The RAI-6 Questionnaire: A New Screening Questionnaire to Monitor Complications of Radioiodine Treatment.

Objective: The aim of this study is to develop a simple and efficient screening questionnaire to be able to routinely monitor potential radioiodine therapy-induced complications. Materials and Methods: A new radioiodine 6 (RAI-6) questionnaire containing six questions adressing salivary, ocular, and nasal symptoms as well as quality of life was developed. Validation of the RAI-6 questionnaire was assessed with a group of fifty-four patients diagnosed with differentiated thyroid carcinoma treated post-operatively with radioiodine therapy, and in a group of fifty healthy volunteers. The patient's group was subdivided into subgroups according to the radioiodine dose received: 23 patients received less or 30 mCi, 28 patients received 100 mCi, and three patients received between 200 and 300 mCi. We asked the patients to complete the RAI-6 questionnaire in a retrospective manner, regarding their situation before radioiodine therapy and regarding their actual symptoms after radioiodine therapy. The time needed to complete the RAI-6 was also assessed both in patients and in healthy volunteers. Results: The mean post radioiodine treatment RAI-6 score were significantly higher than the mean pre radioiodine RAI-6 scores (p < 0.001) and the scores of healthy participants (p < 0.001). The mean total RAI-6 scores increased significantly with increasing radioiodine dose. A total mean RAI-6 score of each question was also analysed and revealed that ocular and nasal discomfort as well as quality of life were the items which affected the patients most after radioiodine treatment. The mean time to fill the RAI-6 questionnaire was 2 min for patients and 49 s for healthy volunteers. Conclusion: The RAI-6 represents a new questionnaire which is easy and quick to complete. This simple screening tool can be recommended for general clinical practise and further epidemiological research.

Assessment of Surgical Complications With Respect to the Surgical Indication: Proposal for a Novel Index.

Introduction: The Clavien-Dindo classification is a broadly accepted surgical complications classification system, grading complications by the extent of therapy necessary to resolve them. A drawback of the method is that it does not consider why the patient was operated on primarily. Methods: We designed a novel index based on Clavien-Dindo but with respect to the surgical indication. We surveyed an international panel of otolaryngologists who filled out a questionnaire with 32 real case-inspired scenarios. Each case was graded for the surgical complication, surgical indication, and a subjective rating whether the complication was acceptable or not. Results: Seventy-seven otolaryngologists responded to the survey. Mean subjective rating and surgical complication grading for each scenario showed an inverse correlation (r 2 = 0.147, p = 0.044). When grading the surgical complication with respect to the surgical indication, the correlation with the subjective rating increased dramatically (r 2 = 0.307, p = 0.0022). Conclusion: We describe a novel index grading surgical complications with respect to the surgical indication. In our survey, most respondents judged a complication as acceptable or not according to its grade but kept in mind the surgical indication. This subjective judgment could be quantified with our novel index.

Cochlear implants in single-sided deafness - clinical results of a Swiss multicentre study.

AIM OF THE STUDY: The aim of this multicentre, prospective, open, nonrandomised clinical trial was to demonstrate the clinical efficiency and outcomes of cochlear implants (CIs) in adult patients with post-lingual single-sided deafness (SSD). METHODS: A group of five left and five right SSD participants were investigated with various clinical tests and questionnaires before and 12 months after CI activation. Changes in hearing thresholds, speech understanding in noise, sound localisation, tinnitus (Tinnitus Handicap Inventory; THI), subjective hearing ability (Speech, Spatial and Qualities of Hearing Scale; SSQ), and quality of life (WHOQOL-BREF) were assessed. In addition, the pre- and postoperative results of the SSD patients were compared with an age- and gender-matched normal hearing control group. RESULTS: Surgery was uncomplicated in all patients. Two years after implantation, 9 of the 10 patients used their CI regularly for an average of more than 11 hours a day. A significant improvement in speech understanding in noise measured in the sound field using the Oldenburg sentence test could be demonstrated in the two situations in which patients with SSD experience the greatest difficulty: speech from the front and noise at the healthy ear, and speech to the implanted ear and noise from the front. The sound localisation test showed significant improvement of the mean localisation error and the root mean square error after CI activation. Furthermore, a significant reduction of the THI was measured, and the SSQ showed a significant improvement in the subscale speech comprehension and in the subscale spatial hearing. Also, quality of life measured with the WHOQOL-BREF showed a general improvement, which was significant in the global subscale. For this questionnaire, there was no significant difference between the normal-hearing control group and the patients after 12 months of CI use. CONCLUSION: This study confirmed the clinical benefit of cochlear implantation in patients with SSD. The significant improvement of speech understanding in noise, sound localisation, tinnitus perception, subjective hearing ability, and in particular the improved quality of life support the recommendation that patients with recently acquired SSD should be offered a CI. (Clinical trial registration number on clinicaltrial.gov: NCT01749592).

