AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial.

BACKGROUND: Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9. METHODS: This single-arm, single-centre trial enrolled children (aged 1-18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing. FINDINGS: Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1-2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40-57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5-4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery. INTERPRETATION: AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.

Traditional Chinese medicine Qingre Huoxue decoction enhances wound healing in through modulation of angiogenic and inflammatory pathways.

This study investigates the therapeutic potential of Qingre Huoxue Decoction (QHD), a traditional Chinese herbal formulation, in promoting wound healing in an imiquimod-induced murine model of psoriasis. The research was driven by the need for effective wound healing strategies in psoriatic conditions, where conventional treatments often fall short. Employing a combination of in vivo and in vitro methodologies, we assessed the effects of QHD on key factors associated with wound healing. Our results showed that QHD treatment significantly reduced the expression of angiogenic proteins HIF-1α, FLT-1, and VEGF, and mitigated inflammatory responses, as evidenced by the decreased levels of pro-inflammatory cytokines and increased expression of IL-10. Furthermore, QHD enhanced the expression of genes essential for wound repair. In vitro assays with HUVECs corroborated the anti-angiogenic effects of QHD. Conclusively, the study highlights QHD's efficacy in enhancing wound healing in psoriatic conditions by modulating angiogenic and inflammatory pathways, presenting a novel therapeutic avenue in psoriasis wound management.

Hearing of Otof-deficient mice restored by trans-splicing of N- and C-terminal otoferlin.

Mutations to the OTOF gene are among the most common reasons for auditory neuropathy. Although cochlear implants are often effective in restoring sound transduction, there are currently no biological treatments for individuals with variants of OTOF. Previous studies have reported the rescue of hearing in DFNB9 mice using OTOF gene replacement although the efficacy needs improvement. Here, we developed a novel dual-AAV-mediated gene therapy system based on the principles of protein trans-splicing, and we show that this system can reverse bilateral deafness in Otof -/- mice after a single unilateral injection. The system effectively expressed exogenous mouse or human otoferlin after injection on postnatal day 0-2. Human otoferlin restored hearing to near wild-type levels for at least 6 months and restored the release of synaptic vesicles in inner hair cells. Our study not only provides a preferential clinical strategy for the treatment of OTOF-related auditory neuropathies, but also describes a route of development for other large-gene therapies and protein engineering techniques.

Associations among Audiometric, Doppler Hydroacoustic, and Subjective Outcomes of Venous Pulsatile Tinnitus.

OBJECTIVE: Venous pulsatile tinnitus (PT) has received increasing attention recently. As analyses of psychophysical and neuropsychological dimensions of venous PT are lacking, this study aimed to quantitatively and qualitatively investigate the correlation among audiometric, hydroacoustic, and subjective outcomes in patients with PT. METHODS: Fifty-five venous PT patients, with or without sigmoid sinus wall anomalies (SSWAs), were subdivided into SSWAs (n = 30) and non-SSWAs (n = 25) groups. Audiometric and hemodynamic evaluations were assessed. Questionnaires including the Tinnitus Handicap Inventory, Hospital Anxiety and Depression Scale (HADS), and Athens Insomnia Scale (AIS) were deployed to evaluate the psychological impacts of PT. RESULTS: Among 55 subjects, PT frequency-related pure-tone audiometry (PTA) was significantly different between ipsilesional non-PT frequency-related PTA (p < 0.01), ipsilateral jugular vein compression PTA (p < 0.01), and contralesional ear PTA (p < 0.01). In contrast with the pulsatility index and flow velocity, bilateral EOET and flow volume were significantly different (p < 0.01). Of the 3 questionnaire types, there was a strong correlation between HADS anxiety and AIS scores (r = 0.658, p < 0.01). The duration of PT was not correlated with subjective outcomes, and there was no statistical significance found among audiometric, hemodynamic, and subjective outcomes between SSWAs and non-SSWAs groups. CONCLUSIONS: (1) The duration of PT was irrelevant to the increase of PTA. (2) Venous PT is the perception of vascular flow sound, in which hydroacoustic characteristics can be highly independent. (3) Anxiety, depression, and sleep disorders commonly prevail among PT patients.

