Ear Disorders Research Articles

Safety study on adverse events of zanubrutinib based on WHO-VigiAccess and FAERS databases.

The study endeavors to elucidate AE signals associated with zanubrutinib data from the WHO-VigiAccess and FAERS databases. The aim is to furnish robust scientific evidence to inform clinical practice and regulatory decisions. We meticulously extracted all AE breports tied to zanubrutinib from the both databases, encompassing the period from the drug's market introduction until 30 April 2024. Retrospective quantitative analysis employing ROR, PRR, and BCPNN methodologies were utilized to analysis. The investigation unveiled 1,304 reports from WHO-VigiAccess and 1,141 reports from FAERS related to zanubrutinib. Among the top 30 reported PTs in both databases, those not recorded in the drug label included pyrexia, dizziness, and death. In the FAERS database, signals for zanubrutinib were detected across 19 SOCs. Systems not covered in the drug label included reproductive system and breast disorders, metabolism and nutrition disorders, ear and labyrinth disorders, among others. Unmentioned signals included intestinal perforation, onychoclasis, night sweats, etc. This study confirms common AEs of zanubrutinib and identifies new ones, highlighting the need for careful monitoring and personalized treatment. It also emphasizes the importance of ongoing drug safety surveillance and patient management to maximize therapeutic benefits and minimize risks.

Serum Otoconin-90 and Otolin-1 Concentrations in Benign Paroxysmal Positional Vertigo.

The aim was to evaluate the value of otolith-associated protein otoconin-90 (OC90) and otolin-1 in the pathogenesis research and clinical treatment of benign paroxysmal positional vertigo (BPPV). The study included 50 patients with BPPV admitted to neurology and otorhinolaryngology departments and 30 healthy subjects with no history of dizziness as a control group. BPPV and controls were similar in terms of gender and age. Otolin-1 concentration was significantly greater in the BPPV group than in the controls (710.44 [584.35-837.39] vs 280.45 [212.7-419.61]; p < 0.001). No statistical significance was found, although OC90 was higher in the BPPV group than in the controls. There was a strong positive correlation between otolin-1 and OC90, a moderate negative correlation between otolin-1 and vitamin D, and a strong negative correlation between OC90 and vitamin D in the BPPV patient group. Otolin-1 had high specificity and AUC values for BPPV (AUC: 0.933; 95% CI: 0.881-0.986, 79.2% sensitivity, 100% specificity with a cutoff greater than 525). High serum concentrations of otolin-1 were associated with an increased risk of BPPV, but high concentrations of OC90 were not. Serum concentrations of otolin-1 can potentially be used as a biomarker for the acute onset of inner ear disorders due to the significant increase in patients with BPPV. Vitamin D has high specificity and sensitivity in patients with BPPV. It also provides evidence that BPPV patients with vitamin D deficiency may improve their symptoms with replacement therapy. More large-scale prospective studies are required to confirm these associations and clarify the exact mechanisms.

Epidemiological Evidence for Upper Respiratory Infections as a Potential Risk Factor for Meniere's Disease: A Korean National Health Sample Cohort Study.

Meniere's disease (MD) is a chronic inner ear disorder characterized by tinnitus, ear fullness, episodic vertigo, and fluctuating hearing loss, which significantly impacts quality of life and poses management challenges. Recent evidence suggests that upper respiratory infections (URIs) may contribute to MD's onset. This study examines the potential link between URIs and MD using data from the Korean National Health Insurance Service-National Sample Cohort (2002-2019). We analyzed 19,721 individuals with MD and 78,884 matched controls, adjusting for demographic factors and comorbidities using propensity score matching. Our results showed that individuals with a URI within one year prior to the index date exhibited a 2.01-fold greater likelihood of developing MD (95% confidence interval [CI] = 1.91-2.11, p < 0.001), while those with URIs within two years demonstrated a 1.54-fold higher probability (95% CI = 1.50-1.59, p < 0.001). Furthermore, we found that even remote URIs occurring up to two years before the index date significantly increased the risk of developing MD, underscoring the need for long-term patient follow-up. Overall, our study suggests that individuals with a history of URI may have an elevated risk of developing MD over multiple time frames, regardless of demographic or health profiles.

