Anteriorly Tilted Coronal CT of Paranasal Sinuses for Endoscopic Sinus Surgery.

Conventional coronal CT scans of paranasal sinuses, aligned perpendicularly to the nasal floor, often deviate significantly from the endoscopic view during sinus surgery. This discrepancy complicates the interpretation of anatomical structures. In response, we propose the utilization of anteriorly tilted coronal CT slices to enhance anatomical understanding. These slices align more closely with the endoscopic view, fostering an intuitive grasp of paranasal sinus anatomy. This study aims to quantify the tilt of the endoscope to the nasal floor during endoscopic sinus surgery. To figure out the tilt of the endoscopically true coronal slices, we calculated the tilt of the endoscope to the nasal floor in the operative setting by taking pictures of the operation and measuring the image and sagittal CT. Fourteen patients (25 sides of paranasal sinuses) were analyzed. Endoscope tilts to the nasal floor were measured at different anatomical landmarks: 16.2 ± 9.7 degrees (lower edge of ground lamella), 29.8 ± 7.9 degrees (central ground lamella), 62.3 ± 10.1 degrees (most superior part), and 25.6 ± 7.0 degrees (optic canal). In conclusion, we showed the actual tilt of the endoscope to the nasal floor during endoscopic sinus surgery. A 30-degree anteriorly tilted coronal scan for frontal recess and sphenoid sinus is more intuitive than a traditional coronal scan, which helps surgeons understand the complex sinus anatomy.

Epidemiology of postoperative bleeding after endoscopic nasal and sinus surgery and factors associated with bleeding.

PURPOSE: Endoscopic nasal and sinus surgery is a surgical procedure frequently performed by otolaryngologists. Postoperative bleeding is detrimental to both healthcare providers and patients. We investigated the epidemiology of postoperative bleeding during endoscopic nasal and sinus surgery and explored possible bleeding triggers. METHODS: We evaluated the patients who underwent endoscopic nasal and sinus surgery. Data regarding the age, sex, presence of hypertension, and abnormal coagulability, including oral anticoagulants, diagnoses, operative procedures, intraoperative use of drills and blood loss, and postoperative antimicrobial administration of eligible patients, were extracted from medical records and retrospectively reviewed. RESULTS: One hundred and eighty-six patients underwent endoscopic nasal or sinus surgery during the study period, and postoperative bleeding occurred in 9 patients (4.8%). Posterior nasal neurotomy (PNN) was the procedure most likely to cause postoperative bleeding (4 surgeries, 13.3%). Postoperative antimicrobial administration significantly reduced the incidence of postoperative bleeding (p = 0.04). CONCLUSIONS: Postoperative bleeding requiring intervention occurs in 4.8% of cases, and PNN is associated with a high risk of postoperative bleeding. Wound infection is a potential cause of postoperative bleeding, and antimicrobial administration should be considered in addition to local treatment.

Propriety of various examinations for subjective symptoms of olfactory disorders.

PURPOSE: In Japan, two types of tests for diagnosing olfactory disorders, T and T (T&T) olfactometry and intravenous olfactory tests, are covered by insurance and performed on patients with olfactory disorders. This study examined the validity of these olfactory tests and whether psychophysical or morphological tests are more helpful in evaluating olfactory disorders. METHODS: We evaluated patients who visited our department and underwent two types of olfaction tests and sinus computed tomography (CT). Data regarding the age, sex, peripheral blood eosinophil percentage, presence of bronchial asthma, diagnoses, olfactory symptom score, results of the two olfactory tests, and CT findings in eligible patients were extracted from medical records and retrospectively reviewed. RESULTS: One hundred and sixty-three patients underwent all tests during the study period. The results of the T&T olfactometry and intravenous olfactory tests were significantly correlated. However, only the results of T&T olfactometry and olfactory cleft opacification on CT were statistically significant predictors of the olfactory symptom scores. CONCLUSION: T&T olfactometry and CT evaluations of olfactory cleft opacification helped evaluate olfactory dysfunction. It is important to note that intravenous olfactory tests are best performed with careful control and not blindly to assess olfactory disorders.

Anatomy and function of the lymphatic vessels in the parietal pleura and their plasticity under inflammation in mice.

