Relapsing Polychondritis with Tracheobronchial Involvement: A Detailed Description of Two Pediatric Cases and Review of the Literature.

Relapsing polychondritis (RP) is a rare immune-mediated disease that primarily affects the cartilaginous structures of the ears, nose and airways. The clinical spectrum ranges from mild to severe disease characterized by progressive destruction of cartilage in the tracheobronchial tree leading to airway obstruction and acute respiratory failure. Early diagnosis is crucial to prevent irreversible airway damage and life-threatening complications. Due to its rarity and variability of symptoms, the diagnosis of RP is often delayed particularly in childhood. To address this and increase awareness of this rare disease, we present a detailed case report of two adolescent females affected by RP. We aim to describe the clinical findings, consequences of a delayed diagnosis and provide a review of the current literature.

Estimating vibration artifacts in preclinical experimental assessment of actuator efficiency in bone-conduction hearing devices.

OBJECTIVES: Test feasibility of a means to distinguish artifact from relevant signal in an experimental method for pre-clinical assessment of bone conduction (BC) stimulation efficiency based on measurement of intracochlear pressure (ICP). METHODS: Experiments were performed on fresh-frozen human temporal bones and cadaver heads. In a first step, fiber optic pressure sensors inserted into the cochlea through cochleostomies were intentionally vibrated to generate relative motion versus the stationary specimen, and the resulting ICP artifact recorded, before and after attaching the sensor fiber to the bone with glue. In a second step, BC stimulation was applied in the conventional location for a commercial bone anchored implant, as well as two alternative locations closer to the otic capsule. Again, ICP was recorded and compared with an estimated artifact, calculated from the previous measurements with intentional vibration of the fiber. RESULTS: Intentional vibration of the sensor fiber creates relative motion between fiber and bone, as intended, and causes an ICP signal. The stimulus does not create substantial promontory vibration, indicating that the measured ICP is all artifact, i.e. would not occur if the sensor were not in place. Fixating the sensor fiber to the bone with glue reduces the ICP artifact by at least 20 dB. BC stimulation also creates relative motion between sensor fiber and bone, as expected, from which an estimated ICP artifact level can be calculated. The ICP signal measured during BC stimulation is well above the estimated artifact, at least in some specimens and at some frequencies, indicating "real" cochlear stimulation, which would result in an auditory percept in a live subject. Stimulation at the alternative locations closer to the otic capsule appear to result in higher ICP (no statistical analysis performed), indicating a trend towards more efficient stimulation than at the conventional location. CONCLUSIONS: Intentional vibration of the fiber optic sensor for measurement of ICP can be used to derive an estimate of the artifact to be expected when measuring ICP during BC stimulation, and to characterize the effectiveness of glues or other means of reducing the artifact caused by relative motion of fiber and bone.

Sjögren's syndrome with and without neurological involvement.

OBJECTIVE: Neurological manifestations of Sjögren's syndrome can be severe but also treatment-responsive. We aimed to systematically evaluate neurological manifestations of primary Sjögren's syndrome and find clinical features allowing sufficient identification of affected patients (pSSN) among those with Sjögren's syndrome without neurological involvement (pSS). METHODS: Para-/clinical features of patients with primary Sjögren's syndrome (2016 ACR/EULAR classification criteria) were compared between pSSN and pSS. At our university-based center, patients with suggestive neurological symptoms undergo screening for Sjögren's syndrome, and newly diagnosed pSS patients are thoroughly evaluated for neurologic involvement. pSSN disease activity was rated by the Neurological Involvement of Sjögren's Syndrome Disease Activity Score (NISSDAI). RESULTS: 512 patients treated for pSS/pSSN at our site between 04/2018 and 07/2022 were included (238 pSSN patients [46%] vs. 274 pSS patients [54%], cross-sectional design). Independent predictors of neurological involvement in Sjögren's syndrome were male sex [p < 0.001], older age at disease onset [p < 0.0001], hospitalization at first presentation [p < 0.001], lower IgG levels [p = 0.04] and higher eosinophil values (treatment-naïve) [p = 0.02]. Univariate regression additionally showed older age at diagnosis [p < 0.001], lower prevalence of rheumatoid factor [p = 0.001], SSA(Ro)/SSB(La) antibodies [p = 0.03; p < 0.001], higher white blood cell count [p = 0.02] and CK levels [p = 0.02] (treatment-naïve) in pSSN. INTERPRETATION: Patients with pSSN had different clinical characteristics than patients with pSS and represented a large proportion of the cohort. Our data suggest that neurological involvement in Sjögren's syndrome has been underestimated. Intensified screening for neurologic involvement should be included in the diagnostic algorithm for Sjögren's syndrome, especially in males of older age and with severe disease course requiring hospitalization.

