Factors affecting fat myringoplasty in elderly patients with chronic otitis media: A case control study.

BACKGROUND: We compared and analyzed the surgical results of fat myringoplasty between elderly and young adult patients with chronic otitis media. We also investigated whether underlying diseases and other factors impact the surgical outcome. METHODS: We retrospectively reviewed the data of 141 patients who underwent fat myringoplasty for chronic otitis media for five years. They were compared by age, sex, underlying disease, perforation size, pre- and postoperative pure tone audiometry, postoperative otorrhea, postoperative re-perforation, and cause of re-perforation. RESULT: Postoperative re-perforation was more common in the elderly group, albeit with no significant difference (p = 0.072). The factors affecting re-perforation were insufficient fat graft (44.4%), postoperative infection (33.3%), and nasal blowing (22.2%). Our findings revealed no significant association between preoperative perforation size and re-perforation (p = 0.391). Additionally, we found no significant relationship between hypertension and re-perforation (p > 0.99), nor between age group and postoperative infection (p = 0.488). Diabetes was also not significant (p = 0.640). Following surgery, both groups exhibited a significant improvement in hearing. CONCLUSION: Although age and underlying conditions play significant roles in the healing process, our results suggest that external factors such as infection, nasal blowing, cough, and insufficient grafted fat tissue have a similarly significant impact on surgical outcomes in elderly patients with COM as they do in adults. In conclusion, the decision to perform surgery in elderly patients with COM should be based on a comprehensive assessment of the patient's overall health status, hearing, use of hearing aids, and the indications for surgery.

The impact of the Cochlear™ Osia® 2 System on patients with mixed or conductive hearing loss: A comparison with Cochlear™ Baha® Attract System outcomes.

OBJECTIVE: This prospective study assessed the efficacy of the Cochlear™ Osia® 2 System compared to the previous Baha® Attract System in patients with mixed or conductive hearing loss (MHL/CHL). METHODS: In this prospective case-control study, 10 patients (2 men and 8 women) with MHL/CHL were implanted with the Osia® 2 System. Their audiological outcomes were compared with 13 patients (2 men and 11 women) who had previously been implanted with the transcutaneous Baha® Attract system. We compared the complications and compliance of the two groups. Also, in the Osia 2 System group, subjective satisfaction was assessed using the Korean version of the International Outcome Inventory for Hearing Aids (K-IOI-HA) questionnaire and the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire. RESULTS: Complications such as poor magnetization, pain & infection, and abnormal noise were more common in the Baha Attract group, although not statistically significant. Also, the Osia 2 group exhibited better compliance. Subjective satisfaction was assessed using the K-IOI-HA and APHAB questionnaires with the Osia 2 group, revealing significantly improved scores in ease of communication, reverberation, background noise, and higher K-IOI-HA scores post-implantation. Postoperative-aided thresholds with both systems were significantly lower than preoperative-unaided thresholds, with the Osia 2 System demonstrating notably high satisfaction levels. Although both systems showed similar preoperative and postoperative word-recognition scores, the Osia 2 System provided greater audiological gain, especially at 2 kHz and 4 kHz frequencies. Additionally, the functional gain of both systems was comparable across all frequencies. CONCLUSIONS: The Osia 2 System demonstrated high subjective satisfaction and improved audiological outcomes compared to the Baha Attract system in patients with conductive or mixed hearing loss. Its superior audiological gain, particularly at critical frequencies, along with better compliance, suggests it as a favorable option for this patient population.

The time-dependent changes in a mouse model of traumatic brain injury with motor dysfunction.