The Influence of Cochlear Implantation on Tinnitus in Patients with Single-Sided Deafness: A Systematic Review.

OBJECTIVES: This systematic review provides an overview of the available studies (published by January 29, 2018) with descriptive data analysis about the influence of cochlear implantation on tinnitus in patients with single-sided deafness (SSD). DATA SOURCES: PubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar. REVIEW METHODS: Original studies about the influence of cochlear implantation on tinnitus, measured with different tinnitus questionnaires or visual analog scale, in patients with SSD were included. The pre- and postimplantation tinnitus scores of the included studies were extracted for the further systematic review. RESULTS: The systematic search yielded 1028 studies. After evaluating titles, abstracts, and full texts, 1011 of these were dismissed. From the remaining 17 studies, 4 showed a low directness of evidence or high risk of bias and were therefore excluded. Due to the nature of cochlear implantation in SSD, only cohort studies and no randomized trials exist, which limits the evaluation in a systematic review. Generally, the mean tinnitus questionnaire scores decreased after cochlear implantation in these 13 studies with a total of 153 patients. The most widely used tinnitus questionnaire was the Tinnitus Handicap Inventory. In these studies, 34.2% of patients demonstrated complete suppression, 53.7% an improvement, 7.3% a stable value, and 4.9% an increase of tinnitus, and none of the patients reported an induction of tinnitus. CONCLUSION: This review shows a clear improvement of tinnitus complaints after cochlear implantation in patients with SSD. Therefore, tinnitus might be considered as an additional indication for cochlear implantation in SSD.

Tinnitus with temporomandibular joint disorders: a specific entity of tinnitus patients?

OBJECTIVE: Tinnitus is frequently associated with temporomandibular joint (TMJ) dysfunction. However, the nature of the relationship is not fully understood. Here the authors compared 30 patients with a confirmed diagnosis of temporomandibular joint dysfunction and tinnitus to a group of 61 patients with tinnitus but without any subjective complaints of TMJ dysfunction with respect to clinical and demographic characteristics. STUDY DESIGN: Case-control study. SETTING: Tertiary referral center. SUBJECTS: Tinnitus patients with and without TMJ dysfunction presenting at the Department of Prosthetic Dentistry and th: Tinnitus Clinic at the University of Regensburg. RESULTS: Tinnitus patients with TMJ disorder had better hearing function (P < .0005), lower age (P = .001), and lower age at tinnitus onset (P = .002) and were more frequently female (P = .003). Their subjectively perceived tinnitus loudness was lower (P = .01), and more of them could modulate their tinnitus by jaw or neck movements (P = .001). CONCLUSION: Classical risk factors for tinnitus (age, male gender, hearing loss) are less relevant in tinnitus patients with TMJ disorder, suggesting a causal role of TMJ pathology in the generation and maintenance of tinnitus. Based on this finding, treatment of TMJ disorder may represent a causally oriented treatment strategy for tinnitus.

The role of soluble adhesion molecules and cytokines in sudden sensorineural hearing loss.

OBJECTIVE: The underlying pathology of sudden sensorineural hearing loss (SSNHL) is still not completely understood. Inflammatory and vascular factors are part of the present discussion. The aim of this study was to learn more about the possible role of adhesion molecules and cytokines in patients with SSNHL. These molecules are thought to contribute to endothelial dysfunction. STUDY DESIGN: Case-control study with planned data collection. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Blood samples of 35 patients presenting with SSNHL of more than 30 dB in at least 3 contiguous frequencies were compared to a gender- and age-matched control group of normal-hearing subjects. Levels of the soluble adhesion molecules intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), endothelial selectin (E-selectin), and concentration of interleukin 6 (IL-6), interleukin 8 (IL-8), and monocyte chemoattractant protein 1 (MCP-1) were measured using established enzyme-linked immunosorbent assays. These parameters as well as fibrinogen and lipid values were statistically analyzed. RESULTS: Levels of soluble ICAM-1, VCAM-1, E-selectin, IL-6, IL-8, and MCP-1 were not significantly elevated in patients with SSNHL. The clinical chemistry and hematologic determinations showed no significant differences between patients and control subjects. CONCLUSION: This study revealed no association concerning SSNHL and typical vascular risk factors such as lipids and fibrinogen. Soluble adhesion molecules were not elevated in the SSNHL group. The role of endothelial dysfunction represented by increased levels of soluble adhesion molecules in the pathogenesis of SSNHL remains unclear. Further studies are necessary to elucidate the vascular etiology of SSNHL.

Tinnitus handicap inventory for evaluating treatment effects: which changes are clinically relevant?

