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Background and Objectives: The aim of this study was to investigate the factors associated with decrease in speech discrimination ability seen in patients with presbycusis and whether aging has a significant effect on the observed decline.Subjects and Methods: We retrospectively analyzed the medical records of patients aged >40 years who had undergone pure-tone audiometry, speech audiometry, and auditory brainstem response for hearing loss at our hospital from January 2019 to June 2021, and investigated the factors that correlated with speech discrimination score.Results: We enrolled 103 patients with 120 ears, with a mean age of 65.8±11.9 years. The pure-tone average of the patients’ thresholds at 0.5, 1, 2, and 4 kHz was 37.2±27.7 dB HL, and their mean speech discrimination score was 82.5%± 22.3%. A correlation analysis revealed a significant negative correlation between the patients’ speech discrimination scores and age. In addition, all variables of pure-tone audiometry and the patients’ auditory brainstem responses were significantly correlated with the speech discrimination scores. The pure-tone average had the strongest negative correlation. On analyzing the significant predictors of lower speech discrimination scores, using a multiple linear regression analysis, pure-tone average and age showed significant results.Conclusions: The speech discrimination ability of older patients with hearing loss significantly decreases with increasing pure-tone average and age.

Objective:We investigated the incidence of sensorineural hearing loss (SNHL) after chronic otitis media (COM) surgery and determined the associated factors.Methods:Data were collected via retrospective medical chart review.Results:Of the 192 patients, 82 underwent tympanoplasty, 26 underwent canal wall up mastoidectomy with tympanoplasty, and 84 underwent canal wall down mastoidectomy with tympanoplasty. After surgery, the average air conduction (AC) hearing threshold improved significantly, from 125 to 1000 Hz, but the average high-frequency AC and bone conduction (BC) hearing thresholds deteriorated significantly. In 21 (11%) cases, the BC hearing threshold worsened by more than 15 dB at 4000 Hz. When we compared these 21 cases to patients in whom hearing was preserved, the former group was found to be significantly younger and had a higher frequency of cholesteatomatous otitis media. However, when comparing the severity of inflammation in patients with temporal bone computed tomography, there was no significant difference between the 2 groups.Conclusions:High-frequency SNHL may develop after surgery to treat COM, especially in young patients with cholesteatoma.

Objectives Due to its rarity and similar sound, typewriter tinnitus (TT) can be misdiagnosed as middle ear myoclonic tinnitus (MEMT). We aim to clarify the characteristics of TT compared to MEMT, and the long-term therapeutic response to carbamazepine. Methods Fourteen patients with TT and 28 patients with MEMT were enrolled. Results TT patients were older than MEMT patients, and their tinnitus symptoms were mostly unilateral. Tinnitus symptoms, which is associated with dizziness, facial spasm, and head motion, were more common in TT, whereas MEMT were more related to noise. Acoustic reflex decay perturbation and low loudness discomfort level were diagnostic signs in MEMT patients, while decreased level of wave II in ABR was the most reliable sign in TT patients. All TT patients exhibited partial or complete response to carbamazepine, but there was a relapse rate after withdrawal of the drug was 60%. Increase in age and longer duration of symptoms were the risk factors of relapse of TT. Conclusion The different characteristics observed in this study will be helpful to diagnose TT and MENT. Duration of tinnitus was the most important long-term prognostic factor of the carbamazepine trial, which indicates the importance of its earlier diagnosis.

ObjectiveTo analyse how the auditory brainstem response changes in patients with sudden sensorineural hearing loss.MethodData were collected via retrospective medical chart review.ResultsForty-three patients were included in this study. The mean latency of auditory brainstem response wave 1 was significantly longer for the affected side than for the unaffected side (p = 0.003). The mean latency of auditory brainstem response wave 1 was significantly shorter, and the mean amplitude of auditory brainstem response wave 1 was significantly larger, in the good response group compared to the poor response group. In forward conditional logistic regression analysis, auditory brainstem response wave 1 latency was an independent predictor of a good response (odds ratio = 34.37, 95 per cent confidence interval = 1.56–757.15, p = 0.025).ConclusionIn patients with sudden sensorineural hearing loss, the latency of wave 1 of the auditory brainstem response was significantly increased and was related to prognosis.

