Assessing the Efficacy of Tragal Pumping in a Novel Tympanostomy Tube-Rat Model.

Objective: Tragal pumping (TP) is a practice of pushing on the tragus to raise pressure within the external auditory canal and is a commonly recommended adjunctive maneuver believed to facilitate the introduction of ototopical medications into the middle ear cavity via a tympanostomy tube. To investigate the efficacy of TP in the penetration of eardrops into the middle ear cavity via tympanostomy tube, we established the novel tympanostomy tube-rat model. We investigated the histology of the middle ear to determine the efficacy in moving fluid into the middle ear. Study Design: Prospective controlled animal study. Setting: Animal laboratory in a university hospital. Methods: Ten rats were recruited, and a tympanostomy tube insertion and green dye eardrops into outer ears were performed on bilateral ears. TP was performed only on 1 ear and was not applied on the other ear in each rat. Green dye in a middle ear cavity in hematoxylin and eosin-stained temporal bone sections was evaluated by blinded experts in microscopic anatomy (staining grade) and by using Image J software (staining level). The results of these 2 methods were statistically validated. Results: The staining grade (P < .001) and the staining level (P < .001) were significantly higher in the ears which we applied TP than in the control ears. The results of 2 methods were significantly and positively correlated (r = .898, P < .001). Conclusion: Our results showed that the TP accelerate the penetration of eardrops into the middle ear cavity in the tympanostomy tube-rat model.

Impact of Reduced Acidic Earwax pH and Earwax-Determinant Genotypes in Acquired Middle Ear Cholesteatoma.

OBJECTIVE: The development of acquired middle ear cholesteatoma is associated with a single nucleotide polymorphism, 538G>A, in the human adenosine triphosphate-binding cassette transporter C11 (ABCC11) gene, which is a determinant of the earwax morphotype, such as wet- and dry-type earwax; however, the mechanism underlying this association is unclear. We focused on the earwax pH and aimed to elucidate the mechanism between ABCC11 genotypes and acquired middle ear cholesteatoma. STUDY DESIGN: Prospective observational study. SETTING: Single-center, academic hospital. METHODS: We recruited 40 patients with acquired middle ear cholesteatoma who underwent surgery and 115 controls with no history of middle ear cholesteatoma. We assessed the earwax pH and ABCC11 genotypes in all participants. Clinical information was collected from the patients with cholesteatoma. RESULTS: The earwax pH was significantly less acidic in patients with cholesteatoma and those carrying wet earwax genotypes (ABCC11 538G/G or 538G/A) than in the controls and those carrying the dry earwax genotype (ABCC11 538A/A), respectively. Furthermore, earwax pH was significantly positively correlated with high preoperative cholesteatoma stages in the patients with cholesteatoma. CONCLUSION: Our results show that the less acidic earwax pH was significantly related to the development and progression of acquired middle ear cholesteatoma. The less acidic earwax pH may play an important role in the mechanism underlying the association between acquired middle ear cholesteatoma and the ABCC11 gene at site 538.

Clinical Approach to Dental Root Canal Filler-Induced Maxillary Sinus Fungal Mass Using Transnasal Endoscopy.

Accidentally extruded root canal filler within the sinuses may induce maxillary sinusitis with fungal mass. The authors describe 2 cases of gutta-percha-induced fungal masses in the left maxillary sinus of 2 women. The lesions were evaluated preoperatively using both computed tomography and magnetic resonance imaging, providing comprehensive insights into the condition. In one patient, the lesion was located such that it could be resected through the middle meatal antrostomy alone. However, the second patient presented with an anteroinferiorly situated lesion that necessitated not only a transnasal approach but also an endoscopic modified medial maxillectomy. Both patients recovered uneventfully after surgery. This case series is the first published report of 2 cases of gutta-percha-induced maxillary sinus fungal masses, with their imaging findings, successfully treated through different routes through transnasal endoscopic surgery. These reports highlight the need for a collaborative approach between dental practitioners and otolaryngologists. In addition to the patient's wishes, surgical interventions must consider the unique characteristics of each case and the potential for collaboration across different medical specialties.

Intravascular papillary endothelial hyperplasia of the maxillary sinus extending into the contralateral nasal cavity.