Inflammatory pleuritis often causes pleural effusions, which are drained through lymphatic vessels (lymphatics) in the parietal pleura. The distribution of button- and zipper-like endothelial junctions can identify the subtypes of lymphatics, the initial, pre-collecting, and collecting lymphatics. Vascular endothelial growth factor receptor (VEGFR)-3 and its ligands VEGF-C/D are crucial lymphangiogenic factors. Currently, in the pleura covering the chest walls, the anatomy of the lymphatics and connecting networks of blood vessels are incompletely understood. Moreover, their pathological and functional plasticity under inflammation and the effects of VEGFR inhibition are unclear. This study aimed to learn the above-unanswered questions and immunostained mouse chest walls as whole-mount specimens. Confocal microscopic images and their 3-dimensional reconstruction analyzed the vasculatures. Repeated intra-pleural cavity lipopolysaccharide challenge induced pleuritis, which was also treated with VEGFR inhibition. Levels of vascular-related factors were evaluated by quantitative real-time polymerase chain reaction. We observed the initial lymphatics in the intercostals, collecting lymphatics under the ribs, and pre-collecting lymphatics connecting both. Arteries branched into capillaries and gathered into veins from the cranial to the caudal side. Lymphatics and blood vessels were in different layers with an adjacent distribution of the lymphatic layer to the pleural cavity. Inflammatory pleuritis elevated expression levels of VEGF-C/D and angiopoietin-2, induced lymphangiogenesis and blood vessel remodeling, and disorganized the lymphatic structures and subtypes. The disorganized lymphatics showed large sheet-like structures with many branches and holes inside. Such lymphatics were abundant in zipper-like endothelial junctions with some button-like junctions. The blood vessels were tortuous and had various diameters and complex networks. Stratified layers of lymphatics and blood vessels were disorganized, with impaired drainage function. VEGFR inhibition partially maintained their structures and drainage function. These findings demonstrate anatomy and pathological changes of the vasculatures in the parietal pleura and their potential as a novel therapeutic target.

Anatomy and pathology of lymphatic vessels under physiological and inflammatory conditions in the mouse diaphragm.

The lymphatic vessels in the parietal pleura drain fluids. Impaired drainage function and excessive fluid entry in the pleural cavity accumulate effusion. The rat diaphragmatic lymphatics drain fluids from the pleura to the muscle layer. Lymphatic subtypes are characterized by the major distribution of discontinuous button-like endothelial junctions (buttons) in initial lymphatics and continuous zipper-like junctions (zippers) in the collecting lymphatics. Inflammation replaced buttons with zippers in tracheal lymphatics. In the mouse diaphragm, the structural relationship between the lymphatics and blood vessels, the presence of lymphatics in the muscle layer, and the distributions of initial and collecting lymphatics are unclear. Moreover, the endothelial junctional alterations and effects of vascular endothelial growth factor receptor (VEGFR) inhibition under pleural inflammation are unclear. We subjected the whole-mount mouse diaphragms to immunohistochemistry. The lymphatics and blood vessels were distributed in different layers of the pleural membrane. Major lymphatic subtypes were initial lymphatics in the pleura and collecting lymphatics in the muscle layer. Chronic pleural inflammation disorganized the stratified layers of the lymphatics and blood vessels and replaced buttons with zippers in the pleural lymphatics, which impaired drainage function. VEGFR inhibition under inflammation maintained the vascular structures and drainage function. In addition, VEGFR inhibition maintained the lymphatic endothelial junctions and reduced the blood vessel permeability under inflammation. These findings may provide new targets for managing pleural effusions caused by inflammation, such as pleuritis and empyema, which are common pneumonia comorbidities.

Effects of zinc deficiency on the regeneration of olfactory epithelium in mice.

