Racial Disparities in Head and Neck Cancer: It's Not Just About Access.

OBJECTIVE: Medical literature identifies stark racial disparities in head and neck cancer (HNC) in the United States, primarily between non-Hispanic white (NHW) and non-Hispanic black (NHB) populations. The etiology of this disparity is often attributed to inequitable access to health care and socioeconomic status (SES). However, other contributors have been reported. We performed a systematic review to better understand the multifactorial landscape driving racial disparities in HNC. DATA SOURCES: A systematic review was conducted in Covidence following Preferred Reporting Items for Systematic Reviews and Meta-analyses Guidelines. A search of PubMed, SCOPUS, and CINAHL for literature published through November 2022 evaluating racial disparities in HNC identified 2309 publications. REVIEW METHODS: Full texts were screened by 2 authors independently, and inconsistencies were resolved by consensus. Three hundred forty publications were ultimately selected and categorized into themes including disparities in access/SES, treatment, lifestyle, and biology. Racial groups examined included NHB and NHW patients but also included Hispanic, Native American, and Asian/Pacific Islander patients to a lesser extent. RESULTS: Of the 340 articles, 192 focused on themes of access/SES, including access to high-quality hospitals, insurance coverage, and transportation contributing to disparate HNC outcomes. Additional themes discussed in 148 articles included incongruities in surgical recommendations, tobacco/alcohol use, human papillomavirus-associated malignancies, and race-informed silencing of tumor suppressor genes. CONCLUSION: Differential access to care plays a significant role in racial disparities in HNC, disproportionately affecting NHB populations. However, there are other significant themes driving racial disparities. Future studies should focus on providing equitable access to care while also addressing these additional sources of disparities in HNC.

Quantitative Simulation of Enzymatic Breakdown of Alcohol in Human Metabolism.

The breakdown of ethanol, the active chemical in alcohol, is tightly regulated by the body, yet alcohol intoxication occurs in thousands of Americans annually. Many factors contribute to the concentration of ethanol in the bloodstream and the tolerance an individual has, including body size, previous drinking experience, and liver functionality. We propose a model that estimates both the blood alcohol concentration and the concentration of acetaldehyde (the toxic intermediate during catabolism) in the liver over time to quantify organ damage for an average person. From the current literature, we derived ordinary differential equations that govern the absorption of ethanol in the body and extended it with the metabolic enzyme mechanisms. We also altered the parameters of our system in order to show the effects of Asian flush, which impairs the body's processing of acetaldehyde. We demonstrated the accumulation of acetaldehyde in Asian flush patients was about 660 times higher compared to those without the disease.Clinical relevance-With further improvements and personalization, our model would be able to quantitatively describe the effects of alcohol consumption without having volunteers go through repetitive trials with extensive exposure to alcohol. Liver damage can also be estimated with the acetaldehyde buildup predicted by the model.

Virtual Tumor Boards for Remote Learning in Head and Neck Surgical Oncology.

Importance: In addition to their patient management value, multidisciplinary tumor boards have been recognized as effective learning tools. However, the value of using a virtual tumor board as a learning tool for head and neck surgical oncology fellows has not been studied. Objective: To describe the structure and content of the American Head and Neck Society (AHNS) Virtual Tumor Board and assess its educational value as perceived by attendees. Design, Setting, and Participants: All sessions of the AHNS Virtual Tumor Board from April 8, 2020, to June 1, 2022, were reviewed. Topics, presenters, participants, and viewership data were collected as of October 15, 2022, from session recordings posted to an online video sharing and social media platform. Additionally, an anonymous, 14-question online survey was designed to elicit feedback from head and neck surgery trainees on virtual tumor board engagement, strengths, and weaknesses. The survey was electronically distributed in June and July 2022 to the 101 fellows enrolled in AHNS-accredited programs between July 1, 2020, and June 30, 2022. Main Outcomes and Measures: The primary aim was to tabulate online viewership of the sessions. The secondary aim was to qualitatively assess the experience of head and neck trainees with the AHNS Virtual Tumor Board using a survey. Results: Forty-two sessions of the virtual tumor board were held between April 8, 2020, and June 1, 2022. Almost all sessions (41 [98%]) were case based. One hundred and sixteen cases were presented, representing 2 to 3 cases per session, by 75 unique faculty members. Each session was viewed a mean of 217 times (range, 64-2216 views). In the 2021 to 2022 academic year, a mean of 60 viewers (range, 30-92 viewers) attended each live session. In all, 29 survey responses were collected from 101 fellows in AHNS-accredited programs (29% response rate). Most respondents felt the format allowed for excellent teaching (18 of 26 respondents [69%]) and discussion (19 of 26 respondents [73%]). Most respondents (22 of 29 respondents [76%]) believed that practicing head and neck surgeons would benefit from the sessions. Conclusions and Relevance: This survey study found that the AHNS Virtual Tumor Board was well-attended and well-reviewed by head and neck surgical oncology trainees. The virtual tumor board format could be used as model of remote learning for other organizations.