INTRODUCTION: Intravascular papillary endothelial hyperplasia (IPEH) predominantly occurs in the subcutaneous and dermal regions and rarely originates from the sinonasal mucosa. CASE PRESENTATION: We report on the case of a 58-year-old male patient who presented with progressive bilateral nasal obstruction, left-sided epiphora, and intermittent epistaxis. Computed tomography revealed a soft tissue opacity in the left maxillary sinus with intersinusoidal nasal wall demineralization, extending into the surrounding ethmoid cells and the right nasal cavity through a contralateral deviation of the nasal septum. Contrast-enhanced T1-weighted magnetic resonance imaging further confirmed these findings. The IPEH originating from the maxillary sinus extended into the contralateral nasal cavity, and it was successfully removed using an endoscopic endonasal approach, avoiding overly aggressive treatment. CONCLUSION: This case report highlights the diagnostic challenges of IPEH in the sinonasal region and the importance of considering IPEH as a differential diagnosis in patients presenting with nasal obstruction, epiphora, and intermittent epistaxis.

A Patient With Lobular Capillary Hemangioma Originating From the Inferior Turbinate Following Cauterization With Silver Nitrate.

Lobular capillary hemangiomas (LCH), which usually originate in the skin and mucous membranes of the oral cavity, are uncommon from the posterior portion of the inferior turbinate. Although the exact cause of LCH in the nasal cavity has not been elucidated, trauma, caused by factors such as intranasal packing and habitual nose-picking, has been reported as one of the causes. In addition, 2 cases of LCH caused by submucosal resection with powered instrumentation to the inferior turbinate have been reported, suggesting that various types of traumas to the nasal mucosa can cause LCH. The authors report the first case of LCH formation in the posterior portion of the inferior turbinate after cauterization with silver nitrate.

Cholesteatoma Surgery With a Dehiscent High Jugular Bulb Treated With Surgery Assisted With Underwater Endoscopy: A Case Report.

A dehiscent high jugular bulb would be a pitfall in middle ear surgery especially for cholesteatoma. We report a case of cholesteatoma attached to a dehiscent high jugular bulb successfully treated with surgery assisted with underwater endoscopy. To the best of our knowledge, no previous study has reported a case of cholesteatoma with dehiscent high jugular bulb treated with surgery assisted with underwater endoscopy. Owing to the risk of jugular bulb injury, underwater endoscopy is a good indication for middle ear cases with a dehiscent high jugular bulb to obtain a clear operative field and avoid an unexpected air embolism.

Creutzfeldt-Jakob disease with dizziness initially presenting to the otolaryngology department.

Creutzfeldt-Jakob disease is a fatal transmissible prion disease of the central nervous system. Dizziness as an initial manifestation of Creutzfeldt-Jakob disease is rare. However, patients with Creutzfeldt-Jakob disease and dizziness may initially visit the otolaryngology department, but this is uncommon. We report the case of a 56-year-old woman with Creutzfeldt-Jakob disease who initially presented with dizziness as an emergency patient to the otolaryngology department. Primary position upbeat nystagmus was identified using a charge-coupled device camera with infrared illumination. Electronystagmography revealed impaired smooth pursuit and diminished optokinetic nystagmus. Based on these findings, we immediately suspected an intracranial cause of dizziness and reached a presumptive diagnosis of sporadic Creutzfeldt-Jakob disease, thus preventing severe transmission. This case emphasizes that Creutzfeldt-Jakob disease should be included as a differential diagnosis for patients with dizziness and abnormal eye movements, such as primary position upbeat nystagmus, which might be caused by intracranial disease.

Upper and Lower Respiratory Mucous Membrane Plasmacytosis with a Cobblestone Appearance: a Case Report.

A 53-year-old woman with a recurrent sore throat, xerostomia, nasal obstruction, and nasal discharge came to our hospital. At the first visit, she did not have a fever, but a blood test showed an intense inflammatory response. She had oral mucosal erosion. She developed dyspnea 2 months later. Nasendoscopy, laryngoscopy, and bronchoscopy showed upper and lower respiratory mucosa cobblestone appearance. Microscopy of the nasal and pharyngeal mucosa biopsy found regular mononuclear inflammatory cell dense submucosal infiltrate, mainly plasma cells. A mucous membrane plasmacytosis diagnosis was made. Prednisolone 1 mg/kg/day rapidly improved bronchial symptoms and cobblestone appearance.