ObjectiveTo determine the factors related to multiple ventilation tube insertions in children with otitis media with effusion.MethodsA retrospective review was performed of 126 ears of 81 children aged less than 12 years who had undergone insertion of a Paparella type 1 ventilation tube for the first time between August 2012 and March 2018.ResultsMean age at the first operation was 4.0 ± 2.2 years, and the mean duration of otitis media with effusion before the first ventilation tube insertion was 5.4 ± 4.5 months. Among 126 ears, 80 (63.5 per cent) had a single ventilation tube insertion and 46 (36.5 per cent) had multiple insertions. On multivariate logistic regression, tympanic membrane retraction, serous middle-ear discharge, and early recurrence of otitis media with effusion were independent predictive factors of multiple ventilation tube insertions.ConclusionTympanic membrane retraction, serous middle-ear discharge, and early recurrence of otitis media with effusion after the first tube extrusion are associated with multiple ventilation tube insertions.

Aims To investigate the effects of the location and size of tympanic membrane (TM) perforation and middle ear cavity volume on conductive hearing loss in patients with TM perforation. Methods Data were collected via a retrospective medical chart review. Results We enrolled 128 patients with a mean age of 45.6 ± 10.1 years. The mean perforation size was 21.2 ± 8.6% of the TM area, and the mean air-bone gap (ABG) was 20.2 ± 8.6 dB HL on pure tone audiometry. Patients were divided into two groups based on mean ABG. Patients with a large ABG had a significantly larger TM perforation area and smaller mastoid volume. The TM perforation was most commonly located in the central section. However, regression analyses showed that the proportion of the perforated TM area was the only independent predictor of a large ABG (odds ratio, 1.053; 95% confidence interval, 1.022–1.085; p = 0.001). When we analyzed the frequencies in which hearing loss occurred due to TM perforation, we confirmed that hearing loss occurred mainly in the low-frequency range. Conclusion In patients with TM perforation, conductive hearing loss occurs mainly at low frequencies and in proportion to the size of the TM perforation.

OBJECTIVES The classical overlay tympanoplasty is technically difficult with some disadvantages and thus less popular. However, it is particularly useful for large, anterior perforations. In this study, we describe the technique of a modified overlay graft in the tympanoplasty coined as the swing-door overlay tympanoplasty and report its outcomes. METHODS Retrospective review of patients undergoing the swing-door overlay tympanoplasty at a tertiary referral center between 2003 and 2016 was performed. Patient who had ossicular abnormality, previous tympanoplasty, and profound hearing loss were excluded. The surgical technique is described in detail. The outcomes were evaluated by the graft success rate, complication rate, and hearing results. The hearing level was determined by four pure-tone average at 0.5, 1, 2, and 4 kHz. Air-bone gap closure was mainly assessed. RESULTS A total of 306 patients (110 males and 196 females) were included. The mean age was 49.1±16.6 years. Follow-up periods ranged from 6 to 108 months with an average of 18.4 months. The overall graft success rate reached 98.4%. Five graft failures occurred with reperforation in three cases and lateralization in two cases. Postoperative complications occurred in 12 cases (3.9%). Air-bone gap changes (closures) were 7.8±12.8, 5.2±12.2, 5.7±10.2, and 6.0± 12.8 dB at 0.5, 1, 2, and 4 kHz, respectively (all P

The production of reactive oxygen species (ROS) by cisplatin is one of the major mechanisms of cisplatin-induced cytotoxicity. We examined the preventive effect of α-lipoic acid (LA) on cisplatin-induced toxicity via its antioxidant effects on in vitro and ex vivo culture systems. To elucidate the mechanism of the antioxidant activity of LA, NRF2 was inhibited using NRF2 siRNA, and the change in antioxidant activity of LA was characterized. MTT assays showed that LA was safe at concentrations up to 0.5 mM in HEI-OC1 cells and had a protective effect against cisplatin-induced cytotoxicity. Intracellular ROS production in HEI-OC1 cells was rapidly increased by cisplatin for up to 48 h. However, treatment with LA significantly reduced the production of ROS and increased the expression of the antioxidant proteins HO-1 and SOD1. Ex vivo, the organs of Corti of the group pretreated with LA exhibited better preservation than the group that received cisplatin alone. We also confirmed the nuclear translocation of NRF2 after LA administration, and that NRF2 inhibition decreased the antioxidant activity of LA. Together, these results indicate that the antioxidant activity of LA was through the activation of the NRF2/HO-1 antioxidant pathway.