OBJECTIVE: To determine the minimum change of the Tinnitus Handicap Inventory (THI) score that could be considered clinically relevant, the authors compared the absolute change of the THI with the Clinical Global Impression­Improvement (CGI-I) score. STUDY DESIGN: International studies register with standardized data collection. SETTING: Tinnitus Research Initiative (TRI). SUBJECTS AND METHODS: Two hundred ten patients of the TRI database were eligible for this study. In the first analysis, the THI score change and CGI-I ratings were compared with equipercentile linking. In a second analysis, the authors categorized the CGI-I into the 4 groups much better or better, minimally better, no change, and worse and calculated the corresponding differences of the THI score and the effect sizes. An effect size separating the minimally better and the no-change groups was chosen, and the referring THI mean score difference was calculated. RESULTS: According to the linking method, a CGI-I value of 3 (minimally better) corresponded to a THI score reduction of 6 to 16, whereas the CGI-I value of 4 (no change) corresponded to the range between improvement by 5 points and worsening by 4 points. For separating the no-change and minimally better groups, an effect size d = 0.5 was determined, resulting in a minimal clinically relevant difference of ΔTHI = 7. CONCLUSION: Two different methods yielded comparable results in identifying a reduction in the THI score of 6 and 7 points, respectively, as the minimal clinically relevant change. This study provides a first orientation for sample size calculations and for planning the design of future studies.

Repetitive transcranial magnetic stimulation for tinnitus treatment: no enhancement by the dopamine and noradrenaline reuptake inhibitor bupropion.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has shown beneficial effects in patients with chronic tinnitus. Recent preclinical data in healthy controls suggest that the effects of low-frequency rTMS can be enhanced by dopaminergic drugs. OBJECTIVE: We investigated whether application of the dopamine reuptake inhibitor bupropion increases the clinical effects of low-frequency rTMS over the auditory cortex in tinnitus patients. SUBJECTS AND METHODS: Eighteen subjects with chronic tinnitus received 10 sessions of 1 Hz rTMS (2000 pulses/day, 110% motor threshold) applied to the left temporal cortex. In addition, these subjects received one dosage of 150 mg bupropion (Wellbutrin XL/Elontril) 4 hours before each TMS session. Treatment outcome was assessed with a tinnitus questionnaire over a 3-month period. Treatment effects were compared with a control group of 100 tinnitus patients matched for age, tinnitus duration, and tinnitus questionnaire baseline scores, who received the same rTMS treatment without prior bupropion application. RESULTS: For the whole sample, there was a significant effect of rTMS treatment over time. There were no significant differences between the bupropion and the control group. CONCLUSIONS: Our data suggest that 150 mg bupropion administration does not enhance the effect of rTMS in the treatment of tinnitus.

Levodopa does not enhance the effect of low-frequency repetitive transcranial magnetic stimulation in tinnitus treatment.

OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) has shown promise for the treatment of tinnitus. Experimental data from motor cortex stimulation in healthy subjects indicate that the suppressing effect of low-frequency rTMS can be enhanced by dopaminergic receptor activation. Here we investigated whether administration of the dopamine precursor levodopa before low-frequency rTMS enhances its efficacy in tinnitus treatment. STUDY DESIGN: Sixteen patients with chronic tinnitus received 100 mg of levodopa before each session of low-frequency rTMS. Results were compared with a matched control group of 16 patients who received the same treatment, but without levodopa. Treatment outcome was assessed with a standardized tinnitus questionnaire. RESULTS: Both stimulation protocols resulted in a significant reduction of tinnitus scores after 10 days of stimulation; however, there was no significant difference between the two groups. CONCLUSION: Our data suggest that 100 mg of levodopa does not enhance the effect of rTMS in the treatment of tinnitus.

Combined temporal and prefrontal transcranial magnetic stimulation for tinnitus treatment: a pilot study.

OBJECTIVES: Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been proposed as a new treatment strategy for patients with chronic tinnitus. However, functional abnormalities in tinnitus patients also involve brain structures used for attentional and emotional processing, such as the dorsolateral prefrontal cortex. Therefore, we have developed a new rTMS treatment strategy for tinnitus patients that consists of a combination of high-frequency prefrontal and low-frequency temporal rTMS. STUDY DESIGN: A total of 32 patients received either low-frequency temporal rTMS or a combination of high-frequency prefrontal and low-frequency temporal rTMS. Treatment effects were assessed with a standardized tinnitus questionnaire (TQ). RESULTS: Directly after therapy there was an improvement of the TQ-score for both groups, but no differences between groups. An evaluation after 3 months revealed a remarkable benefit from the use of combined prefrontal and temporal rTMS treatment. CONCLUSION: These results support recent data that suggest that auditory and nonauditory brain areas are involved in tinnitus pathophysiology.

Which tinnitus patients benefit from transcranial magnetic stimulation?