Subtotal Petrosectomy With Preservation of Chorda Tympani for Petrous Bone Cholesteatoma: Case Report.

A petrous bone cholesteatoma (PBC) is a rare epidermoid cyst of the petrous portion of the temporal bone. The main treatment is subtotal petrosectomy (SP), which generally involves sacrificing the chorda tympani. We report a case of extensive supralabyrinthine PBC in an elderly patient undergoing hemodialysis that was treated by SP with anatomical preservation of the chorda tympani. To the best of our knowledge, preservation of the chorda tympani during SP has not been previously reported. For maintenance of postoperative taste and appetite, preservation of the chorda tympani is a meaningful maneuver whenever possible.

Association Between Earwax-Determinant Genotypes and Acquired Middle Ear Cholesteatoma in a Japanese Population.

OBJECTIVE: A single-nucleotide polymorphism 538G>A in the human ABCC11 gene is a determinant of the earwax morphotype. ABCC11 538GG and GA correspond to wet earwax and 538AA to dry earwax. Despite a putative positive correlation between the frequency of the 538G allele and the prevalence of cholesteatoma, minimal clinical information is currently available. We aimed to evaluate this association between the ABCC11 genotypes and acquired middle ear cholesteatoma. STUDY DESIGN: Case-control study. SETTING: Single-center academic hospital. METHODS: We recruited 67 Japanese patients with acquired middle ear cholesteatoma (cholesteatoma group) and 100 Japanese controls with no history of middle ear cholesteatoma. We assessed the ABCC11 genotypes for all participants. Clinical information was collected from the cholesteatoma group. The genotype data of 104 Japanese people from the 1000 Genomes Project who represent the general population were used. RESULTS: The proportion of participants with ABCC11 538GG or GA was significantly higher in the cholesteatoma group than in the control group or general Japanese population (P < .001). The ABCC11 538G allele frequency was also significantly higher in the cholesteatoma group than in the control group or general Japanese population (P < .001). Multivariate logistic regression analyses revealed a significant association between the ABCC11 genotype and acquired middle ear cholesteatoma (odds ratio, 5.49; 95% CI, 2.61-11.5; P < .001). CONCLUSION: Our results suggest that the ABCC11 genotypes could be associated with the development of acquired middle ear cholesteatoma among Japanese people.

Combined underwater endoscopic and microscopic surgery for external auditory canal cholesteatoma: A case report.

Transcanal endoscopic ear surgery is a minimally invasive procedure that allows a clear visualization of the middle ear. Recently, indications for endoscopic surgery have been expanding. We performed combined underwater endoscopic and microscopic surgery for external auditory canal cholesteatoma, the computer tomography of which indicates the possibility of cholesteatoma not only in the canal wall but also in the mastoid. The 30° endoscope and underwater technique makes the surgical view clear, and we could remove the cholesteatoma without canalplasty. To the best of our knowledge, no case of external auditory canal cholesteatoma treated with underwater endoscopic and microscopic surgery has been previously reported. This case indicates that the procedure could be a good indication for external auditory canal cholesteatoma.

A Case of Aspiration Pneumonia Caused by Cerebrospinal Fluid Leaks Associated with Delayed Identification of Iatrogenic Skull Base Injury during Endoscopic Sinus Surgery.

Cerebrospinal fluid (CSF) leaks associated with endoscopic sinus surgery (ESS) are a rare complication affecting approximately 0.09% of patients. Although meningitis is a well-known complication of CSF leaks, the case we present is a rare and cautionary case of CSF leakage associated with ESS leading to aspiration pneumonia. A 43-year-old man with CSF leaks after ESS was referred to our hospital. After the operation, sometimes, he reported having a serous nasal discharge from the right side when he bent over, and he woke up choking on something every day. He also experienced headache, fever, fatigue, and cough. Interestingly, chest computed tomography (CT) showed a consolidation and ground-glass opacity in the posterior segments of the right upper lobes and superior segments of the bilateral lower lobes. These CT imaging findings were similar to those of aspiration pneumonia in bedridden patients who are always in a supine position. These findings suggest that CSF caused aspiration pneumonia. To the best of our knowledge, no case of aspiration pneumonia caused by CSF during endoscopic sinus surgery has been reported until now. If a patient with CSF leakage after ESS experiences fever, cough, or fatigue, physicians should consider aspiration pneumonia in addition to meningitis.

