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BackgroundWe examined the prognostic value of a panel of biomarkers in patients with squamous cell carcinoma of the head and neck (SCCHN) who were human immunodeficiency virus (HIV) positive (HIV-positive head and neck cancer) and HIV negative (HIV-negative head and neck cancer).MethodsTissue microarrays (TMAs) were constructed using tumors from 41 disease site-matched and age-matched HIV-positive head and neck cancer cases and 44 HIV-negative head and neck cancer controls. Expression of tumor biomarkers was assessed by immunohistochemistry (IHC) and correlations examined with clinical variables.ResultsExpression levels of the studied oncogenic and inflammatory tumor biomarkers were not differentially regulated by HIV status. Among patients with HIV-positive head and neck cancer, laryngeal disease site (P = .003) and Clavien-Dindo classification IV (CD4) counts

Epidermal growth factor receptor (EGFR) and COX-2 inhibitors synergistically inhibit head and neck squamous cell carcinoma tumorigenesis in preclinical studies. We conducted a phase I and pharmacokinetic study with the erlotinib and celecoxib combination in patients with advanced premalignant lesions. Thirty-six subjects with oral leukoplakia, mild, moderate, or severe dysplasia, or carcinoma in situ were screened for study participation; 12 consented and received therapy for a median of 5.38 months. Erlotinib was escalated following a standard 3+3 design at 50, 75, and 100 mg orally daily and celecoxib was fixed at 400 mg twice daily for 6 months. Biopsy of lesions and cytobrush of normal mucosa were performed at baseline, 3, 6, and 12 months. Erlotinib pharmacokinetics were analyzed in 10 subjects. The maximum tolerated dose of erlotinib with celecoxib 400 mg BID was 50 mg per day with skin rash being the main observed toxicity. Overall histologic response rate was 63% (complete response, 43%; partial response, 14%; stable disease, 29%; and disease progression, 14%). With median follow-up of 36 months, mean time to progression to higher-grade dysplasia or carcinoma was 25.4 months. Downregulation of EGFR and p-ERK in follow-up biopsies correlated with response to treatment. Larger average erlotinib V/F (approximately 308 L) and CL/F (8.3 L/h) compared with previous studies may be related to relatively large average bodyweights. Average erlotinib t1/2 was 25.6 hours. Encouraging responses to the celecoxib and erlotinib combination correlated with EGFR pathway inhibition. Although erlotinib-related rash was the main limitation to dose escalation, the intervention was well tolerated.

Significance: Polarized hyperspectral microscopes with the capability of full Stokes vector imaging have potential for many biological and medical applications. Aim: The aim of this study is to investigate polarized hyperspectral imaging (PHSI) for improving the visualization of collagen fibers, which is an important biomarker related to tumor development, and improving the differentiation of normal and tumor cells on pathologic slides. Approach: We customized a polarized hyperspectral microscopic imaging system comprising an upright microscope with a motorized stage, two linear polarizers, two liquid crystal variable retarders (LCVRs), and a compact SnapScan hyperspectral camera. The polarizers and LCVRs worked in tandem with the hyperspectral camera to acquire polarized hyperspectral images, which were further used to calculate four Stokes vectors: S0, S1, S2, and S3. Synthetic RGB images of the Stokes vectors were generated for the visualization of cellular components in PHSI images. Regions of interest of collagen, normal cells, and tumor cells in the synthetic RGB images were selected, and spectral signatures of the selected components were extracted for comparison. Specifically, we qualitatively and quantitatively investigated the enhanced visualization and spectral characteristics of dense fibers and sparse fibers in normal stroma tissue, fibers accumulated within tumors, and fibers accumulated around tumors. Results: By employing our customized polarized hyperspectral microscope, we extract the spectral signatures of Stokes vector parameters of collagen as well as of tumor and normal cells. The measurement of Stokes vector parameters increased the image contrast of collagen fibers and cells in the slides. Conclusions: With the spatial and spectral information from the Stokes vector data cubes (S0, S1, S2, and S3), our PHSI microscope system enhances the visualization of tumor cells and tumor microenvironment components, thus being beneficial for pathology and oncology. [ABSTRACT FROM AUTHOR]

