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Although cancer associated fibroblast (CAF) heterogeneity is recognized in oral squamous cell carcinoma (OSCC), the phenotype and role of CAF subpopulations in OSCC is still unknown. This study aimed to develop a method to identify and spatially define CAF subpopulations on formalin fixed paraffin embedded (FFPE) tissues from primary OSCC. Imaging mass cytometry was used to identify 24 markers (E-cadherin, EGFR, Ki-67, α-SMA, CD140β, FAP, FSP-1/S100A4, CD90/Thy-1, integrin α-11, collagen-1, tenascin-C, caveolin-1, CD4, CD8a, CD16, CD20, CD68, CD163, FoxP3, granzyme B, CD31, podoplanin, CD146, and YAP-1) in HPV-negative OSCC lesions (n=5). Tissue images were segmented employing the Steinbock framework. Unsupervised clustering of single-cell data was carried out using a bioinformatics pipeline developed in R language. Unsupervised clustering identified several major cell types, with E-cadherin+ cells being the most abundant (30% and CD146+ being the least abundant cell type (0.62%). Among the immune component, CD4+ were most abundant (11.72%) followed by CD8+ (10.6%) and CD68+ (10.25%). Two clusters were negative for other major lineage markers and positive for stromal markers. These were defined as CAF-1 (high αSMA, CD140β, and CD90) and CAF-2 (high FAP and collagen-1). CAF-1 subtype was found closer to immune cells whereas CAF-2 were closely located to cancer cells. Based on integrin α-11, FSP-1/S100A4 and podoplanin these could be further dissected in 6 CAF clusters. The pipeline developed here shows promise for understanding clinical implications of CAF heterogeneity in clinical samples from large OSCC patient cohorts with FFPE tissues available in diagnostic biobanks. [ABSTRACT FROM AUTHOR]

Background: This study was performed in order to determine whether monocyte in vitro function is associated with presence, stage and prognosis of head and neck squamous cell carcinoma (HNSCC) disease.Methods: Prospective study describing outcome, after at least five years observation, of patients treated for HNSCC disease in relation to their monocyte function. Sixty-five patients with newly diagnosed HNSCC and eighteen control patients were studied. Monocyte responsiveness was assessed by measuring levels of monocyte in vitro interleukin (IL)-6 and monocyte chemotactic peptide (MCP)-1 secretion after 24 hours of endotoxin stimulation in cultures supplied either with 20% autologous serum (AS) or serum free medium (SFM). Survival, and if relevant, cause of death, was determined at least 5 years following primary diagnosis.Results: All patients, as a group, had higher in vitro monocyte responsiveness in terms of IL-6 (AS) (t = 2.03; p < 0.05) and MCP-1 (SFM) (t = 2.49; p < 0.05) compared to controls. Increased in vitro monocyte IL-6 endotoxin responsiveness under the SFM condition was associated with decreased survival rate (Hazard ratio (HR) = 2.27; Confidence interval (CI) = 1.05-4.88; p < 0.05). The predictive value of monocyte responsiveness, as measured by IL-6, was also retained when adjusted for age, gender and disease stage of patients (HR = 2.67; CI = 1.03-6.92; p < 0.05). With respect to MCP-1, low endotoxin-stimulated responsiveness (AS), analysed by Kaplan-Meier method, predicted decreased survival (chi = 4.0; p < 0.05).Conclusion: In HNSCC patients, changed monocyte in vitro response to endotoxin, as measured by increased IL-6 (SFM) and decreased MCP-1 (AS) responsiveness, are negative prognostic factors. [ABSTRACT FROM AUTHOR]

To examine the survival prediction of head and neck (H&N) Health Related Quality of Life (HRQoL) scores among successfully treated and cognitive functioning H&N squamous cell carcinoma (HNSCC) patients. Through structured interviews, self-reported questionnaires were given to 139 successfully treated HNSCC patients, 67±32months following diagnosis. HRQoL-scores, measured with the EORTC QLQ-H&N35 inventory, self-reported levels of neuroticism, avoidance focused coping, coping by suppression of competing activity, alcohol consumption, smoking status, and heart and lung disease, as well as gender, age, TNM-stage, and tumor site were determined. The mean observation period was 75±4months among the survivors. Twenty-four deaths were observed. A EORTC QLQ-H&N35 sum score, including a dichotomized version (HR 2.73-3.67), was predictive of survival, both directly and after adjustment for all of the above mentioned variables. The H&N HRQoL indices 'feeling ill', 'sexuality', 'open mouth', 'swallowing', and 'pain' specifically predicted survival. The dichotomized H&N HRQoL sum score compared the 4th upper quartile to the three lower quartiles, and a cut off value of 28.5 was designated. Analyses demonstrated that a high risk group with 33% mortality may include only one quarter of the patient population as opposed to 12.5% mortality among the other patients. Our findings indicate a unique survival prediction from EORTC QLQ-H&N35 sum scores in successfully treated HNSCC patients. HRQoL scores, in particular, related to oral health, predicted survival. Furthermore, HRQoL-scores may be a screening tool for identifying patients with high mortality risk. [ABSTRACT FROM AUTHOR]

Background: Our aim was to investigate oral health in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients in relation to long-term survival. We assessed whether the level of alveolar bone loss due to periodontitis at diagnosis, measured from orthopantomogram (OPG), and reported dental health-related quality of life (HRQoL) scores obtained at diagnosis contain prognostic information for HNSCC patients., Methods: A total of 79 patients from a consecutive cohort of 106 diagnosed with HNSCC between November 2002 and June 2005 were included. All patients reported dental HRQoL, OPG-determined alveolar bone loss were measured in 79 patients at diagnosis. Reduced alveolar bone loss (≥ 4 mm) from cement-enamel junction on at least two molars or premolars registered both horizontally and vertically served as indicator of periodontal disease., Results: With alveolar bone loss, we determined increased mortality by univariate analysis (RR = 2.28, CI: 1.22-4.28, p = 0.01) and a strong trend by multivariate analyses adjusted for standard clinical information (RR = 1.95, CI: 0.98-3.87, p = 0.056). Reported lowered dental HRQoL scores predicted long-term survival in both univariate (RR = 3.58, CI: 1.99-6.45, p < 0.001) and multivariate adjusted for standard clinical information (RR = 2.17, CI: 1.17-4.01, p = 0.014). When analyzed with Cox regression, including alveolar bone loss and dental HRQoL, both factors, adjusted by clinical variables, were significant predictors of long-term survival: dental HRQoL (p = 0.007) and present alveolar bone loss (p = 0.034). Non-HNSCC disease-specific long-term survival predicted was also predicted when alveolar bone loss and dental HRQoL were analyzed simultaneously and adjusted for standard clinical information., Conclusions: The degree of alveolar bone loss, as determined by OPG, and dental HRQoL both obtained at the time of HNSCC diagnosis, predicted long-term survival. When analyzed simultaneously, both factors remained significant in both univariate and multivariate analyses, adjusted by pertinent clinical variables, highlighting their unique prognostic value., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Norwegian regional ethics committee (REK VEST 2011 − 125) and performed in accordance with the Declaration of Helsinki. Informed consent to participate was obtained from all the participants in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: Assess the association of hearing on sex-specific overall mortality and death from acute cardiovascular disease and evaluate if these effects are modulated by postural balance., Study Design: Cohort study., Setting: Otolaryngology department at an academic hospital., Methods: Patients underwent standard clinical examination, laboratory examination including stabilometry and audiometry. Pure tone average on the best hearing ear was calculated from 0.5, 1, 2, and 3 kHz. Cause of death was retrieved from the Norwegian Cause of Death Registry., Results: A total of 1036 patients (58.8% women) were followed for 26 ± 3 years. In Cox regression analyses for overall mortality adjusted for age, past medical history, and vestibular disease, 10 dB increase in hearing threshold was associated with a 14% increase in mortality among men (hazard ratio 95% confidence interval: 1.02-1.28, P = .02), but no significant association was seen between hearing and mortality in women (0.92-1.15, P = .60). The same analyses for acute cardiovascular death found that a 10 dB increase in hearing threshold was associated with a 57% increase in hazard ratio in men (1.21-2.05, P < .001), but no significant effect of hearing on survival was seen in women (P = .71). Adjusting for postural balance did not change the association between hearing and mortality., Conclusion: This study finds hearing threshold is associated with overall mortality and acute cardiovascular death among men, with no such association observed among women. Our findings indicate important differences between men and women and suggest that such differences should be taken into consideration in audiological research., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

