Associations Between Risk Perception and HPV Knowledge and Vaccine Uptake: Highlighting the LGBTQ+ Population.

INTRODUCTION: Gay and bisexual males and other LGBTQ+ communities are more frequently exposed to factors associated with an increased risk of human papillomavirus (HPV) acquisition. Vaccination is critical to protect against HPV+ head and neck cancer (HNC). We characterized the association of perceived level of risk of contraction with HPV knowledge, and vaccine decision-making. STUDY DESIGN: Cross-sectional cohort. SETTING: LGBTQ and general survey Reddit forums (control). METHODS: A survey was shared amongst the online forums. Descriptive statistics characterized the data. Multivariable logistic regression was used to understand factors associated with vaccination, self-perceived high risk, and knowledge of HPV + HNC. RESULTS: Of 718 respondents, most were female (41.09%), Caucasian (59.89%), college-educated (33.01%), and insured (77.15%) with a mean age of 30.75 years. Half were vaccinated (49.16%), with most unvaccinated endorsing interest (60.58%). Few dependents were vaccinated (25.91%), with interest in vaccination among parents of unvaccinated children (38.58%). Knowledge of HIV's association with HPV (62.95%), HPV causing HNC (55.57%), and the vaccine's efficacy against HNC (55.57%) was also moderate. Identifying female (P = .042), a self-perceived high-risk (P < .001), and having vaccinated children (P < .001) increased vaccination likelihood; transgender (P = .021), or lesbian or gay sexual identity (P < .001) decreased likelihood. Personal HNC diagnosis (P < .001), self-vaccination (P < .001), having vaccinated children (P < .001), having anal sex (P = .001) or no knowledge of past HPV status (P < .001) increased likelihood of high self-perceived risk. CONCLUSION: Efforts to improve public education regarding the association between HPV and HNC and vaccination efficacy are required to better inform vaccine decision-making among individuals at risk for HPV infection.

Differences in presentation, treatment, and outcomes among minority head and neck cancer patient groups in Los Angeles County.

IMPORTANCE: While minorities represent around 20 % of all HNC patients, these demographics are largely understudied. Furthermore, trends in national studies may not always be fully replicated in locoregional populations, indicating a need for more nuanced study. OBJECTIVE: To better understand our patient population, we sought to understand differences in presentation, management, and outcome between Caucasians and minority groups with HNC. DESIGN: Retrospective cohort analysis of the Los Angeles County Surveillance Epidemiology and End Results (SEER) database. SETTING: Los Angeles County. PARTICIPANTS: All patients in Los Angeles County diagnosed with cancer of the head and neck from January 1, 1988 to December 31, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome in our study was significant differences between racial and ethnic groups in age of diagnosis, sex, socioeconomic quintile, insurance status, stage at diagnosis, treatment modality, time to first treatment, and cancer-specific cause of death. RESULTS: Our 18,510-patient cohort was largely male (64.35 %), white (69.57 %), and were on average 62.84 years old (SD = 20.07). When stratifying patients by race and ethnicity, significant differences were found in average age at diagnosis, sex, socioeconomic quintile, insurance status, and stage at diagnosis, treatment modalities utilized, and time to first treatment (all p < 0.001). Relative to all other head and neck patients, minority groups were significantly younger, had lower proportions of male patients, were less likely to pursue surgery, were more likely to pursue chemotherapy or radiation, and endorsed longer time to first treatment (all p < 0.001). The distribution of socioeconomic quintile (all p < 0.001), insurance status (all p < 0.001), and stage at diagnosis (all p < 0.05) also significantly varied between minority and reference groups. Only African Americans exhibited significantly higher rates of cancer-specific cause of death relative to non-African Americans (p < 0.001). CONCLUSIONS AND RELEVANCE: Pervasive socioeconomic disparities between Caucasian HNC patients and those of other minority racial and ethnic groups in Los Angeles County that likely and significantly impact the diagnosis and management of HNC and its resultant outcomes. We encourage others to similarly examine their local populations to tailor the quality of care provided to patients.

Virtual Versus In-Person Head and Neck Physical Examination Training in Medical Students: A Pilot Assessment.