Background Exposure to urban particulate matter (UPM) has been linked to aggravation of various health problems. Although the effects of UPM on the lower respiratory tract have been extensively studied, more research is required on the impact of UPM on the upper respiratory tract and the underlying mechanisms. Thus, we investigated the cytotoxic effects of UPM on cultured human nasal fibroblasts, the underlying signaling pathways involved, and changes in cytokine levels. Methods Human turbinate tissue specimens were collected during partial turbinectomies performed on 6 patients, and then cultured. The effect of UPM on nasal fibroblast viability was explored. Real-time reverse transcription-polymerase chain reaction was used to measure the mRNA levels of genes encoding cytokines and chemokines (interleukin [IL]-4, IL-6, IL-8, and tumor necrosis factor-α) before and after 24 hours of UPM treatment. Enzyme-linked immunosorbent assays were employed to measure IL-6 and IL-8 levels. The status of the p38 and nuclear factor (NF)-κB signaling pathways was analyzed by Western blotting. Results UPM reduced cell viability in a dose-dependent manner and increased IL-6 and IL-8 expression at both the mRNA and protein levels. UPM induced the phosphorylation of p38 and NF-κB p65; inhibitors of the actions of these proteins repressed phosphorylation and the expression of IL-6 and IL-8. Conclusion UPM induced IL-6 and IL-8 expression by fibroblasts via p38 and NF-κB classical signaling, suggesting that UPM can induce or aggravate allergic and/or chronic rhinitis.

To develop efficient carriers for inner ear drug delivery, we prepared four kinds of phospholipid-based nanoparticles : neutral, anionic, cationic, and cationic-PEG (polyethyleneglycol) particles. PEG was used to maintain long-term particle circulation in the perilymph, avoiding non-specific binding of particles to proteins. All four nanoparticles were about 200 nm in diameter, and their zeta potentials were −4.32, −26.0, +25.8, and −0.28, respectively, for neutral, anionic, cationic, and cationic-PEG nanoparticles. To test particle efficacy in vitro , we used an artificial mucosa 100 μm in thickness to model the round window membrane (RWM) and HEI-OC1 cells, which were treated with particles containing Nile Red dye. Based on the levels of particle penetration and cellular uptake in this model system, we selected an optimal particle for further study. We also observed the movement of particles in ex vivo organotypic cultures of the organ of Corti. In mice, we analyzed the biodistribution of dexamethasone (Dex) in the inner ear after intratympanic injection of Dex-loaded nanoparticles. Then, we tested the therapeutic utility of the Dex-loaded nanoparticles in a mouse model of ototoxicity. In the auditory brainstem response (ABR) test, particle provided improved hearing loss recovery at all tested frequencies, more so than did the Dex sodium phosphate (Dex-SP) solution in current clinical use. Furthermore, quantitative PCR showed that nanoparticles reduced the levels of pro-inflammatory cytokines, exhibiting anti-inflammatory effects superior to those of Dex-SP. Thus, the surface properties of nanoparticles play pivotal roles in particle penetration and distribution after intratympanic injection. Our in vitro screening system using an artificial mucosa will also be valuable in the development of carriers for inner ear drug delivery.

Hearing and cognition are commonly involved in both normal and pathological aging. Current clinical interest lies in whether peripheral hearing loss promotes cognitive decline. In our previous publication, the authors have shown a causal relationship between hearing and cognitive impairments in C57BL/6 mice. Here we extended the follow-up to 12 months to determine the long-term effects of hearing loss on cognition and to observe hippocampal p-tau and lipofuscin. One month old male mice were randomly allocated into two groups, the control (n = 12) and noise-induced hearing loss (NIHL) (n = 12). After baseline hearing and cognitive measurements, the mice in the NIHL group were exposed to 110 dB SPL white noise for 1 h every day for 20 consecutive days. Cognitive function was assessed by radial arm maze and novel object recognition tests. p-Tau was observed by the western blot, immunofluorescence, and immunogold staining. The mice in the NIHL group showed elevated auditory brainstem response thresholds and poorer performances in spatial working and recognition memories than the controls. They exhibited more p-tau and lipofuscin in the hippocampus. The cognitive impact of hearing loss varied with the types of memory. Working memory impairment was reversible, whereas recognition memory impairment was permanent. Our results provide behavioral and histopathological evidence for hearing-related cognitive decline. Early hearing loss is suggested to be one of the important determinants between normal and pathological cognitive aging.