Traumatic brain injury (TBI) results from sudden accidents, leading to brain damage, subsequent organ dysfunction, and potentially death. Despite extensive studies on rodent TBI models, there is still high variability in terms of target points, and this results in significantly different symptoms between models. In this study, we established a more concise and effective TBI mouse model, which included locomotor dysfunctions with increased apoptosis, based on the controlled cortical impact method. Behavioral tests, such as elevated body swing, rotarod, and cylinder tests were performed to assess the validity of our model. To investigate the underlying mechanisms of injury, we analyzed the expression of proteins associated with immune response and the apoptosis signaling pathway via western blotting analysis and immunohistochemistry. Upon TBI induction, the mouse subjects showed motor dysfunctions and asymmetric behavioral assessment. The expression of Bax gradually increased over time and reached its maximum 3 days post-surgery, and then declined. The expression of Mcl-1 showed a similar trend to Bax. Furthermore, the expression of caspase-3, ROCK1, and p53 were highly elevated by 3 days post-surgery and then declined by 7 days post-surgery. Importantly, immunohistochemistry revealed an immediate increase in the level of Bcl-2 at the lesion site upon TBI induction. Also, we found that the expression of neuronal markers, such as NeuN and MAP2, decreased after the surgery. Interestingly, the increase in NFH level was in line with the symptoms of TBI in humans. Collectively, our study demonstrated that the established TBI model induces motor dysfunction, hemorrhaging, infarctions, and apoptosis, closely resembling TBI in humans. Therefore, we predict that our model may be useful for developing effective treatment option for TBI.

Tinnitus reduction after active bone-conduction implantation in patients with single-sided deafness: a prospective multicenter study.

PURPOSE: Single-sided deafness (SSD) presents significant challenges for patients, including compromised sound localization, reduced speech recognition, and often, tinnitus. These issues are typically addressed using interventions such as cochlear implantation (CI) and bone conduction implant (BCI). However, evidence regarding the efficacy of BCI in reducing tinnitus in SSD patients remains limited. This study explored the ability of a novel active transcutaneous BCI (Bonebridge BCI602) to alleviate tinnitus in SSD patients. STUDY DESIGN: Prospective cohort multicenter study. SETTING: Tertiary referral hospitals. METHODS: A prospective multicenter study of 30 SSD patients was conducted. The patients were divided into two groups: those with (n = 19) and without (n = 11) tinnitus. Audiometric assessments, subjective questionnaires including the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Bern Benefit in Single-Sided Deafness (BBSS), and tinnitus evaluations with the Tinnitus Handicap Inventory (THI) and tinnitogram were conducted before and after BCI surgery. RESULTS: THI scores after surgery were significantly reduced in SSD patients with tinnitus. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups; however, the former group exhibited a significantly greater improvement in the APHAB questionnaire score. According to tinnitograms, the loudness of tinnitus decreased, particularly in patients with ipsilateral tinnitus. Patients with residual hearing had greater reductions in their THI scores. However, three patients without residual hearing had a relative worsening of tinnitus after surgery. CONCLUSION: The Bonebridge BCI602 effectively reduced tinnitus in SSD patients, particularly in those with residual hearing. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups. These findings demonstrate the therapeutic potential of BCI for managing SSD and associated tinnitus.

A novel approach for estimating initial sound level for speech reception threshold test.

BACKGROUND: The speech reception threshold (SRT), synonymous with the speech recognition threshold, denotes the minimum hearing level required for an individual to discern 50% of presented speech material. This threshold is measured independently in each ear with a repetitive up-down adjustment of stimulus level starting from the initial SRT value derived from pure tone thresholds (PTTs), measured via pure-tone audiometry (PTA). However, repetitive adjustments in the test contributes to increased fatigue for both patients and audiologists, compromising the reliability of the hearing tests. OBJECTIVE: Determining the first (initial) sound level closer to the finally determined SRT value, is important to reduce the number of repetitions. The existing method to determine the initial sound level is to average the PTTs called pure tone average (PTAv). METHODS: We propose a novel method using a machine learning approach to estimate a more optimal initial sound level for the SRT test. Specifically, a convolutional neural network with 1-dimensional filters (1D CNN) was implemented to predict a superior initial level than the conventional methods. RESULTS: Our approach produced a reduction of 37.92% in the difference between the initial stimulus level and the final SRT value. CONCLUSIONS: This outcome substantiates that our approach can reduce the repetitions for finding the final SRT, and, as the result, the hearing test time can be reduced.