U0126 pretreatment inhibits cisplatin-induced apoptosis and autophagy in HEI-OC1 cells and cochlear hair cells.

Deafness is the most common sensory disorder in the world. Ototoxic drugs are common inducing factors of sensorineural hearing loss, and cochlear hair cell (HC) damage is the main concern of the present studies. Cisplatin is a widely used, highly effective antitumor drug, but some patients have experienced irreversible hearing loss as a result of its application. This hearing loss is closely related to HC apoptosis and autophagy. U0126 is a specific inhibitor of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) signaling pathway and has neuroprotective effects. For example, the neuroprotective effect of U0126 on ischemic stroke has been widely recognized. In neural cells, U0126 can prevent death due to excess glutamate, dopamine, or zinc ions. However, no studies of U0126 and ototoxic drug-induced injury have been reported to date. In the present study, we found that U0126 pretreatment significantly reduced the apoptosis and autophagy of HCs in auditory House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear HCs. In addition, U0126 reduced the cisplatin-induced production of reactive oxygen species as well as the cisplatin-induced decrease in the mitochondrial membrane potential. These findings suggest that U0126 may be a potential therapeutic candidate for the prevention of cisplatin-induced ototoxicity.

Knockdown of sorcin increases HEI-OC1 cell damage induced by cisplatin in vitro.

Hearing loss caused by ototoxic drugs is a kind of acquired hearing loss. Cisplatin is one of the most commonly used drugs and its main action sites are hair cells (HCs). Sorcin is a drug-resistant calcium-binding protein belonging to the small penta-EF-hand protein family. Sorcin is highly expressed in many tissues, including bone, heart, brain, lung, and skin tissues. Single-cell RNA sequencing showed that sorcin was expressed in the outer HCs of mice, but its role remained unknown. We also found that sorcin was highly expressed in the cytoplasm of cochlear HCs and HEI-OC1 cells. After cisplatin injury, the expression of sorcin in HCs and HEI-OC1 cells decreased significantly. SiRNA transfection technology was used to knock down the expression of sorcin. The results showed that the number of apoptotic cells, the expression of cleaved caspased-3, and the expression of Bax increased while the anti-apoptotic factor Bcl-2 decreased in the siRNA-Sorcin + CIS group. The observed increase in apoptosis was related to the increase of reactive oxygen species (ROS) and the destruction of the mitochondrial membrane potential (MMP). Finally, we found that the downregulated sorcin worked by activating the P-ERK1/2 signaling pathway. Overall, this study showed that sorcin can be used as a new target to prevent the ototoxicity of platinum drugs.

Differences in hearing recovery following intratympanic alone or intravenous dexamethasone with rescue intratympanic steroids for sudden sensorineural hearing loss: A randomised trial.

OBJECTIVES: This study aimed to evaluate hearing improvement at different frequencies and the safety of intratympanic (IT) and intravenous (IV) administration of dexamethasone for sudden sensorineural hearing loss (SSNHL). METHODS: SSNHL patients were randomly divided into two groups within 72 hours after onset and received 24 days of dexamethasone therapy. Group A received IT dexamethasone once every other day for 24 days. Group B received IV dexamethasone for 12 days, followed by IT dexamethasone once every other day for the following 12 days. Hearing recovery and side effects were compared. RESULTS: Subgroup analysis was performed to look for variation in hearing improvement in high frequency, low frequency and overall hearing at different time points. There was no evidence of a difference in hearing outcomes between IT dexamethasone and sequential IV plus IT treatments. Side effects of steroids were observed within 90 days after treatment. The local adverse effects of IT injection were mild. The systemic side effects in group B were more serious than those in group A. CONCLUSIONS: IT dexamethasone was safer than IV dexamethasone, and there was no evidence of a difference in hearing outcomes between IT dexamethasone and sequential IV plus IT treatments. It is necessary to make individualised treatment decisions according to the patient's condition.

