Hearing loss and its association with the proteome of perilymph, cerebrospinal fluid, and tumor tissue in patients with vestibular schwannoma.

This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.

Fall-related injury among patients with vestibular schwannoma.

Vestibular schwannoma can cause vestibular dysfunction; however, conflicting evidence exists regarding whether this affects the incidence of fall-related injuries in this patient population. This matched cross-sectional and cohort study assess the risk of fall-related injuries in patients with vestibular schwannoma. The study included patients with vestibular schwannoma treated at a tertiary referral hospital in Sweden between 1988 and 2014. Information on fall-related injuries was obtained from the National Patient Register, and matched population comparisons were randomly selected in a 1:25 ratio. Fall-related injuries occurring pre- (within 5 years before the diagnosis of vestibular schwannoma) and post-diagnostically (up to 3 years after diagnosis or intervention) were registered. The association between vestibular schwannoma and fall-related injuries was estimated using logistic regression and Cox proportional hazards analyses. We identified 1153 patients with vestibular schwannoma (569 [49%] women and 584 [51%] men), and 28815 population comparisons. Among the patients, 9% and 7% had pre- and post-diagnostic fall-related injuries, respectively, and among the comparisons, 8% and 6% had pre- and post-diagnostic fall-related injuries, respectively. There was no increased risk of pre- (OR 1.14; CI 0.92-1.41) or post-diagnostic 1 year (HR 1.16; CI 0.87-1.54) or 3 years (HR 1.11; CI 0.89-1.29) fall-related injury among the total patient cohort. In age-stratified analyses, we found an increased risk of pre-diagnostic fall-related injury among patients aged 50-69 years (OR 1.42; CI 1.10-1.88). Patients who underwent middle fossa surgery, regardless of age, had an increased risk of post-surgery fall-related injury within 3 years of follow-up (HR 2.68; CI 1.06-6.81). We conclude that patients with vestibular schwannoma have a low risk of enduring fall-related injuries. Middle-aged patients with dizziness and fall-related injuries should be considered for a vestibular clinical evaluation. Our results highlight the importance of rehabilitation in avoiding future fall-related injuries among patients undergoing middle fossa surgery.

Six-month mortality has decreased for patients with curative treatment intent for head and neck cancer in Sweden.

BACKGROUND: In general, survival outcomes for patients with Head and Neck Cancer (HNC) has improved over recent decades. However, mortality within six months after diagnosis for curative patients remains at approximately 5%. The aim of this study was to identify risk factors for early death among patients with curative treatment, and furthermore, to analyze whether the risk of early death changed over recent years. MATERIAL AND METHOD: This real-world, population-based, nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included all patients ≥18 years diagnosed with HNC with a curative treatment intent at the multidisciplinary tumor board from 2008 to 2020. A total of 16,786 patients were included. RESULTS: During the study period a total of 618 (3.7%) patients with curative-intended treatment died within six months of diagnosis. Patients diagnosed between 2008 and 2012 had a six-month mortality rate of 4.7% compared to 2.5% for patients diagnosed between 2017 and 2020, indicating a risk reduction of 53% (p <0.001) for death within six months. The mean time to radiation therapy from diagnosis in the 2008-2012 cohort was 38 days, compared to 22 days for the 2017-2020 cohort, (p <0.001). The mean time to surgery from diagnosis was 22 days in 2008-2012, compared to 15 days for the 2017-2020 cohort, (p <0.001). Females had a 20% lower risk of dying within six months compared to males (p = 0.013). For every year older the patient was at diagnosis, a 4.8% (p <0.001) higher risk of dying within six months was observed. Patients with a WHO score of 1 had approximately 2.4-times greater risk of early death compared to WHO 0 patients (p <0.001). The risk of early death among WHO 4 patients was almost 28 times higher than for WHO 0 patients (p <0.001). Patients with a hypopharyngeal tumor site had a 2.5-fold higher risk of dying within six months from diagnosis compared to oropharyngeal tumor patients (p <0.001). CONCLUSIONS: We found that the risk of early death decreased significantly from 2008 to 2020. During this period, the mean time to the start of treatment was significantly reduced both for surgery and oncological treatment regimes. Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site.