Multiplatform molecular profiling uncovers two subgroups of malignant peripheral nerve sheath tumors with distinct therapeutic vulnerabilities.

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive sarcoma, and a lethal neurofibromatosis type 1-related malignancy, with little progress made on treatment strategies. Here, we apply a multiplatform integrated molecular analysis on 108 tumors spanning the spectrum of peripheral nerve sheath tumors to identify candidate drivers of MPNST that can serve as therapeutic targets. Unsupervised analyses of methylome and transcriptome profiles identify two distinct subgroups of MPNSTs with unique targetable oncogenic programs. We establish two subgroups of MPNSTs: SHH pathway activation in MPNST-G1 and WNT/ß-catenin/CCND1 pathway activation in MPNST-G2. Single nuclei RNA sequencing characterizes the complex cellular architecture and demonstrate that malignant cells from MPNST-G1 and MPNST-G2 have neural crest-like and Schwann cell precursor-like cell characteristics, respectively. Further, in pre-clinical models of MPNST we confirm that inhibiting SHH pathway in MPNST-G1 prevent growth and malignant progression, providing the rational for investigating these treatments in clinical trials.

Extensive set of African ancestry-informative markers (AIMs) to study ancestry and population health.

Introduction: Human populations are often highly structured due to differences in genetic ancestry among groups, posing difficulties in associating genes with diseases. Ancestry-informative markers (AIMs) aid in the detection of population stratification and provide an alternative approach to map population-specific alleles to disease. Here, we identify and characterize a novel set of African AIMs that separate populations of African ancestry from other global populations including those of European ancestry. Methods: Using data from the 1000 Genomes Project, highly informative SNP markers from five African subpopulations were selected based on estimates of informativeness (In) and compared against the European population to generate a final set of 46,737 African ancestry-informative markers (AIMs). The AIMs identified were validated using an independent set and functionally annotated using tools like SIFT, PolyPhen. They were also investigated for representation of commonly used SNP arrays. Results: This set of African AIMs effectively separates populations of African ancestry from other global populations and further identifies substructure between populations of African ancestry. When a subset of these AIMs was studied in an independent dataset, they differentiated people who self-identify as African American or Black from those who identify their ancestry as primarily European. Most of the AIMs were found to be in their intergenic and intronic regions with only 0.6% in the coding regions of the genome. Most of the commonly used SNP array investigated contained less than 10% of the AIMs. Discussion: While several functional annotations of both coding and non-coding African AIMs are supported by the literature and linked these high-frequency African alleles to diseases in African populations, more effort is needed to map genes to diseases in these genetically diverse subpopulations. The relative dearth of these African AIMs on current genotyping platforms (the array with the highest fraction, llumina's Omni 5, harbors less than a quarter of AIMs), further demonstrates a greater need to better represent historically understudied populations.

Pediatric septorhinoplasty: Current attitudes and practices by facial plastic and reconstructive surgeons.

OBJECTIVE: There is hesitation to offer pediatric patients rhinoplasty due to concerns about postoperative effect on midface growth. A cross-sectional survey of members of the American Academy of Facial Plastic and Reconstructive Surgery was conducted regarding practice information and attitudes towards pediatric septorhinoplasty. The goal of the study is to describe the current attitudes on pediatric septorhinoplasty. STUDY DESIGN: Cross-sectional survey. SETTING: Community members of the American Academy of Facial Plastic and Reconstructive Surgery society. METHODS: A 19-question survey was distributed to surgeons surveying background information and current attitudes towards pediatric septorhinoplasty practices. Fisher's exact tests were implemented using Monte Carlo methods. RESULTS: There were 94 total respondents. A majority believed septorhinoplasty is safe in patients <16 years of age (n = 68, 72.34 %) with most choosing either 16 years (n = 30, 31.91 %) or 14 years (n = 29, 30.85 %) as the minimum age to consider the procedure. A majority of respondents would not perform any nasal procedures in patients ≤12 years (n = 40, 43.48 %). CONCLUSION: Trends in pediatric rhinoplasty practices have evolved overtime. Despite prior beliefs and studies cautioning against performing septorhinoplasty in pediatric patients (<16 years of age), a majority of practicing facial plastic surgeons believe that pediatric septorhinoplasty can be performed in patients >14 years old. LEVEL OF EVIDENCE: IV.