PD-L1 and PD-1 expressed in trigeminal ganglia may inhibit pain in an acute migraine model.

BACKGROUND: Neurogenic inflammation, mediated by the activation of primary neurons, is thought to be an important factor in migraine pathophysiology. Programmed cell death ligand-1 (PD-L1) can suppress the immune response through the Programmed cell death-1 receptor. However, the role of PD-L1/PD-1 in migraine remains unclear. In this study we evaluated the expression and role of PD-L1/PD-1 in the trigeminal ganglia in an animal model of acute migraine. METHODS: Acute nitroglycerin induces acute mechanical hyperalgesia that can be used as a readout of migraine-like pain. We investigated the expression of PD-L1 and PD-1 in the trigeminal ganglia in a mouse model by means of immunofluorescence labeling, quantitative reverse transcription-polymerase chain reaction and western blotting. We explored the effects of PD-1 in a migraine model by the von Frey test and by analyzing the expression of calcitonin gene-related peptide, interleukin-1ß (IL-1ß), interleukin-18 (IL-18), Tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6) and transient receptor potential vanilloid (TRPV4) after the intravenous injection of a PD-1 inhibitor. RESULTS: PD-L1 and PD-1 immunoreactivity were present in healthy trigeminal ganglia neurons. The mRNA levels of PD-L1 and PD-1 were significantly elevated 2 h, 4 h and 6 h after acute nitroglycerin treatment (p < 0.05). The protein levels of PD-L1 were significantly increased 2 h, 4 h and 6 h after treatment, and PD-1 was significantly increased at 2 h and 6 h. The blockade of PD-1 increased acute nitroglycerin-induced hyperalgesia, and this effect was accompanied by a more significant increase in calcitonin gene-related peptide, IL-1ß, TNF-α, IL-6 and IL-18 in the trigeminal ganglia. CONCLUSION: These findings suggest that PD-L1 and PD-1 might inhibit migraine-like pain by downregulating CGRP and inflammatory factors in the trigeminal ganglia. The use of PD-L1 and PD-1 as analgesics should be further studied.

Comparison of Different Slice Thicknesses in Computed Tomography for Labyrinthine Fistula Evaluation.

OBJECTIVES: The aim of the present study is to assess the impact of different slice thicknesses in computed tomography for labyrinthine fistula evaluation and to determine the appropriate slice thickness. METHODS: A total of 258 patients who underwent mastoidectomy and tympanoplasty for chronic otitis media with cholesteatoma from 2010 to 2014 were reviewed. The radiological diagnoses were compared with intraoperative findings. Sensitivity and specificity of 2.0-, 1.5-, 1.0-, and 0.75-mm-thick computed tomographic (CT) images for the evaluation of labyrinthine fistulae were calculated. Cohen's κ coefficient was also calculated. RESULTS: The sensitivities of 2.0-, 1.5-, 1.0-, and 0.75-mm-thick CT images for the evaluation of labyrinthine fistulae were 76.9, 86.5, 90.4, and 93.3% (observer 1) and 67.3, 76.0, 79.8, and 87.5% (observer 2), respectively. The specificities of 2.0-, 1.5-, 1.0-, and 0.75-mm-thick CT images for labyrinthine fistula evaluation were 96.1, 94.8, 95.5, and 95.5% (observer 1) and 99.4, 97.4, 95.5, and 94.8% (observer 2), respectively. Cohen's κ coefficients were 0.790, 0.788, 0.876, and 0.911 in 2.0-, 1.5-, 1.0-, and 0.75-mm-thick CT images, respectively. CONCLUSIONS: The sensitivity of CT for labyrinthine fistula evaluation increases with decreasing slice thickness, while the specificity does not improve.