Perilymphatic fistula: a historical overview of publication trends

BackgroundPerilymph fistula (PLF) can cause symptoms of dizziness, vertigo, and fluctuating hearing. We hypothesized that publications on PLF have decreased in recent years relative to other inner ear disorders with overlapping symptoms.MethodsWe performed a Scopus search using the terms “perilymphatic fistula” OR “perilymph fistula,” limited to original studies or reviews involving human subjects published in English before 2022. We noted the senior author's institution, country affiliation, and publishing journal. The Kendall rank correlation coefficient test was used to analyze the trend of each variable over the past 30 years. Using the same search strategy, we compared these data to those from vestibular neuritis (VN), Meniere's disease (MD), superior semicircular canal dehiscence (SSCD), and benign paroxysmal positional vertigo (BPPV).ResultsSix hundred and ninety-eight PLF publications were returned. The top publishing country was the United States (n = 334), the top publishing journal was the American Journal of Otology/Otology and Neurotology (n = 68), and the top publishing institution was the University of Pittsburgh (n = 15). In the past 30 years (n = 501), there was no trend in the frequency of annual PLF publications (τ = −0.150, p = 0.265). Still there were positive trends in publications on vestibular neuritis (τ = 0.724, p &amp;lt; 0.001), Meniere's disease (τ = 0.587, p &amp;lt; 0.001), superior canal dehiscence syndrome (τ = 0.840, p &amp;lt; 0.001), and benign paroxysmal positional vertigo (τ = 0.882, p &amp;lt; 0.001) 5,398 PLF cases were identified, of which 4,356 specified the etiology; the majority identified an inciting insult (74.8%, n = 3,257).ConclusionsThe absence of diagnostic criteria for PLF may hinder its appeal to researchers as similar syndromes have had diagnostic consensus documents set forth. Given the greater number of cases with inciting insults, efforts to define a diagnostic criterion should focus on this subtype.

The Role of Pericytes in Inner Ear Disorders: A Comprehensive Review.

Inner ear disorders, including sensorineural hearing loss, Meniere's disease, and vestibular neuritis, are prevalent conditions that significantly impact the quality of life. Despite their high incidence, the underlying pathophysiology of these disorders remains elusive, and current treatment options are often inadequate. Emerging evidence suggests that pericytes, a type of vascular mural cell specialized to maintain the integrity and function of the microvasculature, may play a crucial role in the development and progression of inner ear disorders. The pericytes are present in the microvasculature of both the cochlea and the vestibular system, where they regulate blood flow, maintain the blood-labyrinth barrier, facilitate angiogenesis, and provide trophic support to neurons. Understanding their role in inner ear disorders may provide valuable insights into the pathophysiology of these conditions and lead to the development of novel diagnostic and therapeutic strategies, improving the standard of living. This comprehensive review aims to provide a detailed overview of the role of pericytes in inner ear disorders, highlighting the anatomy and physiology in the microvasculature, and analyzing the mechanisms that contribute to the development of the disorders. Furthermore, we explore the potential pericyte-targeted therapies, including antioxidant, anti-inflammatory, and angiogenic approaches, as well as gene therapy strategies.

Establishing Wideband Tympanometry Clinical Normative Data for the Iranian Young Adult Population

Background and Objectives: Wideband acoustic immittance (WBT) is a new method for assessing middle ear status by using a wide spectrum stimulus instead of the traditional 226 Hz probe tone. This study focuses on establishing normative data for WBT in the Iranian young adults. We aim to provide clinicians with specific norms for the Iranian population to enhance accuracy in diagnosing middle ear conditions and diseases. Methods: The research involved 20 healthy Iranian young adults who underwent WBT measurements. Results: Results showed differences in the WBT parameters compared to other populations, emphasizing the importance of using ethnicity-specific norms in clinical evaluations. Conclusion: The findings can help in diagnosing various middle ear disorders and monitoring treatment progress.

Unveiling a Rare Phenomenon: Sudden Sensorineural Hearing Loss Following Skin Prick Testing.

