Citations

AbstractNew medical compression technologies that are simultaneously low‐profile, facile to don, and dynamic—applying medical compression only when needed—can expand the use of wearable compression, increase patient compliance, and lead to better medical outcomes. Dynamic and conformal wearable compression devices are presented that can be donned in a low‐stiffness state and transition into a high‐stiffness and, consequently, high‐compression state, on‐demand. These devices are enabled by active textiles developed from custom NiTi filaments that remain inactive at room temperature and accomplish actuation proximal to the human body surface. Further, these compression devices exploit NiTi material hysteresis to sustain a high‐compression state post‐heating and upon equilibrium with the body surface temperature for thermally‐comfortable, on‐body performance. Two case study examples—1) a consumer medical compression device and 2) a custom astronaut compression device—demonstrate the generalizability and flexibility of the engineering and design methods to develop a range of dynamic, tunable, and conformal compression devices with different goals and requirements. Further, this work demonstrates a roadmap for developing wearable systems that can accommodate a range of users without sacrificing system performance. This research opens doors for new NiTi‐based medical and consumer applications that interface with the body surface.

Abstract Objectives: We hypothesize that a validated panel of methylated DNA markers (MDMs) for HPV(+)CSCC will be similar to but distinct from a cohort of HPV(+)OPSCC. Methods: Patients were excluded for recurrent tumor, prior pelvic or head or neck cancer/neoplasia, chemotherapy < 1 year, prior therapeutic radiation to the target region, prior transplant, insufficient target tissue (<5mm), or if <18 yrs. MDMs identified from sequenced differentially methylated regions were selected from a panel validated for HPV(+)CSCC and evaluated on DNA from independent FFPE HPV(+)OPSCC, HPV(+)CSCC, normal oropharynx tonsil, and normal cervix tissue using methylation-specific PCR. White blood cells (WBCs) were used as a background control. Results: 34 HPV(+)OPSCC, 36 HPV(+)CSCC, 26 normal tonsil tissue, and 24 normal cervical tissue patients met criteria. The HPV(+)OPSCC cohort was older (57 vs 44 yrs, p=0.027), had more frequent alcohol exposure (85% vs 64%, p=0.02), but similar ACE-27 comorbidity scores (p=0.078) and tobacco use (p=0.066). Tumor stages were stage I (47% and 83%), stage II (44% and 11%) and stage III (9% and 6%) for HPV(+)OPSCC and HPV(+)CSCC, respectively. Twenty-one MDMs were evaluated and areas under the receiver operator characteristic curve (AUC) are reported (Table 1). 95% confidence intervals excluded a non-diagnostic null hypothesis AUC of 0.5. 5/21 (24%) achieved an AUC ≥ 0.90, 15/21 (71%) achieved an AUC ≥ 0.8, and 19/21 (90%) exhibited better than chance classifications relative to control tonsil tissue (all p<0.001). Conclusion: MDMs have the potential to discriminate both HPV(+)OPSCC and HPV(+)CSCC from their normal tissue controls. 90% of the MDMs discovered for HPV(+)CSCC had better than chance discrimination in HPV(+)OPSCC suggesting a distinct signature between the two subtypes. Future discovery efforts specific to HPV(+)OPSCC is warranted. Methylated DNA Markers in HPV(+)OPSCC and HPV(+)CSCC CSCC AUC (95% CI) OPSCC AUC (95% CI) AUC CSCC vs AUC OPSCC Pvalue GRIN2D 0.72 (0.59-0.85) 0.91 (0.83-0.99) 0.019 EMX1 0.93 (0.86-0.99) 0.77 (0.65-0.89) 0.0191 VWC2 0.88 (0.79-0.97) 0.57 (0.42-0.72) 0.0001 ZNF610 0.99 (0.98-1) 0.89 (0.8-0.97) 0.0162 ZNF781.F 0.92 (0.86-0.99) 0.79 (0.67-0.91) 0.0585 TBX15 0.99 (0.96-1) 0.82 (0.72-0.93) 0.0025 TSPYL5 0.94 (0.87-1) 0.82 (0.72-0.93) 0.058 LOC645323 0.95 (0.89-1) 0.88 (0.8-0.97) 0.1952 ASCL1 0.98 (0.93-1) 0.86 (0.76-0.95) 0.0187 ABCB1 0.97 (0.93-1) 0.74 (0.61-0.86) 0.0001 ZNF69 0.89 (0.8-0.97) 0.95 (0.9-1) 0.2017 MAX.chr9 0.97 (0.92-1) 0.82 (0.72-0.93) 0.0113 ARHGAP12 0.91 (0.83-0.99) 0.9 (0.81-1) 0.9223 C1orf114 0.94 (0.86-1) 0.88 (0.8-0.97) 0.3366 MAX.chr6 0.99 (0.97-1) 0.86 (0.76-0.96) 0.0099 NEUROG3 0.95 (0.89-1) 0.7 (0.57-0.83) 0.0001 NID2 0.98 (0.95-1) 0.86 (0.77-0.95) 0.0207 TMEM200C 0.95 (0.89-1) 0.54 (0.39-0.69) 0.0001 TTYH1 0.99 (0.98-1) 0.82 (0.71-0.93) 0.0023 ZNF773 0.93 (0.86-1) 0.9 (0.82-0.98) 0.5696 ZNF781.R 1 (1-1) 0.92 (0.86-0.99) 0.0198 Citation Format: Kathryn M. Van Abel, David M. Routman, Daniel J. Ma, Karen A. Doering, Kelli N. Burger, Patrick H. Foote, William R. Taylor, Douglas W. Mahoney, Calise K. Berger, Xiaoming Cao, Sara S. Then, Alyssa M. Larish, Eric J. Moore, Joaquin G. Garcia, Rondell P. Graham, Jamie N. Bakkum-Gamez, John B. Kisiel. Comparison of methylated DNA markers between human papillomavirus mediated carcinoma in oropharynx and cervical cancer: A pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3742.