3D-real IR MRI of Meniere's disease with partial endolymphatic hydrops.

OBJECTIVES: A three-dimensional inversion-recovery sequence with real reconstruction (3D-real IR) sequence 4 h after intravenous gadolinium injection (IV) has been used to visualize the endolymphatic hydrops (ELH) in Meniere's disease (MD). This study was designed to explore the pathology of MD with partial ELH. METHODS: We collected 338 patients with definite MD, all of whom underwent the IV method. Patients who were found to have partial ELH (vestibular or cochlear) were enrolled. The hearing thresholds of the enrolled patients were analyzed, the regions of interest of the cochlear perilymph and the cerebellum white matter were determined, and the signal intensity ratio in the former to the latter (CC ratio) for both sides in the patients was subsequently evaluated. RESULTS: Of the 338 collected patients with definite MD, 19 patients (5.6%) had unilateral vestibular ELH (N = 18) or cochlear ELH (N = 1), and 4 patients (1.2%) with bilateral ELH had contralateral cochlear ELH. The CC ratio of the affected side (1.44 ±â€¯0.46) was higher than that of the unaffected side (1.15 ±â€¯0.33, P < 0.05) in the 19 patients with unilateral ELH. Conversely, there was no difference between the ratio of the contralateral side (1.18 ±â€¯0.16) and the unaffected side (P > 0.05) in the 4 patients with bilateral ELH. CONCLUSIONS: Partial vestibular ELH was more common than partial cochlear ELH in MD. Moreover, vestibular ELH, rather than cochlear ELH, may correlate with the elevated contrast effect in the affected side, which may better reflect the pathologic mechanism of MD.

Treatment of adhesive otitis media by tympanoplasty combined with fascia grafting catheterization.

PURPOSE: The best surgical method for the management of adhesive otitis media is controversial. The aim of the study was to explore the feasibility and effectiveness of tympanoplasty combined with fascia grafting catheterization in the treatment of adhesive otitis media. METHODS: This was a retrospective study of patients with adhesive otitis media and who underwent tympanoplasty combined with fascia grafting and catheterization between April 2015 and December 2016 at the Eye-Ear-Nose-Throat Hospital Affiliated to Fudan University. All injured ears were examined by pure tone audiometry at 0.5, 1 and 2 kHz before and at 3 months after operation. RESULTS: Thirty-five patients (35 ears) were followed for 12-44 months. The air-conduction pure tone average was 31.7 ± 12.3 dBnHL. Hearing of 28 patients (80%) was improved to a practical level within 40 dBnHL, but 2 patients (6%) had no change in postoperative hearing. Numbers of patients with spontaneous prolapse, artificial removal of tympanic membrane ventilation tube, and unobstructed in place were 15, 12, and 8, respectively. Twenty-seven patients had perforations left after the prolapse and removal of tympanic membrane ventilation tubes, of which 22 (81%) had perforations healing by themselves. All patients had dry ears after operation, without recurrence. Thirty-three patients (94%) had dry ears within 3 months and only 2 patients (6%) for more than 6 months. CONCLUSION: Tympanoplasty combined with fascia grafting catheterization is effective in the treatment of adhesive otitis media.

Post-contrast 3D-FLAIR in idiopathic sudden sensorineural hearing loss.