OBJECTIVES: Chronic tinnitus is associated with hyperactivity of the central auditory system. Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been proposed as a treatment for chronic tinnitus. This study determined the factors that predict a beneficial outcome with rTMS treatment. STUDY DESIGN: Forty-five patients with chronic tinnitus underwent 10 sessions of low-frequency rTMS to their left auditory cortex. The treatment outcome was assessed with a tinnitus questionnaire. Therapeutic success was related to the patients' clinical characteristics. RESULTS: A significant reduction in tinnitus complaints occurred after rTMS. In the questionnaire, 40% of the patients improved by five points or more. Treatment responders were characterized by shorter duration of tinnitus complaints and no hearing impairment. CONCLUSION: Tinnitus-related neuroplastic changes might be less pronounced in patients with normal hearing and a short history of complaints. This could explain why those patients benefitted more from rTMS treatment.

Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus.

OBJECTIVES: The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Recent studies demonstrated focal brain activation in the auditory cortex of patients with chronic tinnitus. Low-frequency repetitive transcranial magnetic stimulation (rTMS) is able to reduce cortical hyperexcitability. STUDY DESIGN: Fusing of the individual PET-scan with the structural MRI-scan (T1, MPRAGE) allowed us to identify exactly the area of increased metabolic activity in the auditory cortex of patients with chronic tinnitus. With the use of a neuronavigational system, this target area was exactly stimulated by the figure 8-shaped magnetic coil. In a prospective study, rTMS (110% motor threshold; 1 Hz; 2000 stimuli/day over 5 days) was performed using a placebo controlled cross-over design. Patients were blinded regarding the stimulus condition. For the sham stimulation a specific sham-coil system was used. Fourteen patients were followed for 6 months. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). SETTING: Tertiary referral medical center. RESULTS: Increased metabolic activation in the auditory cortex was verified in all patients. After 5 days of verum rTMS, a highly significant improvement of the tinnitus score was found whereas the sham treatment did not show any significant changes. The treatment outcome after 6 months still demonstrated significant reduction of tinnitus score. CONCLUSION: These preliminary results demonstrate that neuronavigated rTMS offers new possibilities in the understanding and treatment of chronic tinnitus.

Heat shock protein 70 (Hsp70) membrane expression on head-and-neck cancer biopsy-a target for natural killer (NK) cells.

PURPOSE: Heat shock protein 70 (Hsp70) was detected on the cell membrane of human tumor cell lines, but not on normal cells. Here we studied Hsp70 membrane expression as a target for natural killer (NK) cells on tumor material and control tissues of head-and-neck cancer patients. METHODS AND MATERIALS: Membrane-bound Hsp70 was determined by flow cytometry on single-cell suspensions of tumors and the corresponding normal tissues of head-and-neck cancer patients. The cytolytic activity of NK cells against Hsp70-positive tumor cells was measured in a standard cytotoxicity assay. RESULTS: In total, 54 of 74 primary tumors were found to be Hsp70 membrane-positive (73%); tongue/mouth, 21 of 24 (88%); oropharynx, 13 of 20 (65%); hypopharynx, 3 of 6 (50%); larynx, 8 of 11 (73%); trachea 1 of 2 (50%); esophagus, 4 of 5 (80%); lymph node metastases, 4 of 6 (67%). The corresponding control tissue was negative for membrane-bound Hsp70. Biopsies (6 of 6) of patients after in vivo gamma-irradiation (fractionated 5 x 2 Gy) were strongly Hsp70 membrane-positive. Irradiated, Hsp70-positive tumor cells are targets for Hsp70-peptide stimulated NK cells. CONCLUSION: An irradiation-inducible, tumor-selective Hsp70 membrane localization provides a target structure for Hsp70-peptide stimulated human NK cells.

Langerhans' cell histiocytosis with bilateral temporal bone involvement.

BACKGROUND: Langerhans' cell histiocytosis (LCH) is a rare disease with variable clinical appearance. The etiology of LCH remains unclear to date. It is currently believed that clonal accumulation and proliferation of CD1a-positive Langerhans' cells are causative. METHODS: A 2-year-old boy presented with hypacusis and disturbance of balance. Auditory brainstem-evoked responses (ABRs) revealed severe bilateral labyrinthine hearing loss. Magnetic resonance imaging (MRI) showed inflammatory changes with bone erosion in both temporal bones including labyrinthine systems and mastoid processes. RESULTS: During bilateral surgical exploration, fragile slightly yellowish tissue with necrotic areas was found that turned out to be LCH on histology. Chemotherapy with vinblastine and prednisone was subsequently initiated, leading to continuing complete remission. CONCLUSIONS: The initial presentation of LCH with bilateral temporal bone involvement is a very rare condition. The signs and symptoms of otologic histiocytosis can mimic those of acute and chronic infectious ear disease. Only a surgically obtained biopsy leads to definitive diagnosis and appropriate therapy.