To decipher the interactions between various components of the tumor microenvironment (TME) and tumor cells in a preserved spatial context, a multiparametric approach is essential. In this pursuit, imaging mass cytometry (IMC) emerges as a valuable tool, capable of concurrently analyzing up to 40 parameters at subcellular resolution. In this study, a set of antibodies was selected to spatially resolve multiple cell types and TME elements, including a comprehensive panel targeted at dissecting the heterogeneity of cancer-associated fibroblasts (CAF), a pivotal TME component. This antibody panel was standardized and optimized using formalin-fixed paraffin-embedded tissue (FFPE) samples from different organs/lesions known to express the markers of interest. The final composition of the antibody panel was determined based on the performance of conjugated antibodies in both immunohistochemistry (IHC) and IMC. Tissue images were segmented employing the Steinbock framework. Unsupervised clustering of single-cell data was carried out using a bioinformatics pipeline developed in R program. This paper provides a detailed description of the staining procedure and analysis workflow. Subsequently, the panel underwent validation on clinical FFPE samples from head and neck squamous cell carcinoma (HNSCC). The panel and bioinformatics pipeline established here proved to be robust in characterizing different TME components of HNSCC while maintaining a high degree of spatial detail. The platform we describe shows promise for understanding the clinical implications of TMA heterogeneity in large patient cohorts with FFPE tissues available in diagnostic biobanks worldwide., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Harsh Nitin Dongre reports financial support was provided by 10.13039/501100005416Research Council of Norway, Norway. Daniela Elena Costea reports financial support was provided by Western Norway Regional Health Authority, Norway. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (-) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 ( p < 0.001/ p < 0.001) (DSS/OS), IL-31 ( p = 0.044/ p = 0.07), IL-1RA ( p = 0.004/ p = 0.035), soluble (s)-IL-6Rα p = 0.022/ p = 0.035), and s-gp130 ( p = 0.007/ p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(-) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy.

Background: Somatic TP53 mutations are frequent in head and neck squamous cell carcinoma (HNSCC) and are important pathogenic factors., Objective: To study TP53 mutations relative to the presence of human papillomavirus (HPV) in tumors in HNSCC patients., Methods: Using a custom-made next-generation sequencing (NGS) panel on formalin-fixed, paraffin-embedded tumor tissue, we analyzed somatic TP53 mutations and the TP53 single-nucleotide polymorphism (SNP) codon 72 (P72R; rs1042522) (proline → arginine) from 104 patients with HNSCC., Results: Only 2 of 44 patients with HPV-positive (HPV(+)) HNSCC had a TP53 somatic mutation, as opposed to 42/60 HPV-negative (HPV(-)) HNSCC patients ( p < 0.001). Forty-five different TP53 somatic mutations were detected. Furthermore, in HPV(-) patients, we determined an 80% prevalence of somatic TP53 mutations in the TP53 R72 polymorphism cohort versus 40% in the TP53 P72 cohort ( p = 0.001). A higher percentage of patients with oral cavity SCC had TP53 mutations than HPV(-) oropharyngeal (OP) SCC patients ( p = 0.012). Furthermore, 39/44 HPV(+) tumor patients harbored the TP53 R72 polymorphism in contrast to 42/60 patients in the HPV(-) group ( p = 0.024)., Conclusions: Our observations show that TP53 R72 polymorphism is associated with a tumor being HPV(+). We also report a higher percentage of somatic TP53 mutations with R72 than P72 in HPV(-) HNSCC patients.

Oropharynx squamous cell carcinoma (OPSCC) is of special interest because human papilloma virus (HPV) and/or smoking cause this disease. Influxes of inflammatory cells into such tumors are known to vary with prognoses., Aims: To study whether the density of tumor-infiltrating T lymphocytes and tumor-infiltrating macrophages predicted general 20-year overall survival (OS), as well as OS with only disease-specific survival (DSS) patients included., Methods: Biopsies from patients treated for OPSCC ( n = 180) were stained by immunohistochemistry and the tumor cell macrophage (CD68), pan T lymphocytes (CD3), and regulatory T lymphocytes (Foxp3) densities were determined. The HE-determined percentage of matured tumor cells and the rate of invasion were calculated, and stromal desmoplasia were performed. Tumor HPV presence was studied by PCR. Twenty-year OS and five-year DSS patients were determined., Results: Tumor HPV status strongly predicted survival. High tumor infiltration of CD3, Foxp3 and CD68-positive cells predicted better twenty-year OS, with and without HPV stratification. Foxp3 and CD68 levels predicted OS, and 20-year among DSS patients, primarily among HPV(+) patients. Tumor HE-derived variables did not predict such survival., Conclusions: Tumor HPV status, level of Foxp3 tumor-infiltrating lymphocytes and CD68 tumor-infiltrating macrophages predicted up to 20-year OS of both all patients and disease-specific survived patients.

Objectives: Describe the relationship between unsteadiness, canal paresis, cerebrovascular risk factors, and long-term mortality in patients examined for dizziness of suspected vestibular origin., Study Design: Observational cohort with prospective collection of survival data., Setting: University clinic neurotological unit., Patients: Consecutive patients aged 18-75 years examined in the period 1992-2004 for dizziness of suspected vestibular origin., Outcome Measures: Overall survival. Standardized mortality ratio (SMR). Factors: Unsteadiness, canal paresis, age, sex, patient-reported diabetes, hypertension, heart disease, stroke, or TIA/minor stroke. Patients were classified as steady or unsteady based on static posturography at baseline compared to normative values., Results: The study included 1,561 patients with mean age 48 years and 60 % females. Mean follow-up was 22 years. Unsteadiness was associated with higher age, heart disease, diabetes, hypertension, and cerebrovascular dizziness. There were 336 deaths over 31,335 person-years (SMR 0.96; 95 % confidence interval: 0.86-1.07). Canal paresis was not related to unsteadiness (chi square: p = 0.46) or to mortality (unadjusted Cox hazard ratio: 1.04, 95% CI: 0.80-1.34). Unsteadiness was an independent predictor of mortality (adjusted Cox hazard ratio: 1.44, 95% CI: 1.14-1.82)., Conclusions: Unsteadiness measured by static posturography is associated with higher age, known cerebrovascular risk factors, and with increased long-term mortality, but not with canal paresis in patients evaluated for dizziness. The study highlights the importance of evaluating patients with conspicuous postural instability for non-vestibular causes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Berge, Goplen, Aarstad, Storhaug and Nordahl.)

Objective: The objective was to examine the psychometric properties of two questionnaires in Norwegian for the self-assessment of satisfaction following cochlear implantation., Design: The International Outcome Inventory for Hearing Aids adapted for cochlear implants (IOI-CI) and two revised subscales from the Norwegian translation of the Abbreviated Profile of Hearing Aid Benefit (APHAB) were applied. Internal consistency was tested using Cronbach's α . Testing of psychometric properties included the calculation of inter-item correlations and corrected item-total correlations. Spearman's rho was used to investigate associations. Exploratory principal component analyses with Kaiser normalisation were performed., Study Sample: One hundred and twenty-one patients (51 males) with cochlear implants (27-88 years, M  = 59)., Results: For IOI-CI, Cronbach's α was 0.79. Corrected item-total correlations ranged from 0.29 to 0.69. The factor analysis revealed two components. For APHAB, Cronbach's α was 0.91. Two components were revealed by the factor analysis. Corrected item-total correlations for the two subscales "communication in quiet situations" and "communication in adverse situations" were 0.47-0.81 and 0.58-0.80, respectively. The convergent validity of the questionnaires was adequate as reflected by a Spearman's coefficient of 0.67., Conclusion: Both questionnaires show good psychometric properties.

Head and neck cancer (HNC) is the sixth most common cancer worldwide. Oropharyngeal (OP) cancers are of special interest because of possible underlying HPV infection which is tied to prognosis. Influxes of inflammatory cells into tumors may vary with prognoses. We wanted to study whether the number of tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) in tumors correlated to HPV status and predicted 5-year disease-specific survival (DSS). Formalin-fixed paraffin-embedded (FFPE) biopsies cut sections from 170 patients treated for OP cancer were stained by immunohistochemistry and evaluated for the number of CD68 (+) TAMs, CD3 (+), and Foxp3 (+) (T regulatory) TILs. From FFPE slides HPV by PCR and p16 by immunohistochemistry were established. From FFPE Hematoxylin-Eosin slides, levels of tumor nuclear polymorphism, tumor invasion, desmoplasia, and inflammation were determined as previously published. Levels of TIL CD3 (+) and TIL Foxp3 (+) were increased among the HPV (+) compared to the HPV (-) patients. High levels of TIL Foxp3 (+) and CD68 (+) macrophages predicted better 5-year DSS. TIL Foxp3 (+) levels predicted independent of age, gender, TNM stage, and HPV infection as well as level of stromal desmoplasia, tumor invasion, and nuclear polymorphism, but more pronounced among tumor HPV (+) than HPV (-) patients.