Multicenter Study of Congenital Middle Ear Anomalies. Report on 246 Ears.

OBJECTIVES/HYPOTHESIS: Congenital middle ear anomalies represent a relatively rare condition. This study aimed to describe the characteristics and the surgical outcomes for patients with middle ear anomalies. METHODS: A multicenter study was conducted of consecutive patients with congenital middle ear anomalies who underwent primary surgical treatment between January 2008 and December 2017. Demographics, surgical procedures, and audiometric data were registered into the institutional database. Hearing changes and postoperative air-bone gap (ABG) were evaluated 1 year after surgery. RESULTS: A total of 246 patients (246 ears) (median age: 14 years, range: 4-75 years old) were included in this study. Anomalies were subdivided using the Teunissen and Cremers classification: 53 ears (22%) were categorized as class I, comprising only stapes ankylosis; 35 ears (14%) as class II, having ossicular chain anomalies with stapes ankylosis; 139 ears (57%) as class III, having ossicular chain anomalies with a mobile stapes-footplate; and 19 ears (8%) as class IV, with aplasia of the oval window. Evaluation of hearing outcomes for 198 ears with more than 1 year of follow-up revealed that good postoperative ABG (≤20 dB) was achieved in 82% of class I, 68% of class II, 74% of class III, and 23% of class IV anomalies. The postoperative ABG in class IV was significantly worse than in class I (P < .001) or class III (P < .01). CONCLUSIONS: This study demonstrated that class III anomalies comprised the majority of middle ear anomalies and surgical outcomes for class IV anomalies are unfavorable. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2323-E2328, 2021.

A multicolor and ratiometric fluorescent sensing platform for metal ions based on arene-metal-ion contact.

Despite continuous and active development of fluorescent metal-ion probes, their molecular design for ratiometric detection is restricted by the limited choice of available sensing mechanisms. Here we present a multicolor and ratiometric fluorescent sensing platform for metal ions based on the interaction between the metal ion and the aromatic ring of a fluorophore (arene-metal-ion, AM, coordination). Our molecular design provided the probes possessing a 1,9-bis(2'-pyridyl)-2,5,8-triazanonane as a flexible metal ion binding unit attached to a tricyclic fluorophore. This architecture allows to sense various metal ions, such as Zn(II), Cu(II), Cd(II), Ag(I), and Hg(II) with emission red-shifts. We showed that this probe design is applicable to a series of tricyclic fluorophores, which allow ratiometric detection of the metal ions from the blue to the near-infrared wavelengths. X-ray crystallography and theoretical calculations indicate that the coordinated metal ion has van der Waals contact with the fluorophore, perturbing the dye's electronic structure and ring conformation to induce the emission red-shift. A set of the probes was useful for the differential sensing of eight metal ions in a one-pot single titration via principal component analysis. We also demonstrate that a xanthene fluorophore is applicable to the ratiometric imaging of metal ions under live-cell conditions.

Co-amorphous formation of piroxicam-citric acid to generate supersaturation and improve skin permeation.

The objective of this study was to prepare a co-amorphous formulation of piroxicam (PIR), a non-steroidal anti-inflammatory drug, and citric acid (CA), and evaluate its skin permeation ability. A spray-drying method was employed to prepare the co-amorphous formulation and its physical properties were characterized. X-ray powder diffraction and thermal analysis confirmed a homogeneous amorphous state, and the infrared spectra revealed intermolecular interactions between PIR and CA, suggesting formation of a co-amorphous formulation of PIR and CA. The PIR-CA co-amorphous formulation exhibited no crystallization for 60 days at 4/25/40°C with silica gel. The PIR-CA co-amorphous formulation increased the solubility of PIR in polyethylene glycol 400 compared with that of the pure drug, and physical mixture (PM) of PIR and CA, confirming a supersaturated state in the formulation. The PIR-CA co-amorphous formulation demonstrated higher skin permeation than PIR alone or PM of PIR and CA, and the flux value was consistent with the degree of saturation. Thus, the increase in the skin permeation of PIR from the PIR-CA co-amorphous formulation directly depended on the increased thermodynamic activity by supersaturation in the absence of interactions between the drug and co-former in the vehicle.

