Purpose: To determine the characteristics of current US Otolaryngology-Head and Neck Surgery (Oto-HNS) residents and their medical school. Methods: Data were manually collected between Dec 2022 and Jan 2023 for 1649 residents attending 163 US-based ACGME accredited Oto-HNS residency programs, reflecting the 2018-2022 cohort. All data were collected from publicly available sources including residency and medical school program websites, web of science, and professional networking sites (ex: LinkedIn, Doximity). Data were analyzed to determine the "feeder" schools which contributed the greatest number and percent of residents. Using univariable linear regression models, we characterized factors which were associated with feeder school status. Results: Of 1649 residents analyzed, 364 (22 %) matched to their home program and 918 (56 %) stayed in the region of their medical school. The median [IQR] number of published papers and abstracts was 5 [3, 9] with an h-index of 2 [1,4]. Factors associated with producing a greater percent of Oto-HNS residents include presence of an interest group, presence of a home program, USNWR research rank of the medical school, Doximity reputation rank of the home residency program, average pre-residency h-index of the school's graduates, and total NIH research funding (each p < 0.001). Conclusions: In the changing landscape of residency applications after the USMLE Step 1 exam's transition in January 2022 to pass/fail scoring, it is important to objectively characterize current Oto-HNS residents. Findings from this study will inform prospective residents and residency programs seeking to improve access to Oto-HNS. Future small-scale studies may help further identify driving factors within medical school curricula.

Background: Head and neck cancer (HNC) patients often have dysphagia following surgical and/or chemoradiation treatment, which can lead to reduced quality of life. Some patients suffer from decreased tongue strength and mobility that may cause discomfort and difficulty with swallowing. Our group has developed a patented genioglossus muscle strength trainer (GMST) to increase tongue protrusive force that has been used in patients with sleep apnea. We hypothesized that the GMST device would increase tongue strength in the HNC population.Methods: We conducted an IRB approved, non-randomized, interventional clinical trial of HNC patients with dysphagia to determine the effect of GMST on tongue strength. Our secondary objective was to assess dysphagia quality of life, as determined by questionnaires. Genioglossus muscle strength measurements (measured in Newtons, N) and dysphagia quality of life scores (SWAL-QoL questionnaire) were obtained from enrolled patients at baseline and following 4 weeks of intervention. Treatment was at-home GMST exercise regimen 3 times daily, 5 days per week. Compliance was assessed via review of training logs. Two-sided paired t-tests at significance level alpha = .05 were performed to assess difference in mean GG muscle strength pre- and post-treatment.Results: Out of 10 patients initially enrolled, 7 patients completed the trial. Eighty-six percent were male and the average age was 60. About 5 patients had surgery plus adjuvant radiation and 2 patients had primary radiation. All patients had baseline dysphagia as determined by patient complaint and/or objective measurement (prior modified barium swallow). No adverse events were reported. We observed a statistically significant increase in genioglossus muscle strength (mean change: 4.0 N, 95% CI 1.1-6.9, P = .015) after 4 weeks of treatment. Patients reported reduced swallowing burden and feeling of stigma around eating based on SWAL-QoL results.Conclusions: Our data suggest that protrusive tongue-training exercises utilizing a novel tongue trainer device is well-tolerated and increases genioglossus muscle strength in treated HNC patients complaining of dysphagia. Patient-reported outcomes based on the SWAL-QoL survey indicate improvements in quality-of-life post-treatment, although our results are limited by small sample size. Larger studies are needed to see if this device could have clinically meaningful results for this difficult-to-treat patient population.