The skin prick test (SPT) is a standard method for diagnosing allergic diseases, while sudden sensorineural hearing loss (SSNHL) remains a perplexing condition often of unknown etiology. We present a unique case of SSNHL emerging shortly after an SPT, suggesting a potential link between allergic reactions and inner ear disorders. A 27-year-old male presented with unilateral hearing loss following an SPT for allergic rhinitis. Audiometric findings revealed SSNHL in the affected ear. Treatment with corticosteroids led to a full recovery of hearing function. This case highlights the rare occurrence of SSNHL possibly triggered by a type 1 allergic reaction to an SPT. Prompt corticosteroid therapy proved effective in restoring hearing. Further research is needed to understand the relationship between allergies and SSNHL and explore alternative treatment options.

Android-Based Expert Diagnosis System of Children’s Ear, Nose, and Throat Disorders Using Forward Chaining Method

Ear, nose, and throat disorders are a significant health problem, especially in children. This article discusses the development of an expert system as a diagnosis tool for ENT disorders in children by applying the forward chaining method. The system development was carried out using the waterfall method and built based on android using Kodular. The system can diagnose 36 disorders with 42 symptoms obtained by literature study technique from the book First Aid in Your Home written by Dr Tony Smith and Dr Sue Davidson. The result of this system is able to help the process of diagnosing ENT disorders in children accurately based on knowledge from experts through android applications.

Probe into the treatment of tinnitus by acupuncture combined with medicine under the mechanism of pathophysiology: A review.

Tinnitus is a common medical disorder. The risk factors include hearing loss, ototoxic medications, head injuries, and depression. Therefore, ear disorders, anxiety, and depression should be considered in the treatment of tinnitus. Although considerable research has been conducted on the pathogenesis and treatment of tinnitus, there is currently no effective treatment. Traditional Chinese medicine (TCM) has a certain effect on tinnitus and a large number of clinical trials have been conducted. Its treatment methods vary and include TCM, acupuncture, and music therapy. TCM treatment of tinnitus usually takes the method of comprehensive treatment, not only relying on drugs but also safety. Therefore, this review explores the treatment of tinnitus using acupuncture combined with medicine, based on the new pathophysiological mechanism of tinnitus.

Mining and evaluation of adverse event signals for capmatinib based on the FAERS database.

To conduct a comprehensive data analysis based on the FDA's Adverse Event Reporting System (FAERS) to mine possible adverse event (AE) signals of Capmatinib, providing valuable references for its clinical application. Capmatinib was the primary suspected drug in the search of FAERS database from the second quarter of 2020 to the fourth quarter of 2023. Data processing, screening, and classification were performed using methods such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). A total of 1,991 AE reports directly related to Capmatinib were screened, identifying 269 Preferred Terms (PTs) involving 26 System Organ Classes (SOCs). Besides the AEs recorded in the drug label (such as edema, nausea, fatigue, and dyspnea), the study unearthed other high-risk AEs not listed in the label, including Renal and urinary disorders, Vocal cord paralysis, and Ear and labyrinth disorders. Among these, renal and urinary disorders, and ear and labyrinth disorders had a higher frequency and intensity of signals, suggesting that their mechanisms of occurrence could be a future research direction. This study uncovered new potential AEs of Capmatinib based on the FAERS database, providing reference for its safe clinical use. Special attention should be given to the occurrence of ear and labyrinth disorders and renal and urinary disorders, primarily presenting as pseudo-acute kidney injury, during treatment.

Quantifying the Domino Effect of Septoplasty on Eustachian Tube Function and Nasal Resistance in Patients With Chronic Otitis Media: A Cross-Sectional Study.