Objective: To assess the psychometric properties of a Norwegian translation of the Tinnitus Handicap Inventory (THI-NOR)., Design: A survey was sent by post to patients referred with tinnitus as their main complaint to an audiology department. Patients completed a Norwegian version of the Tinnitus Handicap Inventory (THI-NOR), a Norwegian translation of two revised subscales of the Abbreviated profile of hearing aid benefit (APHAB), the General Health Questionnaire (GHQ-12) as well as questionnaires measuring coping expectancies (TOMCATS) and neuroticism (EPI)., Study Sample: Ninety-nine persons with tinnitus., Results: No associations were found between THI-scores or pure-tone audiometry, gender or age. The proposed subscales of the original THI were not formed by responses from responders. The total scale shows good psychometric properties. Significant correlations were found between distress as measured by the GHQ-12, coping expectancies as measured by TOMCATS and neuroticism as measured by EPI and THI scores., Conclusions: THI-NOR has psychometric properties similar to those of the Danish translation (THI-DK), from which it was adapted, and to the original THI. THI-NOR seems to be a valid measure of the impact of tinnitus on a person's everyday life. Findings show that the suggested subscales of the questionnaire should be interpreted with caution.

Background: Targeted next-generation sequencing (NGS) is increasingly applied in clinical oncology to advance personalized treatment. Despite success in many other tumour types, use of targeted NGS panels for assisting diagnosis and treatment of head and neck squamous cell carcinomas (HNSCC) is still limited., Aim: The focus of this study was to establish a robust NGS panel targeting most frequent cancer mutations in long-term preserved formalin-fixed paraffin-embedded (FFPE) tissue samples of HNSCC from routine diagnostics., Materials and Methods: Tumour DNA obtained from archival FFPE tissue blocks of HNSCC patients treated at Haukeland University Hospital between 2003-2016 (n=111) was subjected to mutational analysis using a custom made AmpliSeq Library PLUS panel targeting 31 genes (Illumina). Associations between mutational burden and clinical and pathological parameters were investigated. Mutation and corresponding clinicopathological data from HNSCC were extracted for selected genes from the Cancer Genome Atlas (TCGA) and used for Chi-square and Kaplan-Meier analysis., Results: The threshold for sufficient number of reads was attained in 104 (93.7%) cases. Although the specific number of PCR amplified reads detected decreased, the number of NGS-annotated mutations did not significantly change with increased tissue preservation time. In HPV-negative carcinomas, mutations were detected mainly in TP53 (73.3%), FAT1 (26.7%) and FLG (16.7%) whereas in HPV-positive, the common mutations were in FLG (24.3%) FAT1 (17%) and FGFR3 (14.6%) genes. Other less common pathogenic mutations, including well reported SNPs were reproducibly identified. Presence of at least one cancer-specific mutations was found to be positively associated with an extensive desmoplastic stroma (p=0.019), and an aggressive type of invasive front (p=0.035), and negatively associated with the degree of differentiation (p=0.041). Analysis of TCGA data corroborated the association between cancer-specific mutations and tumour differentiation and survival analysis showed that tumours with at least one mutation had shorter disease-free and overall survival (p=0.005)., Conclusions: A custom made targeted NGS panel could reliably detect several specific mutations in archival samples of HNSCCs preserved up to 17 years. Using this method novel associations between mutational burden and clinical and pathological parameters were detected and actionable mutations in HPV-positive HNSCC were discovered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dongre, Haave, Fromreide, Erland, Moe, Dhayalan, Riis, Sapkota, Costea, Aarstad and Vintermyr.)

Purpose: The main aim was to map serum levels of IL-1/IL-6 family cytokines and relevant receptors from serum samples taken across treatment in patients with Renal Cell Carcinoma (RCC). Additionally, we explored the possible interactions between these measurements, immunohistochemistry and intratumoral blood flow., Methods: We included 40 patients undergoing open surgery for renal tumors. Blood samples were collected before, during (taken simultaneously from a peripheral site and the renal vein (RV) before clamping) and after surgery. Samples were analyzed for IL-6, IL-27, IL-31, OSM, TNF-α, serum (s)-gp130, s-IL-6Rα, s-IL-33R, IL-1Rα and VEGF. All 35 RCC tumors were histologically subtyped as clear cell (CCRCC), papillary or chromophobe. Immunohistochemistry for the CCRCC group included expression of IL-6/IL-6R. Intratumoral blood flow was determined by calculating intratumoral contrast enhancement on preoperative computerized tomography (CT) imaging., Results: In the CCRCC patients, the intraoperative RV concentration of IL-6 was significantly higher than in both the preoperative and postoperative samples (p = 0.005 and p = 0.032, respectively). Furthermore, the intraoperative ratio showed significantly higher levels of IL-6 in the RV than in the simultaneously drawn peripheral sample. Immunohistochemistry showed general expression of IL-6 (23/24) in both tumor cells and the vasculature (20/23). Moreover, s-IL-6R was expressed in tumor cells in 23/24 studied patients. Increased blood flow in the CCRCC tumors predicted increased IL-6 levels in the RV (p < 0.001). The other cytokines and receptors showed an overall stability across the measurements. However, the intraoperative ratios of IL-33R and gp130 showed significantly higher levels in the RV., Conclusion: Serum levels of IL-6 increased during surgery. Intraoperative IL-6 and s-IL-33R values were higher in the RV compared to the periphery, suggesting secretion from the tumor or tumor microenvironment itself. Supportive of this is an almost general expression of IL-6/s-IL-6R in tumor cells and IL-6 in vasculature in the tumor microenvironment. Other studied cytokines/receptors were remarkably stable across all measurements., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: According to the World Health Organization (WHO), hearing loss (HL) affects up to 15% of the world's adult population. Coping and personality are hypothesized to underlie quality of life (QoL) and distress scores. We aimed to study the importance of personality and coping in persons with HL for self-reported hearing disability, QoL, and distress., Methods: A cross-sectional survey was carried out, including one hundred and fifty-eight adults seeking hearing aids. Pure-tone average hearing thresholds (PTA) were determined for each ear. A revised version of the Abbreviated Profile of Hearing Aid Benefit (APHAB) served as a measure of self-reported hearing disability. Further, the generic part of the European Organization for Research and Treatment (EORTC) QoL questionnaire and the General Health Questionnaire (GHQ) (distress measure) were answered. Levels of neuroticism and the Theoretically Originated Measure of the Cognitive Activation Theory of Stress (TOMCATS) coping expectancy were determined., Results: Hearing disability was determined by PTA (better ear) and level of neuroticism. Distress and QoL were determined by neuroticism and coping., Conclusion: More neuroticism was associated with worse outcome for the variables hearing disability, distress, and QoL. Helplessness and hopelessness were associated with worse hearing disability, increased distress, and lowered QoL. Patient reported hearing disability was also associated with PTA (better ear). There is a need to investigate further the associations between hearing disability and QoL to psychosocial parameters.

Objective: To evaluate mortality among patients referred for suspected vestibular disorder and to examine whether specific symptoms or disorders predict long-term survival among patients with dizziness or vertigo., Study Design: Retrospective cohort study., Methods: This retrospective cohort study analyzed long-term survival data. Consecutive patients examined for suspected vestibular disease at an otolaryngology clinic completed a detailed questionnaire regarding symptoms and comorbidities., Results: The study included 1,931 patients. Their mean age (standard deviation) was 50.5 (16.5) years, and 60% were women. The mean follow-up period was 20.6 years (range, 15.3-27.5 years). The standardized mortality ratio for the entire cohort compared with the Norwegian age- and sex-matched population was 1.03 (95% confidence interval [CI]: 0.94-1.12), illustrating no difference in overall survival. Patients with a cerebrovascular cause of dizziness had higher mortality in adjusted Cox regression analyses (hazard ratio [HR] 1.56, 95% CI: 1.11-2.19), whereas patients reporting periodic or short attacks of dizziness had lower mortality (HR 0.62 [0.50-0.77] and 0.76 [0.63-0.93], respectively). Reported unsteadiness between dizziness attacks was associated with higher mortality with an HR of 1.30 (95% CI: 1.08-1.57)., Conclusion: This long-term study found comparable mortality rates between patients evaluated for suspected vestibular disorder and that of the general population. However, subgroup analyses showed reduced mortality in patients with periodic or short attacks of dizziness and increased mortality in patients with unsteadiness between attacks or cerebrovascular causes of dizziness. The time course of vestibular symptoms should be determined, and thorough evaluation including fall risk and comorbidities must be considered in patients with nonepisodic symptoms., Level of Evidence: 3 Laryngoscope, 131:E2031-E2037, 2021., (© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: An improved understanding of RCC immunology should shed further light on RCC tumor biology. Our objective was to study to what extent serum levels of the IL-6 family of cytokines at diagnosis were relevant to survival., Methods: A total of 118 consecutively patients with RCC, in which the tumor was surgically removed at Haukeland University Hospital during the period from 2007 to 2010, were included. The patients were followed-up for 10 years. The morning before surgery blood was sampled and serum frozen, with levels of IL-6, IL-27, IL-31, OSM, CNTF, IL-6Rα and gp130 determined., Results: Among patients with the highest quartile of IL-6 (> 8 pg/ml) (n = 29), six of nine who had metastasis at diagnosis had such high IL-6 values. Among presumed radically treated patients, a high IL-6 and IL-27 strongly predicted recurrence. In particular, the predictions among patients with large (diameter > 7 cm) tumors were excellent regarding both IL-6 and IL-27 values. High gp130 serum levels predicted an overall survival (OS) among RCC patients with large tumors. Patients with a high IL-6 exhibited a strong expression of IL-6 in endothelial- and vascular smooth muscle cells. Moreover, the level of intra-tumoral CD3-positive cells predicted survival., Conclusions: IL-6 and IL-27 seem to play a role in RCC biology. IL-6 enables the pinpointing of metastatic condition at diagnosis, as well as together with IL-27, the predicting of survival and recurrence. Endothelial cells and vascular smooth muscle cells are both suggested as important sources of IL-6.