Effect of air sterilizers in an outpatient clinic at a tertiary university hospital.

Background: After the COVID-19 outbreak, interest in airborne virus infections has increased. We considered ways to reduce the risk of infection to other people by inactivating the virus before it is inhaled into the heating, ventilation, and air conditioning (HVAC) systems. We installed a recently developed air sterilizer in the newly remodeled outpatient clinic of a tertiary university hospital and confirmed its effectiveness. Methods: After remodeling the ENT outpatient clinic at Chonnam National University Hospital, 15 KOKKOS air sterilizers (Bentech Frontier Co., Ltd., Gwangju, Korea) were installed. Total culturable microorganisms (TCMs) and volatile organic compounds (VOCs) were measured in five separate inspection areas three days before installation, 2 weeks after installation, and 4 weeks after installation. Results: After measurement of TCMs, improvement in air quality occurred 2 weeks after air sterilizer instatement at all timepoints except inspection area 5, and further improvement was achieved after 4 weeks (p < 0.05). After assessment of VOCs, improvement occurred 4 weeks after air sterilizer connection at all points (p < 0.05). Conclusion: KOKKOS air sterilizers are effective in improving air quality in an outpatient clinic at a tertiary university hospital.

Intraoperative Handheld Digital X-ray for Assessment of Intracochlear Positioning of Electrode Arrays in Recipients of Cochlear Implants.

Objectives: This study aims to evaluate the practicality of handheld digital X-ray in determining the position of the electrode array following Cochlear implantation (CI). Methods: A retrospective study was conducted involving 11 patients (12 ears) who underwent intraoperative imaging via handheld X-ray (MINE ALNU®, OTOM, Gwangju, South Korea) post-CI between December 2021 and January 2023. Immediate confirmation of the correct electrode array placement in the cochlea was achieved, with subsequent comparisons made to C-arm image and postoperative transorbital view X-ray. Results: Rapid intraoperative imaging was achieved in all instances. The electrode types used included 9 Nucleus slim modiolar electrodes, 1 Nucleus contour electrode, and 2 Medel flex26 electrodes. A malpositioned electrode array was detected in one patient. The handheld digital X-ray also adeptly visualized the electrodes implanted in pediatric patients. Conclusions: The use of intraoperative handheld digital X-ray using MINE ALNU® proves to be a safe, efficient, straightforward, and reliable method for immediate identification of an inserted electrode array. It has potential to replace the traditional C-arm X-ray for verifying electrode positioning in the operating room.

Efficacy of the Bonebridge BCI602 for Adult Patients with Single-sided Deafness: A Prospective Multicenter Study.

OBJECTIVE: To investigate the safety and efficacy of a novel active transcutaneous bone conduction implant (BCI) device for patients with single-sided deafness (SSD). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral hospitals. METHODS: This prospective multicenter study was conducted at 15 institutions nationwide. Thirty adult (aged ≥19 years) SSD patients were recruited. They underwent implantation of an active transcutaneous BCI device (Bonebridge BCI602). Objective outcomes included aided pure-tone thresholds, aided speech discrimination scores (SDSs), and the Hearing in Noise Test (HINT) and sound localization test results. The Bern Benefit in Single-Sided Deafness (BBSS) questionnaire, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, and the Tinnitus Handicap Inventory (THI) were used to measure subjective benefits. RESULTS: The mean aided pure-tone threshold was 34.2 (11.3), mean (SD), dB HL at 500 to 4000 Hz. The mean total BBSS score was 27.5 (13.8). All APHAB questionnaire domain scores showed significant improvements: ease of communication, 33.6 (23.2) versus 22.6 (21.3), P = .025; reverberation, 44.8 (16.6) versus 32.8 (15.9), P = .002; background noise, 55.5 (23.6) versus 35.2 (18.1), P < .001; and aversiveness, 36.7 (22.8) versus 25.8 (21.4), P = .028. Moreover, the THI scores were significantly reduced [47.4 (30.1) versus 31.1 (27.0), P = .003]. Congenital SSD was a significant factor of subjective benefit (-11.643; 95% confidence interval: -21.946 to -1.340). CONCLUSION: The BCI602 active transcutaneous BCI device can provide functional hearing gain without any adverse effects and is a feasible option for acquired SSD patients with long-term deafness.

