Tissue Transfer for Head and Neck Reconstruction: Current Trends and Review of the Literature.

BACKGROUND/OBJECTIVES: Microvascular free tissue transfer has become essential to head and neck reconstruction and recent advancements in microvascular surgery have led to excellent surgical outcomes. However, there continues to be controversy and a stigma associated with the use of perioperative intravenous vasopressor agents among both surgeons and anesthesiologists. Due to concern for vasoconstriction of peripheral vasculature flowing to the denervated tissue flap, there remains concerns about potential thrombosis, decreased tissue perfusion and ultimately flap failure. This topic becomes even more important as vasopressors play an essential role in new Extended Recovery After Surgery (ERAS) protocols being put in place to optimize postoperative recovery for patients. The purpose of this study was to comprehensively review the role and safety as well as discuss current trends with intraoperative vasopressor agents in free tissue transfer for head and neck reconstruction. METHODS: A scoping literature review was conducted of all studies that examined the use of vasopressor agents during head and neck free flap tissue transfer. Primary and secondary outcomes included free flap survival, arterial thrombosis, venous congestion, need for revision surgery, and other postoperative complications. RESULTS: One prospective and nine retrospective studies were identified. Phenylephrine and ephedrine were the most common vasopressors reported; the rate of vasopressor use ranged from 53% to 85% and administration methods included both bolus and infusion. The included studies did not show any significant association between the use of vasopressors and free flap failure, pedicle thrombosis, or other flap complications. CONCLUSION: The administration of vasopressors during microvascular free tissue transfer for head and neck reconstruction does not seem to be associated with increased flap failure rates or other postoperative morbidities. Moreover, vasopressors may provide overall improved hemodynamic stability and help to limit overall fluid administration and subsequent postoperative complications. Additional prospective investigation is warranted to further elucidate and establish evidence-based recommendations regarding the type, timing, and dose of vasopressors to further enhance free flap survival and patient outcomes.

Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells.

Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of disease progression, as well as in patient-derived cells and established melanoma cell lines. Reducing PANX1 protein levels using shRNA or inhibiting channel function with the channel blockers, carbenoxolone (CBX) and probenecid (PBN), significantly decreased cell growth and migration, and increased melanin production in A375-P and A375-MA2 cell lines. Further, treatment of A375-MA2 tumors in chicken embryo xenografts with CBX or PBN significantly reduced melanoma tumor weight and invasiveness. Blocking PANX1 channels with PBN reduced ATP release in A375-P cells, suggesting a potential role for PANX1 in purinergic signaling of melanoma cells. In addition, cell-surface biotinylation assays indicate that there is an intracellular pool of PANX1 in melanoma cells. PANX1 likely modulates signaling through the Wnt/ß-catenin pathway, because ß-catenin levels were significantly decreased upon PANX1 silencing. Collectively, our findings identify a role for PANX1 in controlling growth and tumorigenic properties of melanoma cells contributing to signaling pathways that modulate melanoma progression.