Objective: Previous studies of the consequences of unilateral hearing loss (UHL) on the functional-structural organization of the brain has included subjects with various degrees of UHL. We suggest that the consequences of a total loss of hearing in one ear might differ from those seen in subjects with residual hearing in the affected ear. Thus, the main aim of the present study was to compare the structural properties of auditory and non-auditory brain regions in persons with complete UHL to those of normal hearing controls. We hypothesize that the consequences of complete UHL following treatment for vestibular schwannoma will differ between ipsi- and contralateral structures, as well as between right- and left side deafness., Design: A 3T Siemens Prisma MR-scanner was used. Anatomical images were acquired using a high-resolution T1-weighted sequence. Grey- and white matter volumes were assessed using voxel-based morphometry., Study Sample: Twenty-two patients with left- or right-side unilateral hearing loss. Fifty normal hearing controls., Results: Reductions in grey- and white matter volumes were seen in cortical and sub-cortical regions, mainly in the right hemisphere including the auditory cortex, lingual gyrus, cuneus, middle temporal gyrus, occipital fusiform gyrus, middle cingulate gyrus and the superior temporal gyrus. Patients displayed reduced grey- and white matter volumes in cerebellar exterior structures ipsilateral to the tumor side., Conclusion: When compared to controls, right side hearing loss yields more widespread reduction of grey matter volume than left side hearing loss. The findings of reduced grey- and white matter volumes in auditory and non-auditory brain regions could be related to problems with speech perception in adverse listening conditions, increased listening effort and reduced quality of life reported by persons with unilateral hearing loss despite normal hearing in the unaffected ear., Competing Interests: The authors declare no conflict of interest., (© 2020 The Author(s).)

C-reactive protein (CRP) has a prognostic impact in head and neck squamous cell carcinoma (HNSCC). However, the acute phase reaction involves many other proteins depending on its inducing events, including various cytokines that can function as reaction inducers. In the present study, we compared the pretreatment acute phase cytokine profile for 144 patients with potentially curative HNSCC. We investigated the systemic levels of interleukin (IL)6 family mediators (glycoprotein (gp130), IL6 receptor (R)α, IL6, IL27, IL31, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), IL1 subfamily members (IL1R antagonist (A), IL33Rα), and tumor necrosis factor (TNF)α. Patient subsets identified from this 10-mediator profile did not differ with regard to disease stage, human papilloma virus (HPV) status, CRP levels, or death cause. Increased CRP, IL6, and IL1RA levels were independent markers for HNSCC-related death in the whole patient population. Furthermore, gp130, IL6Rα, and IL31 were suggested to predict prognosis among tumor HPV-negative patients. Only IL6 predicted survival in HPV-positive patients. Finally, we did a clustering analysis of HPV-negative patients based on six acute phase mediators that showed significant or borderline association with prognosis in Kaplan-Meier analyses; three subsets could then be identified, and they differed in survival ( p < 0.001). To conclude, (i) HPV-negative and HPV-positive HNSCC patients show similar variations of their systemic acute phase profiles; (ii) the prognostic impact of single mediators differs between these two patient subsets; and (iii) for HPV-negative patients, acute phase profiling identifies three patient subsets that differ significantly in survival.

Objective: Data on preoperative distress and health-related quality-of-life (HRQoL) is lacking for patients with newly diagnosed renal tumors. This study aims to compare HRQoL within this group with the general population and to study the relationship between distress, HRQoL, personality, coping, and patient/tumor-related factors. Materials and methods: Between January 2011 and June 2014, 153 patients (100 males/53 females), scheduled for surgery were prospectively included. Distress was determined by the General Health Questionnaire (GHQ), HRQoL by EORTC-QLQ-C30 questionnaire, personality by Eysenck Personality Inventory and coping by COPE questionnaire. HRQoL-data from an age and gender matched Norwegian reference population was used for comparison. Results: The study patients had significantly poorer HRQoL than the reference population. GHQ and HRQoL sum scores had a common variance (CV = r 2 ) of 29-35%. In regression models, the measured variables accounted for 33% of the variance for the GHQ score. Significant predictors of the measured variance were neuroticism (18%), education level (3%) and avoidant coping (2%). Similarly, the measured variables accounted for 33-44% of the variance for the HRQoL sum scores. For all HRQoL sum scores, neuroticism predicted 17-28%, while education predicted 4-11% of the measured variance. Large tumor size, comorbidity, performance status and CRP predicted 2-7% of individual sum scores. Conclusions: For both preoperative distress and HRQoL, personality traits such as neuroticism and education level were the most important predictors. Tumor-related factors and other preexisting conditions seemed to be of lesser importance. Thus, preoperatively screening of psychological factors could be helpful to identify those at risk of poor outcomes.

Objective: To determine if symptoms regarding timing and triggers of dizziness are useful for categorizing patients with dizziness, and to evaluate how patient-reported symptoms predict vestibular asymmetry, postural sway, and vestibular diagnoses., Study Design: Retrospective chart review., Setting: Tertiary referral center., Patients: Patients referred for suspected vestibular disease., Interventions: Patients completed a symptom questionnaire before laboratory testing with static posturography and bithermal caloric tests., Main Outcome Measure: Evaluate whether responses from a symptom questionnaire predict caloric asymmetry, postural balance, and diagnoses., Results: One thousand four hundred fifty seven patients, 60.1% women, mean age 49.9 (±16.6) years were included. Vomiting was the strongest predictor for caloric asymmetry in adjusted analysis, odds ratio (OR): 1.60 (95% confidence interval [CI]: 1.24-2.06), followed by chronic hearing loss OR: 1.59 (1.19-2.13). Patients who reported constant dizziness had impaired postural balance, quantified as 15% increase in postural sway in adjusted analyses (7.25-24.6%). We found no association between caloric asymmetry and postural instability with eyes closed., Conclusion: Most patients were able to describe the timing of their symptoms and a categorization based on timing seems feasible. There seemed to be an over-reporting of triggers and confirmatory testing of triggers is therefore advocated. Vomiting, but not nausea, was a strong indicator of vestibular disease in this primarily outpatient population. Caloric asymmetry and postural balance were not associated, and assessment of fall risk may be warranted in patients who reports constant dizziness, visual disturbances or dizziness triggered by light, darkness or sounds.