OBJECTIVES The aim of this multicenter registry study was to investigate the effectiveness of ventilation tube insertion and the microbiology of otitis media with effusion (OME) in children. This part I study was conducted to evaluate the microbiological profile of children with OME who needed ventilation tube insertion. METHODS Patients

Objective:Cultures obtained from pre-operative middle-ear swabs from patients with chronic otitis media have traditionally been used to guide antibiotic selection. This study investigated changes in the bacterial strains of the middle ear during chronic otitis media surgery.Methods:Pre-operative bacterial cultures of otorrhoea, and peri-operative cultures of the granulation tissue in either the middle ear or mastoid cavity, were obtained. Post-operative cultures were selectively obtained when otorrhoea developed after surgery.Results:Bacterial growth was observed in 45.5 per cent of pre-operative cultures, 13.5 per cent of peri-operative cultures and 4.5 per cent of post-operative cultures. Methicillin-resistant Staphylococcus aureus was identified as the most common bacteria in all pre-operative (32.4 per cent), peri-operative (52.4 per cent) and post-operative (71.4 per cent) tests, and the percentage of Methicillin-resistant S aureus increased from the pre- to the post-operative period.Conclusion:The bacterial culture results for post-operative otorrhoea showed low agreement with those for pre-operative or peri-operative culture, and strain re-identification was required.

Objective: To evaluate the therapeutic effects of middle ear tendon resection (METR) on middle ear myoclonic tinnitus (MEMT) and to investigate its long-term effects on hearing and hyperacusis. Materials and Methods: Thirty-seven patients with MEMT with a mean age of 33.2 ± 11.8 years were included in this study. METR was performed on all 37 MEMT patients (41 ears) between November 2004 and August 2016. The mean follow-up period was 16.1 months. We examined changes in tinnitus and accompanying stress and depression in patients after surgery, and examined the hearing changes and the occurrence of complications including hyperacusis. Results: After surgery, 34 (91.9%) patients exhibited complete resolution of MEMT during their follow-up period, and 3 patients showed a partial response. The mean Visual Analog Scale (VAS) scores for tinnitus severity, the Tinnitus Handicap Inventory (THI), and stress index decreased significantly after surgery (p < 0.05, paired t test). No patient developed hearing loss or hyperacusis following surgery. Preexisting hyperacusis even improved in most of the patients with intractable MEMT after surgery. Recurrence of the symptom occurred in only 1 patient, who underwent revision surgery with improvement. We observed 1 case of postoperative delayed facial palsy with complete recovery in 2 weeks. Conclusions: METR seems to be an effective and safe treatment option for intractable MEMT, considering its high control rate of tinnitus and no long-term harmful effects on hearing and hyperacusis.

This study was performed to evaluate the frequency of bony cochlear nerve canal (BCNC) stenosis and its clinical significance in pediatric patients with unilateral sensorineural hearing loss (SNHL) of unknown etiology.We analyzed the medical records and temporal bone computed tomography (CT) results of patients less than 13 years of age with a diagnosis of unilateral SNHL of unknown etiology between July 2007 and July 2017. We compared the BCNC diameter between both sides and analyzed the age at diagnosis, degree of hearing loss, and accompanying inner ear anomalies.In 42 patients, the mean age at diagnosis was 7.4 ± 3.6 years, and the average hearing level in the affected ear was 87.9 ± 20.0 dB HL (decibels hearing level). The average diameter of the BCNC was 1.22 ± 0.75 mm on the affected side and 1.96 ± 0.52 mm on the normal side. The most suitable criterion for BCNC stenosis appeared to be a diameter of 1.2 mm by the recursive partitioning procedure. With application of this criterion, the rate of BCNC stenosis was significantly greater on the affected side than on the normal side (52.4% vs. 4.8%, respectively; P 0.05). A narrow internal acoustic canal was found in two patients, and vestibular and cochlear anomalies were found in three patients each.Our results suggest that it is reasonable to set a diameter of 1.2 mm as a cutoff for BCNC stenosis, and also that BCNC stenosis is a common cause of unilateral SNHL of unknown etiology in childhood.

Outcomes for patients with chronic myeloid leukemia (CML) have substantially improved due to advances in drug development and rational treatment intervention strategies. Despite these significant advances there are still unanswered questions on patient management regarding how to more reliably predict treatment failure at the time of diagnosis and howto select frontline tyrosine kinase inhibitor (TKI) therapy for optimal outcome. The BCR-ABL1 transcript level at diagnosis has no established prognostic impact and cannot guide frontline TKI selection. BCR-ABL1 mutations are detected in ~50%of TKI resistant patients but are rarely responsible for primary resistance. Other resistance mechanisms are largely uncharacterized and there are no other routine molecular testing strategies to facilitate the evaluation and further stratification of TKI resistance. Advances in next-generation sequencing technology has aided the management of a growing number of other malignancies, enabling the incorporation of somatic mutation profiles in diagnosis, classification, and prognostication.A largely unexplored area in CML research is whether expanded genomic analysis at diagnosis, resistance, and disease transformation can enhance patient management decisions, as has occurred for other cancers. The aim of this article is to review publications that reported mutated cancer-associated genes in CML patients at various disease phases. We discuss the frequency and type of such variants at initial diagnosis and at the time of treatment failure and transformation. Current limitations in the evaluation of mutants and recommendations for future reporting are outlined. The collective evaluation of mutational studies over more than a decade suggests a limited set of cancer-associated genes are indeed recurrently mutated in CML and some at a relatively high frequency. Genomic studies have the potential to lay the foundation for improved diagnostic risk classification according to clinical and genomic risk, and to enable more precise early identification of TKI resistance. Refereed/Peer-reviewed