BML-281 promotes neuronal differentiation by modulating Wnt/Ca2+ and Wnt/PCP signaling pathway.

Histone deacetylase (HDAC) inhibitors promote differentiation through post-translational modifications of histones. BML-281, an HDAC6 inhibitor, has been known to prevent tumors, acute dextran sodium sulfate-associated colitis, and lung injury. However, the neurogenic differentiation effect of BML-281 is poorly understood. In this study, we investigated the effect of BML-281 on neuroblastoma SH-SY5Y cell differentiation into mature neurons by immunocytochemistry (ICC), reverse transcriptase PCR (RT-PCR), quantitative PCR (qPCR), and western blotting analysis. We found that the cells treated with BML-281 showed neurite outgrowth and morphological changes into mature neurons under a microscope. It was confirmed that the gene expression of neuronal markers (NEFL, MAP2, Tuj1, NEFH, and NEFM) was increased with certain concentrations of BML-281. Similarly, the protein expression of neuronal markers (NeuN, Synaptophysin, Tuj1, and NFH) was upregulated with BML-281 compared to untreated cells. Following treatment with BML-281, the expression of Wnt5α increased, and downstream pathways were activated. Interestingly, both Wnt/Ca2+ and Wnt/PCP pathways activated and regulated PKC, Cdc42, RhoA, Rac1/2/3, and p-JNK. Therefore, BML-281 induces the differentiation of SH-SY5Y cells into mature neurons by activating the non-canonical Wnt signaling pathway. From these results, we concluded that BML-281 might be a novel drug to differentiation into neuronal cells through the regulation of Wnt signaling pathway to reduce the neuronal cell death.

Comprehensive investigation of the expression profiles of common long noncoding RNAs during microglial activation.

Microglia, similar to peripheral macrophages, are the primary immune cells of the central nervous system (CNS). Microglia exist in the resting state in the healthy CNS, but can be activated and polarized into either M1 or M2 subtypes for immune defense and the maintenance of CNS homeostasis by multiple stimuli. Several long noncoding RNAs (lncRNAs) mediate human inflammatory diseases and neuropathologies by regulating their target genes. However, the function of common lncRNAs that contribute to microglial activation remains unclear. Thus, we used bioinformatic approaches to identify common lncRNAs involved in microglial activation in vitro. Our study identified several lncRNAs as common regulators of microglial activation. We identified 283 common mRNAs and 53 common lncRNAs during mouse M1 microglial activation processes, whereas 26 common mRNAs and five common lncRNAs were identified during mouse M2 microglial activation processes. A total of 648 common mRNAs and 274 common lncRNAs were identified during the activation of human M1 microglia. In addition, we identified 1,920 common co-expressed pairs in mouse M1 activation processes and 25 common co-expressed pairs in mouse M2 activation processes. Our study provides a comprehensive understanding of common lncRNA expression profiles in microglial activation processes in vitro. The list of common lncRNAs identified in this study provides novel evidence and clues regarding the molecular mechanisms underlying microglial activation.

Dual red and near-infrared light-emitting diode irradiation ameliorates LPS-induced otitis media in a rat model.