Background: Live-attenuated influenza vaccine (LAIV) was licensed for prophylaxis of children 2-17 years old in Europe in 2012 and is administered as a nasal spray. Live-attenuated influenza vaccine induces both mucosal and systemic antibodies and systemic T-cell responses. Tonsils are the lymph nodes serving the upper respiratory tract, acting as both induction and effector site for mucosal immunity., Methods: Here, we have studied the early tonsillar T-cell responses induced in children after LAIV. Thirty-nine children were immunized with trivalent LAIV (containing A/H1N1, A/H3N2, and B viruses) at days 3, 7, and 14 before tonsillectomy. Nonvaccinated controls were included for comparison. Tonsils and peripheral blood (pre- and postvaccination) were collected to study T-cell responses., Results: Tonsillar and systemic T-cell responses differed between influenza strains, and both were found against H3N2 and B viruses, whereas only systemic responses were observed against A/H1N1. A significant increase in cross-reactive tonsillar CD8+ T cells recognizing conserved epitopes from a broad range of seasonal and pandemic viruses occurred at day 14. Tonsillar T cells showed significant cytokine responses (Th1, Th2, and granulocyte-macrophage colony-stimulating factor)., Conclusions: Our findings support the use of LAIV in children to elicit broadly cross-reactive T cells, which are not induced by traditional inactivated influenza vaccines and may provide protection to novel virus strains., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: Patients with voice-related disorders are ideally treated by a multidisciplinary team. Acoustic voice analysis and patient-reported outcome measures are recommended parts of the clinical assessment. The present paper aims at further documenting the importance of acoustic voice analyses, maximum phonation time (MPT) and Voice Handicap Index (VHI) into clinical investigations., Study Design: The participants (N = 80 larynx cancer, N = 32 recurrent palsy, N = 23 dysfunctional, N = 75 degenerative/inflammation (N = 19 various excluded)) were included consecutively at the outpatient laryngology clinic at Haukeland University Hospital. In addition, a control group of 98 healthy subjects were included., Method: Voice samples, MPT, and the VHI scores in addition to standard clinical information were obtained. Acoustic analyses were performed from these samples determining level of jitter, shimmer and Noise-to-Harmonic ratio (NHR) as well as analyzing frequency of a prolonged vowel., Results: Jitter, shimmer, and NHR scores correlated strongly (r ≈ 0.8; P < 0.001) to each other. By Analysis of Variance analyses, we have determined significant dependence on diagnostic group analyzing all the obtained acoustic scores (all P < 0.001). All patient groups but the dysfunctional group scored to some extent worse than the control group (mostly at P < 0.001). In addition, jitter scores from dysfunction group were lower than recurrent palsy group (P < 0.05) and shimmer scores were lower among dysfunctional than the cancer group (P < 0.05). Regarding NHR the cancer patients scored higher than the degenerative/inflammatory group (P < 0.05). The cancer group scored with longer MPT than the degenerative/inflammatory (P < 0.001) and recurrent palsy groups (P < 0.05)., Conclusion: Among larynx disease patients acoustic and MPT analyses segregated with all determined analyses between patients and control conditions except the dysfunctional group, but also to some extent between various patient groups. VHI scores correlated to jitter, shimmer and NHR scores among cancer and degenerative/inflammatory disease patients. Acoustic analyses potentially add information useful to laryngological patient studies., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To study the 10-year overall survival predictions, and mechanisms behind, of head and neck (HN) quality of life (QoL) scores obtained at diagnosis and 6, 9, and 12 months following diagnosis in a cohort of HN squamous cell carcinoma (HNSCC) patients., Methods: Consecutive HNSCC patients (N = 109) subjected to standard workup and treatment self-reported their QoL measured by the EORTC Quality of Life Questionnaire (QLQ) H&N-35 between November 2002 and June 2005. Each QoL index was calculated and additionally aggregated to one sum score. The included patients were at diagnosis younger than 78 years, judged adequately cognitive functioning, and scheduled for curative treatment. Self-reported smoking, alcohol consumption, and socio-demographic information were registered. Twenty-two patients were high-risk (hr)-HPV DNA tumor positive. If the treatment goal was changed to palliative, no new QoL information was collected. All living patients were followed until 10 years after diagnosis., Results: Median survival was 105 months. Significant overall survival predictions were found from the EORTC H&N-35 QLQ sum scores continuously measured at diagnosis (p = 0.006) and obtained at 6 (p = 0.02), 9 (p = 0.002) and 12 (p = 0.05) months. Lower QoL predicted lower overall survival. These sum score survival predictions were in part independent of TNM stage, hr-HPV status, gender, age, alcohol and smoking status. The indices "pain", "swallowing", "social eating", and "feeling ill" were predictive of survival at 3 out of 4 measuring points (diagnosis, 6, 9 and 12 months) in univariate analyses., Conclusion: EORTC H&N-35 QLQ scores at diagnosis and throughout the first year thereafter harbor prognostic power.

Objective: To investigate the relationship between hearing loss (HL) and general quality of life (QoL) in adults seeking hearing aids (HAs). Design: The patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire's general part and a questionnaire measuring self-assessed communication ability (Abbreviated Profile of hearing Aid Benefit-APHAB). These responses were compared with EORTC scores from a general population and patients with former head and neck cancer. Study sample: One-hundred and fifty-eight adults with HL were recruited prior to hearing aid (HA) fitting with one half seeking renewal of their HA. Results: General QoL scores among patients with HL were similar to those in the general population, but higher than in many chronic serious diseases. Patients with unilateral HL reported slightly worse social function and more fatigue than patients with bilateral HL. Self-assessed communication ability correlated with general QoL scores. Also, we found that best ear pure tone average (PTA), cognitive and physical QoL function predicted APHAB scores. Conclusion: In the investigated HL group, general QoL scores seem to be relatively close to those seen in the general population.

Objective: To evaluate the association between hearing and postural balance., Study Design: Retrospective cross-sectional study., Setting: Tertiary care otolaryngology clinic., Subjects and Methods: Patients examined for suspected vestibular disorder were included in this study. The outcome variable was postural sway measured by static posturography during quiet standing with eyes closed. The predictor variable was pure-tone average hearing threshold on the best hearing ear at 0.5, 1, 2, and 3 kHz. Covariates were age, sex, and vestibular disease or vestibular asymmetry assessed by bithermal caloric irrigation., Results: In total, 1075 patients were included. Increased hearing threshold was a strong predictor of increased postural sway (path length) after correcting for age and sex. A 10-dB increase in hearing loss on the best hearing ear predicted a mean 6.0% increase in path length (confidence interval, 2.9%-9.3%, P < .001). Of the covariates, increasing age ( P < .001) and male sex ( P = .009) were significant predictors of increased postural sway. The effect of increased hearing threshold was also significant after adjusting for vestibular disease., Conclusion: Increased hearing threshold was an independent predictor of increased postural instability, and this effect was strongest for the best hearing ear. Unilateral vestibular disease did not seem to explain this association between hearing and postural balance. Reduced hearing is associated with impaired balance, and interventions to prevent falls should be considered for patients at risk.

Background: The aim of this study was to examine periodontal status with a time-efficient screening method from a cohort of newly diagnosed oropharynx squamous cell carcinoma (OPSCC) patients and to study to what extent dental disease level predicted survival. Aims/objective: Can measuring level of dental pathology based on a blind investigation of a routine orthopantogram (OPG) obtained during diagnostic workup reveal prognostic information?, Materials and Methods: We included 97 patients diagnosed between 2003 and 2010. Radiographic alveolar bone loss was measured. At least 4 mm bone loss from cement-enamel junction on at least two teeth was registered as periodontal pathology. The number of missing and filled teeth (MFT), residual roots and apical radiolucencies were noted. Clinical data were determined through hospital patient records., Results: The horizontal bone loss discriminated between hr-HPV(+) versus hr-HPV(-) status, but secondary to age and smoking history at diagnosis. Vertical and horizontal bone loss predicted survival directly, and adjusted by gender, patient, smoking history, TN stage and hr-HPV tumor infection at diagnosis., Conclusions: Degree of periodontal OPG pathology at the time of OPSCC diagnosis to some extent predicted hr-HPV infection, but predicted non-disease-specific long-term survival., Significance: Degree of periodontal OPG pathology at diagnosis predicts prognosis.

Objective: Our main aim was to investigate the blood oxygenation level dependent (BOLD) response to monaural and binaural speech- and non-speech stimuli as measured with fMRI in subjects with single-sided deafness and in normal hearing controls. We hypothesised that the response to monaural stimulation in both normal hearing subjects and persons with single-sided deafness would vary with the complexity and nature of the stimuli and the side of stimulation., Design: Patients with left- and right single-sided deafness and controls with normal hearing receiving either binaural or monaural stimuli were tested using speech and non-speech auditory stimuli in an event-related fMRI experiment., Study Sample: Twenty-two patients with single-sided deafness after treatment for vestibular schwannoma and 50 normal hearing controls., Results: Normal hearing persons receiving right side monaural stimuli activate bilateral temporal regions. Activation following left side monaural stimulation is more right lateralized. Persons with single-sided deafness respond similarly to controls to monaural stimulation. Persons with right side single-sided deafness show activation of frontal cortical regions not seen in persons with left side single-sided deafness following speech stimuli. This is possibly related to increased effort and more frequently reported problems with communication. Right side single-sided deafness is related to increased activation of areas usually related to processing of degraded input, including the thalamus., Conclusion: Hemispheric dominance following monaural auditory stimulation is modulated by the spectral-temporal properties of the stimuli and by which ear is stimulated. Differences between patients with right- and left side deafness suggests that right side deafness is related to increased activation of areas involved in processing of degraded input., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the present study was to explore the relationship between excessive daytime sleepiness (EDS), Peak Nasal Inspiratory Flow (PNIF), and patient reported symptoms from the nose., Methology: Six hundred and fifty one consecutive patients referred to a hospital on suspicion of sleep related breathing disorder (SRBD) were included in the study. Daytime sleepiness was assessed by Epworth Sleepiness Scale (EpSS). Nasal airflow was measured with Peak Nasal Inspiratory Flow (PNIF). Symptoms of sino-nasal dysfunction and diseases were graded on Visual Analogue Scales (VAS)., Results: EpSS score was not correlated with nasal flow as measured by PNIF or nasal obstruction - VAS scores. There were significant associations between daytime sleepiness and patient-reported VAS-scores on nasal discharge, headache, coughing, general health and to some extent sneezing when age, gender, BMI and reported co-morbidity levels were adjusted for., Conclusion: A clinical implication of this is that patients with EDS may be evaluated and treated for sino-nasal disease, while medical and surgical measures to open the nose per se may not be effective therapeutic options. A scientific implication is that the relationship between SRBD and sino-nasal disease should be further investigated.