PURPOSE: Our study investigated correlations between clinical characteristics, particularly hearing recovery, interval time between onset and three-dimensional fluid attenuation inversion recovery magnetic resonance imaging (3D-FLAIR MRI), and the signal intensity of post-contrast 3D-FLAIR MRI in patients with idiopathic sudden sensorineural hearing loss (SSNHL). METHODS: The study enrolled 100 SSNHL patients. The signal intensities and asymmetry ratios of the inner ear structures, including the cochleae, vestibules and vestibulocochlear nerve, were evaluated and calculated. The relationships between the clinical characteristics and MRI findings were assessed. RESULTS: After intravenous gadolinium (Gd) injection, 3D-FLAIR revealed high signal intensities in 65 patients. The corrected asymmetry ratios of cochlea correlated closely with interval time between onset and MRI. The asymmetry ratios of the inner ear structures were significantly lower in patients with final complete to partial hearing recovery. The corrected asymmetry ratios of the inner ear structures correlated with initial/final pure tone audiometry (PTA) and hearing recovery in the affected ear. Notably, it was shown that the corrected asymmetry ratios identified a poor prognosis for hearing recovery, with a sensitivity and specificity of 67.9% and 75.0% in the cochlea, 83.3% and 75.0% in the vestibule, and 52.4% and 81.2% in the vestibulocochlear nerve, respectively. CONCLUSIONS: Post-contrast 3D-FLAIR after intravenous Gd injection in SSNHL can be used to assess the permeability of the blood-labyrinth and blood-nerve barriers. The asymmetry ratios of the inner ear structures may identify patients with poor prognosis for hearing recovery. Signal characteristics are closely related to interval time between onset and MRI.

Quantitative evaluation of endolymphatic hydrops with MRI through intravenous gadolinium administration and VEMP in unilateral definite Meniere's disease.

PURPOSE: To help clinicians to further understand the significance of vestibular-evoked myogenic potential (VEMP) examinations to diagnose MD and the quantitative relationship between VEMP and MRI in assessing the location and degree of endolymphatic hydrops (EH) in definite Meniere's disease (MD) patients. METHODS: Fifty-six patients with unilateral definite MD participated in this study, which used MRIs through intravenous gadolinium administration (IV-Gd), audiometry, caloric tests and VEMP tests. The VEMP results of 26 healthy volunteers were used as a normal reference value. RESULTS: The participants were found through MRI to have differing degrees of vestibular and cochlear EH. Quantitative comparison of MRI and VEMP results found that the response rates of oVEMP decreased with cochlear EH increasing; the asymmetry ratio (AR) of oVEMP can be used to find whether cochlear EH or not, and the P1-N1 amplitude was lower in the extreme cochlear EH group (P < 0.01). The AR of cVEMP was larger in severe vestibular EH group than that of the mild or no vestibular EH group (P < 0.01). The correlation between the degree of cochlear EH and the mean PTA threshold was statistically significant (P < 0.05). The duration of MD correlated positively with vestibular EH (P < 0.05). The abnormal rate of caloric tests was higher in severe vestibular EH group than that of the mild or no vestibular EH group (P < 0.05). CONCLUSIONS: The advantages of MRIs by IV-Gd administration were obvious in assessing the location and degree of EH. oVEMP and PTA can be indirectly used to evaluate the extent of cochlear EH, cVEMP and caloric tests can be used to assess the extent of vestibular EH on the condition of absent MRIs.

Detection of Gallibacterium anatis by TaqMan fluorescent quantitative PCR.

To better understand the prevalence of Gallibacterium anatis in different poultry species, a rapid and accurate method was developed to detect G. anatis using a TaqMan fluorescent quantitative polymerase chain reaction (qPCR). Specific primers and a TaqMan probe were designed based on the reference gtxA gene sequence. The qPCR standard curve showed a good linear relationship, and the method showed good reproducibility, sensitivity, and specificity, indicating its suitability for G. anatis identification and quantitative analysis. A comparison of the detection results in 160 clinical swab samples showed that the detection rate (54.4%) of the qPCR for G. anatis was better than that of two conventional methods: gyrB gene-based qPCR for G. anatis (51.9%) and culture-based identification (34.4%). G. anatis was detected in layer chicken (77.3%), Silkie chicken (72.7%), and duck (27.1%) with relatively high detection rates, whereas dove (8.8%) and quail (3.0%) showed lower detection rates, indicating the different prevalence of G. anatis in different fowl species.

Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells.