Cochlear Implantation in Obliterated Cochlea: A Retrospective Analysis and Comparison between the IES Stiff Custom-Made Device and the Split-Array and Regular Electrodes.

Anatomical malformations, obliterations of the cochlea, or re-implantations pose particular challenges in cochlear implantation. Treatment methods rely on radiological and intraoperative findings and include incomplete insertion, the implantation of a double array, and radical cochleostomy. In addition, a stiff electrode array, e.g., the IE stiff (IES) custom-made device (CMD, MED-EL), was prescribed individually for those special cases and pre-inserted prior to facilitate cochlear implantation in challenging cases. Data on outcomes after implantation in obliterated cochleae are usually based on individual case reports since standardised procedures are lacking. A retrospective analysis was conducted to analyse our cases on obliterated cochleae treated with MED-EL devices in order to allow the different cases to be compared. Impedances and speech perception data of patients treated with the IES CMD and the double array were retrospectively compared to patients treated with a STANDARD or FLEX electrode array (the REGULAR group). Patients with a Split-Array CMD had a poor speech perception when compared to patients treated with the IES CMD device. Thus, the IES CMD can successfully be used in patients with obliterated cochleae who would otherwise be non-users, candidates for a Split-Array CMD, or candidates for partial insertion with insufficient cochlear coverage.

Middle Ear Transducer: Long Term Stability of the Latest Generation T2.

OBJECTIVES/HYPOTHESIS: Comparing long term stability of the Middle Ear Transducers (MET) of the 1st generation T1 (Otologics LLC) with the current generation T2 (Cochlear Ltd.) in all our clinical cases with standard incus coupling. STUDY DESIGN: Retrospective chart review. METHODS: 52 ears implanted with a MET device between 2008 and 2016 were analyzed retrospectively. All patients suffered from sensorineural hearing loss and the actuator was coupled to the body of the incus (standard coupling). 23 ears were implanted with the transducer T1 (Otologics LLC) between 2008 and 2011 and 29 ears were implanted with the current transducer T2 since 2011 (Otologics LLC/Cochlear Ltd.). Latest available in situ and bone conduction (BC) thresholds were exploited for a follow-up period of up to 7 years after first fitting. Long term stability of coupling and actuator performance was evaluated by tracking differences between in situ and BC thresholds. RESULTS: In the T1 group, 9 out of 23 implants were still used by the patients at their last follow-up visit (average observation time 3.7 yrs.; min 1.0 yrs., max 7.4 yrs.). In 9 patients a technical failure identified by a decrease of in situ threshold of more than 15 dB compared to BC thresholds [Δ (in situ - BC)] lead to non-usage of the implant and 7 explantations. Five other explantations occurred due to medical reasons such as BC threshold decrease, infection, or insufficient speech intelligibility with the device. In the T2 group, 23 out of 29 implants were still used at the most current follow-up visit (average observation time 3.3 yrs.; min 1.0 yrs., max 4.8 yrs.). No technical failures were observed up to more than 4 years after implantation. Five T2 patients discontinued using the device due to insufficient benefit; two of these patients were explanted. One patient had to be explanted before the activation of the device due to disorders of wound healing. Nevertheless, a small but significant decrease of hearing loss corrected coupling efficiency [Δ (in situ - BC)] was seen in the T2 group. CONCLUSIONS: In contrast to the T1 transducers of the earlier generation of MET systems where technical failures occurred frequently, no technical failures were detected after 29 implantations with the current T2 transducers. However, a small but significant decline of transmission efficiency was observable even in the T2 implanted group.