Background Eustachian tube dysfunction is characterized by insufficient dilation, leading to secondary pathologies in the middle ear. By comparing pre- and post-operative grades of Eustachian tube functionand nasal resistance measurements, this study seeks to determine if septoplasty can improve Eustachian tube function in cases where nasal septal deviation is likely to cause mechanical dysfunction. We also aim to validate the JainBhalerao endoscopic classification of nasal septal deviation by assessing its utility in identifying septal deviations at a higher risk of causing Eustachian tube dysfunction. The ultimate goal is to establish guidelines for aural indications of septoplasty in treating Eustachian tube dysfunction-related middle ear disorders. Material and methods This prospective observational study was carried out from 1stJune 2022 to 31st March 2024 in the Department of Otorhinolaryngology at Acharya Vinoba Bhave Rural Hospital, involving 66 patients diagnosed with chronic otitis media and a deviated nasal septum with Eustachian tube dysfunction. Pre-operative and post-operative improvement in Eustachian tube function and Nasal resistance and their correlation werestudied using dynamic slow-motion video endoscopy and active anterior rhinomanometry, respectively. Statistical analysis included the chi-square test. Results Sixty-six patients diagnosed with chronic otitis media and deviated nasal septum with Eustachian tube dysfunction included in this study had a mean age of 35.6 years with 43 (65.2%) male predominance. Gross luminal narrowing and discrepancy of the volume of both nasal cavities led to higher degrees of Eustachian tube dysfunction due to pressure drop on the affected side, as observed in types 6, 7, and 8 as per Jain Bhalerao classification of deviated nasal septum. Nasal resistance measured using active anterior Rhinomanometry (Rhinodebitometry) showed a positive association of severity of nasal resistance in the types 6, 7, and 8 DNS of the Jain Bhalerao classification of deviated nasal septum. It demonstrated an improvement in the grade of Eustachian tube function and nasal resistance post-septoplasty. Conclusion The deviated nasal septum is one of the causes of Eustachian tube dysfunction and increased nasal resistance. Certain types of DNS are adversely associated with the causation of greater degrees of Eustachian tube dysfunction of mechanical type. Nasal septal deviation correction improved Eustachian dysfunction and nasal resistance after septoplasty.

Mammalian Inner Ear-Resident Immune Cells-A Scoping Review.

Several studies have demonstrated the presence of resident immune cells in the healthy inner ear. This scoping review aimed to systematize this knowledge by collecting the data on resident immune cells in the inner ear of different species under steady-state conditions. The databases PubMed, MEDLINE (Ovid), CINAHL (EBSCO), and LIVIVO were used to identify articles. Systematic reviews, experimental studies, and clinical data in English and German were included without time limitations. The search yielded 49 eligible articles published between 1979 and 2022. Resident immune cells, including macrophages, lymphocytes, leukocytes, and mast cells, have been observed in various mammalian inner ear structures under steady-state conditions. However, the physiological function of these cells in the healthy cochlea remains unclear, providing an opportunity for basic research in inner ear biology. This review highlights the need for further investigation into the role of these cells, which is crucial for advancing the development of therapeutic methods for treating inner ear disorders, potentially transforming the field of otolaryngology and immunology.

Passive smoker exposure as a risk factor of otitis media with effusion in children

Otitis media with effusion (OME) is a middle ear disorder often found in children and can cause hearing loss, delayed language acquisition, and behavioral disorders. Cigarette smoke exposure is one of the environmental factors that may raise the incidence of OME. This study aimed to identify the prevalence of OME and the risk of cigarette smoke to OME using urinary cotinine level examination, along with the characteristics of smoking history in the family. This cross-sectional study included 398 children aged 0-14 who underwent history taking, questionnaire completion, ear/nose/throat (ENT) examination, and tympanometry. OME patients based on ENT and tympanometry examination underwent urinary cotinine examination using lateral flow chromatographic immunoassay technique. Of the 398 children, five children were diagnosed with OME. The prevalence rate of OME was 1.3%. No OME patients were exposed to cigarette smoke based on urine cotinine levels of &amp;gt;200 ng/mL. However, based on history taking, one of five patients with OME is a passive smoker, with characteristics of active smoking history in the family one person (the father). In conclusion, there was no proportion of positive urinary cotinine levels in children with OME.

Safety profile of levonorgestrel intrauterine system: Analysis of spontaneous reports submitted to FAERS