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 µg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg-1·d-1, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

Prognostic and influencing factors of tinnitus in chronic otitis media after tympanoplasty.

The purpose of this study is to investigate what characteristics of tinnitus in patients with chronic otitis media was reduced after tympanoplasty and to assess the relationship between post-operative tinnitus reduction and pre-operative tinnitus tone, tinnitus duration, post-operative hearing recovery, and tympanogram. Medical records were prospective between March 2013 and May 2016. Audiologic evaluation by pure tone audiometry and acoustic impedance and tinnitus assessment using scores on the Tinnitus Handicap Inventory (THI) was conducted preoperatively and 6 months post-operatively. The data were analyzed using the Wilcoxon test, Student's and paired t test, and ANOVA. The pre-operative incidence of tinnitus in patients with COM was 47%. There was a very significant difference between pre-operative and post-operative mean THI scores (p < 0.05). Tinnitus was reduced or alleviated in 83% of tinnitus patients. Pre-operative low-tone tinnitus was significantly reduced 6 months after surgery. After surgery, air-conducted hearing improvement at 250, 500, and 1000 Hz in the tinnitus significant recovery group was greater than the tinnitus non-significant recovery group (p < 0.05). Tinnitus reduction in tympanogram A was significantly greater than in tympanograms B or C (p < 0.05). There was no statistically significant correlation between tinnitus duration and tinnitus reduction (p > 0.05). There was no significant effect of presence cholesteatoma and dry period on the gain THI (p > 0.05). The types of tympanoplasty had no effect on tinnitus improvement (p > 0.05). No patients experienced new tinnitus after surgery. Following tympanoplasty, most patients experienced a reduction in tinnitus. Pre-operative low-tone tinnitus is easier to reduce after tympanoplasty. Post-operative normal tympanogram and improved low-frequency AC hearing were important to tinnitus reduction.

Long-Term Outcomes after Performing Tympanoplasty without Mastoidectomy for Active and Inactive Noncholesteatomatous Chronic Otitis Media.

OBJECTIVE: This study aimed to assess long-term outcomes after performing tympanoplasty without mastoidectomy (TWOM) for active and inactive noncholesteatomatous chronic otitis media (COM) and to estimate the optimal time for surgery. METHODS: The patients were placed into an active ear group (group A) and an inactive ear group (group B). All patients were followed up for 5 years after TWOM. RESULTS: Ninety-two cases among 113 achieved dry ears in half a month to 1 month. The tympanic pressure gradually improved 3-6 months after the operation. A total of 69/72 ears achieved dry ears in the active ear group, and 37 ears had effective hearing improvement. In all, 40/41 ears achieved dry ears in the inactive ear group, and 20 ears had effective hearing improvement. There was no difference in the recurrence rate or hearing improvement in the two groups. CONCLUSION: With good quality control of the surgical treatment of TWOM, there are no differences in long-term outcomes in noncholesteatomatous COM in different chronic infection conditions.

Using coronary computerized tomographic images to predict the bulging second genu of the facial nerve in mastoidectomy.

The aim of the present study is to determine whether coronary CT images of the temporal bone are useful to predict a bulging second genu of the facial nerve (SGFN) in mastoidectomy by measuring and comparing the heights of the SGFN above the prominence of the lateral semicircular canal (PLSC) in medial-to-lateral dimension on coronary CT images and in mastoidectomy. The relationship between the SGFN and the PLSC in medial-to-lateral dimension, which may have big variability, can be evaluated on the coronary CT images of the temporal bone. The heights of the SGFN above the PLSC in medial-to-lateral dimension were measured on coronary CT images and in mastoidectomy in 184 patients. If the SGFN is above the PLSC in medial-to-lateral dimension, we called the SGFN a bulging SGFN. The data measured on CT images and in surgery were described in histograms and compared. The sensitivity and the specificity in the diagnosis of a bulging SGFN on CT images were calculated by comparison with surgical measurement. Cohen's kappa coefficient was calculated. The heights of the SGFN above the PLSC measured in medial-to-lateral dimension varied from -2.9 to 2.9 mm on coronary CT images and varied from -3.0 to 3.0 mm in surgery. The data measured in surgery showed that the SGFN was above the PLSC in medial-to-lateral dimension in 27.7% (51/184) patients, at least 1 mm above the PLSC in 15.8% (29/184) patients and at least 2 mm above the PLSC in 6.0% (13/184) patients. The sensitivity and the specificity for CT diagnosis of a bulging SGFN were 100% (51/51) and 91.0% (121/133), respectively. Bulging SGFN can be predicted by measuring the height of the SGFN above the PLSC on coronary CT images of the temporal bone.