Prognostic value of bone marrow and tumor 18 F-FDG uptake on PET/CT in patients with oropharyngeal cancer and the interplay between inflammation and FDG uptake.

AIMS: To examine the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) for disease recurrence and survival in patients with oropharyngeal squamous cell carcinoma (OP-SCC). The secondary aims were to evaluate the prognostic value of PET/CT parameters for the primary oropharyngeal tumor and total tumor burden, and to assess the correlation between FDG uptake variables and serum inflammatory markers. METHODS: This was an observational study of 91 patients with OP-SCC who underwent pretreatment FDG-PET/CT. The patients' blood samples were collected before treatment, and treatment was administered with the intention to cure. The median follow-up time was 40 months. The PET parameters measured were SUVmean BM for the assessment of BM FDG uptake, SUVmean , SUVmax , total lesion glycolysis (TLG), and metabolic tumor volume (MTV) for the evaluation of primary oropharyngeal tumor and total tumor burden. Blood samples were analyzed to determine each patient's white cell, red cell, and platelet cell counts, hemoglobin, and C-reactive protein level. In a subgroup of 33 patients, blood serum was analyzed to evaluate the expression of serum immune proteins using a proximity extension assay (Olink Proteomics). RESULTS: The univariate analysis revealed that SUVmean BM and tumor-specific parameters (SUVmax tumor, SUVmean total, SUVmax total, MTVtotal, TLGtotal) were significantly associated with recurrence-free survival (RFS). After adjusting for age, sex, and stage only SUVmean BM remained significantly associated with RFS. Spearman's correlation identified several correlations between PET parameters and inflammatory markers. CONCLUSIONS: Our results show that several FDG-PET/CT parameters may have a prognostic value of treatment outcome in patients with OP-SCC. However, SUVmean BM was the only independent PET parameter that showed a prognostic value for RFS in the study cohort. Moreover, the study findings might suggest an association between systemic inflammation and the metabolic activity in the BM.

Pretreatment fat-free mass index correlates with early death in patients with head and neck squamous cell carcinoma.

BACKGROUND: A significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) are malnourished at diagnosis. In this study, we investigated how pretreatment body mass index (BMI) and fat-free mass index (FFMI) correlate with early death, and whether these measurements are useful markers of prognosis for risk stratification of head and neck cancer patients. METHODS: Patients (n = 404) with newly diagnosed, curable HNSCC and WHO performance status 0-2 were prospectively included and met with a study representative before treatment initiation, as well as up to four follow-up visits. All patients provided an estimate of body weight at 6 months prior to diagnosis. Bioelectrical impedance analysis (BIA) was performed for all patients before treatment initiation. RESULTS: Most patients had oropharyngeal (46%), oral cavity (28%), or laryngeal cancer (12%). Forty-five (11%) patients met the standardized criteria for malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) at diagnosis. FFMI at diagnosis was lower in patients who died within 6 and 12 months after the start of treatment than in patients who survived these time points (p = 0.035 and p = 0.005, respectively). CONCLUSIONS: In this study, pretreatment FFMI was an independent prognostic factor for death within 6 and 12 months after the start of treatment in patients with HNSCC. Pretreatment BMI was not an independent risk factor for death within 6 and 12 months after treatment termination. Thus, FFMI may be useful for risk stratification of patients with head and neck cancer.

Mapping the impact of malnutrition as defined by the Global Leadership Initiative on Malnutrition and nutrition impact symptoms on the possibility of returning to work after treatment for head and neck cancer.