OBJECTIVE: To compare the effect of virtual and in-person head and neck physical examination training events on medical student confidence in performing examination maneuvers and seeking mentorship from otolaryngology faculty and residents. METHODS: Training events were held with first-year medical student volunteers in 2020 (in-person) and 2021 (virtual). Participants in both cohorts were given didactics on head and neck cancer, trained to perform a head and neck physical examination, and demonstrated their clinical skills to otolaryngology faculty and residents. Pre- and post-training surveys were utilized to assess the following outcomes: participant head and neck cancer knowledge, confidence in performing examination maneuvers, and confidence in seeking mentorship in otolaryngology. Differences in outcomes between training settings were assessed by comparing participant survey responses pre- and post- training. RESULTS: Both in-person and virtual training modalities improved participant confidence in performing the physical examination. There was no significant difference in the degree of improvement between training types. In-person training significantly increased participant confidence in seeking mentorship from otolaryngology faculty and residents (P = .003), while virtual training did not (P = .194). CONCLUSION: Virtual training modalities are feasible methods of teaching the head and neck physical examination. Instruction through a video conferencing platform has the potential to be incorporated into traditional in-person medical education in a permanent fashion. This pilot study can inform future studies directly comparing in-person and virtual physical examination training modalities.

Restoration of atypical protein kinase C ζ function in autosomal dominant polycystic kidney disease ameliorates disease progression.

Autosomal dominant polycystic kidney disease (ADPKD) affects more than 500,000 individuals in the United States alone. In most cases, ADPKD is caused by a loss-of-function mutation in the PKD1 gene, which encodes polycystin-1 (PC1). Previous studies reported that PC1 interacts with atypical protein kinase C (aPKC). Here we show that PC1 binds to the ζ isoform of aPKC (PKCζ) and identify two PKCζ phosphorylation sites on PC1's C-terminal tail. PKCζ expression is down-regulated in patients with ADPKD and orthologous and nonorthologous PKD mouse models. We find that the US Food and Drug Administration-approved drug FTY720 restores PKCζ expression in in vitro and in vivo models of polycystic kidney disease (PKD) and this correlates with ameliorated disease progression in multiple PKD mouse models. Importantly, we show that FTY720 treatment is less effective in PKCζ null versions of these PKD mouse models, elucidating a PKCζ-specific mechanism of action that includes inhibiting STAT3 activity and cyst-lining cell proliferation. Taken together, our results reveal that PKCζ down-regulation is a hallmark of PKD and that its stabilization by FTY720 may represent a therapeutic approach to the treat the disease.

Use of ICG Angiography in Head and Neck Reconstruction With the Supraclavicular Artery Island Flap.

PURPOSE: Adequate distal skin paddle perfusion is essential to preventing postoperative flap necrosis in head and neck reconstruction. To describe the use of indocyanine green angiography (ICGA), to assess skin paddle perfusion in the setting of head and neck reconstruction with the supraclavicular artery island flap at a single institution and assess the effect of ICGA use on the rate of postoperative skin paddle necrosis. METHODS: A retrospective cohort study consistently of patients who underwent head and neck reconstruction with a supraclavicular artery island flap for any indication at a tertiary medical center from 2010 to 2018. The predictor variable was ICGA use. The primary outcome was rate of skin paddle necrosis. Secondary outcomes included rates of post-operative overall complications, dehiscence, fistula, and reoperation. Covariates included demographic, operative, flap perfusion assessment, and postoperative variables. Retrospective assessment of distal flap perfusion was performed on available ICGA video recordings. Descriptive and bivariate statistics were computed. Statistical significance was set at P ≤ .05. RESULTS: A total of 104 patients were included and ICGA was used in 23 cases. In 10 of these cases, flap trimming was performed due to concern of flap hypoperfusion on ICGA. The median relative distal flap perfusion was 16.7 ± 2.6% in trimmed flaps, compared to 35 ± 13.2% in untrimmed flaps. ICGA use was not associated with rate of skin paddle necrosis (P = .76). CONCLUSIONS: ICGA is a viable method of assessing intraoperative supraclavicular artery island skin paddle perfusion and can help determine the need for distal flap trimming when tissue viability based on clinical findings alone is uncertain. ICGA use for skin paddles with uncertain perfusion on intraoperative clinical findings prevented a potential increase in postoperative necrosis compared to that of skin paddles with adequate perfusion on intraoperative clinical findings. Future studies are required to determine the minimum distal perfusion value that indicates hypoperfusion and the need for flap modification.

Supraclavicular Artery Island Flap: Critical Appraisal and Comparison to Alternate Reconstruction.

