Diagnostic and Imaging Findings in Inflammatory Opacifications of the Middle Ear: A Review of the Literature.

Opacification in the middle ear and mastoid region can stem from a wide range of factors. In terms of diagnostic imaging, CT is the primary tool due to its exceptional spatial resolution, particularly for examining the temporal bone and ossicles. MRI complements this by offering detailed soft tissue lesion characterization and assessing involvement in the inner ear and cranial nerves. This study focuses on inflammatory causes of opacification in the middle ear and mastoid, with an emphasis on the utility of CT and MRI. This comprehensive review aimed to provide a practical framework for considering potential differential diagnoses.

Middle Ear Tophi: A Case Series of Two Unusual Lesions and a Report of Facial Weakness and Review of the Literature.

OBJECTIVE: Tophaceous lesions of the middle ear from calcium pyrophosphate deposition disease (CPPD, or pseudogout) and gout are infrequently reported. Recognizing its characteristic findings will allow clinicians to accurately narrow the differential diagnosis of bony-appearing middle ear lesions and improve management. PATIENTS: Two consecutive cases of tophaceous middle ear lesions presenting to a tertiary care center between January 2021 and December 2021. Neither with previous rheumatologic history. INTERVENTIONS: Surgical excision of tophaceous middle ear lesions. MAIN OUTCOME MEASURE: Improvements in facial weakness and conductive hearing loss. RESULTS: The first case was a 66-year-old gentleman with progressive conductive loss, ipsilateral progressive facial weakness over years, and an opaque, irregular-appearing tympanic membrane anterior to the malleus found to have CPPD on surgical pathology, with immediate postoperative improvement of facial function. The second was a 75-year-old gentleman with progressive conductive loss and similar appearing tympanic membrane as case 1, previously diagnosed with tympanosclerosis, found to have gout on surgical pathology. In both cases, the CT showed a heterogenous, bony-appearing lesion in the middle ear, and both tophaceous lesions were a of gritty, chalky consistency intraoperatively. CONCLUSION: Tophaceous lesions of the middle ear are rare but have similar findings. Notably, the tympanic membrane can appear opaque and irregular, and the CT demonstrates a radiopaque, heterogeneous appearance. Facial weakness is an unusual finding. Specimens of suspected tophi must be sent to pathology without formalin for accurate diagnosis.

Blue laser for the exclusive endoscopic transcanal approach to middle ear paraganglioma.

BACKGROUND: The management of glomus tympanicum tumours can be challenging. Blue laser coagulation may improve bleeding control thus facilitating an endoscopic transcanal excision. The objective of this presentation is to illustrate the authors' experience using this novel tool. METHODS: Case report of a patient that underwent exclusive endoscopic transcanal blue laser surgery of a class A2 glomus tympanicum tumour in a tertiary referral center. CONCLUSION: The present study provides evidence of the safety and efficacy of endoscopic blue laser surgery, for the minimally invasive treatment of early-stage glomus tympanicum tumours.

Oral and middle ear delivery of otitis media standard of care antibiotics, but not biofilm-targeted antibodies, alter chinchilla nasopharyngeal and fecal microbiomes.

Otitis media (OM) is one of the most globally pervasive pediatric conditions. Translocation of nasopharynx-resident opportunistic pathogens like nontypeable Haemophilus influenzae (NTHi) assimilates into polymicrobial middle ear biofilms, which promote OM pathogenesis and substantially diminish antibiotic efficacy. Oral or tympanostomy tube (TT)-delivered antibiotics remain the standard of care (SOC) despite consequences including secondary infection, dysbiosis, and antimicrobial resistance. Monoclonal antibodies (mAb) against two biofilm-associated structural proteins, NTHi-specific type IV pilus PilA (anti-rsPilA) and protective tip-region epitopes of NTHi integration host factor (anti-tip-chimer), were previously shown to disrupt biofilms and restore antibiotic sensitivity in vitro. However, the additional criterion for clinical relevance includes the absence of consequential microbiome alterations. Here, nine chinchilla cohorts (n = 3/cohort) without disease were established to evaluate whether TT delivery of mAbs disrupted nasopharyngeal or fecal microbiomes relative to SOC-OM antibiotics. Cohort treatments included a 7d regimen of oral amoxicillin-clavulanate (AC) or 2d regimen of TT-delivered mAb, AC, Trimethoprim-sulfamethoxazole (TS), ofloxacin, or saline. Fecal and nasopharyngeal lavage (NPL) samples were collected before and several days post treatment (DPT) for 16S sequencing. While antibiotic-treated cohorts displayed beta-diversity shifts (PERMANOVA, P < 0.05) and reductions in alpha diversity (q < 0.20) relative to baseline, mAb antibodies failed to affect diversity, indicating maintenance of a eubiotic state. Taxonomic and longitudinal analyses showed blooms in opportunistic pathogens (ANCOM) and greater magnitudes of compositional change (P < 0.05) following broad-spectrum antibiotic but not mAb treatments. Collectively, results showed broad-spectrum antibiotics induced significant fecal and nasopharyngeal microbiome disruption regardless of delivery route. Excitingly, biofilm-targeting antibodies had little effect on fecal and nasopharyngeal microbiomes.