PURPOSE: This study aimed to investigate whether malnutrition or nutrition impact symptoms (NIS) affect the possibility of returning to work after treatment for head and neck cancer. METHODS: Patients of working age with head and neck cancer were followed up from treatment initiation to 3 months (n = 238), 1 year (n = 182), and 2 years (n = 130) after treatment completion. The observed decrease in the number of patients over time was due to retirement, lack of follow-up, or death. Returning to work was dichotomised as yes or no. Malnutrition was diagnosed 7 weeks after treatment initiation using the Global Leadership Initiative on Malnutrition (GLIM) criteria. This time-point corresponds to the end of chemoradiotherapy or radiotherapy (with or without prior surgery), except for patients who underwent exclusive surgery. NIS were scored on a Likert scale (1-5) at each follow-up using the Head and Neck Patient Symptom Checklist© (HNSC©). Nonparametric tests were used to analyse the ability of patients with/without malnutrition and high/low NIS scores to return to work. RESULTS: At 3 months, 1 year, and 2 years after treatment completion, 135/238 (56.7%), 49/182 (26.9%), and 23/130 (17.7%) patients had not returned to work. Patients with malnutrition at 7 weeks after treatment initiation were more likely to not return to work at 3 months than those without malnutrition, 70.5% compared to 47.1% (p < 0.001). At all three follow-up time-points, patients reporting high scores for a number of NIS had more often not returned to work, with this pattern being most distinct at 2 years. CONCLUSION: Malnutrition according to the GLIM criteria at 7 weeks after treatment initiation and NIS assessed by the HNSC© at subsequent follow-ups were predictors of the return-to-work process after treatment for up to 2 years. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03343236 (date of registration 17/11/2017).

Predicting Return to Work after Head and Neck Cancer Treatment Is Challenging Due to Factors That Affect Work Ability.

Striving to return to work is of great importance to many cancer survivors. The purpose of the study is to prospectively investigate the factors that hinder and facilitate return to work (RTW) at 3 and 12 months after the end of treatment in head and neck cancer (HNC) survivors and whether these factors influence the ability to continue working after treatment. Participants (n = 227) aged ≤ 65 years at diagnosis with HNC were included. Data were collected before the start of treatment and at 3 and 12 months after the end of treatment. The Rubin causal model was used for statistical analysis. Within the 3-month follow-up period, 92 participants had RTW and 30 had retired. At the 12-month follow-up, 80 of these participants were still working, another 51 participants had RTW, and five participants working still suffered from cancer. The hindrance to RTW within 3 months was advanced tumour stage (stage III and IV) (p = 0.0038). Hindrances to RTW at the 12-month follow-up were oral cancer (p = 0.0210) and larynx cancer (p = 0.0041), and facilitators were living in a relationship (p = 0.0445) and a white-collar job (p = 0.00267). Participants with early tumour stage (stage I and II) (p = 0.0019) and a white-collar job (p = 0.0185) had earlier RTW. The conclusion is that disease factors were the most important hindrances to RTW, and type of work and living with a spouse or partner were nonclinical factors influencing RTW.

Perceptions of life and experiences of health care support among individuals one year after head and neck cancer treatment - An interview study.

PURPOSE: To examine how individuals treated for head and neck cancer perceive life one year after the end of treatment and how they experience supportive efforts from health care. METHODS: A semi-structured interview study of 21 patients was performed one year after the end of treatment. The patients gave their views concerning physical, psychological, and return-to-work issues, and their experiences concerning rehabilitative efforts from health care and particularly the contact nurse were captured. A thematic analysis was conducted. RESULTS: One year after treatment the patients were still suffering from side effects and from fear of recurrence, but they strived to live as they did before the cancer diagnosis, such as having returned to work and resuming leisure activities. Moreover, the rehabilitative efforts from health care had ended. Having access to a contact nurse, also known as a clinical nurse specialist, was positive, however, the participants lacked regular long-term follow-ups with the contact nurse regarding rehabilitation needs. Improvement possibilities were seen in clarifying the role of the contact nurse and that the contact nurse should show engagement and make the initial contact with the patients. CONCLUSION: Despite the sequelae from treatment, the patients strived to live as before their diagnosis. By regular, engaged, and long-term follow-ups by the contact nurse, remaining needs may be uncovered, and appropriate individualized support and rehabilitation can be offered.

Loco-Regional Control and Sustained Difference in Serum Immune Protein Expression in Patients Treated for p16-Positive and p16-Negative Head and Neck Squamous Cell Carcinoma.