PURPOSE Representativeness in acute leukemia clinical research is essential for achieving health equity. The National Cancer Institute's mandate for Comprehensive Cancer Centers (CCCs) to define and assume responsibility for cancer control and treatment across a geographic catchment area provides an enforceable mechanism to target and potentially remediate participatory inequities. METHODS We examined enrollee characteristics across 15 Cancer and Leukemia Group B/Alliance cooperative group adult acute leukemia clinical trials (N = 3,734) from 1998 to 2013, including participation in optional companion biobanks. We determined enrollment odds by race-ethnicity for all participants adjusted for national incidence, and for those enrolled at CCCs adjusted for catchment area incidence. We modeled biobank participation by sociodemographics using logistic regression. RESULTS Non-Hispanic (NH)-White patients were more likely to be enrolled than NH-Black, NH-Asian, or Hispanic patients (odds ratio [OR], 0.75, 0.48, and 0.44, respectively; all P < .001), but less likely than NH-Native American patients (OR, 1.91; P < .001), adjusted for national incidence. Enrollment odds were lower for NH-Black, NH-Asian, and Hispanic patients at CCCs adjusted for catchment area incidence (OR, 0.57, 0.26, and 0.32, respectively; P < .001); differences were driven by overenrollment of NH-White patients from outside self-defined catchment areas (18.1% v 12.3%; χ2 P = .01) and by CCCs with less absolute enrollee diversity (rank sum P = .03). Among all enrollees, NH-White race-ethnicity and lower neighborhood deprivation correlated with biobank participation (OR, 1.81 and 1.45, respectively; P = .01 and .03). For CCC enrollees, the correlation of race-ethnicity with biobank participation was attenuated by a measure accounting for their site's degree of enrollment disparity but not neighborhood deprivation. CONCLUSION Acute leukemia clinical research disparities are substantial and driven by structural trial enrollment barriers at CCCs. Real-time CCC access and enrollment monitoring is needed to better align research participation with local populations.

AbstractObjectiveEsthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. The goal of this study was to update our oncologic outcomes for this disease and explore prognostic factors associated with survival.Materials and methodsWe performed a retrospective analysis of patients with ENB treated at a single tertiary care institution from January 1, 1960, to January 1, 2020. Univariate and multivariate analysis was performed. Overall survival (OS), progression‐free survival (PFS), and distant metastasis–free survival (DMFS) were reported.ResultsAmong 143 included patients, the 5‐year OS was 82.3% and the 5‐year PFS was 51.6%; 5‐year OS and PFS have improved in the modern era (2005–present). Delayed regional nodal metastasis was the most common site of recurrence in 22% of patients (median, 57 months). On univariate analysis, modified Kadish staging (mKadish) had a negative effect on OS, PFS, and DMFS (p < 0.05). Higher Hyams grade had a negative effect on PFS and DMFS (p < 0.05). Positive margin status had a negative effect on PFS (p < 0.05). Orbital invasion demonstrated worsening OS (hazard ratio, 3.1; p < 0.05). On multivariable analysis, high Hyams grade (3 or 4), high mKadish stage (C+D), and increasing age were independent negative prognostic factors for OS (p < 0.05). High Hyams grade (3+4), high mKadish stage (C+D), age, and positive margin status were independent negative prognostic factors for PFS (p < 0.05). High Hyams grade (3+4) was an independent negative prognostic factor for DMFS (p < 0.05).ConclusionsPatients with low Hyams grade and mKadish stage have favorable 5‐year OS, PFS, and DMFS.