[Specialist consensus on endoscopic surgery of the middle ear mastoid].

This article discusses otoscopic middle ear mastoid surgery from multiple perspectives. Firstly, it discusses the indications and contraindications for surgery from the nature of the lesion and the imaging manifestations; secondly, it recommends the applicable equipment and describes the surgical approach in detail; finally, it summarizes the principles of the management of the operative cavity of the mastoid process in the middle ear from the perspectives of function and reconstruction. The purpose of this article is to illustrate otoscopic middle ear mastoid surgery with the aim of providing reference or guidance for performing related surgeries.

Non-rigid point cloud registration for middle ear diagnostics with endoscopic optical coherence tomography.

PURPOSE: Middle ear infection is the most prevalent inflammatory disease, especially among the pediatric population. Current diagnostic methods are subjective and depend on visual cues from an otoscope, which is limited for otologists to identify pathology. To address this shortcoming, endoscopic optical coherence tomography (OCT) provides both morphological and functional in vivo measurements of the middle ear. However, due to the shadow of prior structures, interpretation of OCT images is challenging and time-consuming. To facilitate fast diagnosis and measurement, improvement in the readability of OCT data is achieved by merging morphological knowledge from ex vivo middle ear models with OCT volumetric data, so that OCT applications can be further promoted in daily clinical settings. METHODS: We propose C2P-Net: a two-staged non-rigid registration pipeline for complete to partial point clouds, which are sampled from ex vivo and in vivo OCT models, respectively. To overcome the lack of labeled training data, a fast and effective generation pipeline in Blender3D is designed to simulate middle ear shapes and extract in vivo noisy and partial point clouds. RESULTS: We evaluate the performance of C2P-Net through experiments on both synthetic and real OCT datasets. The results demonstrate that C2P-Net is generalized to unseen middle ear point clouds and capable of handling realistic noise and incompleteness in synthetic and real OCT data. CONCLUSIONS: In this work, we aim to enable diagnosis of middle ear structures with the assistance of OCT images. We propose C2P-Net: a two-staged non-rigid registration pipeline for point clouds to support the interpretation of in vivo noisy and partial OCT images for the first time. Code is available at: https://gitlab.com/nct_tso_public/c2p-net.

Experience in the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma.

OBJECTIVE: To discuss the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma. METHODS: We retrospectively analyzed all cases of sigmoid sinus thrombophlebitis caused by middle ear cholesteatoma over a period of 7 years. 7 male and 2 female patients, ranging in age from 9 to 66 years, were diagnosed with sigmoid sinus thrombophlebitis by clinical presentation and radiological examination. By executing a modified mastoidectomy and tympanoplasty (canal wall-down tympanoplasty) to entirely remove the cholesteatoma-like mastoid epithelium, all patients were effectively treated surgically without opening the sigmoid sinus. All patients were treated with broad-spectrum antibiotics, but no anticoagulants were used. RESULTS: 9 patients had otogenic symptoms such as ear pus, tympanic membrane perforation, and hearing loss. In the initial stage of the surgery, modified mastoidectomy and tympanoplasty were performed on 8 of the 9 patients. 1 patient with a brain abscess underwent puncturing (drainage of the abscess) to relieve cranial pressure, and 4 months later, a modified mastoidectomy and tympanoplasty were carried out. Following surgery and medication, the clinical symptoms of every patient improved. After the follow-up of 6 months to 7 years, 3 patients were re-examined for MRV and showed partial sigmoid sinus recovery with recanalization. 4 months following middle ear surgery, the extent of a patient's brain abscess lesions was significantly reduced. 1 patient experienced facial paralysis after surgery and recovered in 3 months. None of the patients had a secondary illness, an infection, or an abscess in a distant organ. CONCLUSION: The key to a better prognosis is an adequate course of perioperative antibiotic medication coupled with surgical treatment. A stable sigmoid sinus thrombus can remain for a long time after middle ear lesions have been removed, and it is less likely to cause infection and abscesses in the distant organs. The restoration of middle ear ventilation is facilitated by tympanoplasty. It is important to work more closely with multidisciplinary teams such as neurology and neurosurgery when deciding whether to perform lateral sinusotomies to remove thrombus or whether to administer anticoagulation.