Single Intravenous High Dose Administration of Prednisolone Has No Influence on Postoperative Impedances in the Majority of Cochlear Implant Patients.

OBJECTIVE: To evaluate effect of prednisolone on the impedances after cochlear implantation. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS AND INTERVENTION: A total of 130 patients underwent cochlear implantation with a Med-El Flex28 synchrony device between 2012 and 2016 and met the inclusion criteria. Only patients with full datasets regarding impedance measurements perioperatively, at first fitting (before and after chronic electric stimulation) and at 3 and 12 months appointments afterward were included. Patients (n = 101) received a single intravenous administration of at least 200 mg prednisolone intraoperatively and control patients (n = 29) did not receive any steroids at all. Patients receiving low dose steroids during surgery were excluded. MAIN OUTCOME MEASURES: Mean values for impedances were calculated over all electrode contacts and separately for basal, medial, and apical regions. RESULTS: Impedances increased significantly from perioperative measures to first fitting in both groups. Mainly at the basal region of the electrode array, impedances were slightly lower in the steroid group compared with controls. However, the majority of the patients showed increased impedances whether they received steroid treatment or not. CONCLUSION: The present study shows a slight but statistically significant reduction of the mean value of postoperative impedances at the basal electrode contacts in patients receiving a single systemic high dose application of prednisolone. Less than half of the patients showed a decrease in impedances and whether this decrease is clinically relevant remains to be elucidated.

The Impact of Two-Stage Subtotal Petrosectomy and Round Window Vibroplasty on Bone Conduction Thresholds.

OBJECTIVE: To evaluate possible increases in bone conduction (BC) hearing thresholds in patients undergoing subtotal petrosectomy (SP) with fat obliteration and blind sac closure of the outer ear canal and subsequent round window vibroplasty. PATIENTS AND INTERVENTIONS: Between 1997 and 2013, 43 patients (45 ears) with combined hearing loss and recurrent chronic otitis or status post formation of a radical cavity underwent SP around 6 months prior to implantation of a Vibrant SoundbridgeTM. Pure tone audiograms (0.5, 1, 1.5, 2, 3, 4, and 6 kHz) prior to SP, after SP, prior to implantation, after implantation, and at first fitting around 5 weeks after implantation were collected and statistically analyzed. RESULTS: The comparison between BC thresholds before SP and at first fitting showed an overall decline during the two-step procedure between 2.8 and 6 dB that was significant (p < 0.05, Student t test) at 2, 3, 4, and 6 kHz. CONCLUSION: In some cases, SP is the only way to eradicate chronic otitis and to achieve a suitable environment for the implantation of active middle ear implants. The present data demonstrate a relatively small but significant decline in BC thresholds throughout the whole procedure. Knowledge of its extent is mandatory for a correct indication for later implantation of a Vibrant SoundbridgeTM.

Cochlear implantation in patients with definite Meniere's disease.

The exact pathomechanism of deafening in Meniere's disease (MD) is still unknown; intoxication of hair cells and neural damage from endolymphatic hydrops is discussed. In the literature, there are only a few reports on hearing outcome of MD patients after treatment with cochlear implantation (CI) whereby especially the comparison of MD vs. non-MD patients with CI differs. In this retrospective study, results in speech understanding [Freiburger Einsilber (FES65) and Hochmair-Schulz-Moser test in quiet (HSM) and in noise (HSM + 10 dB)] of 27 implanted MD patients were collected and compared to a matched standard CI cohort. Alternative diagnoses were excluded as far as possible by re-analyzing neuroradiologic imaging. After first fitting, MD patients showed significantly better results in FES and HSM testing compared to controls. At 1-year refitting, this effect could not be seen anymore. To conclude, cochlear implantation is a safe and effective treatment for deafness in MD patients. Results in speech understanding are at least equal compared to general CI recipients. To the best of our knowledge, this retrospective study examined the largest collective of CI users deafened by MD so far.