Background: Oropharyngeal squamous cell carcinoma (OPSCC) positive for human papillomavirus (HPV) increases wolrd wide., Aims/objectives: The objective for this study has been to evaluate tumor phenotypes and tumor host responses with respect to five-year disease-specific survival (DSS) in HPV(+) and HPV(-) patients., Material and Methods: Two hundred patients with OPSCC have been treated between 1992 and 2010. Histopathology slides from these patients have been morphologically evaluated in formalin-fixed, paraffin-embedded (FFPE) stained with hematoxylin-eosin (HE). From HE-stained sections tumor phenotype (keratinization, fraction of mature cancer cells and pattern of invasion) and tumor host responses (inflammation and stromal desmoplasia) were evaluated with respect to five years DSS., Results: High tumor inflammatory response and low stromal desmoplasia had an independent effect predicting better five-year DSS among all patients and when analyzed separately in the HPV(-) and HPV(+) cohort of patients using a Cox regression survival analysis that also included standard clinical prognostic variables among OPSCC patients., Conclusion: Tumor host responses, inflammation and stromal desmoplasia may become part of routine work-up in OPSCC patients due to prognostic value., Significance: We present a method, accessible in most clinical locations and would give important additional information about prognosis in OPSCC patients.

Background: To the best of our knowledge, no empirically based consensus has been reached as to if, and to what extent, persons with hearing loss (HL) have reduced generic Quality of life (QoL). There seems to be limited knowledge regarding to what extent a hearing aid (HA) would improve QoL. The main aim of the present study was to review studies about the relationship between HL and QoL. A supporting aim was to study the association between distress and HL., Methods: Literature databases (Cinahl, Pub Med and Web of Science) were searched to identify relevant journal articles published in the period from January 2000 to March 17, 2016. We performed a primary search pertaining to the relationship between HL, HA and QoL (search number one) followed by a supporting search pertaining to the relationship between distress/mood/anxiety and HL (search number two). After checking for duplications and screening the titles of the papers, we read the abstracts of the remaining papers. The most relevant papers were read thoroughly, leaving us with the journal articles that met the inclusion criteria., Results: Twenty journal articles were included in the present review: 13 were found in the primary search (HL and QoL), and seven in the supporting search (HL and distress). The literature yields equivocal findings regarding the association between generic QoL and HL. A strong association between distress and HL was shown, where distressed persons tend to have a lowered generic QoL. It is suggested that QoL is lowered among HL patients. Some studies suggest an increased generic QoL following the use of HA, especially during the first few months after initiation of treatment. Other studies suggest that HA use is one of several possible factors that contribute to improve generic QoL., Conclusions: The majority of the studies suggest that HL is associated with reduced generic QoL. Using hearing aids seem to improve general QoL at follow-up within the first year. HL is a risk factor for distress. Further research is needed to explore the relationship between HL and generic QoL, in addition to the importance of influencing variables on this relationship., Competing Interests: Not applicable due to study design and article type.Not applicable due to study design and article type.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: To evaluate the 5- and 10-year survival prediction of health-related quality of life (HRQoL) scores obtained at diagnosis and at 6, 9 and 12 months after diagnosis in a cohort of curable head and neck squamous cell carcinoma (HNSCC) patients., Materials and Methods: HNSCC patients (n = 109) reported their HRQoL measured by the EORTC Quality of Life Questionnaire (QLQ) general (C30) questionnaire. At diagnosis, the included patients were below 78 years of age and at diagnosis planned treated with curative intent. Clinical variables and self-reported smoking, alcohol consumption and socio-demographic information were registered. From diagnostic blocks, we found 22 patients to be human papillomavirus (HPV) positive. New HRQoL scores were not obtained if the patient treatment changed from curative to palliative throughout the HRQoL data acquisition. Survival was determined from the National Population Register of Norway., Results: Decreased survival with low HRQoL scores from EORTC QLQ scores was demonstrated with HRQoL scores obtained from different time points of the four time points studied. These survival predictions were mostly independent of HPV status, gender, age, TNM stage, tumor site, alcohol consumption, present smoking status and whether comorbidities were present at diagnosis; as well as to some extent with an adjustment of the same HRQoL score/index obtained at diagnosis. The specific indices "physical function", "general pain" and "sleep disturbance" were in particular predictive of survival., Conclusion: HRQoL scores obtained throughout the first year after diagnosis contained prognostic power to overall survival when measured both at 5 and 10 years of observation.

Background: Difficulty in following and understanding conversation in different daily life situations is a common complaint among persons with hearing loss. To the best of our knowledge, there is currently no published validated Norwegian questionnaire available that allows for a self-assessment of unaided communication ability in a population with hearing loss., Purpose: The aims of the present study were to investigate a questionnaire for the self-assessment of communication ability, examine the psychometric properties of this questionnaire, and explore how demographic variables such as degree of hearing loss, age, and sex influence response patterns., Research Design: A questionnaire based on the subscales of the Norwegian translation of the Abbreviated Profile of Hearing Aid Benefit was applied to a group of hearing aid users and normal-hearing controls., Study Sample: A total of 108 patients with bilateral hearing loss, and 101 controls with self-reported normal hearing., Data Collection and Analysis: The psychometric properties were evaluated. Associations and differences between outcome scores and descriptive variables were examined. A regression analysis was performed to investigate whether descriptive variables could predict outcome., Results: The measures of reliability suggest that the questionnaire has satisfactory psychometric properties, with the outcome of the questionnaire correlating to hearing loss severity, thus indicating that the concurrent validity of the questionnaire is good., Conclusions: The findings indicate that the proposed questionnaire is a valid measure of self-assessed communication ability in both quiet and adverse listening conditions in participants with and without hearing loss., (American Academy of Audiology)

Objectives: Patients with voice-related disorders are often treated by a multidisciplinary team including assessment by patient-reported outcome measures. The present paper aims at documenting the importance of including general health-related quality of life (HRQoL) measures to clinical investigations., Study Design: The participants (N = 80 larynx cancer, N = 32 recurrent palsy, N = 23 dysfunctional, N = 75 degenerative/inflammation, N = 19 various) were included consecutively at the laryngology clinic at Haukeland University Hospital. In addition, HRQoL data were included from one national group with laryngectomies (N = 105), one group with various patients formerly treated for head and neck squamous cell carcinoma (N = 96), and one population-based reference group (N = 1956)., Method: Obtained were the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ), the Voice Handicap Index (VHI), and the Eysenck Personality Inventory (EPI) neuroticism scores., Results: By analysis of variance, we have determined significant dependence of groups analyzing the sum global QoL/health index (F = 9.47; P <0.001), the functional HRQoL sum score (F 5,2373  = 7.14, P <0.001), and the symptom sum HRQoL scores (F 7,2381  = 8.13; P <0.001). In particular, patients with recurrent palsy and laryngeal cancer had lowered HRQoL. At the index levels, in particular dyspnea scores, were scored depending on larynx disease group (F 7,2288  = 24.4; P <0.001). The VHI score correlated with the EORTC H&N35 "speech" index with a common variance of 52%. VHI scores correlated with level of neuroticism with 8% common variance (P <0.001) and EORTC scores with 22% (P <0.001)., Conclusion: In particular, among patients with voice-related disease, those with recurrent palsy and laryngeal cancer had lower HRQoL. Furthermore, the HRQoL and VHI scores were inversely tied to neuroticism., (Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

MCP-1/IL-6 in vitro monocyte secretion upon coculture with autologous fragment spheroids was studied in relation to patient 5- and 10-year overall survival rates in head and neck squamous cell carcinoma (HNSCC) patients (n = 65) diagnosed between 1998 and 2005, nine of whom had an human papilloma virus (HPV) tumour infection. The spheroids were harvested from malignant or benign tissue during primary surgery. Two weeks following surgery, freshly isolated autologous monocytes and benign or malignant spheroids were cocultured 24 h in vitro. The IL-6 secretion was expressed as a fraction of the lipopolysaccharide (LPS) response from the same batch of monocytes. HPV status was obtained by employing PCR analyses of primary diagnostic blocks. IL-6/MCP-1 response levels were not found to be dependent on HPV infection status. MCP-1 secretion did not predict prognosis, nor did in vitro IL-6 monocyte background or LPS-stimulated IL-6 secretion. At 5-year observation, dichotomized IL-6 levels following monocyte coculture, with both malignant and benign spheroids, showed a strong trend towards predicting survival, that is a low monocyte malignant coculture response showed a survival of 31 ± 17 versus 58 ± 17% with a high such response (P = 0.057). When studying monocyte IL-6 coculture responses evaluating benign and malignant spheroid results statistically together, a prediction of survival up to 10 years was found (hazard ratio = 0.48; confidence interval = 0.24-0.96; P < 0.05) with double low IL-6 responses. This survival prediction was also present after an adjustment for HPV tumour infection status. In conclusion, monocyte IL-6 in vitro secretion in cocultures with autologous spheroids/serum from HNSCCs predicted 5- and 10-year survivals, both with and without tumour HPV tumour adjustment., (© 2016 The Foundation for the Scandinavian Journal of Immunology.)