The levonorgestrel-releasing intrauterine system (LNG-IUS) is an established, long-acting contraceptive option. With the widespread use of the LNG-IUS, drug-reported adverse events (AEs) have also garnered significant attention. In this study, we conducted a real-world analysis using the FDA's Adverse Event Reporting System (FAERS) database to assess the incidence of AEs associated with LNG-IUS use. Data from FAERS spanning from 2004Q1 to 2024Q1 were reviewed, with a focus on reports in which LNG-IUS was the primary suspected and secondary suspect drug. Signal detection was carried out utilizing Standardized MedDRA Queries (SMQ) and Preferred Terms (PT), with reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) employed to identify Signals of Disproportionate Reporting (SDR) for AEs. A positive SDR was defined when all three methods indicated significance. Analysis of 13 SMQs revealed notable SDRs in ear and eye disorders, cardiac arrhythmias, and lipodystrophy. Of the 61 suspected SDRs identified at the PT level, nearly half were not previously documented in labeling. Key potential signals of AEs associated with LNG-IUS use included increased heart rate, papilledema, idiopathic intracranial hypertension, cervical dysplasia, ruptured ovarian cyst, and uterine embedment and perforation. The findings underscore the importance of signal detection using FAERS data for identifying safety concerns related to LNG-IUS. Long-term observational studies are warranted to confirm and further elucidate these potential safety signals.

The Optimal Head Position Following Intratympanic Injection: A Research Based on HRCT Reconstruction.

Objective: This study aimed to investigate the optimal head position (OHP) following intratympanic injection, a critical intervention in treating inner ear disorders. Identifying OHP is essential to maximize drug retention in the middle ear, thereby significantly enhancing the therapeutic efficacy by mitigating the significant issue of injectate leakage through the eustachian tube (ET). Exploratory various positions of ET orifice and round window (RW) were investigated and associated with head movements. Methods: Twenty-two (10 males and 12 females) anonymized high-resolution computed tomography (HRCT) datasets of patients without structural ear disease were selected from January 2022 to December 2022 in the study. The subjects were categorized into two groups: children (≤18 years) and adult group (>18 years). The reconstruction of the ET orifice and RW from HRCT were analyzed using Mimics software and the distances from the center point of ET orifice or the center point of RW to the reference plane were defined as distance of ET orifice (DET) and distance of RW (DRW). Results: In the supine position, the OHP for intratympanic injection was 23°of pronation and 24° of posterior extension, and the maximum distance between the ET orifice and RW (DET-RW) was 9.29 ± 2.13 mm. As the head position extended posteriorly beyond 43°, DET was relatively high compared with DRW, resulting in the OHP a fully posteriorly extended 90° of the head being the optimal position with DET-RW of 2.13 ± 1.60 mm in the supine position, however, it is not realized in human beings. Moreover, the OHP had no obvious relevance corresponding to age following intratympanic injections. Conclusion: Our study suggested that OHP after intratympanic injections treatment consists of supine position, along with a slight pronation and posterior extension.

Risks for Enlisted Navy Divers Compared to Other Enlisted Sailors: An Examination of Illnesses That May Be Associated With Exposure to Contaminated Water Diving.

Illnesses among Navy divers degrade readiness, decrease manpower levels, and increase costs for medical care. Prior research has shown that Navy divers have high rates of the types of illnesses that might be because of diving in contaminated water. The objectives of this study were to examine medical records of U.S. Navy Sailors from 2016 to 2022 and determine if divers have higher incidence rates of health conditions that might be associated with contaminated water diving compared to non-divers. For this retrospective cohort study, we used data from the Defense Medical Epidemiology Database (DMED). The DMED is operated by the Armed Forces Health Surveillance Division and uses data from the Defense Manpower Data Center to classify occupations. The DMED provides free online access to a de-identified subset of data contained within the Defense Medical Surveillance System.The population was U.S. Navy enlisted males, aged 25 to 29 years. Divers were compared to non-divers using 8 selected diagnoses that may reasonably be associated with diving in contaminated water. During the study period, the database contained a total of 5,474 diver and 827,406 non-diver person-years. Of the 8 diagnoses, the ones with the largest number of cases for divers were upper respiratory infections with 128 and ear disorders with 62. The relative risks (RRs) for divers compared to non-divers were higher for otitis externa (RR = 1.44; confidence interval = 1.03, 2.01) and for ear disorders (RR = 1.15; confidence interval = 0.89, 1.47); for the other 6 diagnoses, the divers had lower rates than the non-divers. The high RRs found for otitis externa and ear disorders support the need to devote resources to better understand the reasons for these higher risks and to develop, test, and implement targeted risk-reduction strategies. Future studies should attempt to link verified contaminated water exposures with adverse health outcomes and calculate risks based on criteria such as age and dive factors.