[FGF23 tumor induced osteomalacia with localization of neoplasm in the tympanic cavity]. / FRF23-indutsirovannaya osteomalyatsiya opukholevogo geneza s lokalizatsiei novoobrazovaniya v barabannoi polosti.

Tumor induced osteomalacia is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients complain of progressive bone pain, muscle weakness and brittle fractures. Delayed diagnosis of osteomalacia caused by a tumor is often found in clinical practice. When verifying the exact localization of the neoplasm, radical removal within healthy tissues is recommended. The article considers a clinical example of FGF23 tumor induced osteomalacia with localization of neoplasm in the tympanic cavity.

Proto-oncogene mutations in middle ear cholesteatoma contribute to its pathogenesis.

BACKGROUND: Chronic inflammation causes bone destruction in middle ear cholesteatomas (MECs). However, the causes of their neoplastic features remain unknown. The present study demonstrated for the first time that neoplastic features of MEC are based on proto-oncogene mutations. RESULTS: DNA was extracted from MEC and blood samples of five patients to detect somatic mutations using depth-depth exome sequencing. Exons with somatic variants were analyzed using an additional 17 MEC/blood test pairs. Variants detected in MECs but not in blood were considered pathogenic variant candidates. We analyzed the correlation between proto-oncogene (NOTCH1 and MYC) variants and the presence of bone destruction and granulation tissue formation. MYC and NOTCH1 variants were detected in two and five of the 22 samples, respectively. Two of the NOTCH1 variants were located in its specific functional domain, one was truncating and the other was a splice donor site variant. Mutations of the two genes in attic cholesteatomas (n = 14) were significantly related with bone destruction (p = 0.0148) but not with granulation tissue formation (p = 0.399). CONCLUSIONS: This is the first study to demonstrate a relationship between neoplastic features of MEC and proto-oncogene mutations.

High-Resolution Computed Tomography in Middle Ear Cholesteatoma: How Much Do We Need It?

Background and Objectives: The diagnosis of cholesteatoma is usually clinic, and the only efficient treatment is surgical. High-resolution computed tomography (HRCT) is not considered absolutely necessary for the management of an uncomplicated cholesteatoma, but unsuspected situations from a clinical point of view can be discovered using the scans, warning the surgeon. Our objective is to compare HRCT scan information with intraoperative findings in patients with cholesteatoma and analyze the usefulness of a preoperative HRCT scan from a surgical point of view. Materials and Methods: This is a prospective descriptive study conducted in the Department of Otolaryngology, Victor Babes University of Medicine and Pharmacy Timisoara, Romania, from May 2021 to April 2022. It was carried out on 46 patients with a clinical diagnosis of cholesteatoma who were consequently operated on in our department. All patients received full clinical and audiological examinations. In all cases, an HRCT scan was performed preoperatively as a mandatory investigation. Preoperative HRCT scans were analyzed, and their findings were compared to the intraoperative notes. The two sets of observations were analyzed using standard statistical methods. Results: Extensive cholesteatoma was the most common type of disease, involving 46% of the patients, followed by pars flaccida cholesteatoma (35%) and pars tensa cholesteatoma (19%). Eroded scutum was the most frequent lesion involving 70% of the patients, followed by incus erosion (67%). Comparison of the HRCT and intraoperative findings revealed a very good correlation for tegmen tympani erosion, sigmoid plate erosion, scutum and malleus erosion, and a moderate-to-good correlation for lateral semicircular canal erosion, incus and stapes erosion, and fallopian canal erosion. Conclusions: HRCT is a valuable tool in the preoperative assessment of cholesteatoma, helping in making surgical decisions. It can accurately predict the extent of disease and is helpful for detecting unapparent dangerous situations. However, it is not very accurate in detecting fallopian canal and stapes erosion.