PurposeWe investigated the efficacy and underlying molecular mechanism of a novel chemopreventive strategy combining EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) with cyclooxygenase-2 inhibitor (COX-2I).Experimental designWe examined the inhibition of tumor cell growth by combined EGFR-TKI (erlotinib) and COX-2I (celecoxib) treatment using head and neck cancer cell lines and a preventive xenograft model. We studied the antiangiogenic activity of these agents and examined the affected signaling pathways by immunoblotting analysis in tumor cell lysates and immunohistochemistry (IHC) and enzyme immunoassay (EIA) analyses on the mouse xenograft tissues and blood, respectively. Biomarkers in these signaling pathways were studied by IHC, EIA, and an antibody array analysis in samples collected from participants in a phase I chemoprevention trial of erlotinib and celecoxib.ResultsThe combined treatment inhibited head and neck cancer cell growth significantly more potently than either single agent alone in cell line and xenograft models, and resulted in greater inhibition of cell-cycle progression at G1 phase than either single drug. The combined treatment modulated the EGFR and mTOR signaling pathways. A phase I chemoprevention trial of combined erlotinib and celecoxib revealed an overall pathologic response rate of 71% at time of data analysis. Analysis of tissue samples from participants consistently showed downregulation of EGFR, pERK, and pS6 levels after treatment, which correlated with clinical response.ConclusionTreatment with erlotinib combined with celecoxib offers an effective chemopreventive approach through inhibition of EGFR and mTOR pathways, which may serve as potential biomarkers to monitor the intervention of this combination in the clinic. Clin Cancer Res; 19(5); 1244-56. ©2013 AACR.

Drawing on work--family enrichment theory, we explore whether inclusive leadership leads to employees' work-to-family positive spillover, which further improves their family performance. We also focus on the moderating role of complementary values. A time-lagged study was conducted and the sample included 292 employees from two hotels. The results indicate that inclusive leadership triggers employees' work-to-family positive spillover, and then their family performance is enhanced. Moreover, employees' complementary values may strengthen the positive effect of inclusive leadership. We also provide theoretical and practical implications of the results. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this paper is to examine factors associated with discharge destination after acquired brain injury in a publicly insured population using the Anderson Behavioral Model as a framework. Methods We utilized a retrospective cohort design. Inpatient data from provincial acute care records from fiscal years 2003/4 to 2006/7 with a diagnostic code of traumatic brain injury (TBI) and non-traumatic brain injury (nTBI) in Ontario, Canada were obtained for the study. Using multinomial logistic regression models, we examined predisposing, need and enabling factors from inpatient records in relation to major discharge outcomes such as discharge to home, inpatient rehabilitation and other institutionalized care. Results Multinomial logistic regression revealed that need factors were strongly correlated with discharge destinations overall. Higher scores on the Charlson Comorbidity Index were associated with discharge to other institutionalized care in the nTBI population. Length of stay and special care days were identified as markers for severity and were both strongly positively correlated with discharge to other institutionalized care and inpatient rehabilitation, compared to discharge home, in both nTBI and TBI populations. Injury by motor vehicle collisions was found to be positively correlated with discharge to inpatient rehabilitation and other institutionalized care for patients with TBI. Controlling for need factors, rural location was associated with discharge to home versus inpatient rehabilitation. Conclusions These findings show that need factors (Charlson Comorbidity Index, length of stay, and number of special care days) are most significant in terms of discharge destination. However, there is evidence that other factors such as rural location and access to supplemental insurance (e.g., through motor vehicle insurance) may influence discharge destination outcomes as well. These findings should be considered in creating more equitable access to healthcare services across the continuum of care.

Abstract Background It is essential to use a definition that is precise and accurate for the surveillance of traumatic brain injuries (TBI) and spinal cord injuries (SCI). This paper reviews the International Classification of Diseases 10th revision (ICD-10) definitions used internationally to inform the definition for neurotrauma surveillance using administrative data in Ontario, Canada. Methods PubMed, Web of Science, Medline and the grey literature were searched for keywords "spinal cord injuries" or "brain injuries" and "international classification of diseases". All papers and reports that used an ICD-10 definition were included. To determine the ICD-10 codes for inclusion consensus across papers and additional evidence were sought to look at the correlation between the condition and brain or spinal injuries. Results Twenty-four articles and reports were identified; 15 unique definitions for TBI and 7 for SCI were found. The definitions recommended for use in Ontario by this paper are F07.2, S02.0, S02.1, S02.3, S02.7, S02.8, S02.9, S06, S07.1, T90.2, and T90.5 for traumatic brain injuries and S14.0, S14.1, S24.0, S24.1, S34.1, S34.0, S34.3, T06.0, T06.1 and T91.3 for spinal cord injuries. Conclusions Internationally, inconsistent definitions are used to define brain and spinal cord injuries. An abstraction study of data would be an asset in understanding the effects of inclusion and exclusion of codes in the definition. This paper offers a definition of neurotrauma for surveillance in Ontario, but the definition could be applied to other countries that have mandated administrative data collection.