The olfactory epithelium can regenerate after damage; however, the regeneration process is affected by various factors, such as viral infections, head trauma, and medications. Zinc is an essential trace element that has important roles in organ development, growth, and maturation. Zinc also helps regulate neurotransmission in the brain; nevertheless, its relationship with olfactory epithelium regeneration remains unclear. Therefore, we used a severe zinc deficiency mouse model to investigate the effects of zinc deficiency on olfactory epithelium regeneration. Male wild-type C57BL/6 mice were divided into zinc-deficient and control diet groups at the age of 4 weeks, and methimazole was administered at the age of 8 weeks to induce severe olfactory epithelium damage. We evaluated the olfactory epithelium before and 7, 14, and 28 days after methimazole administration by histologically analyzing paraffin sections. RNA sequencing was also performed at the age of 8 weeks before methimazole administration to examine changes in gene expression caused by zinc deficiency. In the zinc-deficient group, the regenerated olfactory epithelium thickness was decreased at all time points, and the numbers of Ki-67-positive, GAP43-positive, and olfactory marker protein-positive cells (i.e. proliferating cells, immature olfactory neurons, and mature olfactory neurons, respectively) failed to increase at some time points. Additionally, RNA sequencing revealed several changes in gene expression, such as a decrease in the expression of extracellular matrix-related genes and an increase in that of inflammatory response-related genes, in the zinc-deficient group. Therefore, zinc deficiency delays olfactory epithelium regeneration after damage in mice.

Familial Paget's disease of bone with ocular manifestations and a novel TNFRSF11A duplication variant (72dup27).

INTRODUCTION: Paget's disease of bone (PDB) is a skeletal disorder characterized by disorganized bone remodeling due to abnormal osteoclasts. Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) gene encodes the receptor activator of nuclear factor kappa B (RANK), which has a critical role in osteoclast function. There are five types of rare PDB and related osteolytic disorders due to TNFRSF11A tandem duplication variants so far, including familial expansile osteolysis (84dup18), expansile skeletal hyperphosphatasia (84dup15), early-onset familial PDB (77dup27), juvenile PDB (87dup15), and panostotic expansile bone disease (90dup12). MATERIALS AND METHODS: We reviewed a Japanese family with PDB, and performed whole-genome sequencing to identify a causative variant. RESULTS: This family had bone symptoms, hyperphosphatasia, hearing loss, tooth loss, and ocular manifestations such as angioid streaks or early-onset glaucoma. We identified a novel duplication variant of TNFRSF11A (72dup27). Angioid streaks were recognized in Juvenile Paget's disease due to loss-of-function variants in the gene TNFRSF11B, and thought to be specific for this disease. However, the novel recognition of angioid streaks in our family raised the possibility of occurrence even in bone disorders due to TNFRSF11A duplication variants and the association of RANKL-RANK signal pathway as the pathogenesis. Glaucoma has conversely not been reported in any case of Paget's disease. It is not certain whether glaucoma is coincidental or specific for PDB with 72dup27. CONCLUSION: Our new findings might suggest a broad spectrum of phenotypes in bone disorders with TNFRSF11A duplication variants.

The Transition of Pediatric Tracheobronchial Foreign Body Cases in the Past 36 Years: A Retrospective Single-Center Study in Japan.

Tracheobronchial foreign bodies (TFBs) are pediatric airway emergencies frequently seen. We aimed to examine the changes in the clinical characteristics of pediatric TFB patients in a single institution within the past 36 years. We retrospectively reviewed the data of 85 patients aged 0-10 years with TFBs lodged in the trachea or bronchus admitted at the Department of Otolaryngology-Head and Neck Surgery at Tohoku University Hospital between 1986 and 2021. We also compared the characteristics, diagnostic methods, and treatments of the previous 64 cases (1986-2005) with those of the recent 21 cases (2006-2021). The number of TFB patients decreased later in this study (3.2 vs. 1.3 patients per year). The proportion of TFB patients aged > 3 years was significantly higher in the later period (6.3% vs. 23.8%, p = 0.038). Peanut was the most common cause of TFBs in both periods, and the overall incidence of peanut aspiration significantly decreased in the later period (68.8% vs. 38.1%, p = 0.019). No patient had an undetected TFB for more than 1 month after the onset of symptoms in the later period. Foreign body extraction using rigid bronchoscopy was performed in all patients earlier, whereas flexible bronchoscopy was used in 14.3% later. Our study revealed a recent trend in the clinical characteristics of pediatric TFB patients in a single institution in Northeast Japan. The prevention and treatment of pediatric TFBs should be considered following the recent trends.

Effects of Ndufs4 Deletion on Hearing after Various Acoustic Exposures.