Expression of MMP-14 and its role in bone destruction in middle ear cholesteatoma: A prospective observational study.

Cholesteatoma is a noncancerous cystic lesion caused by an abnormal growth of keratinizing squamous epithelium which is invasive and capable of destroying structures. A prospective study on the expression of membrane type1-matrix metalloproteinases (MMP-14) and its related influencing factors in middle ear cholesteatoma was conducted to fully understand the pathogenesis of cholesteatoma in the molecular level. We examined the expression of MMP-14 by immunohistochemical staining 39 middle ear cholesteatoma specimens and 10 external auditory meatus epithelial cell specimens. The cholesteatoma specimens were divided into 4 groups according to the degree of destruction of the ossicles during surgery. The associated factors affecting MMP-14 expression were analyzed using statistical methods; The positive expression of MMP-14 in the epithelium of the external auditory canal was significantly different between middle ear cholesteatoma and normal patients (P < .05); Gender, age, and the degree of hearing loss had no statistically significant effect on MMP-14 expression (P > .05); The expression of MMP-14 was positively correlated with the severity of bone destruction (R = 0.535, P < .05); MMP-14 plays an important role in the pathological development of the epithelium of cholesteatoma; MMP-14 expression in middle ear cholesteatoma tissue was not strongly correlated with the level of hearing loss, age or gender, but was positively correlated with the degree of middle ear bone destruction.

Congenital Retrosigmoid Cholesteatoma: Case Series and Literature Review.

BACKGROUND: This study aimed to discuss 3 cases of congenital cholesteatoma located posterior to the sigmoid sinus, with no/minimal involvement of mastoid, and compare them with cases presented in the literature to better define this rare entity. METHODS: Retrospective chart analysis of 3 congenital cholesteatomas located posterior to the sigmoid sinus treated surgically in 2 skull-base centers and literature review. Though congenital cholesteatoma can arise outside the middle ear, only a few cases presenting in the retrosigmoid occipital bone have been described earlier. RESULTS: In all 3 patients, there was a delay in the presentation, as symptoms were nonspecific or lacking, leading in 1 case to severe complications. Computed tomography and magnetic resonance imaging, especially diffusion-weighted imaging scans, allowed accurate diagnosis and surgical planning. Surgery happened to be challenging due to the tight adherence of the cholesteatoma to the thinned dural surface. Complete excision was achieved in all the cases. CONCLUSION: Congenital cholesteatoma located posterior to the sigmoid sinus is a rare entity and is even more exceptional after a critical review of the literature. Complete excision is quintessential to prevent intradural extension or infection. The most important surgical issue is the management of the posterior fossa dura and the sigmoid sinus. We recommend meticulous dissection with slow peeling of the epithelial lining from the dura. Bipolar coagulation of the dura may help in avoiding recidivism. Moreover, cerebrospinal fluid (CSF) leak during dissection has to be avoided as long as possible, because the loss of tension of the already thinned dura makes its peeling particularly difficult.

Diagnosis and management of bilateral lipoma of the middle ear.

INTRODUCTION: Middle ear lipomas are rare, accounting for less than 1% of all middle ear tumours. To our knowledge there have been only 16 reported patients with middle ear lipoma. Only one of these had bilateral congenital middle ear lipomas. The aim of this review is to comprehensive overview the diagnosis and management of congenital lipomas of the middle ear. METHODS: A literature review was performed searching multiple data bases, using the key words "middle ear", AND "lipoma", AND "congenital". A total of 116 articles were identified. One hundred were excluded on various criteria, leaving 16 articles for detailed review. Additionally, we report the second case of bilateral congenital middle ear lipoma. RESULTS: Based on this case report and literature review, the incidence of middle ear lipomas is greater in paediatric patients than in adult patients. Middle ear lipomas are distributed evenly between males and females. Three patients had recognised genetic syndromes, while five had prior ventilation tube placement. Clinically patients present with conductive hearing loss and middle ear effusions. In some cases, presence of a white or yellow mass behind the anterior aspect of the tympanic membrane is recognised. The most common location of the masses is in the anterosuperior quadrant of the middle ear, the site of predilection for small congenital cholesteatomas. An MRI scan is most useful in distinguishing between lipoma and cholesteatoma. All cases reported surgical excision of the middle ear lipoma. There was no evidence of recurrence noted up to 4 years follow up. CONCLUSION: Though rare, congenital lipomas of the middle ear should be a differential diagnosis of a middle ear masses. Early identification can allow surgical lipoma resection with minimal disruption to the ossicular chain. Though there is currently no consensus regarding management, surgical removal and appropriate reconstruction of the ossicular chain if needed, is appropriate.