Racial survival disparities in head and neck cancer clinical trials.

BACKGROUND: Survival disparities between Black and White head and neck cancer patients are well documented, with access to care and socioeconomic status as major contributors. We set out to assess the role of self-reported race in head and neck cancer by evaluating treatment outcomes of patients enrolled in clinical trials, where access to care and socioeconomic status confounders are minimized. METHODS: Clinical trial data from the Radiation Therapy Oncology Group studies were obtained. Studies were included if they were therapeutic trials that employed survival as an endpoint. Studies that did not report survival as an endpoint were excluded; 7 Radiation Therapy Oncology Group Studies were included for study. For each Black patient enrolled in a clinical trial, a study arm-matched White patient was used as a control. RESULTS: A total of 468 Black participants were identified and matched with 468 White study arm-specific controls. White participants had better outcomes than Black participants in 60% of matched pairs (P < .001). Black participants were consistently more likely to have worse outcomes. When outcomes were measured by progression-free survival or disease-free survival, the failure rate was statistically significantly higher in Black participants (hazard ratio [HR] = 1.50, P < .001). Failure was largely due to locoregional failure, and Black participants were at higher risk (subdistribution HR =1.51, P = .002). The development of distant metastasis within the paired cohorts was not statistically significantly different. CONCLUSION: In this study of clinical trial participants using self-reported race, Black participants consistently had worse outcomes in comparison to study arm-specific White controls. Further study is needed to confirm these findings and to explore causes underlying this disparity.

Osteoradionecrosis rate in oropharynx cancer treated with dose volume histogram based constraints.

OBJECTIVES: Mandibular dose constraints are designed to limit high dose to small volumes to avoid osteoradionecrosis (ORN). Based upon a published experience, intermediate-dose constraints were introduced but have not been independently validated. We hypothesize that these constraints lower ORN rate without compromising other organs at risk (OAR). METHODS: Oropharyngeal cancer patients treated with standard fractionation adjuvant/definitive VMAT from 01/2014-08/2020 were included. In 09/2017, mandibular dose constraint was changed from historical constraint (HC) of D 0.1 cc < 70 Gy to modified constraints (MC) of V 44 Gy < 42%, V 58 Gy < 25%, D 0.5 cc < 70 Gy. OAR dosimetric changes and ORN development were evaluated. Regression modelling predicted long-term ORN cases in MC group. RESULTS: There were 174 patients, 71 in MC group. Seven cases of ORN in HC group at a median follow up (FU) of 39 months and 1 case of ORN in MC group at a median FU of 11 months were observed. More patients in the MC group met V 44 Gy (87% vs 62%, p < 0.01) and V 58 Gy constraints (92% vs 73%, p < 0.01). Mean doses to OARs did not rise. Mandible V 44 Gy and V 58 Gy were significantly associated with ORN (p < 0.01 and p = 0.03, respectively) across all patients. In the HC group, V 44 Gy was independently associated with ORN (p = 0.01). To account for shorter FU in MC group, logistic regression of ORN based on V 44 Gy in HC patients was performed. This predicts 3.2 ORN cases in the MC group (95% CI: 0.00-6.4). CONCLUSION: Achieving V 44 Gy and V 58 Gy was successful in 87% of cases without sacrificing target coverage or OARs and resulted in non-significant ORN decrease.

Interleukin-17 Inhibitor Combination Therapies for the Treatment of Psoriasis: A Systematic Review.

Objective: Although biologics are highly effective in the treatment of psoriasis, some patients consistently fail monotherapy. For these patients, combination therapy is commonly employed. However, evidence-based recommendations for combination therapy in the treatment of psoriasis with interleukin-17 (IL-17) inhibitors are currently lacking. Therefore, we aimed to conduct a systematic review of existing literature discussing the efficacy and safety of IL-17 inhibitors in combination with other therapeutic modalities in the treatment of psoriasis. Methods of Literature Search: By way of a search of PubMed, Cochrane, and Web of Science databases in March 2021, we identified peer-reviewed articles with data on the safety and/or efficacy of IL-17 inhibitor combination therapies in adults with psoriasis and/or psoriatic arthritis (PsA). A modified version of the 2011 Oxford Centre for Evidence-Based Medicine Scheme was utilized for assessing study quality. Results: Twenty-four articles with a total of 3,154 patients met inclusion/exclusion criteria. These articles comprised six post-hoc/subgroup analyses of randomized controlled trials (RCTs), four uncontrolled clinical trials, three case series, and 11 case reports that provided data on IL-17 inhibitor therapy in combination with conventional disease-modifying antirheumatic drugs (cDMARDs), apremilast, acitretin, topical therapy, phototherapy, and/or medications for comorbid diseases. Limitations: Our results are limited by the lack of data from RCTs. Conclusion: Although cDMARDs are often used in psoriasis combination therapies, the current literature suggests concomitant cDMARDs with IL-17 inhibitor therapy provides no added benefit compared to IL-17 inhibitor monotherapy. However, IL-17 inhibitor in combination with apremilast or acitretin shows efficacy and safety in case series/reports and may allow for a reduction in medication dosing and/or frequency, thereby minimizing costs and adverse events. Future RCTs investigating IL-17 inhibitor therapy in combination with acitretin or apremilast are warranted.