Ultrathin Electrolyte Membranes with PFSA-Vinylon Intermediate Layers for PEM Fuel Cells.

We prepared ultrathin PFSA/PFSA-vinylon/PFSA laminated electrolyte membranes (thickness = 10 µm) for fuel cells without using a reinforcing material. Nafion and Aquivion solutions were used as PFSA polymers. Vinylon was synthesized by formalizing polyvinyl alcohol. From the current-voltage measurements using ultrathin PFSA/PFSA-vinylon/PFSA membranes; the cell resistances are significantly lower than that using a 50 µm Nafion membrane. A high current density was obtained under both low- and high-humidity conditions. Ultrathin PFSA/PFSA-vinylon/PFSA laminated membranes will help to further improve the performance of PEMFCs.

"Passenger gene" problem in transgenic C57BL/6 mice used in hearing research.

Despite recent advances in genome engineering technologies, traditional transgenic mice generated on a mixed genetic background of C57BL/6 and 129/Sv mice remain widely used in age-related hearing loss (AHL) research, since C57BL/6 mice exhibit early onset and progression of AHL due to a mutation in cadherin 23-encoding gene (Cdh23753G>A). In these transgenic mice, backcrossing for more than 10 generations results in replacement of the donor background (129/Sv) with that of the recipient (C57BL/6), so that approximately 99.9% of genes are C57BL/6-derived and are considered congenic. However, the regions flanking the target gene may still be of 129/Sv origin, creating a so-called "passenger gene problem" where the normal 129/Sv-derived Cdh23753G allele can travel with the target gene. In this study, we investigated the role of fatty acid-binding protein 7 (Fabp7), which is important for cellular uptake and intracellular trafficking of fatty acids in the cochlea, using traditional Fabp7 knockout (KO) mice on the C57BL/6 background. We found that Fabp7 KO mice showed delayed AHL progression and milder cochlear degeneration. However, the genotype of the Cdh23 region flanking Fabp7 was still that of 129/Sv origin (Cdh23753GG). Our findings reveal the potential risk of contamination for traditional transgenic mice generated on the C57BL/6 background.

Efficient Protocol for Accurately Calculating 13C Chemical Shifts of Conformationally Flexible Natural Products: Scope, Assessment, and Limitations.

An efficient protocol for calculating 13C NMR chemical shifts for natural products with multiple degrees of conformational freedom is described. This involves a multistep procedure starting from molecular mechanics and ending with a large basis set density functional model to obtain accurate Boltzmann conformer weights, followed by empirically corrected density functional NMR calculations for the individual conformers. The accuracy of the protocol (average rms <4 ppm) was determined by application to ∼925 diverse natural products, the structures of which have been confirmed either by X-ray crystallography or independent synthesis. The protocol was then applied to ∼ 2275 natural products, the structures of which were elucidated mainly by NMR and MS data. Five to ten percent of the latter compounds exhibited rms errors significantly in excess of 4 ppm, suggesting possible structural or signal assignment errors. Both data sets are available from an online browser ( NMR.wavefun.com ). The procedure can be and has been fully automated and is practical using present-generation personal computers, requiring a few hours or days depending on the size of the molecule and number of accessible conformers.

12OHJA, 12OGlcJA, and JA-L-Val as airborne MeJA metabolites.

It has been reported that airborne methyl jasmonate (MeJA) was metabolized into jasmonic acid (JA) and jasmonoyl isoleucine (JA-L-Ile). In this report, jasmonoyl valine (JA-L-Val), 12-hydroxy JA (12OHJA), and 12-glucosyloxy JA (12OGlcJA) were identified as metabolites originating from airborne MeJA using tomato (Solanum lycopersicum). Furthermore, the preferable conversion of (-)-MeJA (natural form) into 12OHJA, 12OGlcJA, JA-L-Ile, and JA-L-Val was observed.