The main prognostic factors for patients with head and neck cancer are the tumour site and stage, yet immunological and metabolic factors are certainly important, although knowledge is still limited. Expression of the biomarker p16INK4a (p16) in oropharyngeal cancer tumour tissue is one of the few biomarkers for the diagnosis and prognosis of head and neck cancer. The association between p16 expression in the tumour and the systemic immune response in the blood compartment has not been established. This study aimed to assess whether there is a difference in serum immune protein expression profiles between patients with p16+ and p16- head and squamous cell carcinoma (HNCC). The serum immune protein expression profiles, using the Olink® immunoassay, of 132 patients with p16+ and p16- tumours were compared before treatment and one year after treatment. A significant difference in the serum immune protein expression profile was observed both before and one year after treatment. In the p16- group, a low expression of four proteins: IL12RB1, CD28, CCL3, and GZMA before treatment conferred a higher rate of failure. Based on the sustained difference between serum immune proteins, we hypothesise that the immunological system is still adapted to the tumour p16 status one year after tumour eradication or that a fundamental difference exists in the immunological system between patients with p16+ and p16- tumours.

Hydrogen Gas Inhalation Attenuates Acute Impulse Noise Trauma: A Preclinical In Vivo Study.

OBJECTIVE: Molecular hydrogen (H2) has shown therapeutic potential in several oxidative stress-related conditions in humans, is well-tolerated, and is easily administered via inhalation.The aim of this preclinical in vivo study was to investigate whether impulse noise trauma can be prevented by H2 when inhaled immediately after impulse noise exposure. METHODS: Guinea pigs (n = 26) were subjected to impulse noise (n = 400; 156 dB SPL; 0.33/s; n = 11; the Noise group), to impulse noise immediately followed by H2 inhalation (2 mol%; 500 ml/min; 1 hour; n = 10; the Noise + H2 group), or to H2 inhalation (n = 5; the H2 group). The acoustically evoked ABR threshold at 3.15, 6.30, 12.5, 20.0, and 30.0 kHz was assessed before and 4 days after impulse noise and/or H2 exposure. The cochleae were harvested after the final ABR assessment for quantification of hair cells. RESULTS: Noise exposure caused ABR threshold elevations at all frequencies (median 35, 35, 30, 35, and 35 dB SPL, the Noise group; 20, 25, 10, 13, and 20 dB SPL, the Noise + H2 group; P < .05) but significantly less so in the Noise + H2 group (P < .05). Outer hair cell (OHC) loss was in the apical, mid, and basal regions 8.8%, 53%, and 14% in the Noise group and 3.5%, 22%, and 1.2% in the Noise + H2 group. The corresponding inner hair cell (IHC) loss was 0.1%, 14%, and 3.5% in the Noise group and 0%, 2.8%, and 0% in the Noise + H2 group. The difference between the groups was significant in the basal region for OHCs (P = .003) and apical (P = .033) and basal (P = .048) regions for IHCs. CONCLUSIONS: Acute acoustic trauma can be reduced by H2 when inhaled immediately after impulse noise exposure.

Higher Risk of Recurrence in Patients Treated for Head and Neck Cancer with Low BMI and Elevated Levels of C-Reactive Protein.

This prospective study identifies high-risk groups for recurrence of head and neck cancer by BMI and circulating inflammatory response markers. Head and neck cancer patients from three Swedish hospitals were included (n = 272). Leukocyte and thrombocyte counts, CRP levels, and BMI were measured pre-treatment and post-treatment. Associations between the four factors and treatment failure (residual tumor, loco-regional failure, general failure/distant metastasis) were assessed using a Cox proportional hazards model adjusted for sex, age at the initial visit, smoking status, cancer stage, and hemoglobin count. CRP level was the only significant single variable, with an average increase in risk of recurrence of 74% (p = 0.018) for every doubling. The predictive power of a combined model using all variables was highest during the initial months after treatment, with AUC under the ROC curve 0.75 at the 0-3 month timepoints. Patients with elevated pre- and post-treatment CRP levels are at higher risk for recurrence of disease. Male patients with low post-treatment BMI, advanced stage, and high CRP at any time post treatment are at high risk for recurrence. The combined model may be useful for stratifying post-treatment patients into low and high-risk groups, to enable more detailed follow-up or additional treatment regimens.

Longitudinal Changes in the Fatty Acid Profile in Patients with Head and Neck Cancer: Associations with Treatment and Inflammatory Response.