OBJECTIVES/HYPOTHESIS: The supraclavicular artery island (SAI) flap may be a good option for selected head and neck reconstruction due to its reliability, ease of harvest, and favorable color match. The objective of this study was to examine the rates of complications for the SAI flap in head and neck oncologic reconstruction, with examination of risk factors and comparisons to alternative flaps often considered the gold-standard soft-tissue flaps for head and neck reconstruction: the pectoralis myocutaneous (PMC), radial forearm free flap (RFFF), and anterolateral thigh (ALT) flaps. STUDY DESIGN: Retrospective cohort study. METHODS: Consecutive SAI flaps were compared to PMC, RFFF, and ALT flaps (non-SAI flap group), all performed by the senior author from 2010 to 2018. The non-SAI flaps were included if an SAI flap could have been performed as an alternate flap. The groups were compared based on demographics, flap dimensions, site of reconstruction, operating time, total hospital stay, total hospital costs, and complications. RESULTS: One hundred seven SAI flaps and 194 non-SAI flaps were identified. SAI flaps were used less commonly than non-SAI flaps for mucosal defects (P < .001). The SAI flap dimensions were narrower but longer than non-SAI flaps (P < .001). SAI flaps had higher rates of total complications, partial flap necrosis, flap dehiscence at the recipient site, fistula, donor site dehiscence, and minor complications compared to non-SAI flaps (all P < .05). SAI flaps had higher rates of total complications, recipient site dehiscence, fistula, and minor complications in both the oral cavity and all mucosal sites compared to non-SAI flaps (all P < .05). SAI flaps for mucosal reconstruction were associated with higher rates of total complications (54% vs. 34%, P = .04), flap dehiscence at the recipient site (32% vs. 14%, P = .03), and major complications (21% vs. 5%, P = .02), compared to cutaneous reconstruction. Complications were equivalent between SAI flaps and non-SAI flaps for cutaneous reconstruction (all P > .05). Multivariate analysis showed that SAI flaps were associated with any postoperative complication (odds ratio [OR]: 3.47, 95% confidence interval [CI]: 1.85-6.54), partial flap necrosis (OR: 5.69, 95% CI: 1.83-17.7), flap dehiscence (OR: 5.36, 95% CI: 2.29-12.5), donor site complications (OR: 11.6, 95% CI: 3.27-41.0), and minor complications (OR: 5.17, 95% CI: 2.42-11.0). Within the SAI flap group, SAI flap length >24 cm was associated with postoperative complications on multivariate analysis (OR: 5.09, 95% CI: 1.02-25.5, P = .048). CONCLUSIONS: The SAI flap is best suited for cutaneous reconstruction of the face, neck, and parotid/temporal bone regions due to the favorable color match; the thin, pliable nature of the skin; ease of harvest; and equivalent complication rates compared to alternate soft-tissue flaps. However, the SAI flap is associated with more complications for oral cavity and mucosal site reconstruction when compared to RFFF and ALT flaps and should be used in selected cases that do not require complex folding. For all sites, flaps longer than 24 cm should be used with caution. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:S1-S14, 2022.

18FDG-PET/CT Specificity for the Detection of Lymphoma Recurrence in the Tonsils.

OBJECTIVE: In patients with a history of lymphoma who demonstrate palatine tonsil uptake on posttreatment PET/CT (positron emission tomography/computed tomography), tonsillectomy is often performed to evaluate for lymphoma recurrence. However, predictive clinical and imaging factors for true tonsil recurrence in this setting are not well established; this will be explored herein. STUDY DESIGN: Retrospective case series. SETTING: Patients treated at a tertiary medical center from January 2008 to May 2020. METHODS: Chart review was performed on all patients with a history of treated lymphoma in clinical remission who presented for evaluation of abnormal PET/CT imaging findings and subsequently underwent tonsillectomy. RESULTS: Among 15 patients who met inclusion criteria, 14 had benign findings on surgical pathology, yielding a false-positive rate of 93%. The patient with malignancy was identified on biopsy after inconclusive surgical pathology and is the only documented case of recurrence in this specific patient population throughout the literature. The patient presented with B symptoms, irregularly shaped tonsils, increased lymph node activity on PET/CT, and uptrending bilateral tonsil activity but with one of the lowest maximum standardized uptake values of the cohort. The singular distinguishing feature for the patient with recurrent disease was a prior tonsil biopsy suspicious for recurrence, which prompted the otolaryngology referral. CONCLUSION: PET/CT lacks specificity in identifying lymphoma recurrence in the oropharynx. Clinical and radiographic features that were previously considered concerning for recurrence are most likely not indicative of malignancy in this patient population. Our findings call into question whether tonsillectomy should be routinely performed in this patient population.

Risk Factors for Plate Extrusion After Mandibular Reconstruction With Vascularized Free Flap.