External auditory canal sebaceous carcinoma.

The incidence of sebaceous carcinoma (SC) in the outer one-third of the external auditory canal is considered extremely rare, and only eight case reports have been published. We present a case of a male patient in his late 70s known case of hypertension on indapamide. His medical history included a postspinal tumour that had been treated with surgery and radiation more than 40 years ago and current complaints of right ear pain and purulent discharge. A right ear soft granular tissue mass was found. Complete debulking of the right ear mass was done in conjunction with middle ear exploration, moderately differentiated SC diagnosis was made based on the histopathological analysis. The patient was free of recurrence but then died of an unrelated pulmonary infection. SC should be suspected in elderly patients who present with long-term complaints of a mass with or without otalgia, and these patients should be examined for the presence of such tumours especially if they report a history of radiation. Additionally, more research is warranted to investigate the association of diuretics with SC.

Monozygotic twins and cholesteatomas: nature or nuture?

PURPOSE: Cholesteatoma is a rare middle ear pathology. It can be classified into acquired and congenital forms. Although benign, cholesteatomas can cause significant morbidity including hearing loss, infection, facial palsy and thrombosis. Congenital cholesteatomas are incredibly rare and bilateral disease has not commonly been published in the literature. METHOD: We describe the case of female identical (monozygotic, monochorionic, diamniotic) twins who both developed congenital cholesteatomas. In this report, we review the aetiology, treatment, embryology and pathology of cholesteatoma. RESULTS: The patients have been followed up 15 years after their initial surgery with promising results - pure-tone audiometry and repeat scans have not illustrated any disease recurrence. CONCLUSION: This paper presents one of the only cases of female monozygotic twins presenting with unilateral and bilateral cholesteatomas.

Otitis Media in Children with Down Syndrome Is Associated with Shifts in the Nasopharyngeal and Middle Ear Microbiotas.

Background: Otitis media (OM) is defined as middle ear (ME) inflammation that is usually due to infection. Globally, OM is a leading cause of hearing loss and is the most frequently diagnosed disease in young children. For OM, pediatric patients with Down syndrome (DS) demonstrate higher incidence rates, greater severity, and poorer outcomes. However, to date, no studies have investigated the bacterial profiles of children with DS and OM. Method: We aimed to determine if there are differences in composition of bacterial profiles or the relative abundance of individual taxa within the ME and nasopharyngeal (NP) microbiotas of pediatric OM patients with DS (n = 11) compared with those without DS (n = 84). We sequenced the 16S rRNA genes and analyzed the sequence data for diversity indices and relative abundance of individual taxa. Results: Individuals with DS demonstrated increased biodiversity in their ME and NP microbiotas. In children with OM, DS was associated with increased biodiversity and higher relative abundance of specific taxa in the ME. Conclusion: Our findings suggest that dysbioses in the NP of DS children contributes to their increased susceptibility to OM compared with controls. These findings suggest that DS influences regulation of the mucosal microbiota and contributes to OM pathology.

Effect of Bioabsorbable Poly (dl-Lactide ε-Caprolactone) on Healing of Experimentally Injured Acute Traumatic Middle Ear Mucosa Damage.