Objective: Otitis media (OM) is an infectious and inflammatory disease of the middle ear (ME) that often recurs and requires long-term antibiotic treatment. Light emitting diode (LED)-based devices have shown therapeutic efficacy in reducing inflammation. This study aimed to investigate the anti-inflammatory effects of red and near-infrared (NIR) LED irradiation on lipopolysaccharide (LPS)-induced OM in rats, human middle ear epithelial cells (HMEECs), and murine macrophage cells (RAW 264.7). Methods: An animal model was established by LPS injection (2.0 mg/mL) into the ME of rats via the tympanic membrane. A red/NIR LED system was used to irradiate the rats (655/842 nm, intensity: 102 mW/m2, time: 30 min/day for 3 days and cells (653/842 nm, intensity: 49.4 mW/m2, time: 3 h) after LPS exposure. Hematoxylin and eosin staining was performed to examine pathomorphological changes in the tympanic cavity of the ME of the rats. Enzyme-linked immunosorbent assay, immunoblotting, and RT-qPCR analyses were used to determine the mRNA and protein expression levels of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α). Mitogen-activated protein kinases (MAPKs) signaling was examined to elucidate the molecular mechanism underlying the reduction of LPS-induced pro-inflammatory cytokines following LED irradiation. Results: The ME mucosal thickness and inflammatory cell deposits were increased by LPS injection, which were reduced by LED irradiation. The protein expression levels of IL-1ß, IL-6, and TNF-α were significantly reduced in the LED-irradiated OM group. LED irradiation strongly inhibited the production of LPS-stimulated IL-1ß, IL-6, and TNF-α in HMEECs and RAW 264.7 cells without cytotoxicity in vitro. Furthermore, the phosphorylation of ERK, p38, and JNK was inhibited by LED irradiation. Conclusion: This study demonstrated that red/NIR LED irradiation effectively suppressed inflammation caused by OM. Moreover, red/NIR LED irradiation reduced pro-inflammatory cytokine production in HMEECs and RAW 264.7 cells through the blockade of MAPK signaling.

Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction.

Mesenchymal stem cells (MSCs) have therapeutic effects on neurodegenerative diseases (NDDs) known by their secreted molecules, referred to as the "secretome". The mitochondrial complex I inhibitor, rotenone (ROT), reproduces α-synuclein (α-syn) aggregation seen in Parkinson's disease (PD). In this present study, we examined the neuroprotective effects of the secretome from neural-induced human adipose tissue-derived stem cells (NI-ADSC-SM) during ROT toxicity in SH-SY5Y cells. Exposure to ROT significantly impaired the mitophagy by increased LRRK2, mitochondrial fission, and endoplasmic reticulum (ER) stress (ERS). ROT also increased the levels of calcium (Ca2+), VDAC, and GRP75, and decreased phosphorylated (p)-IP3R Ser1756/total (t)-IP3R1. However, NI-ADSC-SM treatment decreased Ca2+ levels along with LRRK2, insoluble ubiquitin, mitochondrial fission by halting p-DRP1 Ser616, ERS by reducing p-PERK Thr981, p-/t-IRE1α, p-SAPK, ATF4, and CHOP. In addition, NI-ADSC-SM restored the mitophagy, mitochondrial fusion, and tethering to the ER. These data suggest that NI-ADSC-SM decreases ROT-induced dysfunction in mitochondria and the ER, which subsequently stabilized tethering in mitochondria-associated membranes in SH-SY5Y cells.

Valproic Acid Inhibits Progressive Hereditary Hearing Loss in a KCNQ4 Variant Model through HDAC1 Suppression.

Genetic or congenital hearing loss still has no definitive cure. Among genes related to genetic hearing loss, the potassium voltage-gated channel subfamily Q member 4 (KCNQ4) is known to play an essential role in maintaining ion homeostasis and regulating hair cell membrane potential. Variants of the KCNQ4 show reductions in the potassium channel activity and were responsible for non-syndromic progressive hearing loss. KCNQ4 has been known to possess a diverse variant. Among those variants, the KCNQ4 p.W276S variant produced greater hair cell loss related to an absence of potassium recycling. Valproic acid (VPA) is an important and commonly used histone deacetylase (HDAC) inhibitor for class I (HDAC1, 2, 3, and 8) and class IIa (HDAC4, 5, 7, and 9). In the current study, systemic injections of VPA attenuated hearing loss and protected the cochlear hair cells from cell death in the KCNQ4 p.W276S mouse model. VPA activated its known downstream target, the survival motor neuron gene, and increased acetylation of histone H4 in the cochlea, demonstrating that VPA treatment directly affects the cochlea. In addition, treatment with VPA increased the KCNQ4 binding with HSP90ß by inhibiting HDAC1 activation in HEI-OC1 in an in vitro study. VPA is a candidate drug for inhibiting late-onset progressive hereditary hearing loss from the KCNQ4 p.W276S variant.