PURPOSE: Plate extrusion after mandibular reconstruction is a complication that imposes significant morbidity on the patient. The goal of this study is to estimate the incidence of plate extrusion after mandible reconstruction with a vascularized free flap and to identify the factors associated with plate extrusion. METHODS: This was a retrospective cohort study involving patients who underwent mandibular reconstruction from October 2008 to July 2019 at LAC + USC or Keck Hospital of USC. Inclusion criteria were age ≥ 18 years, single-stage mandibular reconstruction with vascularized free flap, and follow-up of at least 12 months. Relevant demographic, intraoperative, and postoperative data were collected. The primary outcome was postoperative plate extrusion within the 12-month follow-up. Descriptive, univariate, and multivariate analyses were performed. Statistical significance was set at P ≤ .05. RESULTS: A total of 102 patients were included in this study. The majority received a fibula free flap (90%) for a malignant neoplasm (76%). All patients had at least 12 months of follow-up. The rate of plate extrusion was 16%, with the majority of those patients undergoing plate removal (69%). After adjusting for postoperative fistula, soft tissue, and length of hospitalization, we found that any history of smoking (odds ratio = 12.8; confidence interval, 1.57 to 104.2), number of osteotomies (odds ratio 3.07; confidence interval, 1.09 to 8.6), flap nonviability (odds ratio = 18.2; confidence interval, 2.22 to 148.8) were associated with plate extrusion on multivariate analysis. Postoperative soft tissue infection approached significance. CONCLUSIONS: This study demonstrates that smoking history, number of osteotomies, and flap nonviability are associated with plate extrusion after mandible reconstruction. Performing fewer osteotomies when possible to avoid excessively small flap bone segments and minimizing postoperative complications may improve long-term outcomes after mandibular reconstruction.

Squamous Cell Carcinoma Metastasis to the Supraclavicular Artery Island Flap Donor Site.

A rare complication of flap reconstruction following oncologic ablation is metastasis to the donor site. We present a novel case of cutaneous squamous cell carcinoma (SCCA) recurrence at the right upper-extremity donor site following tonsillar SCCA resection with supraclavicular artery island flap reconstruction. Following surgery, the patient presented with cutaneous recurrence at the right upper-extremity donor site. Biopsy confirmed metastasis from the oropharyngeal primary. The patient developed two subsequent right upper-extremity recurrences before he died. The most likely mechanism of metastasis is direct implantation via contamination. This case demonstrates the importance of maintaining separate surgical fields and instruments during oncologic ablation and reconstruction. Laryngoscope, 131:E440-E442, 2021.

Identification of targets of IL-13 and STAT6 signaling in polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening, highly prevalent monogenic disease caused by mutations in polycystin-1 (PC1) in 85% of patients. We have previously identified a COOH-terminal cleavage fragment of PC1, PC1-p30, which interacts with the transcription factor STAT6 to promote transcription. STAT6 is aberrantly active in PKD mouse models and human ADPKD, and genetic removal or pharmacological inhibition of STAT6 attenuates disease progression. High levels of IL-13, a STAT6-activating cytokine, are found in the cyst fluid of PKD mouse models and increased IL-13 receptors in ADPKD patient tissue, suggesting that a positive feedback loop exists between IL-13 and STAT6 is activated in cystic epithelial cells and contributes to disease progression. In this study, we aimed to identify genes aberrantly regulated by STAT6 to better understand how increased IL-13/STAT6 signaling may contribute to PKD progression. We demonstrate that the expression of periostin, galectin-3, and IL-24 is upregulated in various forms of PKD and that their aberrant regulation is mediated by IL-13 and STAT6 activity. Periostin and galectin-3 have previously been implicated in PKD progression. We support these findings by showing that periostin expression is increased after IL-13 treatment in kidney epithelial cells, that galectin-3 expression is increased after injecting IL-13 in vivo and that IL-24 expression is upregulated by both IL-13 treatment and PC1-p30 overexpression in mouse and human kidney cells. Overall, these findings provide insight into the possible mechanisms by which increased IL-13/STAT6 signaling contributes to PKD progression and suggest potential therapeutic targets.

X-ray Absorption Spectroscopy and Spectromicroscopy of Supported Lipid Bilayers.

The C 1s, O 1s, and N 1s X-ray absorption spectra of three lipid species, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and 1,2-dioleoyl-3-trimethylammonium-propane (chloride salt) (DOTAP), have been recorded using transmission detection in a scanning transmission X-ray microscope. The spectra are presented on an absolute intensity scale (i.e., optical density per nm) to allow their use as reference standards for spectromicroscopic analysis of supported lipid bilayers. Examples of C 1s based spectromicroscopic mapping of saturated and unsaturated domains in dry lipid bilayers of DOPC and DSPC at several compositions are presented. The results are compared with fluorescence microscopy of the same area. Challenges for extending this work to studies of wet lipid bilayers interacting with antimicrobial peptides are discussed.