Pediatric sellar teratoma - Case report and review of the literature.

BACKGROUND: Intracranial teratoma represents a rare neoplasm, occurring predominantly during childhood. Characteristic symptoms depend on the location but are mainly hydrocephalus, visual disturbances, hypopituitarism, and diabetes insipidus. Initial diagnosis can be challenging due to similar radiological features in both teratomas and other lesions such as craniopharyngiomas. Gross total resection is recommended if feasible and associated with a good prognosis. CASE DESCRIPTION: A 10-year-old girl presented with newly diagnosed growth retardation, fatigue, cephalgia and bilateral hemianopia. Further laboratory analysis confirmed central hypothyroidism and hypercortisolism. Cranial magnetic resonance imaging showed a cystic space-occupying lesion in the sellar and suprasellar compartment with compression of the optic chiasm without hydrocephalus present, suspicious of craniopharyngioma. Subsequently, an endonasal endoscopic transsphenoidal near-total tumor resection with decompression of the optic chiasm was performed. During postoperative recovery the patient developed transient diabetes insipidus, the bilateral hemianopia remained unchanged. The patient could be discharged in a stable condition, while hormone replacement for multiple pituitary hormone deficiency was required. Surprisingly, histopathology revealed conspicuous areas of skin with formation of hairs and squamous epithelia, compatible with a mature teratoma. CONCLUSIONS: We present an extremely rare case of pediatric sellar teratoma originating from the pituitary gland and a review of literature focusing on the variation in presentation and treatment. Sellar teratomas are often mistaken for craniopharyngioma due to their similar radiographic appearances. However, the primary goal of treatment for both pathologies is to decompress eloquent surrounding structures such as the optic tract, and if applicable, resolution of hydrocephalus while avoiding damage to the pituitary stalk and especially the hypothalamic structures. If feasible, the aim of surgery should be gross total resection.

The Role of Endonasal Endoscopic Skull Base Repair in Posttraumatic Tension Pneumocephalus.

OBJECTIVES: Information about the endonasal endoscopic approach (EEA) for the management of posttraumatic tension pneumocephalus (PTTP) remains scarce. Concomitant rhinoliquorrhea and posttraumatic hydrocephalus (PTH) can complicate the clinical course. METHODS: The authors systematically reviewed pertinent articles published between 1961 and December 2020 and identified 6 patients with PTTP treated by EEA in 5 reports. Additionally, the authors share their institutional experience including a seventh patient, where an EEA resolved a recurrent PTTP without rhinoliquorrhea. RESULTS: Seven PTTP cases in which EEA was used as part of the treatment regime were included in this review. All cases presented with a defect in the anterior skull base, and 3 of them had concomitant rhinoliquorrhea. A transcranial approach was performed in 6/7 cases before EEA was considered to treat PTTP. In 4/7 cases, the PTTP resolved after the first intent; in 2/ 7 cases a second repair was necessary because of recurrent PTTP, 1 with and 1 without rhinoliquorrhea, and 1/7 case because of recurrent rhinoliquorrhea only. Overall, PTTP treated by EEA resolved with a mean radiological resolution time of 69 days (range 23-150 days), with no late recurrences. Only 1 patient developed a cerebrospinal fluid diversion infection probably related to a first incomplete EEA skull base defects repair. A permanent cerebrospinal fluid diversion was necessary in 3/7 cases. CONCLUSIONS: Endonasal endoscopic approach repair of air conduits is a safe and efficacious second-line approach after failed transcranial approaches for symptomatic PTTP. However, the strength of recommendation for EEA remains low until further evidence is presented.

Training visual attention in a naturalistic visual environment.

The efficiency of training visual attention in the central and peripheral visual field was investigated by means of a visual detection task that was performed in a naturalistic visual environment including numerous, time-varying visual distractors. We investigated the minimum number of repetitions of the training required to obtain the top performance and whether intra-day training improved performance as efficiently as inter-day training. Additionally, our research aimed to find out whether exposure to a demanding task such as a microsurgical intervention may cancel out the effects of training. Results showed that performance in visual attention peaked within three (for tasks in the central visual field) to seven (for tasks in the periphery) days subsequent to training. Intra-day training had no significant effect on performance. When attention training was administered after exposure to stress, improvement of attentional performance was more pronounced than when training was completed before the exposure. Our findings support the implementation of training in situ at work for more efficient results. Practitioner Summary: Visual attention is important in an increasing number of workplaces, such as with surveillance, inspection, or driving. This study shows that it is possible to train visual attention efficiently within three to seven days. Because our study was executed in a naturalistic environment, training results are more likely to reflect the effects in the real workplace.

[Conservative and surgical rehabilitation of hearing loss]. / Apparative und operative Rehabilitation des Hörvermögens.