Sigmoid Sinus Wall Anomalies Can Progress and May Not Be Congenital.

OBJECTIVE: Sigmoid sinus wall anomalies (SSWA) are closely linked to venous pulsatile tinnitus (PT). This study aims to demonstrate that SSWA develops progressively rather than being congenital. METHODS: We retrospectively analyzed 42 PT patients with SSWA who had at least two non-operative CT scans at our clinic. CT images were longitudinally assessed to track SSWA progression, while MRI and Doppler ultrasound evaluated transverse sinus stenosis and venous hemodynamics. Changes in PT perception were tracked using the tinnitus handicap inventory (THI) questionnaire. RESULTS: Among the 42 SSWA patients, 12 (28.6%) exhibited progression. Anastomosis between diploic vein and diverticulum was significantly higher compared to the dehiscence cohort (p < 0.01). Within the diverticulum group, seven individuals (30.4%) experienced enlargement, with a mean diverticular wall expansion of 5.9% ± 11.4%. Progressive erosion was observed in two cases (12.5%) in the dehiscence cohort, with a mean sigmoid plate erosion of 3.8% ± 10.1%. In cases progressing from dehiscence to diverticulum, three subjects transitioned, with a mean sigmoid sinus wall length expansion of 43.8% ± 31.9%. SSWA progression showed a significant negative correlation with QBILATERAL (r = -0.857, p = 0.014), and there was a significant difference between initial and revisit THI scores (p < 0.01). CONCLUSION: SSWA can undergo morphological progression, indicating it is a progressive clinical condition rather than congenital. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Microdrill Versus Diode Laser in Endoscopic Stapedotomy: A Comparative Study.

BACKGROUND: Microdrill and diode laser are two different methods used in endoscopic stapedotomy for otosclerosis. These two methods have not been compared in endoscopic stapedotomy. AIMS/OBJECTIVES: To analyze the differences between microdrill and diode laser in endoscopic stapedotomy for otosclerosis. MATERIALS AND METHODS: This is a randomized clinical trial; patients with otosclerosis were randomly divided into microdrill group (group A: n = 69) and diode laser group (group B: n = 62). Differences between the two groups were then compared. RESULTS: The preoperative air-bone gap (ABG) was 25.40 ± 10.88 dBHL in group A and 24.84 ± 12.23 dBHL in group B, with no significant between-group difference ( p > 0.05). The postoperative ABG in group A was 13.27 ± 9.91 dBHL versus 11.79 ± 10.82 dBHL in group B, and there was no significant difference between the groups ( p > 0.05). The surgical time in group B (64 ± 31.23 minutes) was significantly longer than that in group A (48 ± 25.62 minutes) ( p = 0.02). There were no significant between-group differences in basic patient-related data, preoperative air conduction (AC), preoperative bone conduction (BC), postoperative AC, distribution of postoperative ABG, preoperative ABG at different frequencies, and postoperative ABG at different frequencies. There was also no significant between-group difference in the average bleeding volume or number of patients with postoperative dizziness. CONCLUSION AND SIGNIFICANCE: The postoperative improvement in hearing level in the two group was equivalent, but group A had the advantage of a shorter operation time. LEVEL OF EVIDENCE: 4.