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis.

Importance: There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease. Objectives: To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location. Design, Setting, and Participants: This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade. Main Outcomes and Measures: The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022. Results: Of the 1328 patients (mean [SD] age, 52 [15] years; 993 [75%] women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (183 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median [range] cm, 2.6 [0.2-10.5]; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median [range] cm, 1.7 [0.05-8.8]; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries. Conclusions and Relevance: This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.

Risk of Skin Cancer with Phototherapy in Moderate-to-Severe Psoriasis: An Updated Systematic Review.

Phototherapy is a standard treatment for moderate-to-severe psoriasis. However, concern remains regarding the associated cutaneous carcinogenic risk. Our objective is to conduct a systematic review of skin cancer risk for psoriasis patients treated with phototherapy. To achieve our goal, we searched Cochrane, PubMed, and Embase databases. We aimed to evaluate existing literature (from July 1, 2010, to December 31, 2020) on phototherapy for all Fitzpatrick skin phototypes (FSP) which includes 71 articles, and eight articles being categorized in this review. Five studies did not report an increased skin cancer risk with narrowband-ultraviolet blue (UVB) and unspecified UVB for FSP II through VI, with one study not reporting FSP. Three studies did report an increased risk of skin cancer with narrowband-UVB and broadband-UVB for FSP I-VI, with one study also not specifying skin phototypes or UVB phototherapy type. Additionally, a study with psoralen and ultraviolet A with and without narrowband-UVB demonstrated an increased risk of skin cancer in phototypes III and IV. The most commonly reported secondary outcomes with phototherapy were actinic keratosis (123) and solar lentigines (10). Numerous patients were also on additional therapies including methotrexate, acitretin, and biologics. Study limitations include publication bias due to limited number of studies published on this topic in the last ten years along with heterogeneity in reporting. The relationship between phototherapy, psoriasis, and cutaneous oncogenic risk remains contradictory. While phototherapy for psoriasis is an efficacious therapy, further studies are needed to understand the cutaneous oncogenic risk based on FSP to help clinicals tailor treatment recommendations based on skin phototypes.

An Extra Set of Intelligent Eyes: Application of Artificial Intelligence in Imaging of Abdominopelvic Pathologies in Emergency Radiology.

Imaging in the emergent setting carries high stakes. With increased demand for dedicated on-site service, emergency radiologists face increasingly large image volumes that require rapid turnaround times. However, novel artificial intelligence (AI) algorithms may assist trauma and emergency radiologists with efficient and accurate medical image analysis, providing an opportunity to augment human decision making, including outcome prediction and treatment planning. While traditional radiology practice involves visual assessment of medical images for detection and characterization of pathologies, AI algorithms can automatically identify subtle disease states and provide quantitative characterization of disease severity based on morphologic image details, such as geometry and fluid flow. Taken together, the benefits provided by implementing AI in radiology have the potential to improve workflow efficiency, engender faster turnaround results for complex cases, and reduce heavy workloads. Although analysis of AI applications within abdominopelvic imaging has primarily focused on oncologic detection, localization, and treatment response, several promising algorithms have been developed for use in the emergency setting. This article aims to establish a general understanding of the AI algorithms used in emergent image-based tasks and to discuss the challenges associated with the implementation of AI into the clinical workflow.

Minimally Oxidized-LDL-Driven Alterations in the Level of Pathological Mediators and Biological Processes in Carotid Atherosclerosis.