Objective To analyze surgical outcomes of cartilage-fascia composite canalplasty (CFCC) for external auditory canal cholesteatoma (EACC). Study design Retrospective case review study. Setting Tertiary referral center. Patients A total of 13 patients with EACC (n = 14 ears due to one patient with bilateral EACC). Intervention Surgical method of CFCC using well designed-conchal cartilage and temporalis muscle fascia after complete removal of EACC. Main outcome measures Clinical characteristics and EACC stages were determined by oto-endoscopic examination and computed tomography (CT) findings. The surgical results of CFCC were analyzed. Results The median age of patients was 43 years (range, 12-75 yr), with a male to female ratio of 6 to 7. EACC stages were from II to IV. Cortical bone erosion in the inferior part of the bony EAC was the most common finding. All patients had satisfactory results: no more ear symptoms related with cholesteatoma and no need of dressing. Postoperative hearing gain was observed in four patients. No complications or recurrence occurred during the mean follow-up period of 34.4 months. Conclusion Surgical technique of CFCC was effective for EACC not responding to conservative management.

We used antioxidant-containing nanoparticles (NPs) to treat acute hearing loss. Alpha-lipoic acid (ALA) served as the antioxidant; we employed Pluronic F127 to fabricate NPs. In vitro, ALA-NPs protected cells of the organ of Corti in HEI-OC1 mice, triggering nuclear translocation of NRF2 and increases in the levels of antioxidant proteins, including Nrf2, HO-1, SOD-1, and SOD-2. In vivo, the hearing of mice that received ALA-NP injections into the middle ear cavity was better preserved after induction of ototoxicity than in control animals. The cochlear Nrf2 level increased in test mice, indicating that the ALA-NPs protected hearing via the antioxidant mechanism observed in vitro. ALA-NPs effectively protected against acute hearing loss by activating the Nrf2/HO-1 pathway.

Moderate hearing loss in young mice caused decreases in cognition associated with spatial working and recognition memories in 6 months. These results provide evidence for a causal relationship between hearing loss and cognitive impairment.Hypothesized mechanisms to connect sensory and cognitive functions include the sensory-deprivation, information-degradation, and common-cause hypotheses. This study intended to investigate the effect of hearing loss on cognitive function, as estimated by radial arm maze (RAM) and novel object recognition (NOR) tasks in mice through age- and hearing-matched longitudinal work during a 6-month period.Twenty-four male C57BL/6 mice aged 1 month with normal ABR thresholds were used. Twelve mice in the hearing loss (HL) group were exposed to white noise at 110 dB SPL for 60 min every day for 20 days. At post-noise 6 months, all mice underwent RAM and one-trial NOR test. RAM performance measures and NOR discrimination index were compared between two groups.At 6 months after noise exposure, all mice in the experimental group had moderate hearing loss. Most of the RAM performances improved gradually within each group across five trials, probably due to learning effect. The HL group showed lower performance scores than the control group in several trial points in the RAM task. The contact time with the novel object was shorter in the HL group than in the control group.

Objective: To investigate the time course of tinnitus changes in patients receiving cochlear implantation (CI) in a prospective, multicenter setting and to determine related factors. Materials and Methods: A total of 79 adult patients who underwent CI were included in this study. We used the same questionnaires sequentially 5 times. The questionnaires included the Visual Analog Scale (VAS) for tinnitus severity, the Tinnitus Handicap Inventory (THI), Beck's Depression Index (BDI), and the Brief Encounter Psychosocial Instrument (BEPSI) for stress assessment. Results: Tinnitus was present in 59 (74.7%) of the 79 study subjects. After CI, tinnitus was eliminated in 10 patients (25%) and improved in 16 patients (40%) of the 40 patients who completed the final questionnaires, and most of the tinnitus reduction occurred in the early period of CI use. In an analysis of psychological functioning with CI, BDI was reduced significantly after CI. Multiple linear regression analysis revealed that preoperative auditory steady-state response (ASSR), THI, and final BDI score were significantly associated with the changes in tinnitus after CI. Conclusions: Most of the tinnitus reduction occurred within 1 month after CI use, and the changes were significantly associated with THI, ASSR, and BDI scores 6 months after CI. CI is a valuable therapeutic modality in tinnitus of a deafened ear.