ObjectivesTo measure baseline human papillomavirus (HPV) vaccination rates among tertiary and community‐based Otolaryngology – Head and Neck Surgery (Oto‐HNS) clinic patients and to determine risk factors for under‐vaccination.MethodsRetrospective chart review of patients aged 9 to 26 years presenting to an Oto‐HNS clinic from 2017 to 2019. Patients were considered complete for HPV vaccination if they received two doses of HPV vaccine with the first dose received before age 15 years or three doses of HPV vaccine otherwise.Results8,532 unique patients met the criteria. At the index visit, 3,110 (36.5%) had completed the HPV series, 5,422 (63.5%) were due for one or more doses, with 4,981 (58.4%) eligible for vaccination at the time of their appointment. Of those dues, most (3,148/5,422 or 58%) were past due by age (≥13 years old). Of the 3,148 patients past due, 745 (23.7%) were partially vaccinated and 2,403 (76.3%) were vaccine naïve. Male sex and younger age were both independently associated with incomplete vaccination (p < 0.0001).ConclusionThis study demonstrates that the implementation of on‐site HPV vaccination has the potential to increase the opportunities for vaccination among vaccine‐eligible patients, especially among young males. Otolaryngologists have the potential to provide meaningful preventive services in the fight against HPV‐mediated disease.Level of Evidence3 Laryngoscope, 133:116–123, 2023

Background: Normal weight adults gain leg fat gain via adipocyte hyperplasia and upper body subcutaneous (UBSQ) fat gain via adipocyte hypertrophy. Objective: To understand whether regional fat loss mirrors fat gain and whether leg fat loss results in decreased adipocyte number vs. size. Design: We assessed UBSQ, leg and visceral fat gain and loss in response to over- and underfeeding in 23 young, healthy normal weight adults (15 men). Participants gained ∼5% weight over 8 weeks and lost ∼80% of gained fat over the following 8 weeks. We measured abdominal subcutaneous and femoral adipocyte size and number after weight gain and loss. Results: Volunteers gained 3.1 ± 2.1 kg of body fat with overfeeding and lost 2.4 ± 1.7 kg with calorie restriction. Although upper body subcutaneous (UBSQ) fat and visceral fat gains were completely reversed with weight loss, leg fat had not yet returned to baseline values by 8 weeks. Abdominal and femoral adipocyte size decreased significantly with weight loss, but the number of adipocytes did not decrease. Abdominal adipocyte size decreases correlated (rho= 0.76, p = 0.001) with UBSQ fat mass decreases and femoral adipocyte size decreases correlated (rho= 0.49, p=0.05) with leg fat mass decreases. Conclusion: UBSQ and visceral fat depots increase and decrease proportionately with short term weight gain and loss, whereas gain and loss of leg fat are less well linked. Loss of lower body fat is due to reduced fat cell size, not number, which may result in long-term increases in leg fat cell number. This may have implications for long-term weight control.

Objectives To identify the differences in sensitivity and accuracy between ultrasound‐guided and palpation‐guided fine needle aspirations (FNA) of suspicious lymph nodes in patients with human papillomavirus (HPV) (+) oropharyngeal squamous cell carcinoma (OPSCC). Additional objectives included identifying patient specific factors affecting biopsy accuracy and evaluating potential differences in accuracy between fine and core needle biopsies. Study Design Retrospective chart review. Materials and Methods A retrospective study of diagnostic sensitivity was completed at a single tertiary care center between 1/1/2006–12/31/2016. Participants included patients who underwent pretreatment FNA biopsy with HPV(+)OPSCC confirmed pathologically following neck dissection or excisional lymph node biopsy. A true positive (TP) on FNA biopsy was defined as an FNA biopsy concerning for squamous cell carcinoma (SCC) that was confirmed on excisional biopsy or neck dissection. A false negative (FN) was defined as a negative FNA but metastatic disease identified on excisional biopsy or neck dissection. Sensitivity was calculated as TPs/(TPs + FNs). Sensitivity was compared among techniques using chi‐square and Fisher exact tests. Results A total of 209 FNA biopsies among 198 patients were included in the study, including 31 (15%) palpation‐guided FNAs, 160 (77%) ultrasound‐guided FNAs, and 18 (9%) ultrasound‐guided FNA + core biopsies. Sensitivity was significantly different among palpation‐guided FNA, ultrasound‐guided FNA, and ultrasound‐guided FNA + core biopsies (48% vs. 83% vs. 94%, respectively; P < .001) but there was no significant difference in sensitivity between ultrasound‐guided FNA versus ultrasound‐guided FNA + core biopsies ( P = .31). Conclusion The use of ultrasound guidance in FNA biopsies of nodal metastases in HPV(+)OPSCC improves sensitivity compared to palpation guidance alone. Ultrasound guided biopsies are preferred in patients with suspected nodal metastasis from HPV(+)OPSCC. Level of Evidence 3 Laryngoscope , 132:2396–2402, 2022