BACKGROUND: Postoperative adhesion is an important complication after middle-ear surgeries. Although many materials have been tried to prevent this complication, the use of Poly (dl-lactide ε-caprolactone) as an anti-adhesive material after middle-ear surgery has not yet been reported. The aim of this study was to evaluate the anti-adhesive effect of poly (dl-lactide ε-caprolactone) on the ears of rats with middle-ear mucosa damage. METHODS: In our study, 14 Wistar albino rats and 28 ears in total were used. The rats were randomly divided into 4 groups. Middle ear mucosa damage was performed in all groups with a transcanal approach under otomicroscopy in sterile conditions. The effects of poly (dl-lactide ε-caprolactone), silicone sheet, and absorbable gelatin sponge were compared histologically with the secondary healing group. In addition, hearing evaluation was performed before the procedure and on the 28th postoperative day. RESULTS: No significant difference was observed in transient otoacoustic emission and distortion product otoacoustic emissions tests performed before and after the surgical procedure when the groups were compared. While adhesion was observed in the tympanic membrane in the absorbable gelatin sponge group, no adhesion was observed in the other groups. In the absorbable gelatin sponge group, increased fibroblastic activity, inflammation, and neovascularization were observed in the middle-ear mucosa. No significant difference was observed in silicone sheet, poly (dl-lactide ε-caprolactone), and control groups in terms of fibroblastic activity, inflammation, and neovascularization. CONCLUSION: It can be concluded that absorbable poly (dl-lactide ε-caprolactone) is nonototoxic and biocompatible with the rat's middle ear cavity by short-term evaluation.

Imaging guidance for cholesteatoma surgery using tissue autofluorescence.

Significance: Cholesteatoma is an expansile destructive lesion of the middle ear and mastoid, which can result in significant complications by eroding adjacent bony structures. Currently, there is an inability to accurately distinguish cholesteatoma tissue margins from middle ear mucosa tissue, causing a high recidivism rate. Accurately differentiating cholesteatoma and mucosa will enable a more complete removal of the tissue. Aim: Develop an imaging system to enhance the visibility of cholesteatoma tissue and margins during surgery. Approach: Cholesteatoma and mucosa tissue samples were excised from the inner ear of patients and illuminated with 405, 450, and 520 nm narrowband lights. Measurements were made with a spectroradiometer equipped with a series of different longpass filters. Images were obtained using a red-green-blue (RGB) digital camera equipped with a long pass filter to block reflected light. Results: Cholesteatoma tissue fluoresced under 405 and 450 nm illumination. Middle ear mucosa tissue did not fluoresce under the same illumination and measurement conditions. All measurements were negligible under 520 nm illumination conditions. All spectroradiometric measurements of cholesteatoma tissue fluorescence can be predicted by a linear combination of emissions from keratin and flavin adenine dinucleotide. We built a prototype of a fluorescence imaging system using a 495 nm longpass filter in combination with an RGB camera. The system was used to capture calibrated digital camera images of cholesteatoma and mucosa tissue samples. The results confirm that cholesteatoma emits light when it is illuminated with 405 and 450 nm, whereas mucosa tissue does not. Conclusions: We prototyped an imaging system that is capable of measuring cholesteatoma tissue autofluorescence.

Design of medical tympanostomy conduits with selective fluid transport properties.

Implantable tubes, shunts, and other medical conduits are crucial for treating a wide range of conditions from ears and eyes to brain and liver but often impose serious risks of device infection, obstruction, migration, unreliable function, and tissue damage. Efforts to alleviate these complications remain at an impasse because of fundamentally conflicting design requirements: Millimeter-scale size is required to minimize invasiveness but exacerbates occlusion and malfunction. Here, we present a rational design strategy that reconciles these trade-offs in an implantable tube that is even smaller than the current standard of care. Using tympanostomy tubes (ear tubes) as an exemplary case, we developed an iterative screening algorithm and show how unique curved lumen geometries of the liquid-infused conduit can be designed to co-optimize drug delivery, effusion drainage, water resistance, and biocontamination/ingrowth prevention in a single subcapillary-length-scale device. Through extensive in vitro studies, we demonstrate that the engineered tubes enabled selective uni- and bidirectional fluid transport; nearly eliminated adhesion and growth of common pathogenic bacteria, blood, and cells; and prevented tissue ingrowth. The engineered tubes also enabled complete eardrum healing and hearing preservation and exhibited more efficient and rapid antibiotic delivery to the middle ear in healthy chinchillas compared with current tympanostomy tubes, without resulting in ototoxicity at up to 24 weeks. The design principle and optimization algorithm presented here may enable tubes to be customized for a wide range of patient needs.