We changed the primary oropharynx squamous cell carcinoma (OPSCC) treatment recommendation from primary radiation therapy (RT) to tumor surgery and neck dissection, followed by RT around the year 2000 with apparently improved survival. However, high-risk human papilloma virus (hr-HPV)-16-caused OPSCCs have increased during this period. Furthermore, hr-HPV+ OPSCC carry a better prognosis than hr-HPV-negative patients. We have, therefore, evaluated the 5-year survival in the period from 1992 to 1999 versus 2000 to 2008 stratified by hr-HPV tumor infection status. Ninety-six OPSCC patients were treated from 1992 to 1999 compared with 136 patients from 2000 to 2008. The 5-year disease-specific survival (DDS) and overall survival (OS) were recorded, while the health-related quality of life (HRQoL) scores were obtained from some of the cured patients. Thirty-eight (40 %) in the first period and 86 OPSCCs (63 %) in the second period were hr-HPV+. In the first period, 16 versus 62 patients in the last period were treated by neck dissection, primary tumor surgery, and RT. DSS among all the hr-HPV-negative patients in the first period was 51 versus 55 % in the second period, and the corresponding OS was 33 versus 31 %, respectively. The DSS among all the hr-HPV+ patients was 78 % in the first period versus 77 % in the second period, while the OS was 71 versus 69 %, respectively. The HRQoL scores among successfully treated patients were worse following surgery, plus RT than RT only. The hr-HPV-adjusted 5-year survival in OPSCC patients was similar between the two time periods. A decreased HRQoL was associated with surgical therapy, which indicates that hr-HPV+ OPSCC patients may be treated by primary RT followed by major surgery only if RT treatment fails.

Background: Tonsils play a key role in eliciting immune responses against respiratory pathogens. Little is known about how tonsils contribute to the local immune response after intranasal vaccination. Here, we uniquely report the mucosal humoral responses in tonsils and saliva after intranasal live attenuated influenza vaccine (LAIV) vaccination in children., Methods: Blood, saliva, and tonsils samples were collected from 39 children before and after LAIV vaccination and from 16 age-matched, nonvaccinated controls. Serum antibody responses were determined by a hemagglutination inhibition (HI) assay. The salivary immunoglobulin A (IgA) level was measured by an enzyme-linked immunosorbent assay. Antibody-secreting cell (ASC) and memory B-cell (MBC) responses were enumerated in tonsils and blood., Results: Significant increases were observed in levels of serum antibodies and salivary IgA to influenza A(H3N2) and influenza B virus strains as early as 14 days after vaccination but not to influenza A(H1N1). Influenza virus-specific salivary IgA levels correlated with serum HI responses, making this a new possible indicator of vaccine immunogenicity in children. LAIV augmented influenza virus-specific B-cell responses in tonsils and blood. Tonsillar MBC responses correlated with systemic MBC and serological responses. Naive children showed significant increases in MBC counts after LAIV vaccination., Conclusions: This is the first study to demonstrate that LAIV elicits humoral B-cell responses in tonsils of young children. Furthermore, salivary IgA analysis represents an easy method for measuring immunogenicity after vaccination., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: Congenital laryngomalacia (CLM) is the major cause of stridor in infants. Most cases are expected to resolve before 2 years of age, but long-term respiratory prospects are poorly described. We aimed to investigate if CLM was associated with altered laryngeal structure or function in later life., Methods: Twenty of 23 (87%) infants hospitalised at Haukeland University Hospital during 1990-2000 for CLM without comorbidities and matched controls were assessed at mean age 13 years. Past and current respiratory morbidity was recorded in a questionnaire, and spirometry performed according to standard quality criteria. Laryngoscopy was performed at rest and continuously throughout a maximal treadmill exercise test (continuous laryngoscopy exercise test (CLE-test)), and scored and classified in a blinded fashion according to preset criteria., Results: In the CLM group, laryngeal anatomy supporting CLM in infancy was described at rest in nine (45%) adolescents. Eleven (55%) reported breathing difficulties in relation to exercise, of whom 7 had similarities to CLM at rest and 10 had supraglottic obstruction during CLE-test. Overall, 6/20 had symptoms during exercise and similarities to CLM at rest and obstruction during CLE-test. In the control group, one adolescent reported breathing difficulty during exercise and two had laryngeal obstruction during CLE-test. The two groups differed significantly from each other regarding laryngoscopy scores, obtained at rest and during exercise (p=0.001 or less)., Conclusions: CLM had left footprints that increased the risk of later exercise-induced symptoms and laryngeal obstruction. The findings underline the heterogeneity of childhood respiratory disease and the importance of considering early life factors., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: This paper aims to provide a review of studies using neuroimaging to measure functional-structural reorganisation of the neuronal network for auditory perception after unilateral hearing loss., Design: A literature search was performed in PubMed. Search criterions were peer reviewed original research papers in English completed by the 11th of March 2015., Study Sample: Twelve studies were found to use neuroimaging in subjects with unilateral hearing loss. An additional five papers not identified by the literature search were provided by a reviewer. Thus, a total of 17 studies were included in the review., Results: Four different neuroimaging methods were used in these studies: Functional magnetic resonance imaging (fMRI) (n = 11), diffusion tensor imaging (DTI) (n = 4), T1/T2 volumetric images (n = 2), magnetic resonance spectroscopy (MRS) (n = 1). One study utilized two imaging methods (fMRI and T1 volumetric images)., Conclusion: Neuroimaging techniques could provide valuable information regarding the effects of unilateral hearing loss on both auditory and non-auditory performance. fMRI-studies showing a bilateral BOLD-response in patients with unilateral hearing loss have not yet been followed by DTI studies confirming their microstructural correlates. In addition, the review shows that an auditory modality-specific deficit could affect multi-modal brain regions and their connections., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Studying health-related quality of life (HRQoL) following cancer treatment has become part of a growing number of standardized treatment protocols. The European Organization for Research and Treatment of Cancer (EORTC) has developed HRQoL questionnaires aimed at cancer patients. A disease-specific part is not available for renal cell carcinoma (RCC) patients, and the present aim was to develop an EORTC-compatible RCC-specific HRQoL questionnaire., Material and Methods: In total 413 RCC patients were treated with radical or partial nephrectomies in Western Norway during the period from 1997 to 2010. Three hundred and nine patients with histologically proven cancer were still alive at the inclusion time point and 185 RCC patients (71% response rate) returned the questionnaires. We determined HRQoL by the EORTC-QLQ C30 questionnaire. We also asked 13 candidates questions aimed at constituting a disease-specific part. Furthermore, we tested parts of personality by the Eysenck Personality Inventory and coping by the COPE questionnaire. Given tumor treatment, TNM stage, alcohol consumption level and smoking levels were also determined from the hospital records., Results: A factor analysis showed that five factors were formed: one general symptomatic, one general functional, one with disease-specific questions (flank pain, blood in the urine, flank edema, urinary tract infection), one about sexuality and one about weight loss or gain. Ten RCC-specific HRQoL questions were derived from a factor analysis, including four questions related particularly to pain, mobility and social functioning, also representing a short version of the EORTC C30. The psychometric properties and the relation to other psychological and clinical variables were further determined to be satisfactory., Conclusions: The suggested disease-specific EORTC-QLQ-style RCC10 version adds important information about the HRQoL of RCC patients, providing additional apparent value to the general questionnaire and personality variables, as well as being psychometrically satisfactory. The questionnaire has a potential as a "stand alone" HRQoL questionnaire among RCC patients.

The aim of this study is to determine to what extent the Voice Handicap Index-Norwegian (VHI-N) is scored depending on specific laryngological disease. In a multi-center study, 126 healthy subjects and 355 patients with different voice-related diseases answered the VHI-N. The VHI-N scores showed high Cronbach's alpha. Analyses of variance were performed with VHI-N dependent and specific voice-related disease as independent variable, and showed highly significant dependence by group allocation (F(7,461) = 28.0; p < 0.001). When studying post hoc analyses secondary to this ANOVA analysis, we have shown that the control group scored lower than the entire patient groups (all p < 0.001) except the dysplasia group. Aphonic patients scored higher than all the other groups (all p < 0.001) except those with spasmodic dysphonia. The cancer patient group furthermore scored lower than patient groups with recurrent palsy, dysfunctional disease or spasmodic dysphonia (all p < 0.001). In addition, patients with recurrent palsy scored higher than patients with degenerative/inflammatory disease (p < 0.001). No influences of patient age, gender, or smoking were observed in the VHI-N scores. The VHI-N is a psychometrically well-functioning instrument, also at disease-specific levels and discriminates well between health and voice diseases, as well as between different voice-related diseases. The VHI-N may be recommended to be used when monitoring voice-related disease treatment.