OBJECTIVE:To evaluate national trends in racial disparities for patients undergoing head and neck reconstructive surgery. METHODS:Retrospective analysis using the 2008 to 2021 American College of Surgeons National Surgical Quality Improvement Program database. Patients receiving microvascular free tissue transfer were eligible for inclusion. Pediatric patients and those treated by non-otolaryngologists were excluded. Outcomes were analyzed with univariate and multivariable models. RESULTS:A total of 5831 head and neck free flap cases were analyzed, 4869 (83.5%) were White, 560 (9.6%) were Black or African American, and 402 (6.9%) were Asian, Native American, or other groups (ANAOG). The proportion of Black or African American patients and ANAOG patients undergoing free tissue transfer increased significantly over the time period (p = 0.047 and p = 0.010, respectively). However, there was a downtrend that started around 2017. In a multivariable model, Black or African American race was not associated with readmission (OR = 0.99 [95% CI 0.74, 1.31], p > 0.05), returning to the operating room (OR = 1.20 [95% CI 0.96, 1.49], p > 0.05), or any post-operative complication (OR = 0.83 [95% CI 0.68, 1.01], p > 0.05). There were also no significant associations found in the ANAOG population on multivariate analysis (p > 0.05 for all). CONCLUSION:The percentage of free tissue transfer performed in patients from minority backgrounds with head and neck cancer has been increasing in the United States. Outcomes after head and neck microvascular reconstruction are similar when stratified by race. However, racial disparities remain and further work is necessary to reduce these disparities. LEVEL OF EVIDENCE:4 Laryngoscope, 135:635-640, 2025.

Syphilis is an infectious disease caused by the spirochete Treponema pallidum. Rates have been rising in the US and globally. Known as the “Great Imitator,” syphilis can involve head and neck subsites, and often can masquerade as possible carcinoma of the head and neck. Here, we present three distinct cases of syphilis presenting as suspected head and neck malignancy involving the oropharynx, larynx and oral cavity. All cases were diagnosed on surgical pathologic examination of diseased tissues and treated. It is important for practicing otolaryngologists to understand head and neck manifestations of syphilis to facilitate proper diagnosis and treatment. Laryngoscope , 134:236–239, 2024

Background: While the microbiome of oral squamous cell carcinoma has been intensely studied, little is known about the role of bacteria in laryngeal squamous cell carcinoma (LSCC). Our group recently demonstrated that pathogenic bacteria, such as Fusobacterium, are associated with oral cavity cancer and influence checkpoint ligand expression. To understand the potential role of bacteria in LSCC, we comprehensively profiled the intra-tumoral bacterial microbiome. Methods: DNA from tumor and adjacent normal tissue was isolated from formalin-fixed paraffin-embedded (FFPE) samples for 18 patients with early-stage (stage 1-2) and 27 patients with advanced-stage (stage 3-4) LSCC, diagnosed and treated between 2009 and 2020. 16S rRNA bacterial gene sequencing was performed. Established bioinformatics pipelines were used to characterize the intra-tumoral microbiome and correlate with clinical outcomes. Spatial profiling using Fluorescence In Situ Hybridization (FISH) with 16S bacterial probes was also performed. Machine learning algorithms were used to generate predictions relative to clinical outcomes. Results: Of the 27 patients with advanced-stage LSCC, the most commonly involved subsite was the supraglottis (N= 18, 66.7%), while the majority of the 18 patients with early-stage tumors had SCCA of the glottis (N=14, 78%). Bacterial alpha diversity in tumors was decreased when comparing the early and advanced-stage tumor samples with adjacent normal tissues. Advanced-stage tumors had significantly increased alpha diversity compared to early-stage tumors (p=0.021). With increased bacterial diversity of the advanced-stage tumors, there were also relative increases in pathogenic bacteria abundance, including Fusobacterium, Capnocytophaga, Prevotella, and Leptotrichia, when compared to early-stage tumor samples. There was a significant decrease in Rothia and Novosphingobium in the advanced-stage samples compared to normal adjacent and early-stage tumors (p<0.05). Using machine learning algorithms and receiver operating characteristic curves, the bacterial composition of tumor samples was able to effectively predict the group stage (AUC=0.83). In contrast, normal adjacent tissue microbiome composition was less likely to provide an accurate prediction (AUC=0.34). FISH revealed bacteria within the tumor cells and adjacent to cell membranes in all LSCC subsites examined. Conclusions: Little is known about the bacterial profile of LSCC. Here, we demonstrate that bacterial diversity increased in advanced-stage LSCC when compared to early-stage tumors. While advanced LSCC has a more diverse microbial community, this appears to be accounted for by increased pathogenic bacteria within the advanced-stage group, such as Fusobacterium (associated with oral and colon cancer), Capnocytophaga (associated with periodontitis), Prevotella (associated with GI disease and periodontitis), and Leptotrichia (associated with bacterial biofilms). Additional studies are needed to determine the mechanistic role of pathogenic bacteria in the development and progression of LSCC. Citation Format: Natalie Silver, David Hoying, Eric Lamarre, Brandon Prendes, Jamie Ku, Jin Dai, Daniel McGrail, Joseph Scharpf, August Culbert, Shauna Campbell, Emrullah Yilmaz, Jessica Geiger, Akeesha Shah, Jeffrey Myers, Kristiann Fredenburg, Neil Woody, Shlomo Koyfman. Characterizing the intra-tumoral microbiome of laryngeal squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-090.