Outcomes of Endoscopic Tympanoplasty for Large Perforations: A Multicenter Retrospective Study in South Korea.

OBJECTIVES: Endoscopic tympanoplasty (ET) provides minimally invasive transcanal access to the middle ear and improves middle ear visibility for the treatment of tympanic membrane (TM) perforations. However, the literature on surgical outcomes for large TM perforations is lacking and limited to small series. This study aimed to evaluate the clinical benefits of ET for large TM perforations. METHODS: This retrospective cohort study was conducted at nine tertiary referral hospitals in South Korea, where 252 patients who underwent ET as primary surgery from September 2019 to August 2021 were included. The outcome measures included the graft success rate and pre- and postoperative audiometric data. RESULTS: In 239 patients, the graft success rate of ET for large or subtotal perforations was 86.2% (206 patients), while the graft failure rate was 13.8% (33 patients). The graft failure rate was directly correlated with surgical techniques, including overlay and medial or lateral underlay tympanoplasty (P=0.027). Lateral underlay tympanoplasty showed the most favorable. RESULTS: Sex, laterality, etiology, site and size of perforation, operation time, and graft materials did not vary significantly between the graft success and failure groups (P>0.05). The mean air-bone gap (ABG) improved significantly in both groups (graft success group: 10.0±0.6 dB and graft failure group: 7.7±0.3 dB; P<0.001). However, the ABG improvement did not significantly differ between the groups. Analysis of covariance revealed that the postoperative 500-Hz bone conduction threshold improved after successful ET (adjusted coefficient, -11.351; 95% confidence interval, -21.491 to -1.212; P=0.028). CONCLUSION: This study involved the largest population to date of large TM perforations treated by ET. The study findings suggest that ET is feasible and effective in treating large TM perforations.

Protective Effect of Avenanthramide-C on Auditory Hair Cells against Oxidative Stress, Inflammatory Cytokines, and DNA Damage in Cisplatin-Induced Ototoxicity.

Cisplatin-induced ototoxicity leads to hearing impairment, possibly through reactive oxygen species (ROS) production and DNA damage in cochlear hair cells (HC), although the exact mechanism is unknown. Avenanthramide-C (AVN-C), a natural, potent antioxidant, was evaluated in three study groups of normal adult C57Bl/6 mice (control, cisplatin, and AVN-C+cisplatin) for the prevention of cisplatin-induced hearing loss. Auditory brainstem responses and immunohistochemistry of outer hair cells (OHCs) were ascertained. Cell survival, ROS production, Phospho-H2AX-enabled tracking of DNA damage-repair kinetics, and expression levels of inflammatory cytokines (TNF-α, IL-1ß, IL6, iNOS, and COX2) were assessed using House Ear Institute-Organ of Corti 1 (HEI-OC1 Cells). In the in vivo mouse model, following cisplatin-induced damage, AVN-C decreased the hearing thresholds and sheltered all cochlear turns' OHCs. In HEI-OC1 cells, AVN-C preserved cell viability and decreased ROS production, whereas cisplatin enhanced both ROS levels and cell viability. In HEI-OC1 cells, AVN-C downregulated IL6, IL-1ß, TNF-α, iNOS, and COX2 production that was upregulated by cisplatin treatment. AVN-C attenuated the cisplatin-enhanced nuclear H2AX activation. AVN-C had a strong protective effect against cisplatin-induced ototoxicity through inhibition of ROS and inflammatory cytokine production and DNA damage and is thus a promising candidate for preventing cisplatin-induced sensorineural hearing loss.

Outcomes of Endoscopic Congenital Cholesteatoma Removal in South Korea.