Low incidence of peripheral arterial disease in patients receiving dasatinib in clinical trials

Background The safety and clinical effectiveness data of peramivir in the real clinical field are limited. A prospective observational study was conducted based on the post-marketing surveillance data to evaluate the post-marketing safety and effectiveness of peramivir in Korean adults with seasonal influenza. Methods Among adults aged 20 years or older who were diagnosed with influenza A or B, patients who started peramivir within 48 hours from the initial symptoms of influenza were enrolled. All adverse events (AEs) that occurred within 7 days after administration of peramivir were checked. For the evaluation of effectiveness, changes in the severity of influenza symptoms and daily living performance were examined before and 7 days after the administration of peramivir. The date on which influenza related symptoms disappeared was checked. Results A total of 3,024 patients were enrolled for safety evaluation and 2,939 patients were for effectiveness evaluation. In the safety evaluation, 42 AEs were observed in 35 (1.16%) patients. The most common AE was fever. AEs were mostly rated as mild in severity. Serious AEs were observed in 10 patients and two of them died. However, both deaths were considered to be less relevant to peramivir. In the effectiveness evaluation, the severity of influenza symptoms decreased by 10.68 ± 4.01 points and daily living performance was improved 5.59 ± 2.16 points. Influenza related symptoms disappeared on average 3.02 ± 2.39 days after peramivir administration. Conclusion Peramivir showed a tolerable safety profile and acceptable effectiveness in Korean adult patients with seasonal influenza.

Objectives:This study was conducted to investigate the angles and orientation of semicircular canals, and the coplanarity of functional canal pairs.Methods:Fluid signals in semicircular canals were reconstructed with three-dimensional reconstruction software using 20 temporal bone magnetic resonance images of normal subjects. The angles between each pair of semicircular canals were measured.Results:The mean angles between the anterior and horizontal semicircular canal plane, the horizontal and posterior semicircular canal plane, and the anterior and posterior semicircular canal plane were 83.7°, 82.5° and 88.4°, respectively. Pairs of contralateral synergistic canal planes were formed 15.1° between the right and left horizontal semicircular canal planes, 21.2° between the right anterior and left posterior semicircular canal, and 21.7° between the left anterior and right posterior semicircular canal.Conclusion:Each semicircular canal makes an almost right angle with other canals, but synergistically acting functional canal pairs of both ears do not lie in exactly the same plane.

Objectives Vascular tinnitus is the most common form of pulsatile tinnitus, particularly when the tinnitus corresponds with the pulse of patients. In this study, we reviewed the 10-year clinical data on vascular tinnitus of our tinnitus clinic to investigate the frequency of the underlying etiologies, to introduce a diagnostic protocol, and to evaluate the treatment outcomes. Methods We retrospectively collected the data of 57 patients who were diagnosed as vascular tinnitus between April 2001 and December 2011. Careful history taking, otoscopy, thorough physical examinations, audiometry, laboratory tests, as well as radiologic examinations were performed according to our diagnostic protocol to find the origin of pulsatile tinnitus. Treatment options were individualized based on the specific etiology, and the outcomes were assessed using patient's subjective reports at the follow-up interviews. Results High jugular bulb was the most common cause (47.4%) of vascular tinnitus, and venous hum was the next (17.5%). Dural arteriovenous fistula, intracranial aneurysm, atherosclerotic carotid artery disease, and hypertension were less common causes. Vascular tinnitus was alleviated in most patients after the appropriate treatment: surgical intervention, tinnitus retraining therapy, reassurance, and medications. Conclusion Vascular tinnitus can be successfully diagnosed by the regular use of the suggested protocol. Many patients with vascular tinnitus have treatable underlying etiologies. Treatment of those etiologies or at least counseling about the tinnitus itself can benefit the patients with troublesome vascular tinnitus.