A review of Meniere’s disease – reflection of published MRI, ECochG and newer otoconial theory from Aotearoa New Zealand

ABSTRACT Vertigo, or the symptom of an hallucination of motion, is usually caused by disorders of the inner ear. Buried in the bone of the otic capsule, the inner ear is the most difficult human sensory organ to image and investigate. As an inner ear disorder, Meniere’s disease (MD) is characterised as recurrent vertiginous attacks, fluctuating hearing loss which can be progressive, tinnitus and aural fullness. Post-mortem studies, and now MRI inner ear imaging, show an excess of endolymph or endolymphatic hydrops (ELH) which has been assumed to usually commence in the cochlea. However, the cause of the initial hydrops is still debated. This paper reflects on the research published in Ōtautahi Christchurch, Aotearoa New Zealand. There is evidence from post-mortem studies, electrophysiological test, and some inner ear imaging that endolymphatic obstruction from clumps of detached saccular otoconia may be a cause of MD.

A real-world pharmacovigilance study of FDA adverse event reporting system events for atogepant

ABSTRACT Background Atogepant, an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist, is being investigated for the treatment of migraine. Methods We collected data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Four algorithms (ROR, PRR, BCPNN, and EBGM) were used as measures to detect signals of atogepant-associated adverse events (AEs) in real-world data. Result Of the 3,552,072 reports, 2876 expressly stated the use of atogepant. Women accounted for the majority of adverse events (AEs), with a notable age concentration of 45–65 years. The percentage of reported adverse events was the highest in the United States. Significant system organ categories (SOC) included nervous system disorders, gastrointestinal disorders, nervous system disorders, surgical and medical procedures, ear and labyrinth disorders. Notably, preferred terms (PTs) related to atogepant include migraine, constipation, nausea, vertigo, somnolence, decreased appetite, dizziness and fatigue. Unexpected adverse events such as abnormal dreams, self-injurious ideation, brain fog, tension headache, nightmare, brain neoplasm, feeling abnormal, euphoric mood, hyperacusis and post concussion syndrome were also identified. Conclusions The present investigation has detected new and unexpected signals of atogepant-related adverse drug reactions (ADRs). In order to confirm these solve safety issues that were previously overlooked, more research is necessary.

Generation of four induced pluripotent stem cell lines (KEIUi004-A, KEIUi005-A, KEIUi006-A, and KEIUi007-A) from patients with sensorineural hearing loss with mutation in EYA4 gene

Disease-related cells differentiated from patient-derived iPSCs are useful for elucidating the pathophysiological mechanisms underlying these diseases. In this study, four iPSC lines were established from independent patients with sensorineural hearing loss and a mutation in EYA4. These iPSCs showed pluripotency, the capacity to differentiate into three germ layers, and normal karyotypes, suggesting that these lines are useful for the pathological study of sensorineural hearing loss and drug screening for ear disorders.

The Subjective Visual Vertical and Electrocochleography Tests in Individuals with Meniere's Disease.

Meniere's disease is an inner ear disorder not associated with central brain structure involvement. Although the ECochG test has been commonly used to diagnose Meniere's disease recently, it has not demonstrated high sensitivity. Therefore, it is recommended that other complementary tests alongside the ECochG test be used to diagnose Meniere's disease. The SVV test has gained popularity recently for this reason, and in this study, it was decided to use the SVV test in both static and dynamic modes, along with the ECochG test, as a tool for diagnosing Meniere's disease and evaluating its diagnostic features. The study was conducted on 53 patients with confirmed unilateral Meniere's disease and a normal group. Means were calculated with a 95% confidence interval for the groups, and the corresponding graphs were plotted. Independent t-tests were used to examine the difference in SVV results between the normal and Meniere's groups. The ROC curve was then used to determine the cutoff point and calculate. After investigating the cutoff point for the three SVV conditions (tilted towards the lesion), a cutoff point of 2.1 degrees with a sensitivity and specificity of approximately 0.7 was identified as the best condition for distinguishing the Meniere's group from the healthy group. Finally, based on the findings, it can be concluded that the SVV test has relatively low sensitivity for diagnosing Meniere's disease. Therefore, more than relying solely on its results to identify Meniere's disease is required, and it is suggested that other measures alongside the ECochG and SVV tests be included in future studies for further investigation.