Mitochondrial dysfunction can cause cochlear dysfunction and accelerate noise-induced hearing loss (NIHL). NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and has a role in the assembly and stabilization of complex I. However, the involvement of Ndufs4 in the pathogenesis of NIHL has not been reported. The aim of this study was to evaluate whether Ndufs4 deletion causes vulnerability to noise exposures. The wild-type (WT) and Ndufs4 knockout (KO) mice with C57BL/6J genetic background were used. Cochlear histology and hearing thresholds were assessed after noise exposure at 100 or 86 dB sound pressure level (SPL). Immunostaining showed the widespread expression of Ndufs4 in the cochlea. After noise exposure at 100 dB SPL, auditory brainstem response (ABR) threshold shifts at 4 kHz in Ndufs4 KO mice were significantly higher than that in WT mice. After noise exposure at 86 dB SPL, ABR threshold shifts, wave 1 amplitudes, and the number of synapses in the inner hair cells were not significantly different. RNA sequencing revealed the decreased expression of energy generation-related genes inNdufs4 KO mice. Ndufs4 deficiency accelerates permanent low-frequency threshold shifts after moderate noise exposure.

Immunohistochemical Localization of D-ß-Aspartic Acid and Periostin in Vocal Fold Polyps.

Long-term voice abuse or sudden vocal fold microvascular disruption may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and also in various otolaryngological diseases. D-ß-aspartic acid is the major isomer of D-aspartic acid found in elderly tissue. In this study we investigated the expression and the role of D-ß-aspartic acid and periostin in the formation of vocal fold polyps. The expression patterns of D-ß-aspartic acid and periostin in 36 surgical specimens of vocal fold polyps from 36 patients were investigated immunohistochemically. In the epithelium of vocal polyps, D-ß-aspartic acid was expressed in all cases. Expression of D-ß-aspartic acid was detected in 25 samples obtained from patients with vocal fold polyps stroma. Expression of periostin was detected in 28 samples obtained from patients with vocal fold polyps. Two patterns of D-ß-aspartic acid expression were observed in vocal fold polyps stroma: positive type and negative type. The following four patterns of periostin expression were observed in vocal fold polyps: negative type, superficial type, infiltrative type, and diffuse type. An association was observed between D-ß-aspartic acid expression patterns and periostin expression patterns. From these findings we speculate that periostin and D-ß-aspartic acid participate in certain pathological changes in vocal fold polyps, such as extracellular matrix accumulation, local fibrosis, and the formation and development of vocal fold polyps.

Videofluoroscopic Dysphagia Scale as an Additional Indicator of Gastrostomy in Patients with Amyotrophic Lateral Sclerosis with Dysphagia.

Pseudobulbar palsy and bulbar palsy cause dysphagia in patients with amyotrophic lateral sclerosis (ALS). Dysphagia in patients with ALS not only increases the risk of aspiration and pneumonia but also leads to malnutrition and weight loss, which are poor prognostic factors. Gastrostomy is the preferred route of feeding and nutritional support in patients with dysphagia. However, there are no established standards to determine the ideal timing of gastrostomy for patients with ALS. Therefore, we used the videofluoroscopic dysphagia scale (VDS), which objectively quantifies swallowing function, in videofluoroscopic swallowing study (VFSS) to investigate whether this scale at diagnosis can be a useful predictor for the timing of gastrostomy. We retrospectively evaluated 22 patients with ALS who were diagnosed at our hospital. We assessed the VDS scores in all patients within 3 months of diagnosis. A decline in the ALS functional rating scale revised (ALSFRS-R) scores was used as an indicator of disease progression. As a result, we found that the VDS score of the pharyngeal phase and the total VDS score were significantly correlated with the ΔALSFRS-R scores. These scores were also associated with the existing indicators for the timing of gastrostomy, i.e., decreased body weight and percent-predicted forced vital capacity. We demonstrated the noninferiority of the VDS scores relative to the existing indicators. In addition, the VDS score of the pharyngeal phase was significantly correlated with the time from diagnosis to gastrostomy. The VDS score could estimate the timing of gastrostomy in patients with ALS with dysphagia at diagnosis.

Effects of Unilateral Vagotomy on LPS-Induced Aspiration Pneumonia in Mice.