This pilot study was performed to investigate the therapeutic effect of Valsalva maneuver on otitis media in adults and to evaluate the prognostic factors for the good response.Thirty nine ears of 32 adult patients who were diagnosed as otitis media with effusion and managed by one-week Valsalva maneuver (20/day) without any other medication were included in this study. Its therapeutic efficacy was evaluated and the prognostic factors which predict the response of Valsalva maneuver were analyzed by comparing various clinical and audiological factors between success and failure groups.Mean duration of otitis media in the study subjects was 30.9 days (SD 31.6 days). A success rate of 1-week Valsalva maneuver as a single therapeutic modality was up to 64.1% (25/39 ears) and hearing was significantly recovered in success group. No recurrence or side effects were observed. Successful Valsalva maneuver checked and confirmed as bulging of the tympanic membrane by otoendoscopic examination was an excellent indicator of therapeutic response in a week (p0.05). Age, sex, duration of otitis media, history of previous upper respiratory tract infection, initial hearing levels and type of audiogram were not significant prognostic factors for the therapeutic efficacy of Valsalva maneuver.One-week Valsalva maneuver seems to be considered as a first line therapeutic modality in otitis media with effusion in adult patients who demonstrate the successful maneuver result on oto-endoscopic examination.

Exposure to urban particulate matter (UPM) has been linked to aggravation of various health problems. Although the effects of UPM on the lower respiratory tract have been extensively studied, more research is required on the impact of UPM on the upper respiratory tract and the underlying mechanisms. Thus, we investigated the cytotoxic effects of UPM on cultured human nasal fibroblasts, the underlying signaling pathways involved, and changes in cytokine levels.Human turbinate tissue specimens were collected during partial turbinectomies performed on 6 patients, and then cultured. The effect of UPM on nasal fibroblast viability was explored. Real-time reverse transcription-polymerase chain reaction was used to measure the mRNA levels of genes encoding cytokines and chemokines (interleukin [IL]-4, IL-6, IL-8, and tumor necrosis factor-α) before and after 24 hours of UPM treatment. Enzyme-linked immunosorbent assays were employed to measure IL-6 and IL-8 levels. The status of the p38 and nuclear factor (NF)-κB signaling pathways was analyzed by Western blotting.UPM reduced cell viability in a dose-dependent manner and increased IL-6 and IL-8 expression at both the mRNA and protein levels. UPM induced the phosphorylation of p38 and NF-κB p65; inhibitors of the actions of these proteins repressed phosphorylation and the expression of IL-6 and IL-8.UPM induced IL-6 and IL-8 expression by fibroblasts via p38 and NF-κB classical signaling, suggesting that UPM can induce or aggravate allergic and/or chronic rhinitis.

Nanoparticles are promising therapeutic options for inner ear disease. In this report, we review in vivo animal studies in the otologic field using nanoparticles over the past 5 years. Many studies have used nanoparticles to deliver drugs, genes, and growth factors, and functional and morphological changes have been observed. The constituents of nanoparticles are also diversifying into various biocompatible materials, including poly(lactic-co-glycolic acid) (PLGA). The safe and effective delivery of drugs or genes in the inner ear will be a breakthrough for the treatment of inner ear diseases, including age-related hearing loss.

Few studies are available that compare PBSC and BM from unrelated donors, especially in adult high-risk ALL. To determine which graft source is superior in adult high-risk ALL, we analyzed the long-term outcomes of 106 consecutive transplants from 8/8-matched or 7/8-matched unrelated donors (38 PBSC vs 68 BM). All patients received a uniform strategy of pre-transplant therapy, myeloablative conditioning and GVHD prophylaxis. At 5 years, PBSC transplants showed higher incidence of chronic GVHD than did BM transplants (74.3% vs 46.7%, P=0.001). PBSC transplants showed outcomes comparable to those of BM transplants for relapse (23.7% vs 28.1%), non-relapse mortality (18.4% vs 25.0%), disease-free survival (57.9% vs 46.9%) and OS (57.9% vs 50.0%). In a separate comparison of outcomes between the two graft sources according to the presence of a Ph chromosome, no significant advantage of PBSC over BM was found in both subgroups of patients. Our data suggest that the outcomes of unrelated donor transplantation are similar between PBSC and BM in adult high-risk ALL. Whether PBSC should be the preferred graft source for a specific subgroup of adult ALL needs to be further investigated.