Background: There is conflicting evidence regarding the role of peritumoral lymphatic vessel density (LVD) and blood microvessel density (MVD) in the metastasis and prognosis of head and neck squamous cell carcinoma (HNSCC). Existing studies are limited to one or two head and neck subsites and/or small sample sizes. A larger study incorporating multiple sub‐sites is needed to address the role of peritumoral LVD and MVD in HNSCC metastasis and prognosis. Methods: Tissue samples from 200 HNSCC cases were stained simultaneously using immunohistochemistry (IHC) for markers of peritumoral LVD (lymphatic vessel marker D240) and MVD (blood vessel marker CD31). Of the stained slides, 166 and 167 were evaluable for LVD and MVD, respectively. The results were then correlated with clinicopathologic features and patient outcomes. Results: Patients with metastatic disease were more likely to have high peritumoral MVD. Through multivariable analyses, MVD was not significantly related to DFS and OS, while low LVD was related to higher risk of disease progression and poor survival. Conclusions: Peritumoral MVD was found to be positively associated with metastasis, while LVD was found to be inversely related to both metastasis and progression of HNSCC. These findings may suggest a prognostic role of both peritumoral LVD and MVD in patients with HNSCC. In the current study, we used a larger sample size which incorporates multiple sub‐sites to address the role of peritumoral LVD and MVD in HNSCC metastasis and prognosis. It was found that peritumoral MVD was positively associated with metastasis, while LVD was inversely related to both metastasis and progression of HNSCC. These findings may suggest a prognostic role of both peritumoral LVD and MVD in patients with HNSCC. [ABSTRACT FROM AUTHOR]

A label-free, hyperspectral imaging (HSI) approach has been proposed for tumor margin assessment. HSI data, i.e., hypercube (x,y,λ), consist of a series of high-resolution images of the same field of view that are acquired at different wavelengths. Every pixel on an HSI image has an optical spectrum. In this pilot clinical study, a pipeline of a machine-learning-based quantification method for HSI data was implemented and evaluated in patient specimens. Spectral features from HSI data were used for the classification of cancer and normal tissue. Surgical tissue specimens were collected from 16 human patients who underwent head and neck (H&N) cancer surgery. HSI, autofluorescence images, and fluorescence images with 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) and proflavine were acquired from each specimen. Digitized histologic slides were examined by an H&N pathologist. The HSI and classification method were able to distinguish between cancer and normal tissue from the oral cavity with an average accuracy of 90% ± 8%, sensitivity of 89% ± 9%, and specificity of 91% ± 6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94% ± 6%, sensitivity of 94% ± 6%, and specificity of 95% ± 6%. HSI outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study demonstrated the feasibility of label-free, HSI for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the HSI technology is warranted for its application in image-guided surgery. [ABSTRACT FROM AUTHOR]

T lymphocytes expressing CD57 and lacking costimulatory receptors CD27/CD28 have been reported to accumulate with aging, chronic infection, and cancer. These cells are described as senescent, with inability to proliferate but enhanced cytolytic and cytokine-producing capacity. However, robust functional studies on these cells taken directly from cancer patients are lacking. We isolated these T cells and their CD27/28+ counterparts from blood and tumor samples of 50 patients with previously untreated head and neck cancer. Functional studies confirmed that these cells have enhanced ability to degranulate and produce IFN-γ. They also retain the ability to proliferate, thus are not senescent. These data suggest that CD27/28-CD57+ CD8+ T cells are a subset of highly differentiated, CD45RA+ effector memory (T EMRA ) cells with retained proliferative capacity. Patients with > 34% of these cells among CD8+ T cells in the blood had a higher rate of locoregional disease relapse, suggesting these cells may have prognostic significance., Competing Interests: NCS discloses consulting fees from Sensorion, Regeneron, and GeoVax in addition to research funding from Astex Pharmaceuticals. The authors have no conflicting financial interests related to this work., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

As the COVID-19 pandemic continues to unfold and states experience the impacts of reopened economies, it is critical to efficiently manage new outbreaks through widespread testing and monitoring of both new and possible cases. Existing labor-intensive public health workflows may benefit from information collection directly from individuals through patient-reported outcomes (PROs) systems. Our objective was to develop a reusable, mobile-friendly application for collecting PROs and experiences to support COVID-19 symptom self-monitoring and data sharing with appropriate public health agencies, using Fast Healthcare Interoperability Resources (FHIR) for interoperability. We conducted a needs assessment and designed and developed StayHome, a mobile PRO administration tool. FHIR serves as the primary data model and driver of business logic. Keycloak, AWS, Docker, and other technologies were used for deployment. Several FHIR modules were used to create a novel "FHIR-native" application design. By leveraging FHIR to shape not only the interface strategy but also the information architecture of the application, StayHome enables the consistent standards-based representation of data and reduces the barrier to integration with public health information systems. FHIR supported rapid application development by providing a domain-appropriate data model and tooling. FHIR modules and implementation guides were referenced in design and implementation. However, there are gaps in the FHIR specification which must be recognized and addressed appropriately. StayHome is live and accessible to the public at https://stayhome.app. The code and resources required to build and deploy the application are available from https://github.com/uwcirg/stayhome-project., (This is an Open Access article. Authors own copyright of their articles appearing in the Journal of Public Health Informatics. Readers may copy articles without permission of the copyright owner(s), as long as the author and OJPHI are acknowledged in the copy and the copy is used for educational, not-for-profit purposes.)