Prevention and Treatment of Life-Threatening COVID-19 May Be Possible with Oxygen Treatment.

Most SARS CoV-2 infections probably occur unnoticed or cause only cause a mild common cold that does not require medical intervention. A significant proportion of more severe cases is characterized by early neurological symptoms such as headache, fatigue, and impaired consciousness, including respiratory distress. These symptoms suggest hypoxia, specifically affecting the brain. The condition is best explained by primary replication of the virus in the nasal respiratory and/or the olfactory epithelia, followed by an invasion of the virus into the central nervous system, including the respiratory centers, either along a transneural route, through disruption of the blood-brain barrier, or both. In patients, presenting with early dyspnea, the primary goal of therapy should be the reversal of brain hypoxia as efficiently as possible. The first approach should be intermittent treatment with 100% oxygen using a tight oronasal mask or a hood. If this does not help within a few hours, an enclosure is needed to increase the ambient pressure. This management approach is well established in the hypoxia-related diseases in diving and aerospace medicine and preserves the patient's spontaneous breathing. Preliminary research evidence indicates that even a small elevation of the ambient pressure might be lifesaving. Other neurological symptoms, presenting particularly in long COVID-19, suggest imbalance of the autonomous nervous system, i.e., dysautonomia. These patients could benefit from vagal nerve stimulation.

Stress and Tinnitus; Transcutaneous Auricular Vagal Nerve Stimulation Attenuates Tinnitus-Triggered Stress Reaction.

INTRODUCTION: Tinnitus can become a strong stressor for some individuals, leading to imbalance of the autonomous nervous system with reduction of parasympathetic activity. It can manifest itself as sleep disturbances, anxiety and even depression. This condition can be reversed by bioelectrical vagal nerve stimulation (VNS). Conventional invasive VNS is an approved treatment for epilepsy and depression. Transcutaneous VNS (taVNS) stimulating the auricular branch of the vagus nerve has been shown to activate the vagal pathways similarly as an implanted VNS. Therefore, taVNS might also be a therapeutic alternative in health conditions such as tinnitus-related mental stress (TRMS). This retrospective study in 171 TRMS patients reports the clinical features, psychophysiological characteristics, and results of the heart rate variability (HRV) tests before and after test-taVNS. This study also reports the therapy outcomes of 113 TRMS patients treated with taVNS, in combination with standard tinnitus therapy. METHODS: Diagnostic tinnitus and hearing profiles were defined. To detect possible cardiac adverse effects, test-taVNS with heart rate monitoring as well as pre- and post-stimulation HRV tests were performed. Daily taVNS home therapy was prescribed thereafter. To assess therapeutic usefulness of taVNS, 1-year follow-up outcome was studied. Results of HRV tests were retrospectively analyzed and correlated to diagnostic data. RESULTS: The large majority of patients with TRMS suffer from associated symptoms such as sleep disturbances and anxiety. Baseline HRV data showed that more than three quarters of the 171 patients had increased sympathetic activity before test-taVNS. Test-taVNS shifted mean values of different HRV parameters toward increased parasympathetic activity in about 80% of patients. Test-taVNS did not cause any cardiac or other side effects. No significant adverse effects were reported in follow-up questionnaires. CONCLUSION: TRMS is an example of a stress condition in which patients may benefit from taVNS. As revealed by HRV, test-taVNS improved parasympathetic function, most efficiently in patients with a low starting HRV level. Our tinnitus treatment program, including taVNS, effectively alleviated tinnitus stress and handicap. For wider clinical use, there is a great need for more knowledge about the optimal methodology and parameters of taVNS.

Tonsillar surface swab bacterial culture results differ from those of the tonsillar core in recurrent tonsillitis.

OBJECTIVES/HYPOTHESIS: We aimed to determine whether there was a difference between core and surface bacteriology of Finnish adults with recurrent or chronic tonsillitis to understand whether a surface swab is worthwhile and which bacteria are involved. STUDY DESIGN: Case series. METHODS: Uninflamed tonsillar surface swabs and core biopsies were taken prior to and during surgery, respectively, in 103 patients aged 16 to 66 years undergoing tonsillectomy for recurrent or chronic tonsillitis. The McNemar test was used to determine differences between the surface and core in the most prevalent bacterial species. RESULTS: Twenty-seven bacterial species were isolated in addition to normal flora and were more commonly found in the core (1.11 surface and 4.75 core bacteria isolated per patient). Viridans group streptococci were the most commonly detected bacteria, found in 88% of the patients, mainly in the core. The bacteria in general were mainly isolated from the core. Of the 10 most prevalent bacteria, only group C ß-hemolytic streptococci showed no difference between detection from core and surface swabs. Other bacteria found mainly in the core include Prevotella melaninogenica, Staphylococcus aureus, and fusobacteria. CONCLUSIONS: There is discord between the surface and core bacteria. A different population of bacteria exists in the core, especially anaerobic bacteria, suggesting that a core sample may be useful in evaluating recurrent and chronic tonsillitis. LEVEL OF EVIDENCE: 4 Laryngoscope, 2019.