Local delivery systems for treatment of intractable inner ear disorders have been attempted by many investigators.To evaluate the permeability and safety of a drug delivery system for the inner ear using a poly(2-hydroxyethyl aspartamide) (PHEA) polymersome.One-month-old male C57/BL6 mice were used. We administered the same amount of the fluorescent dye, Nile red, into the middle ear in two forms: loaded in PHEA polymersomes (NP group) or diluted in ethanol (NR group). At 1 day after administration, we harvested the cochlea and counted visible red particles in the tissues of cochlea under confocal microscopy and compared the groups. In a safety evaluation, 1 week after the same surgery, we conducted hearing tests and histological evaluations of the bulla and cochlea, and compared the results with those of the sham operation and negative control groups.In terms of permeability, the number of red particles in the organ of Corti was increased significantly in the NP group, and three subjects in the NP group showed uptake of red particles in inner hair cells. However, there was no statistically significant difference in the observations in the lateral wall or modiolus. In safety tests, the NP and sham-operation groups showed decreased DPOAE responses and mildly swollen middle ear mucosa, compared with the negative control group, which was thought to be the result of postoperative changes.PHEA nanoparticles may have utility as a drug carrier into the inner ear in terms of both permeability and safety.

The aim of the following study is to evaluate immediate protective effect of ear plug from noise morphologically and functionally. An 1-month aged 29 male C57BL/6 mice. Subjects were divided into four groups as normal control(G1), bilaterally plugged group (G2), unilaterally plugged group (G3) and noise control group (G4) and later 3 groups were exposed to 110 sound pressure level white noise for 60 min. Immediately after noise exposure, audiologic tests were performed and cochlear morphology and expression levels of a-synuclein in the cochlea were investigated. There were no functional changes in G2 and plugged ears of G3 after noise exposure, whereas unplugged ears of G3 and G4 showed significant hearing loss. In morphological study, there were a significant degeneration of the organ of Corti and mean number and diameter of efferent buttons, in unplugged ears of G3 and G4. Plugged ears of G3 also showed mild changes in morphological study. Reduction of a-synuclein was observed at the efferent terminals or cochlear extracts after noise exposure. The protective effect of ear plug on noise exposure was proven morphologically and functionally in the animal model of noise-induced hearing loss. Further study on cellular or ultrastructural level with ear plug will be needed to reveal more precise mechanism.

Objectives The authors have treated chronic tinnitus patients using a combination of a simplified tinnitus retraining therapy (TRT) and medications, which we called modified TRT. In this clinical setting, we have attempted small-group counseling to find a time-effective equivalent of individual counseling. The aim of the present study was to evaluate the effectiveness of small-group counseling by comparing the treatment outcomes between individual and small-group counseling. Methods The patients who had distressing chronic tinnitus with normal hearing or mild hearing loss were included. The subjects were placed into the small-group (group 1:4) or the individual (group 1:1) counseling group, and underwent a modified TRT composed of a single session of directive counseling and ambient sound stimulation. In addition, alprazolam (0.25 mg) and ginkgo biloba extract (80 mg) were administered orally to the subjects for 3 months. The 3- and 6- month outcomes were assessed using the follow-up rates and tinnitus severity scores: awareness, tinnitus handicap inventory (THI), loudness, annoyance, and effect on life. The treatment responses were classified as improvement, no changes, and worsening. Results Of the total 149 patients (77 in group 1:1; 72 in group 1:4), 104 patients completed the protocol at 3 months, and 55 patients at 6 months. The follow-up rates were similar in both groups. Over the period of 6 months, all scores declined significantly except the loudness score at 3 months in both groups. Treatment responses showed no between-group differences. The success rate based on THI was 70% in group 1:1, and 64% in group 1:4 at 6 months. Conclusion The small-group counseling of our modified TRT was comparable to the individual counseling for tinnitus relief. We suggest that this protocol can be implemented effectively in any crowded otolaryngology clinics.

Ji Young Yoon,1 Keum-Jin Yang,2 Shi-Nae Park,3 Dong-Kee Kim,3 Jong-Duk Kim1 1Department of Chemical and Biomolecular Engineering, BK 21 Plus Program, Korea Advanced Institute of Science and Technology, Guseong-Dong, Yuseong-Gu, Daejeon, 2Clinical Research Institute, St Mary’s Hospital, Daejeon, 3Department of Otolaryngology – Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Abstract: Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner ear cells has a diameter of 120–140nm and a zeta potential of 20–25mV. Different types of genes were complexed with the Dex-loaded PCA nanoparticle (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA nanoparticles and Lipofectamine® reagent in HEI-OC1 cells. In addition, after loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was downregulated according to real-time polymerase chain reaction for 24h, compared with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex, increased expression of BDNF was observed for 30h, and its signaling pathway resulted in an increase in phosphorylation of Akt, observed by Western blotting. Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect and enhanced gene expression. Keywords: cell-penetrating peptide, nanoparticle, dexamethasone, gene delivery, brain-derived neurotrophic factor

Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better quality of life.