The global burden of cerebrovascular disease, especially cerebral infarction has been increasing at an alarming rate with the atherosclerosis in carotid arteries as the primary risk factor. Despite the active involvement of minimally oxidized LDL (oxLDL) in atherosclerosis, limited information is available regarding the role of oxLDL in the pathogenesis of cerebrovascular diseases. The present study utilized the carotid bifurcation tissues and isolated carotid SMCs challenged with oxLDL from clinically relevant minimally invasive minimally-oxLDL-induced carotid atheroma microswine model to examine the levels of pro-atherogenic and pro-inflammatory mediators and cellular processes following immunostaining approaches. The immunopositivity of IL18, PDGFRA, IL17, LOX1, TLR4, MYF5, IL1B, and PDPN were increased in the carotid artery bifurcation tissues with a concomitant decrease in DAMPs, HMGB1 and S100B in oxLDL (600µg)-treated group compared to non-intervention control. Moreover, the cultured SMCs displayed increased level of IL18, LOX1, TLR4, MYF5, NLRP3, and PDPN upon challenging with oxLDL (100 mg/ml) compared to non-treatment control. In addition, the SMCs treated with oxLDL were resistant to the peroxidation of lipids as evident from lipid peroxidation staining. Also, the oxLDL displayed compromised mitochondrial membrane potential based on mitochondrial pore transition assay and increased hypertrophy due to decreased level of microtubules. Overall, oxLDL alters the expression status of pathological mediators and multiple biological processes in carotid SMCs aggravating carotid atherosclerosis. The understanding regarding the molecular mechanisms underlying oxLDL-driven pathological events would open novel translational avenues in the management of carotid atherosclerosis.

Switching Catalyst Selectivity via the Introduction of a Pendant Nitrophenyl Group.

The conversion of abundant small molecules to value-added products serves as an attractive method to store renewable energy in chemical bonds. A family of macrocyclic cobalt aminopyridine complexes was previously reported to reduce CO2 to CO with 98% faradaic efficiency through the formation of hydrogen-bonding networks and with the number of secondary amines affecting catalyst performance. One of these aminopyridine macrocycles, (NH)1(NMe)3-bridged calix[4]pyridine (L5), was modified with a nitrophenyl group to form LNO2 and metalated with a cobalt(II) precursor to generate CoLNO2, which would allow for probing the positioning and steric effects on catalysis. The addition of a nitrophenyl moiety to the ligand backbone results in a drastic shift in selectivity. Large current increases in the presence of added protons and CoLNO2 are observed under both N2 and CO2. The current increases under N2 are ∼30 times larger than the ones under CO2, suggesting a change in the selectivity of CoLNO2 to favor H2 production versus CO2 reduction. H2 is determined to be the dominant reduction product by gas chromatography, reaching faradaic efficiencies up to 76% under N2 with TFE and 71% under CO2 with H2O, in addition to small amounts of formate. X-ray photoelectron spectroscopy (XPS) reveals the presence of a cobalt-containing heterogeneous deposit on the working electrode surface, indicating the addition of the nitrophenyl group reduces the electrochemical stability of the catalyst. These observed catalytic behaviors are demonstrably different relative to the tetra-NH bridged macrocycle, which shows 98% faradaic efficiency for CO2-to-CO conversion with TFE, highlighting the importance of pendant hydrogen bond donors and electrochemically robust functional groups for selective CO2 conversion.

DNA methylation-based prognostic subtypes of chordoma tumors in tissue and plasma.

BACKGROUND: Chordomas are rare malignant bone cancers of the skull-base and spine. Patient survival is variable and not reliably predicted using clinical factors or molecular features. This study identifies prognostic epigenetic chordoma subtypes that are detected noninvasively using plasma methylomes. METHODS: Methylation profiles of 68 chordoma surgical samples were obtained between 1996 and 2018 across three international centers along with matched plasma methylomes where available. RESULTS: Consensus clustering identified two stable tissue clusters with a disease-specific survival difference that was independent of clinical factors in a multivariate Cox analysis (HR = 14.2, 95%CI: 2.1-94.8, P = 0.0063). Immune-related pathways with genes hypomethylated at promoters and increased immune cell abundance were observed in the poor-performing "Immune-infiltrated" subtype. Cell-to-cell interaction plus extracellular matrix pathway hypomethylation and higher tumor purity were observed in the better-performing "Cellular" subtype. The findings were validated in additional DNA methylation and RNA sequencing datasets as well as with immunohistochemical staining. Plasma methylomes distinguished chordomas from other clinical differential diagnoses by applying fifty chordoma-versus-other binomial generalized linear models in random 20% testing sets (mean AUROC = 0.84, 95%CI: 0.52-1.00). Tissue-based and plasma-based methylation signals were highly correlated in both prognostic clusters. Additionally, leave-one-out models accurately classified all tumors into their correct cluster based on plasma methylation data. CONCLUSIONS: Here, we show the first identification of prognostic epigenetic chordoma subtypes and first use of plasma methylome-based biomarkers to noninvasively diagnose and subtype chordomas. These results may transform patient management by allowing treatment aggressiveness to be balanced with patient risk according to prognosis.