Studies on fatty acids (FAs) in patients with head and neck cancer (HNC) are limited. We aimed to investigate the longitudinal changes of circulating FAs in patients with HNC and to examine potential correlations of FA changes with treatment. The secondary aims were to investigate correlations of FAs with cytokines and patient-related factors, and if any FAs correlated with disease recurrence or death. A total of 174 patients with HNC were included before treatment and followed-up at three time points after the start of the treatment through blood sampling and body weight measurements. Serum FA profiling was assessed by gas chromatography. The total follow-up time was 3 years. The levels of almost all FAs changed from baseline to 7 weeks. The change in FA 14:0 was associated with treatment and the change in 18:3n-6 was associated with the patients' pre-treatment BMI. FAs 14:0 and 18:0 were correlated with weight changes from baseline to 7 weeks. IL-6 was correlated with three FAs at 7 weeks and with two FAs at 1 year. Patients with higher levels 20:5n-3 at 3 months had a higher risk of all-cause death within 3 years (HR 2.75, 95% CI 1.22-6.21). Treatment, inflammation, and weight loss contributed in a complex manner to the altered FA profile in the studied cohort. The association between IL-6 and FAs in patients with HNC is in line with earlier studies and suggests the opportunity for regulating inflammation in HNC patients through modulation of FAs.

Serum Proteomics in Patients with Head and Neck Cancer: Peripheral Blood Immune Response to Treatment.

In this real-world study, the aims were to prospectively evaluate the expression of inflammatory proteins in serum collected from head and neck cancer patients before and after treatment, and to assess whether there were differences in expression associated with treatment modalities. The mixed study cohort consisted of 180 patients with head and neck cancer. The most common tumor sites were the oropharynx (n = 81), the oral cavity (n = 53), and the larynx (n = 22). Blood tests for proteomics analysis were carried out before treatment, 7 weeks after the start of treatment, and 3 and 12 months after the termination of treatment. Sera were analyzed for 83 proteins using an immuno-oncology biomarker panel (Olink, Uppsala, Sweden). Patients were divided into four treatment groups: surgery alone (Surg group, n = 24), radiotherapy with or without surgery (RT group, n = 94), radiotherapy with concomitant cisplatin (CRT group, n = 47), and radiotherapy with concomitant targeted therapy (RT Cetux group, n = 15). For the overall cohort, the expression levels of 15 of the 83 proteins changed significantly between the pretreatment sample and the sample taken 7 weeks after the start of treatment. At 7 weeks after the start of treatment, 13 proteins showed lower expression in the CRT group compared to the RT group. The majority of the inflammatory proteins had returned to their pretreatment levels after 12 months. It was clearly demonstrated that cisplatin-based chemoradiation has immunological effects in patients with head and neck cancer. This analysis draws attention to several inflammatory proteins that are of interest for further studies.

Internet-based support for informal caregivers to individuals with head and neck cancer (Carer eSupport): a study protocol for the development and feasibility testing of a complex online intervention.

INTRODUCTION: It is strongly recommended that randomised controlled trials are preceded with an exploration of the needs of the target population and feasibility testing of the intervention. The present study protocol is set out to describe these steps in the development of a complex intervention.The past decades' transition of care from inpatient to outpatient settings has increased the complexity of caregivers' responsibilities, which they may not be prepared for. There is a need to support informal caregivers (ICs) to prepare them for caregiving and decrease the caregiver burden. The main aim of this study is to describe the development of an internet-based intervention (Carer eSupport) to improve ICs' ability to support individuals with head and neck cancer and to describe the testing of the feasibility and acceptability of Carer eSupport. METHODS AND ANALYSIS: This is a multicentre study involving the ear, nose and throat clinics and the oncology and radiotherapy clinics at three university hospitals. The study protocol comprises two phases, development and feasibility testing, using the Medical Research Council framework for developing a complex intervention. Carer eSupport will be based on the results from focus group discussions with ICs and healthcare professionals (planned for n=6-8 in respective groups) and scientific evidence, the Social Cognitive Theory and the Theory of Acceptance and Use of Technology. The feasibility testing will include 30 ICs who will have access to Carer eSupport for 1 month. The feasibility testing will be evaluated with a mixed-method design. ETHICS AND DISSEMINATION: All procedures have been approved by the Ethics Committee at Uppsala University (Dnr: 2020-04650). Informed consent will be obtained before enrolment of patients, their ICs and healthcare staff. The feasibility testing is registered at Clinicaltrials.gov (Identifier: NCT05028452). Findings will be disseminated in peer-reviewed journal publications. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (Identifier: NCT05028452).