Respiratory-related dysphagia and aspiration pneumonia can be attributed to multiple causes. However, reproduction of multiple factor-related respiratory distress and aspiration pneumonia in a single animal model is challenging. To validate animals with vagal nerve palsy as novel models for severe aspiration pneumonia associated with respiratory distress, we investigated the effects of unilateral vagotomy on the swallowing function and severity of pneumonia after forced aspiration in mice. Unilateral vagotomy was performed in C57BL6 male mice that subsequently underwent evaluation of swallowing function by videofluoroscopic swallow study (VFSS) and histological assessments for aspiration pneumonia induced by lipopolysaccharide (LPS). VFSS examinations demonstrated that unilateral vagotomy did not cause apparent aspiration in mice, but it resulted in a significant loss of body weight (BW) due to decreased oral intake. In addition, when aspiration pneumonia was induced by forced administration of LPS, significantly prolonged BW loss and severe infiltration of inflammatory cells associated with aspiration pneumonia were observed in the mice that underwent unilateral vagotomy. In conclusion, the vagotomized mice showed appropriate characteristics as a model of aspiration pneumonia caused by multiple factors, including the paralysis of vocal fold movement and respiratory distress. This model can help elucidate the pathogenesis of aspiration pneumonia and the treatment methods for the respiration-compromised model.

Expression of Periostin in Vocal Fold Polyps.

Long-term voice abuse or sudden vocal fold microvascular disruption may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and also in various otolaryngological diseases. The aim of this article was to investigate the expression and the role of periostin in the formation of vocal fold polyps. The expression patterns of periostin in 59 surgical specimens of vocal fold polyps from 54 patients were investigated immunohistochemically. Normal vocal fold mucosa specimens from 5 patients who had undergone total laryngectomy were used as the control group. Retrospective study with planned data collection was conducted at Tohoku Medical and Pharmaceutical University. Expression of periostin was detected in 43 (72.9%) samples and four patterns of periostin expression were observed in vocal fold polyps: negative type, superficial type, infiltrative type, and diffuse type. An association was observed between periostin expression patterns and the histological subtypes of vocal fold polyps. The infiltrative pattern of periostin expression was significantly dominant in vascular-hyaline types. Expression of transforming growth factor-ß (TGF-ß) was also detected in the vocal fold polyps. Our results confirmed that periostin might be involved in certain pathological changes in vocal fold polyps, such as extracellular matrix accumulation, local fibrosis, and formation and development of vocal fold polyps.

Loudness functions for patients with functional hearing loss.

OBJECTIVES: To compare the loudness functions (loudness ratings as a function of sound level) obtained from patients diagnosed as having functional hearing loss (FHL) with those for patients with sensorineural hearing loss (SNHL) and healthy volunteers. DESIGN: Loudness functions for a 1000 Hz tone for patients with FHL and SNHL were assessed based on the categorical loudness scaling method. The data were compared with control data obtained in our facilities. STUDY SAMPLE: 18 patients (33 ears) with FHL and 10 patients (19 ears) with SNHL. RESULTS: For patients with SNHL and healthy volunteers, loudness increased progressively with increasing sound level above the audiometric threshold, with no exceptions. However, for about 70% of the patients with FHL, a different type of loudness function was obtained; the thresholds determined from the loudness function, which were defined as the minimum sound levels at which loudness could be judged, were 10 dB or more lower than the audiometric threshold (>10 dB), and/or the loudness ratings were elevated for a sound at the audiometric threshold. CONCLUSIONS: The results support the hypothesis that patients with FHL often make threshold judgments based on a certain loudness.

Malignancies in Patients with IgG4-Related Diseases in Head and Neck Regions.