Hearing disorder from music; a neglected dysfunction.

CONCLUSION: Music-induced acute acoustic trauma is not inevitably linked to hearing dysfunction as validated by conventional pure tone audiometry. Tinnitus is often in combination with hyperacusis. Our results point at 'silent hearing loss' as the underlying pathology, having afferent nerve terminal damage rather than hair cell loss as the structural correlate. OBJECTIVES: Exposure to loud music is one of the most common causes of acute acoustic trauma, which adolescents and teenagers experience by voluntary exposure to loud music of sound levels up to 110 dB(A). METHODS: The clinical and psychophysical data of 104 consecutive patients with music-induced hearing disorder (MIHD) were analyzed to construct individual hearing and tinnitus profiles. In all cases, tinnitus was the presenting symptom. RESULTS: Hearing abilities were normal in about two-thirds of the tinnitus patients. Tinnitus was experienced most often as a high-frequency tone (83%). The Tinnitus Handicap Inventory (THI) scores ranged from 0 to 94 with an average score of 43.1. Visual analog scales (VAS) were used to assess tinnitus loudness (average 42.4) and annoyance (average 54.2), and tinnitus awareness was estimated (average 60.3). All VAS values correlated strongly with the THI. Hyperacusis was present in 65% and 71% of the patients reported sleeping disorders.

Attenuation of Positive Valence in Ratings of Affective Sounds by Tinnitus Patients.

Affective processing appears to be altered in tinnitus, and the condition is to a large extent characterized by the emotional reaction to the phantom sound. Psychophysiological models of tinnitus and supporting brain imaging studies have suggested a role for the limbic system in the emergence and maintenance of tinnitus. It is not clear whether the tinnitus-related changes in these systems are specific for tinnitus only, or whether they affect emotional processing more generally. In this study, we aimed to quantify possible deviations in affective processing in tinnitus patients by behavioral and physiological measures. Tinnitus patients rated the valence and arousal of sounds from the International Affective Digitized Sounds database. Sounds were chosen based on the normative valence ratings, that is, negative, neutral, or positive. The individual autonomic response was measured simultaneously with pupillometry. We found that the subjective ratings of the sounds by tinnitus patients differed significantly from the normative ratings. The difference was most pronounced for positive sounds, where sounds were rated lower on both valence and arousal scales. Negative and neutral sounds were rated differently only for arousal. Pupil measurements paralleled the behavioral results, showing a dampened response to positive sounds. Taken together, our findings suggest that affective processing is altered in tinnitus patients. The results are in line with earlier studies in depressed patients, which have provided evidence in favor of the so-called positive attenuation hypothesis of depression. Thus, the current results highlight the close link between tinnitus and depression.

Non-invasive vagus nerve stimulation reduces sympathetic preponderance in patients with tinnitus.

CONCLUSION: Transcutaneous vagal nerve stimulation (tVNS) might offer a targeted, patient-friendly, and low-cost therapeutic tool for tinnitus patients with sympathovagal imbalance. OBJECTIVES: Conventionally, VNS has been performed to treat severe epilepsy and depression with an electrode implanted to the cervical trunk of vagus nerve. This study investigated the acute effects of tVNS on autonomic nervous system (ANS) imbalance, which often occurs in patients with tinnitus-triggered stress. METHODS: This study retrospectively analysed records of 97 patients who had undergone ANS function testing by heart rate variability (HRV) measurement immediately before and after a 15-60 min tVNS stimulation. RESULTS: The pre-treatment HRV recording showed sympathetic preponderance/reduced parasympathetic activity in about three quarters (73%) of patients. Active tVNS significantly increased variability of R-R intervals in 75% of patients and HRV age was decreased in 70% of patients. Either the variability of R-R intervals was increased or the HRV age decreased in 90% of the patients. These results indicate that tVNS can induce a shift in ANS function from sympathetic preponderance towards parasympathetic predominance. tVNS caused no major morbidity, and heart rate monitoring during the tVNS treatment showed no cardiac or circulatory effects (e.g. bradycardia) in any of the patients.

c-Jun N-Terminal Phosphorylation: Biomarker for Cellular Stress Rather than Cell Death in the Injured Cochlea.