Background Deep inferior epigastric perforator (DIEP) flaps are commonly used for autologous breast reconstruction, but reported rates of venous thromboembolism (VTE) are up to 6.8%. This study aimed to determine the incidence of VTE based on preoperative Caprini score following DIEP breast reconstruction. Methods This retrospective study included patients who underwent DIEP flaps for breast reconstruction between January 1, 2016 and December 31, 2020 at a tertiary-level, academic institution. Demographics, operative characteristics, and VTE events were recorded. Receiver operating characteristic analysis was performed to determine the area under the curve (AUC) of the Caprini score for VTE. Univariate and multivariate analyses assessed risk factors associated with VTE. Results This study included 524 patients (mean age 51.2 +/- 9.6 years). There were 123 (23.5%) patients with the Caprini score of 0 to 4, 366 (69.8%) with scores 5 to 6, 27 (5.2%) with scores 7 to 8, and 8 (1.5%) patients with scores >8. Postoperative VTE occurred in 11 (2.1%) patients, at a median time of 9 days (range 1-30) after surgery. VTE incidence by the Caprini score was 1.9% for scores 3 to 4, 0.8% for scores 5 to 6, 3.3% for scores 7 to 8, and 13% for scores >8. The Caprini score achieved an AUC of 0.70. A Caprini score >8 was significantly predictive of VTE on multivariable analysis relative to scores 5 to 6 (odds ratio = 43.41, 95% confidence interval = 7.46-252.76, p < 0.001). Conclusion In patients undergoing DIEP breast reconstruction, VTE incidence was highest (13%) in Caprini scores greater than eight despite chemoprophylaxis. Future studies are needed to assess the role of extended chemoprophylaxis in patients with high Caprini scores.

In the operating room, patient safety is of paramount importance. Medical students and junior trainees, despite their primary role as students, may play active roles in assessing patient safety and reporting suspected errors. Active consent is one layer of patient safety that is continuously assessed by several team members. This article examines an instance where patient consent may have been violated. Through the lens of trainee and senior perspectives, we discuss the ethical principles at stake and provide recommendations for medical student and junior trainee involvement in patient care when an error is suspected.

Background: Deep inferior epigastric perforator (DIEP) flaps are the standard for autologous breast reconstruction. This study investigated risk factors for DIEP complications in a large, contemporary cohort to optimize surgical evaluation and planning. Methods: This retrospective study included patients who underwent DIEP breast reconstruction between 2016 and 2020 at an academic institution. Demographics, treatment, and outcomes were evaluated in univariable and multivariable regression models for postoperative complications. Results: In total, 802 DIEP flaps were performed in 524 patients (mean age, 51.2 ± 9.6 years; mean body mass index, 29.3 ± 4.5). Most patients (87%) had breast cancer; 15% were BRCA-positive. There were 282 (53%) delayed and 242 (46%) immediate reconstructions and 278 (53%) bilateral and 246 (47%) unilateral reconstructions. Overall complications occurred in 81 patients (15.5%), including venous congestion (3.4%), breast hematoma (3.6%), infection (3.6%), partial flap loss (3.2%), total flap loss (2.3%), and arterial thrombosis (1.3%). Longer operative time was significantly associated with bilateral immediate reconstructions and higher body mass index. Prolonged operative time (OR, 1.16; P = 0.001) and immediate reconstruction (OR, 1.92; P = 0.013) were significant predictors of overall complications. Partial flap loss was associated with bilateral immediate reconstructions, higher body mass index, current smoking status, and longer operative time. Conclusions: Prolonged operative time is a significant risk factor for overall complications and partial flap loss in DIEP breast reconstruction. For each additional hour of surgical time, the risk of developing overall complications increases by 16%. These findings suggest that reducing operative time through co-surgeon approaches, consistency in surgical teams, and counseling patients with more risk factors toward delayed reconstructions may mitigate complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Radiotherapy (RT) has demonstrated synergy with immune checkpoint blockade (ICB) in preclinical models. However, its potential as an immunoadjuvant is limited by low immunogenicity at low radiation doses and immunosuppression at high radiation doses. It is hypothesized that radiosensitizers can enhance both the anticancer and immunogenic effects of low-dose radiation. Herein the authors report the antitumor immunity of combined RT and immunotherapy with dimethylaminomicheliolide (DMAMCL), a prodrug of the anti-inflammatory sesquiterpene lactone micheliolide (MCL). DMAMCL sensitized cancer cells to a single fraction of RT in vitro by inducing apoptosis and DNA double-strand breaks. DMAMCL with 5 fractions of 2 Gy focal X-ray irradiation led to significant anticancer efficacy in subcutaneous and spontaneous models of murine cancer. DMAMCL-sensitized RT upregulated programmed death-ligand 1 (PD-L1) expression in the tumors. Combination of DMAMCL-sensitized RT with anti-PD-L1 ICB significantly enhanced antitumor efficacy by increasing tumor-infiltrating CD4+ and CD8+ T cells and establishing immune memory.