Importance: Transcanal endoscopic ear surgery (TEES) provides minimally invasive transcanal access to the middle ear and improves middle ear visibility during cholesteatoma resection. However, the literature on outcomes following TEES alone for the removal of congenital cholesteatoma (CC) is lacking and limited to small series. Objective: To assess outcomes of TEES for CC limited to the middle ear and/or mastoid antrum and to explore the risk factors associated with recidivism (ie, recurrent and/or residual cholesteatoma). Design, Setting, and Participants: This cohort study evaluated retrospective, multicenter data for 271 children with CC who underwent TEES at 9 tertiary referral hospitals in South Korea between January 1, 2013, and December 31, 2021, and had a follow-up of at least 6 months after surgery. Main Outcomes and Measures: Outcomes included the incidence of residual cholesteatoma and audiometric data after TEES. A multivariable analysis using Cox proportional hazards regression models was used to assess associations between cholesteatoma characteristics and recidivism, with hazard ratios (HRs) and 95% CIs reported. Results: Of the 271 patients (mean [SD] age, 3.5 [2.9] years; 194 [71.6%] boys, 77 [28.4%] girls), 190 had Potsic stage I CC (70.1%), 21 (7.7%) had stage II, 57 (21.0%) had stage III, and 3 (1.1%) had stage IV. Thirty-six patients (13.3%) with residual cholesteatoma were found, including 15 (7.9%) with Potsic stage I, 3 (14.3%) with stage II, and 18 (31.6%) with stage III. In the multivariable analysis, invasion of the malleus (HR, 2.257; 95% CI, 1.074-4.743) and posterosuperior quadrant location (HR, 3.078; 95% CI, 1.540-6.151) were associated with the incidence of recidivism. Overall, hearing loss (>25 dB on auditory behavioral test or >30 dB of auditory evoked responses) decreased from 24.4% to 17.7% after TEES. Conclusions and Relevance: This cohort study involved the largest known population to date of CC removed by TEES. The findings suggest that TEES may be feasible and effective for the removal of CC limited to the middle ear and/or mastoid antrum in children.

Identification and Characterization of mRNA and lncRNA Expression Profiles in Age-Related Hearing Loss.

OBJECTIVES: Age-related hearing loss (ARHL), or presbycusis, is caused by disorders of sensory hair cells and auditory neurons. Many studies have suggested that the accumulation of mitochondrial DNA damage, the production of reactive oxygen species, noise, inflammation, and decreased antioxidant function are associated with subsequent cochlear senescence in response to aging stress. Long non-coding RNA (lncRNA) has been reported to play important roles in various diseases. However, the function of lncRNA in ARHL remains unclear. In this study, we analyzed the common expression profiles of messenger RNA (mRNA) and lncRNA through ARHL-related RNA-sequencing datasets. METHODS: We selected and downloaded three different sets of RNA-sequencing data for ARHL. We performed differential expression analysis to find common mRNA and lncRNA profiles in the cochleae of aged mice compared to young mice. Gene Ontology (GO) analysis was used for functional exploration. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to validate mRNAs and lncRNAs. In addition, we performed trans target prediction analysis with differentially expressed mRNAs and lncRNAs to understand the function of these mRNAs and lncRNAs in ARHL. RESULTS: We identified 112 common mRNAs and 10 common lncRNAs in the cochleae of aged mice compared to young mice. GO analysis showed that the 112 upregulated mRNAs were enriched in the defense response pathway. When we performed qRT-PCR with 1 mM H2O2-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, the qRT-PCR. RESULTS: were consistent with the RNA-sequencing analysis data. lncRNA-mRNA networks were constructed using the 10 common lncRNAs and 112 common mRNAs in ARHL. CONCLUSION: Our study provides a comprehensive understanding of the common mRNA and lncRNA expression profiles in ARHL. Knowledge of ARHL-associated mRNAs and lncRNAs could be useful for better understanding ARHL and these mRNAs and lncRNAs might be a potential therapeutic target for preventing ARHL.

The Function of Cochlear Implant After Cardioversion in a Patient With Atrial Flutter: A Case Report.