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized disease, characterized by high serum IgG4 concentrations and IgG4-producing plasma cell expansion with fibrotic or sclerotic changes in affected organs. Recent work has focused on the relationship between IgG4-RD and malignancies, but there is no report of malignancies associated with IgG4-RD in head and neck regions. The aim of this study was to analyze the clinicopathological characteristics of malignancies in patients with IgG4-RD in head and neck regions. We retrospectively analyzed 26 patients with IgG4-RD (12 men and 14 women aged 60.6 ± 11.6 years). The mean follow-up period was 26.6 months (from 12 to 96 months). These patients were divided into single-lesion group (n = 12) with IgG4-RD only in head and neck regions and multiple-lesion group (n = 14) with IgG4-RD in other regions. There was no significant difference in serum IgG4 concentrations between the single-lesion group (459.4 ± 336.4 mg/dL) and the multiple-lesion group (908.0 ± 739.2 mg/dL) (P = 0.07), whereas the IgG4/IgG ratio was significantly lower in the single-lesion group (22.8 ± 11.0%; n = 11) compared with the multiple-lesion group (31.7 ± 15.0%; n = 11, P = 0.02). Among the 26 patients, two patients (7.7%), both in the multiple-lesion group, developed life-threatening malignancies (salivary duct carcinoma in the submandibular gland and lymphoma in the orbital tissue). All physicians need to keep in mind the possible coexistence of malignancies in patients with IgG4-RD with high IgG4/IgG ratio and multiple lesions at the time of diagnosis.

Computed tomography findings of the bony portion of the Eustachian tube with or without patulous Eustachian tube patients.

To investigate the bony segment of the Eustachian tube (ET) using sitting 3D-computed tomography (CT) scans in Patulous Eustachian tube (PET) patients. A retrospective survey of medical records in Sen-En Hospital identified 43 patients and 43 ears with PET and 30 patients and 30 ears with sensorineural hearing loss or vertigo patients as the control. Diagnosis of PET was based on the Proposal on PET Diagnosis Criteria announced by the Otological Society of Japan in 2012. Patients were examined by cone beam CT (Accuitomo; Morita, Kyoto, Japan) in the sitting position. The heights and widths at the tympanic orifice, the middle portion, and isthmus were measured. The lumen of the bony portion was divided into three shapes: peritubal cells (PTC) poor type, PTC good with prominence type, and PTC good without prominence type. In PET patients and the control group, the PTC poor type was identified in nine (21%) and seven ears (23%), PTC good with prominence type was identified in 14 (33%) and seven ears (23%), and PTC good without prominence type was identified in 19 (45%) and 16 ears (53%), respectively. There was no significant difference between the two groups. At the tympanic orifice portion, the average height of the ET lumen was 5.99 ± 1.29 and 6.04 ± 1.41 mm, and the average width of the ET lumen was 2.81 ± 0.82 and 2.78 ± 0.57 mm in the PET and control groups, respectively. The PTC good with prominence type had a significantly smaller width in the tympanic orifice portion than the other types in each group (p < 0.05). The width of the ET lumen in the tympanic orifice averaged 2.87 ± 0.38 and 3.10 ± 0.45 mm in the PTC poor type, 2.23 ± 0.70 and 2.22 ± 0.48 mm in the PTC good with prominence type, and 3.21 ± 0.87 and 2.90 ± 0.50 mm in the PTC good without prominence type in the PET and control groups, respectively. The shape of the bony portion of the ET in PET patients is almost identical to that of controls. Thus, the bony portion has no influence on the pathology of patulous Eustachian tube syndrome. The PTC good with prominence type has a significantly smaller tympanic orifice portion width than the other types. Preoperative evaluation of the bony portion of the ET could provide useful information for ET surgeons.

Effect of intratympanic application of efinaconazole 10 % solution in the guinea pig.

Efinaconazole 10 % solution is a new triazole antifungal agent developed for the topical treatment of fungal infections of the nails. The current study examined the effect of intratympanic application of efinaconazole 10 % solution in the guinea pig ear. Sixteen male Hartley guinea pigs (weight 501-620 g) were divided into 3 groups to be treated with efinaconazole 10 % solution, gentamicin (50 mg/mL), or saline solution. Topical solutions of 0.2 mL were applied through a small hole made at the tympanic bulla once daily for 7 consecutive days. Post-intervention auditory brainstem responses were obtained 7 days after the last treatment. The extent of middle ear damage and hair cell loss was investigated. The efinaconazole- and gentamicin-treated groups showed severe deterioration in auditory brainstem response threshold. Middle ear examination revealed extensive changes in the efinaconazole-treated group and medium changes in the gentamicin-treated group. Hair cells were preserved in the efinaconazole- and saline-treated groups, but severe damage was seen in the gentamicin group. In conclusion, efinaconazole 10 % solution applied intratympanically to the guinea pig middle ear caused significant middle ear inflammation and hearing impairment.