Prevention of auditory hair cell death offers therapeutic potential to rescue hearing. Pharmacological blockade of JNK/c-Jun signaling attenuates injury-induced hair cell loss, but with unsolved mechanisms. We have characterized the c-Jun stress response in the mouse cochlea challenged with acoustic overstimulation and ototoxins, by studying the dynamics of c-Jun N-terminal phosphorylation. It occurred acutely in glial-like supporting cells, inner hair cells, and the cells of the cochlear ion trafficking route, and was rapidly downregulated after exposures. Notably, death-prone outer hair cells lacked c-Jun phosphorylation. As phosphorylation was triggered also by nontraumatic noise levels and none of the cells showing this activation were lost, c-Jun phosphorylation is a biomarker for cochlear stress rather than an indicator of a death-prone fate of hair cells. Preconditioning with a mild noise exposure before a stronger traumatizing noise exposure attenuated the cochlear c-Jun stress response, suggesting that the known protective effect of sound preconditioning on hearing is linked to suppression of c-Jun activation. Finally, mice with mutations in the c-Jun N-terminal phosphoacceptor sites showed partial, but significant, hair cell protection. These data identify the c-Jun stress response as a paracrine mechanism that mediates outer hair cell death.

Transcutaneous vagus nerve stimulation modulates tinnitus-related beta- and gamma-band activity.

OBJECTIVES: The ability of a treatment method to interfere with tinnitus-related neural activity patterns, such as cortical gamma rhythms, has been suggested to indicate its potential in relieving tinnitus. Therapeutic modulation of gamma-band oscillations with vagus nerve stimulation has been recently reported in epileptic patients. The aim of this study was to investigate the effects of transcutaneous vagus nerve stimulation (tVNS) on neural oscillatory patterns. DESIGN: We calculated the power spectral density and synchrony of magnetoencephalography recordings during auditory stimulation in seven tinnitus patients and eight normal-hearing control subjects. Comparisons between subject groups were performed to reveal electrophysiological markers of tinnitus. tVNS-specific effects within each group were studied by comparing recording blocks with and without tVNS. We also investigated the correlation of each measure with individual ratings of tinnitus distress, as measured by the tinnitus handicap inventory questionnaire. RESULTS: Tinnitus patients differed from controls in the baseline condition (no tVNS applied), measured by both cortical oscillatory power and synchronization, particularly at beta and gamma frequencies. Importantly, we found tVNS-induced changes in synchrony, correlating strongly with tinnitus handicap inventory scores, at whole-head beta-band (r = -0.857, p = 0.007), whole-head gamma-band (r = -0.952, p = 0.0003), and frontal gamma-band (r = -0.952, p = 0.0003). CONCLUSIONS: We conclude that tVNS was successful in modulating tinnitus-related beta- and gamma-band activity and thus could have potential as a treatment method for tinnitus.

Transcutaneous vagus nerve stimulation in tinnitus: a pilot study.

CONCLUSIONS: This pilot study shows that transcutaneous vagus nerve stimulation (tVNS), if combined with sound therapy (ST), reduces the severity of tinnitus and tinnitus-associated distress. Our magnetoencephalography (MEG) results show that auditory cortical activation can be modulated by the application of tVNS. Thus, tVNS might offer a new avenue to treat tinnitus and tinnitus-associated distress. OBJECTIVES: Recent studies suggest that tinnitus can be improved by tailored ST or by VNS plus ST. Our aims were to study whether tVNS has therapeutic effects on patients with tinnitus and, additionally, if tVNS has effects on acoustically evoked neuronal activity of the auditory cortex. METHODS: The clinical efficacy was studied by a short-term tVNS plus ST trial in 10 patients with tinnitus using disease-specific and general well-being questionnaires. tVNS was delivered to the left tragus. The acute effects of tVNS were evaluated in eight patients in the MEG study in which the N1m response was analyzed in terms of source level amplitude and latency in the presence or absence of tVNS. RESULTS: The treatment with tVNS plus ST produced improved mood and decreased tinnitus handicap scores, indicating reduced tinnitus severity. The application of tVNS decreased the amplitude of auditory N1m responses in both hemispheres.

Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

Differential sensitivity of the inner ear sensory cell populations to forced cell cycle re-entry and p53 induction.