Addressing symptoms that affect patients' eating according to the Head and Neck Patient Symptom Checklist©.

PURPOSE: The purpose of this prospective study was to assess which nutritional impact symptoms (NIS) interfere with oral intake in patients with head and neck cancer (HNC) and how the symptoms interfere with body weight loss, up to 1 year after treatment. METHODS: This was a prospective study of 197 patients with HNC planned for treatment with curative intention. Body weight was measured before the start of treatment, at 7 weeks after the start of treatment, and at 6 and 12 months after completion of treatment. NIS and NIS interfering with oral intake at each follow-up were examined with the Head and Neck Patient Symptom Checklist© (HNSC©). RESULTS: At 7 weeks of follow-up, patients experienced the greatest symptom and interference burden, and 12 months after treatment the NIS scorings had not returned to baseline. One year after treatment, the highest scored NIS to interfere with oral intake was swallowing problems, chewing difficulties, and loss of appetite. At all 3 follow-ups, the total cumulative NIS and NIS interfering with oral intake were associated with body weight loss. Factors increasing the risk for a body weight loss of ≥ 10% at 12 months after treatment were pain, loss of appetite, feeling full, sore mouth, difficulty swallowing, taste changes, and dry mouth. Women scored higher than men in NIS and NIS interfering with oral intake. Furthermore, during the study period about half of the population had a body weight loss > 5%. CONCLUSION: Because both nutritional and clinical factors may affect body weight, this study highlights the importance of a holistic approach when addressing the patients' nutritional issues. TRIAL REGISTRATION: ClinicalTrials.gov NCT03343236, date of registration: November 17, 2017.

The Acute Effects of Furosemide on Na-K-Cl Cotransporter-1, Fetuin-A and Pigment Epithelium-Derived Factor in the Guinea Pig Cochlea.

Background: Furosemide is a loop diuretic used to treat edema; however, it also targets the Na-K-Cl cotransporter-1 (NKCC1) in the inner ear. In very high doses, furosemide abolishes the endocochlear potential (EP). The aim of the study was to gain a deeper understanding of the temporal course of the acute effects of furosemide in the inner ear, including the protein localization of Fetuin-A and PEDF in guinea pig cochleae. Material and Method: Adult guinea pigs were given an intravenous injection of furosemide in a dose of 100 mg per kg of body weight. The cochleae were studied using immunohistochemistry in controls and at four intervals: 3 min, 30 min, 60 min and 120 min. Also, cochleae of untreated guinea pigs were tested for Fetuin-A and PEDF mRNA using RNAscope® technology. Results: At 3 min, NKCC1 staining was abolished in the type II fibrocytes in the spiral ligament, followed by a recovery period of up to 120 min. In the stria vascularis, the lowest staining intensity of NKCC1 presented after 30 min. The spiral ganglion showed a stable staining intensity for the full 120 min. Fetuin-A protein and mRNA were detected in the spiral ganglion type I neurons, inner and outer hair cells, pillar cells, Deiters cells and the stria vascularis. Furosemide induced an increased staining intensity of Fetuin-A at 120 min. PEDF protein and mRNA were found in the spiral ganglia type I neurons, the stria vascularis, and in type I and type II fibrocytes of the spiral ligament. PEDF protein staining intensity was high in the pillar cells in the organ of Corti. Furosemide induced an increased staining intensity of PEDF in type I neurons and pillar cells after 120 min. Conclusion: The results indicate rapid furosemide-induced changes of NKCC1 in the type II fibrocytes. This could be part of the mechanism that causes reduction of the EP within minutes after high dose furosemide injection. Fetuin-A and PEDF are present in many cells of the cochlea and probably increase after furosemide exposure, possibly as an otoprotective response.

Mandibular resection in patients with head and neck cancer: acute and long-term complications after reconstruction.