Highly biocompatible behaviour and slow degradation of a LDH (layered double hydroxide)-coating on implants in the middle ear of rabbits.

Chronic inflammation can irreversibly damage components of the ossicular chain which may lead to sound conduction deafness. The replacement of impaired ossicles with prostheses does not reduce the risk of bacterial infections which may lead to loss of function of the implant and consequently to additional damage of the connected structures such as inner ear, meninges and brain. Therefore, implants that could do both, reconstruct the sound conduction and in addition provide antibacterial protection are of high interest for ear surgery. Layered double hydroxides (LDHs) are promising novel biomaterials that have previously been used as an antibiotic-releasing implant coating to curb bacterial infections in the middle ear. However, animal studies of LDHs are scarce and there exist only few additional data on the biocompatibility and hardly any on the biodegradation of these compounds. In this study, middle ear prostheses were coated with an LDH compound, using suspensions of nanoparticles of an LDH containing Mg and Al as well as carbonate ions. These coatings were characterized and implanted into the middle ear of healthy rabbits for 10 days. Analysis of the explanted prostheses showed only little signs of degradation. A stable health constitution was observed throughout the whole experiment in every animal. The results show that LDH-based implant coatings are biocompatible and dissolve only slowly in the middle ear. They, therefore, appear as promising materials for the construction of controlled drug delivery vehicles.

Nanoporous silica coatings as a drug delivery system for ciprofloxacin: outcome of variable release rates in the infected middle ear of rabbits.

HYPOTHESIS: The present study was performed to examine the impact of the release rate of ciprofloxacin from prostheses coated with nanoporous silica layers on the outcome of an acute bacterial infection of the middle ear of rabbits. BACKGROUND: Middle ear prostheses are often implanted in an infectious environment because of chronic otitis media and cholesteatoma. Bacterial colonization leads to healing disorders after surgery and may lead to the extrusion of the implants. Nanoporous silica layers appear promising as a drug delivery system for antibiotics placed on implants. Before clinical applications can be envisioned, it is necessary to find an optimal release rate. METHODS: White New Zealand rabbits were provided unilaterally with either a "slow release" or a "burst release" ciprofloxacin-containing middle ear Bioverit II prosthesis. After implantation, the middle ears were infected with a solution of Pseudomonas aeruginosa. Afterwards, animals were monitored clinically and, after 3 months, sacrificed to perform necropsy and microbiologic examinations. RESULTS: In the "slow release" group, 7 of 12 animals had to be euthanized preterm because of their poor clinical condition compared with 2 of 12 animals of the "burst release" group (p < 0.05). Clinical and microbiologic examination also showed a better outcome for animals of the burst release group. CONCLUSION: A burst release of ciprofloxacin from middle ear implants is important to combat a perioperative infection with Ps. aeruginosa in the middle ear model of the rabbit.

Layered double hydroxides as efficient drug delivery system of ciprofloxacin in the middle ear: an animal study in rabbits.

Chronic otitis media is a common disease often accompanied by recurrent bacterial infections. These may lead to the destruction of the middle ear bones such that prostheses have to be implanted to restore sound transmission. Surface coatings with layered double hydroxides (LDHs) are evaluated here as a possibility for drug delivery systems with convenient advantages such as low cytotoxicity and easy synthesis. Male New Zealand White rabbits were implanted with Bioverit(®) II middle ear prostheses coated with the LDH Mg(4)Al(2)(OH)(12)(SO(4))(2)·6H(2)O impregnated with ciprofloxacin. 12 (group 1) were directly infected with Pseudomonas aeruginosa and another 12 (group 2) 1 week after the implantation. Clinical outcome, blood counts, histological analyses and microbiological examination showed an excellent antimicrobial activity for group 1, whereas this effect was attenuated in animals where infection was performed 1 week after implantation. This is the first study to demonstrate an efficient drug delivery system with an LDH coating on prostheses in the middle ear.