AbstractCheckpoint blockade immunotherapy (CBI) awakes a host innate immune system and reactivates cytotoxic T cells to elicit durable response in some cancer patients. Now, a cationic nanoscale metal–organic framework, W‐TBP, is used to facilitate tumor antigen presentation by enabling immunogenic photodynamic therapy (PDT) and promoting the maturation of dendritic cells (DCs). Comprised of dinuclear WVI secondary building units and photosensitizing 5,10,15,20‐tetra(p‐benzoato)porphyrin (TBP) ligands, cationic W‐TBP mediates PDT to release tumor associated antigens and delivers immunostimulatory CpG oligodeoxynucleotides to DCs. The enhanced antigen presentation synergizes with CBI to expand and reinvigorate cytotoxic T cells, leading to superb anticancer efficacy and robust abscopal effects with >97 % tumor regression in a bilateral breast cancer model.

Background Advanced oral cavity squamous cell carcinoma (OSCC) is an aggressive disease, with 5-year overall survival rates below 50%. 1 While smoking and alcohol are the most established risk factors, there is growing evidence implicating the role of the oral microbiome in promoting immunosuppres-sive states in OSCC. 2-6 The objective of this study was to evaluate the taxonomic profile of oral bacteria in advanced OSCC patients and correlate with clinicopathologic features. approved this study of patients diagnosed with treated from Samples were taken from tumor and paired adjacent normal tissues at the time of surgery and snap frozen. Demographics, clinical and pathologic information was collected. DNA from 51 samples was isolated and 16s rRNA gene sequencing was performed after PCR amplification of the V1-V3 regions of the 16s rRNA gene for paired samples. 16S rRNA sequences were processed using DADA2, implemented in QIIME2 package, and taxonomic assignments were made using RDA classifier using the Human Oral Microbiome Data-base V15.22 as the reference database. Sequencing reads proc-essing, denoising, dereplicating, chimeras filtering, and amplicon sequence variants (ASVs) generation was done using DADA2. The association between clinicopathological factors and bacterial profiles was evaluated using R Software.

Checkpoint blockade elicits durable responses in immunogenic cancers, but it is largely ineffective in immunologically ‘cold’ tumours. Here we report the design, synthesis and performance of a bismuth-based nanoscale metal–organic framework that modulates the immunological and mechanical properties of the tumour microenvironment for enhanced radiotherapy–radiodynamic therapy. In mice with non-immunogenic prostate and pancreatic tumours irradiated with low X-ray doses, the intratumoural injection of the radiosensitizer mediated potent outcomes via the repolarization of immunosuppressive M2 macrophages into immunostimulatory M1 macrophages, the reduction of the concentration of intratumoural transforming growth factor beta (TGF-β) and of collagen density, and the inactivation of cancer-associated fibroblasts. When intravenously injected in combination with checkpoint-blockade therapy, the radiosensitizer mediated the reversal of immunosuppression in primary and distant tumours via the systemic reduction of TGF-β levels, which led to the downregulation of collagen expression, the stimulation of T-cell infiltration in the tumours and a robust abscopal effect. Nanoscale radiosensitizers that stimulate anti-tumour immunity and T-cell infiltration may enhance the therapeutic outcomes of checkpoint blockade in other tumour types. A nanoscale metal–organic framework that modulates the immunological and mechanical properties of the tumour microenvironment enhances the outcomes of radiotherapy–radiodynamic therapy, especially when combined with checkpoint blockade.