BACKGROUND: The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient. AIMS/OBJECTIVES: This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions. MATERIAL AND METHODS: We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24). RESULTS: Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien-Dindo ≥ IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication. CONCLUSIONS: A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien-Dindo grade IIIa-V events was significantly lower for patients treated with primary closure without grafts. SIGNIFICANCE: The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.

A national study of health-related quality of life in patients with cancer of the base of the tongue compared to the general population and to patients with tonsillar carcinoma.

BACKGROUND: This exploratory, registry-based, cross-sectional study aimed to evaluate patients' health-related quality of life (HRQOL) in a subsite of oropharyngeal cancer: cancer of the base of the tongue (CBT). METHODS: CBT patients, treated with curative intent, completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 15 months after diagnosis. The HRQOL of CBT patients was compared to reference scores from the general population and to that of tonsillar carcinoma patients. RESULTS: The 190 CBT patients scored significantly worse than members of the general population on most scales. CBT patients with human papilloma virus (HPV)-positive tumors had significantly better HRQOL on 8 of 28 scales than HPV-negative patients. Compared to 405 tonsillar carcinoma patients, CBT patients had significantly worse HRQOL on 8 of the 28 scales, the majority local head and neck related problems. CONCLUSION: One year after treatment, CBT patients' HRQOL was significantly worse in many areas compared to that of the general population and slightly worse than that of tonsillar carcinoma patients.

Circulating fatty acids in patients with head and neck cancer after treatment: an explorative study with a one-year perspective.

BACKGROUND: Unintended weight loss and nutritional problems are often seen in patients with head and neck cancer, but changes in lipid metabolism are poorly studied. AIM/OBJECTIVES: The present study aimed to explore the longitudinal changes in circulating fatty acid (FA) composition in patients with head and neck cancer. MATERIALS AND METHODS: This study included 27 patients with head and neck cancer. Treatment consisted of single modality or combined modality treatments. The patients were assessed by repeated blood sampling and body weight assessments before treatment started and on three occasions after the start of treatment. FA profiling included gas chromatography analysis of unsaturated FAs and saturated FAs in serum. RESULTS: The values of three fatty acids - FA 14:0, FA 18:3n3, and FA 20:3n6 - changed in a specific pattern over the course of the study and the change in FA 14:0 correlated with weight changes. CONCLUSIONS AND SIGNIFICANCE: This study showed altered profiles of both saturated and unsaturated FAs. An improved understanding of the metabolic pathways in patients with head and neck cancer supports the development of better nutritional surveillance and nutritional treatments.

Inhalation of Molecular Hydrogen, a Rescue Treatment for Noise-Induced Hearing Loss.

Noise exposure is the most important external factor causing acquired hearing loss in humans, and it is strongly associated with the production of reactive oxygen species (ROS) in the cochlea. Several studies reported that the administration of various compounds with antioxidant effects can treat oxidative stress-induced hearing loss. However, traditional systemic drug administration to the human inner ear is problematic and has not been successful in a clinical setting. Thus, there is an urgent need to develop rescue treatment for patients with acute acoustic injuries. Hydrogen gas has antioxidant effects, rapid distribution, and distributes systemically after inhalation.The purpose of this study was to determine the protective efficacy of a single dose of molecular hydrogen (H2) on cochlear structures. Guinea pigs were divided into six groups and sacrificed immediately after or at 1 or 2 weeks. The animals were exposed to broadband noise for 2 h directly followed by 1-h inhalation of 2% H2 or room air. Electrophysiological hearing thresholds using frequency-specific auditory brainstem response (ABR) were measured prior to noise exposure and before sacrifice. ABR thresholds were significantly lower in H2-treated animals at 2 weeks after exposure, with significant preservation of outer hair cells in the entire cochlea. Quantification of synaptophysin immunoreactivity revealed that H2 inhalation protected the cochlear inner hair cell synaptic structures containing synaptophysin. The inflammatory response was greater in the stria vascularis, showing increased Iba1 due to H2 inhalation.Repeated administration of H2 inhalation may further improve the therapeutic effect. This animal model does not reproduce conditions in humans, highlighting the need for additional real-life studies in humans.