Hearing loss in older people can cause communication impairments, decreased quality of life, social isolation, depression, and dementia. Cochlear implant surgery is an effective treatment for older patients with hearing loss who cannot achieve satisfactory audiologic outcomes with hearing aids. However, older people have an increased risk of heart disease and often take medications that affect heart rhythm. Herein, we report a case of an 80-year-old woman who underwent cardioversion at 50J after cochlear implant surgery. Electrical impedance before and after cardioversion showed only minor changes without abnormality, and the cochlear implant functioned well. We believe that the electronic circuits of the cochlear implant may have been relatively tolerant to the electrical shock from the external defibrillator. Typically, cardioversion should be avoided in cochlear implant recipients because it may damage the implant. If cardioversion cannot be avoided, we strongly recommend starting cardioversion at the lowest energy level (50 J) and removing the sound processor of the implant during the procedure.

Natural killer cells have a synergistic anti-tumor effect in combination with chemoradiotherapy against head and neck cancer.

BACKGROUND: The use of natural killer (NK) cells is a promising approach in the field of cancer immunotherapy; however, combination treatments are required to enhance the effects of NK cell immunotherapy. In this study, we assessed the potential of irradiation and cisplatin as a chemoradiotherapy (CRT) regimen to augment the effects of NK cell immunotherapy in head and neck squamous cell carcinoma (HNSCC). METHODS: NK cells were expanded using our recently established K562-OX40 ligand and membrane-bound interleukin (IL)-18 and IL-21 feeder cells in the presence of IL-2/IL-15 from peripheral blood of healthy donors. RESULTS: The results showed an increase in the purity of NK cells and expression of activation markers such as NKG2D and lymphocyte function-associated antigen 1 during the expansion process, which is positively correlated to the NK cell infiltration and overall survival in patients with HNSCC. CRT induced NK cell activation ligand (ULBP2) and adhesion molecules (ICAM-1, -2 and -3) on HNSCC, leading to enhanced cytotoxicity of NK cells against HNSCC. CONCLUSIONS: Our findings suggest that the NK cells have a potent anti-tumor effect in combination with CRT against HNSCC.

Autophagy Signaling by Neural-Induced Human Adipose Tissue-Derived Stem Cell-Conditioned Medium during Rotenone-Induced Toxicity in SH-SY5Y Cells.

Rotenone (ROT) inhibits mitochondrial complex I, leading to reactive oxygen species formation, which causes neurodegeneration and alpha-synuclein (α-syn) aggregation and, consequently, Parkinson's disease. We previously found that a neurogenic differentiated human adipose tissue-derived stem cell-conditioned medium (NI-hADSC-CM) was protective against ROT-induced toxicity in SH-SY5Y cells. In the present study, ROT significantly decreased the phospho (p)-mTORC1/total (t)-mTOR, p-mTORC2/t-mTOR, and p-/t-ULK1 ratios and the ATG13 level by increasing the DEPTOR level and p-/t-AMPK ratio. Moreover, ROT increased the p-/t-Akt ratio and glycogen synthase kinase-3ß (GSK3ß) activity by decreasing the p-/t-ERK1/2 ratios and beclin-1 level. ROT also promoted the lipidation of LC3B-I to LC3B-II by inducing autophagosome formation in Triton X-100-soluble and -insoluble cell lysate fractions. Additionally, the levels of ATG3, 5, 7, and 12 were decreased, along with those of lysosomal LAMP1, LAMP2, and TFEB, leading to lysosomal dysfunction. However, NI-hADSC-CM treatment increased the p-mTORC1, p-mTORC2, p-ULK1, p-Akt, p-ERK1/2, ATG13, and beclin-1 levels and decreased the p-AMPK level and GSK3ß activity in response to ROT-induced toxicity. Additionally, NI-hADSC-CM restored the LC3B-I level, increased the p62 level, and normalized the ATG and lysosomal protein amounts to control levels. Autophagy array revealed that the secreted proteins in NI-hADSC-CM could be crucial in the neuroprotection. Taken together, our results showed that the neuroprotective effects of NI-hADSC-CM on the autophagy signaling pathways could alleviate the aggregation of α-syn in Parkinson's disease and other neurodegenerative disorders.