Previous studies have shown that the maintenance of post-mitotic state is critical for the life-long survival of the inner ear mechanosensory cells, the hair cells. A general concept is that differentiated, post-mitotic cells rapidly die following cell cycle re-entry. Here we have compared the response of postnatal cochlear (auditory) and utricular (balance) hair cells to forced cell cycle reactivation and p53 up-regulation. Forced S-phase entry was triggered through the human papillomavirus-16 E7 oncogene misexpression in explant cultures. It induced DNA damage and p53 induction in cochlear outer hair cells and these cells were rapidly lost, before entry into mitosis. The death was attenuated by p53 inactivation. In contrast, despite DNA damage and p53 induction, utricular hair cells showed longer term survival and a proportion of them progressed into mitosis. Consistently, pharmacological elevation of p53 levels by nutlin-3a led to a death-prone phenotype of cochlear outer hair cells, while other hair cell populations were death-resistant. These data have important clinical implications as they show the importance of p53 in sensory cells that are essential in hearing function.

Complication rates of radiofrequency surgery in the upper airways: a single institution experience.

CONCLUSION: Radiofrequency (RF) surgery of the upper airways appears to be a safe procedure with an acceptable incidence of minor and moderate complications. OBJECTIVES: RF surgery is increasingly used in the treatment of patients with sleep disordered breathing and inferior turbinate hypertrophy. Our aim was to investigate the incidence and the severity of the complications of RF surgery in the upper airways. PATIENTS AND METHODS: This was a retrospective, observational study at a tertiary care centre, academic teaching hospital during 1 year. Data from medical records were collected on 753 consecutive patients treated with RF surgery of the inferior turbinate, soft palate and base of the tongue. Patients with synchronous surgical treatment were excluded. RESULTS: In all, 413 patients (66.3% males) with a mean age of 44.7 years (range 8-83 years) were treated with 2926 RF surgery ablations in 524 treatment sessions. There were no severe complications. The overall incidence of minor and moderate complications was low, i.e. 2.7% (11/524) and 0.6% (3/524) of the treatment sessions, and 0.5% (11/2926) and 0.1% (3/2926) of the ablations, respectively.

The effect of tightened hearing protection regulations on military noise-induced tinnitus.

The objective of this study was to investigate the effect of tightened hearing protection regulations on tinnitus in the Finnish Defence Forces. The initial study group comprised 252 officers and non-commissioned officers (NCOs), of which 229 were included in the final study group. Subjective symptoms of tinnitus and audiometric test results for these officers and NCOs examined before retirement, from 1984 to 1986 (Period I), and 2003 to 2005 (Period II), were reviewed. Changes in tinnitus reports between the two time periods, during which regulations had been revised, were investigated. Prevalence of tinnitus showed a decline both in officers (from 68% to 63%) and in NCOs (from 76% to 72%) between the two study periods, in accordance with tightened hearing protection regulations. The Cox regression analysis showed a significantly decreased hazard ratio for constant or disturbing tinnitus for Period II. Tinnitus prevalence, especially constant or disturbing tinnitus, in the Finnish Defence Forces was diminished by tightened hearing protection regulations. Tinnitus might be more persistent than hearing loss and does not necessarily improve in direct relation to hearing loss after protective measures.

[Tinnitus]. / Tinnitus.

Tinnitus is a symptom caused by the dysfunction of the auditory system associated with hyperactive networks of the central auditory tract. Intimate relationship of the auditory tract with the limbic system may lead to a stress reaction with subsequent sleep disturbances, distress and depression. The target of tinnitus treatment shoud be the annoyance caused by tinnitus, not the sensation itself. Optimally, all tinnitus patients should be treated according to the TRT-principles including careful diagnostics, informational counceling and sound-based therapies. Some patients need sleep therapy as well as anti-depressive therapy.

Assessment of submucosal radiofrequency tonsil reduction by magnetic resonance imaging.

OBJECTIVES: The primary objective was to assess the efficacy of submucosal radiofrequency tonsil reduction (SRFTR) in adults by magnetic resonance imaging (MRI). The secondary objective was to evaluate the morbidity of SRFTR. METHODS: A prospective, longitudinal clinical study with a follow-up time of 12 months was conducted of 10 consecutive patients with the median age of 24.5 years (range 19-55 years) with obstructive palatine tonsil hypertrophy. SRFTR was delivered in an outpatient setting in a tertiary care centre, academic teaching hospital. MAIN OUTCOME MEASURES: The change in tonsillar volume after SRFTR was evaluated with MRI by two radiologists independently and blinded to the treatment results. The morbidity was assessed with a visual analogue scale (VAS), a questionnaire for the pain medication needed, and inflammatory laboratory parameters. VAS and use of pain medication results were compared with those of two earlier cohort groups undergoing conventional tonsillectomy with two different techniques at our department. RESULTS: The tonsil volume reduced significantly with a median reduction in the total tonsil volume of 12.6% (range 3.7-41.5%, pretreatment vs posttreatment volume, p < .01). VAS of the morbidity symptoms and the amount of pain medication needed were significantly lower in the SRFTR group than in the two historical tonsillectomy groups. The laboratory parameters showed a significant change. CONCLUSION: SRFTR in adults with obstructive palatine tonsil hypertrophy is a minimally invasive procedure causing a tonsil volume reduction demonstrated by MRI. The procedure seems to be associated with acceptable morbidity.