Cancer vaccines have been actively pursued to bolster antitumor immunity. Here, we designed nanoscale metal-organic frameworks (nMOFs) as locally activable immunotherapeutics to release danger-associated molecular patterns (DAMPs) and tumor antigens and deliver pathogen-associated molecular patterns (PAMPs) for in situ personalized cancer vaccination. When activated by x-rays, nMOFs effectively generate reactive oxygen species to release DAMPs and tumor antigens while delivering CpG oligodeoxynucleotides as PAMPs to facilitate the maturation of antigen-presenting cells. Together, DAMPs, tumor antigens, and PAMPs expand cytotoxic T cells in tumor-draining lymph nodes to reinvigorate the adaptive immune system for local tumor regression. When treated in combination with an immune checkpoint inhibitor, the local therapeutic effects of nMOF-based vaccines were extended to distant tumors via attenuating T cell exhaustion. Our work demonstrates the potential of nMOFs as x-ray-activable in situ cancer vaccines to awaken the host's innate and adaptive immune systems for systemic antitumor immunity.

Herein we report the design of a bacteriochlorin-based nanoscale metal-organic framework, Zr-TBB, for highly effective photodynamic therapy via both type I and type II mechanisms. The framework of Zr-TBB stabilizes 5,10,15,20-tetra(p-benzoato)bacteriochlorin (TBB) ligands toward oxygen and light via geometrical constraint. Upon 740 nm light irradiation, Zr-TBB efficiently generates various reactive oxygen species, including singlet oxygen, superoxide anion, hydrogen peroxide, and hydroxyl radicals, to afford superb antitumor efficacy on mouse models of breast and colon cancers, with cure rates of 40% and 60%, respectively.

Nanoscale metal-organic frameworks (nMOFs) are excellent radiosensitizers for radiotherapy-radiodynamic therapy (RT-RDT). Herein, we report surface modification of a Hf-DBP nMOF for the co-delivery of a hydrophobic small-molecule toll-like receptor 7 agonist, imiquimod (IMD), and a hydrophilic macromolecule, anti-CD47 antibody (αCD47), for macrophage modulation and reversal of immunosuppression in tumors. IMD repolarizes immunosuppressive M2 macrophages to immunostimulatory M1 macrophages, while αCD47 blocks CD47 tumor cell surface marker to promote phagocytosis. Upon X-ray irradiation, IMD@Hf-DBP/αCD47 effectively modulates the immunosuppressive tumor microenvironment and activates innate immunity to orchestrate adaptive immunity when synergized with an anti-PD-L1 immune checkpoint inhibitor, leading to complete eradication of both primary and distant tumors on a bilateral colorectal tumor model. nMOFs thus provide a unique platform to co-deliver multiple immunoadjuvants for macrophage therapy to induce systematic immune responses and superb antitumor efficacy.

As a monolayered version of nanoscale metal-organic frameworks (nMOFs), nanoscale metal-organic layers (nMOLs) represent an emerging class of highly tunable two-dimensional materials for hierarchical functionalization and with facile access to analytes. Here we report the design of the first nMOL-based biosensor for ratiometric pH and oxygen sensing in mitochondria. Cationic Hf-12-Ru nMOL was solvothermally synthesized by laterally connecting Hf-12 secondary building units (SBUs) with oxygen-sensitive Ru(bpy)(3)(2+)-derived DBBRu ligands (bpy = 2,2'-bipyridine). The Hf-12-Ru nMOL was then covalently functionalized with pH-sensitive fluorescein isothiocyanate and pH/oxygen-independent Rhodamine-B isothiocyanate through thiourea linkages to afford Hf-12-Ru-F/R as a mitochondria-targeted ratiometric sensor for pH and O-2 in live cells. High-resolution confocal microscope imaging with Hf-12-Ru-F/R revealed a positive correlation between pH and local O-2 concentration in mitochondria. Our work shows the potential of nMOL-based ratiometric biosensors in sensing and imaging of biologically important analytes in live cells.