The study was performed in order to determine whether peripheral blood monocyte in vitro function, and lymphocyte in vivo activation at diagnosis, was associated with HPV tumor infection status and 15-year survival in head and neck squamous cell carcinoma (HNSCC) patients. Sixty-five patients from a consecutive cohort of newly diagnosed HNSCCs, together with 18 control patients, were included in the study. Monocyte responsiveness was assessed by measuring monocyte in vitro interleukin (IL)-6 secretions after 24 hours of LPS stimulation in cultures with a serum-free medium. T lymphocyte activation was determined as the fraction of CD71-positive cells on CD3-positive cells by flow cytometry, whereas HPV infection was determined by PCR on formalin-fixed paraffin-embedded (FFPE) tumor tissue. Disease-specific survivals and overall survivals were determined 15 years following inclusion. HPV-positive HNSCC patients had a lower monocyte LPS-stimulated IL-6 response. A high LPS-stimulated monocyte IL-6 response predicted a decreased survival rate (P=0.019). A high percentage of CD71-positive T lymphocytes also predicted an impaired prognosis (P=0.021). The predictive power of IL-6 monocyte LPS-stimulated responses was retained when adjusted for age, gender and TNM stage of the patients. The monocyte and T lymphocyte survival predictions were independent of each other. The survival was particularly low with a combined high activated monocyte and T lymphocyte status. In a multivariate analysis, IL-6 secretion and the percentage of CD71-positive T lymphocytes both uniquely predicted survival independent of HPV infection status. It is postulated that the natural and adaptive immune systems are separately and additionally linked to the clinical aggressiveness of HNSCCs.

Background: The live attenuated influenza vaccine (LAIV) is the preferred vaccine for children, but the mechanisms behind protective immune responses are unclear, and the duration of immunity remains to be elucidated. This study reports on the longevity of B-cell and T-cell responses elicited by the LAIV., Methods: Thirty-eight children (3-17 years old) were administered seasonal LAIV. Blood samples were collected before vaccination with sequential sampling up to 1 year after vaccination. Humoral responses were evaluated by a hemagglutination inhibition assay, and memory B-cell responses were evaluated by an enzyme-linked immunosorbent spot assay (ELISpot). T-cell responses were evaluated by interferon γ (IFN-γ) ELISpot analysis, and intracellular cytokine staining of CD4(+) T cells for detection of IFN-γ, interleukin 2, and tumor necrosis factor α was performed using flow cytometry., Results: LAIV induced significant increases in B-cell and T-cell responses, which were sustained at least 1 year after vaccination. Strain variations were observed, in which the B strain elicited stronger responses. IFN-γ-expressing T cell counts increased significantly, and remained higher than prevaccination levels 1 year later. Expression of T-helper type 1 intracellular cytokines (interleukin 2, IFN-γ, and tumor necrosis factor α) increased after 1 dose and were boosted after the second dose. Hemagglutination inhibition titers were sustained for 1 year. Vaccine-induced memory B cell counts were significantly increased, and the response persisted for one year., Conclusions: LAIV elicited B-cell and T-cell responses that persisted for at least 1 year in children. This is a novel finding that will aid future vaccine policy., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

This study was performed to determine whether peripheral blood (PB) monocyte and/or lymphocyte activation at diagnosis were associated with long-term prognosis in patients with head and neck squamous cell carcinoma (HNSCC), and to what extent such prognostic properties relate to human papilloma virus (HPV)-associated tumor infection of the included patients. This was a long-term prospective study describing patient survival in relation to PB T lymphocyte and monocyte activation in patients observed for up to 14 years following diagnosis. Sixty-four patients from a consecutive cohort of newly diagnosed HNSCC patients along with 16 non-cancer control patients were included over a period of almost 2 years. Monocyte responsiveness was assessed at diagnosis (N = 56 HNSCC/16 non-cancer controls) by measuring net levels of spontaneous vs lipopolysaccharide-induced monocyte chemotactic protein (MCP)-1 secretion in vitro. PB T lymphocyte activation was determined (N = 58 HNSCC/16 controls) by measuring the percentage of T cells expressing CD69 by flow cytometry. Whether HPV infection or not was determined by PCR analysis on formalin fixed paraffin-embedded tumor tissue. Tumor HPV-positive patients had better prognosis than HPV-negative patients. A low net MCP-1 response in monocytes predicted increased survival (Relative risk (RR) = 2.1; Confidence interval (CI): 1.1-4.0; p < 0.05). A low percentage of CD69 positive T lymphocytes also predicted better prognosis (RR = 2.6; CI: 1.3-5.0; p = 0.005). The predictive power of MCP-1 monocyte and CD69 T lymphocyte measures were retained when adjusted for age and gender of the patients and shown to be independent of each other (N = 50 HNSCC/16 controls). The results were similar in HPV tumor-positive and -negative patients. Patients with high monocyte- and/or T lymphocyte activation status had low survival with 8% 5 year overall survival (OS) compared to 65% 5 year OS for patients with dual low activation levels (RR = 0.27; CI: 0.14-0.56; p < 0.001), mostly secondary to disease-specific survival. Both tumor HPV-positive and -negative HNSCC patients with high percentage of CD69 positive T lymphocytes and/or high monocyte MCP-1 secretion had low long-term survival. The data suggest that the general inflammatory and adaptive immune systems are independently linked to the clinical aggressiveness of both tumor HPV-negative and -positive HNSCC patients., (© 2015 APMIS. Published by John Wiley & Sons Ltd.)

Objective: To investigate whether health-related quality of life (HRQoL) depends on psychosocial factors, rather than on factors related to the cancer treatment, this study explored the associations between HRQoL, personality, choice of coping and clinical parameters in surgically treated renal cell carcinoma (RCC) patients., Materials and Methods: After exclusions (e.g. death, dementia), 260 patients were found to be eligible and invited to participate. The response rate was 71%. HRQoL was determined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), personality by the Eysenck Personality Inventory and coping by the COPE Questionnaire. Given tumour treatment, TNM stage and patient-reported comorbidity were also determined. The HRQoL indices were also summarized in general quality of life/health, functional sum and symptom sum scores., Results: EORTC C30 sum scores were negatively associated with the personality trait of neuroticism [common variance (CV) 19-36%]. Avoidant choice of coping inversely accounted for 9-18% of the total HRQoL variance, while reported coping by humour was to some extent negatively associated with HRQoL score (CVmax 4%). Indeed, all of the quality of life indices except for one were significantly negatively correlated with neuroticism and avoidance coping. Patients with low HRQoL due to treatment, secondary to flank or open surgery, reported a closer association between problem-focused choice of coping and HRQoL than the other patients. Moreover, present comorbidities were uniquely associated with a lowered HRQoL., Conclusions: HRQoL is related to treatment-related factors in RCC patients, but shown here to be more strongly associated with psychological factors and present comorbidity. These findings suggest that attention should be paid to supportive treatment of RCC patients.

Objective: The aim of this study was to determine whether concentrations of vascular endothelial growth factor (VEGF) in blood taken preoperatively can predict subtype, survival and recurrence in patients with renal cell carcinoma (RCC)., Materials and Methods: The patient group consisted of 124 patients with an RCC that was surgically removed with nephrectomy or nephron-sparing surgery at Haukeland University Hospital from 2007 to 2010. All subtypes and stages were included. Preoperative blood samples were taken on the day of surgery, and the samples were prepared and frozen at -80 °C. The level of VEGF in serum was analysed using Luminex® immunobead technology. The patients were followed until death or to 31 October 2014 (>4.5 years)., Results: Patients with higher levels of VEGF were more likely to have clear cell RCC [odds ratio (OR) 2.43, p = 0.046], as were older patients (OR 1.04, p = 0.024). In a multivariate analysis, high VEGF, stage and nuclear grade all had a significant predictive value for cancer-specific survival (OR 4.56, p = 0.017; OR 11.54, p < 0.001; and OR 7.85, p = 0.015, respectively). VEGF, stage and nuclear grade predicted recurrence in patients presumed to have been radically treated (OR 4.37, p = 0.03; OR 5.02, p = 0.011; and OR 6.57, p = 0.008, respectively)., Conclusions: Tumour stage and a high level of serum VEGF were predictors for an increased risk of recurrence and cancer-specific death. Furthermore, the study showed that serum VEGF may be used to determine the subtype of RCC preoperatively.