Radiofrequency surgery of the soft palate in the treatment of mild obstructive sleep apnea is not effective as a single-stage procedure: A randomized single-blinded placebo-controlled trial.

OBJECTIVES/HYPOTHESIS: Radiofrequency (RF) surgery of the soft palate (SP) is an established treatment option for the treatment of snoring. Due to its minimally invasive character, it has received attention in the management of mild obstructive sleep apnea syndrome (OSAS). STUDY DESIGN: The aim of this study was to assess the efficacy and the occurrence of adverse events after single-stage SP RF surgery in patients with mild OSAS in a randomized single-blinded placebo-controlled trial in an outpatient department at a tertiary care center, academic teaching hospital. METHODS: Thirty-two patients with mild OSAS (apnea-hypopnea index [AHI] 5-15, body mass index <35) were randomized to receive a single session of RF surgery or placebo (insertion of applicator without energy delivery) with local anesthesia. The primary outcome measures were (AHI), Epworth Sleepiness Scale, and a 36-item short-form health survey quality-of-life questionnaire. The secondary measures were the soft tissue airway parameters in cephalometric radiographs, snoring scores, and rates of adverse events. RESULTS: Neither objectively measured significances (active AHI 11.0 [5.0-9.0] to 13.0 [2.0-26.0] and placebo AHI 12.0 [5.0-8.0] to 11.0 [1.0-29.0], P = .628), nor were trends of a diminishing effect on symptoms of mild OSAS found in the treatment arms. No significant changes in the soft tissue airway parameters occurred. One patient (5.9%) in the active treatment group was cured. CONCLUSIONS: RF surgery of SP is not recommended as a single-stage approach in mild OSAS.

Hypertonic saline injections to enhance the radiofrequency thermal ablation effect in the treatment of base of tongue in obstructive sleep apnoea patients: a pilot study.

CONCLUSION: Hypertonic saline (HS) infiltration in the base of the tongue (BOT) in multilevel radiofrequency ablation (RFA) treatment was followed by significant acute complications in terms of soft tissue swelling. Three patients were defined as cured. No significant changes in the measured parameters were encountered, although, several of them showed a clear trend. New treatment modalities are needed to keep multilevel RFA treatment as a minimally invasive procedure. OBJECTIVES: To assess the efficacy and morbidity of RFA of the soft palate (SP) and BOT infiltrated with HS in obstructive sleep apnoea in a prospective, non-randomized clinical study. PATIENTS AND METHODS: The inclusion criteria were age between 30 and 65 years, habitual snoring and excessive daytime sleepiness, a body mass index < or =33, and an apnoea-hypopnoea index > or =20. RFA of the SP and the BOT was delivered under local anaesthesia. HS solution was injected before the treatment into the BOT. The morbidity of the procedure was assessed with a visual analogue scale, and efficacy by separate questionnaires and sleep registration. The volume changes induced by the procedure were evaluated with cephalometric radiographs (CRs). RESULTS: Twelve males and one female with a median age of 50 years (range 41-62) entered the study. Six patients (46%) had more postoperative swelling in the upper airway than expected. Three patients were defined as cured. The trend in the questionnaires was clear, but not significant. In the soft tissue airway CR measurements no significant changes were encountered, although a trend towards volume reduction was seen in the posterior airway space measure.

The effect of improved hearing protection regulations in the prevention of military noise-induced hearing loss.

CONCLUSION: Hearing protection regulations have improved the hearing test results of soldiers in the Finnish Defense Forces. OBJECTIVES: To investigate the effect of revised regulations regarding usage of hearing protectors of professional soldiers in the Finnish Defense Forces. SUBJECTS AND METHODS: The medical records of non-commissioned officers and officers examined at the Central Military Hospital ENT Department from 1984 to 1986 (Period I) and 2003 to 2005 (Period II) were reviewed. The study group comprised 252 persons. Changes in hearing between the two time periods, during which regulations were revised, were investigated. RESULTS: Hearing test results improved both in non-commissioned officers and in officers between the two study periods, in accordance with tightened hearing protection regulations. Improvement was found, especially in the high frequencies; however, the results were milder than expected, particularly in officers.