According to WHO 360 million people are hard of hearing. Hearing disorders are not only seen in elderly but also in children. Clinically we differentiate between hearing disorders concerning the transmission of sound from the outer ear to the cochlea (conductive hearing loss) and disorders with reduced sound perception concerning the inner ear an related structures (sensorineural hearing loss). This article summarizes common surgical and technical possibilities for rehabilitation. For each pathology we graphically illustrate the generic working principle of the rehabilitation including the indication range in an exemplary audiogram.

Metformin Protects Auditory Hair Cells from Gentamicin-Induced Toxicity in vitro.

Metformin is a commonly used antidiabetic drug. It has been shown that this drug activates the AMP-activated protein kinase, which inhibits downstream the mammalian target of rapamycin. In addition, several studies indicate that metformin reduces intracellular reactive oxygen species. Our data, using an in vitro rat model, indicate that metformin is able to protect auditory hair cells (HCs) from gentamicin-induced apoptotic cell death. Moreover, metformin has no toxic effect on spiral ganglion neuronal survival or outgrowth in vitro. These results suggest a protective effect of metformin on auditory HC survival in gentamicin-induced HC loss in vitro.

Endoscopic transnasal approach to anterior and middle cranial base lesions.

We present our experience in managing pathologies involving the anterior and middle cranial base using an endoscopic transnasal approach, highlighting the surgical technique, indications, and complications. The different types of endoscopic approaches used include the transtuberculum/transplanum, transcribiform, transsellar, and cavernous sinus approaches. The common indications include repair of cerebrospinal fluid leaks (both spontaneous and post traumatic) and excision of pituitary adenomas, meningiomas, craniopharyngiomas, esthesioneuroblastomas, and other malignancies of the anterior cranial base. Careful reconstruction is performed with the multilayer technique utilizing fat, fascia lata, and fibrin sealant. The endoscopic transnasal approach, coupled with the present-day sophisticated neuronavigation systems, allows access to lesions in the midline extending from the cribriform plate to the craniovertebral junction. However, preoperative planning and careful selection of cases with evaluation of each case on an individual basis with regard to the lateral extension of the lesion are imperative.

Inhibition of MMP-2 but not MMP-9 influences inner ear spiral ganglion neurons in vitro.

Matrix metalloproteinases (MMPs) play an important role in modeling of the extracellular matrix. There is increasing evidence that these proteases are important in neurite elongation and axonal guidance during development in the central nervous system and retina. Moreover, they are also expressed after acute injury and can be the key mediators of pathogenesis. However, the role of MMPs in the inner ear is largely unknown. Our group recently demonstrated that general inhibition of MMPs resulted in auditory hair cell loss in vitro. In the present study, we investigated the role of MMPs in inner ear spiral ganglion neuron (SGN) survival, neuritogenesis and neurite extension by blocking MMPs known to be involved in axonal guidance, neurite elongation, and apoptosis in other neuronal systems. Spiral ganglion (SG) explants from 5-day-old Wistar rats were treated with different concentrations of the general MMP inhibitor GM6001, a specific MMP-2 inhibitor, and a specific MMP-9 inhibitor, in vitro. The general inhibitor of MMPs and the specific inhibition of MMP-2 significantly reduced both the number of neurites that extended from SG explants, as well as the length of individual neurites. However, neither the general inhibitor of MMPs nor the specific inhibition of MMP-2 influenced SGN survival. Inhibition of MMP-9 had no influence on SGNs. The data suggest that MMPs, and more specifically MMP-2, influence the growth of developing afferent neurites in the mammalian inner ear in vivo.

Varicella mimicking complications of acute rhinosinusitis in an infant.

Varicella is the manifestation of primary infection with the varicella-zoster virus, mainly affecting preschool and school-aged children. The children suffer from a generalised, vesicular rash and fever. Despite the infection's typically non-threatening course, a variety of severe complications have been described.The authors present the case of a female infant suffering from varicella and developing preseptal cellulitis with a frontal abscess while being treated with intravenous antibiotics. Otorhinolaryngology consultation was sought since the clinical image was highly suggestive for sinusitis complications, namely orbital cellulitis and frontal bone osteomyelitis (Pott's puffy tumour). However, the child was below the age of frontal sinus development and there was no other apparent sign of sinonasal involvement. Ultrasonography revealed a mid-frontal collection without signs of abscess formation preseptally or postseptally, leading to the diagnosis of cutaneous superinfection of varicella lesions. The frontal abscess was drained, and the child fully recovered under antibiotic treatment.

[New manifestation of a type 2-inflammation in the upper respiratory tract with nasal polyposis under treatment with an asthma biologic]. / Neumanifestation einer Typ-2-Inflammation im Bereich der oberen Atemwege mit Polyposis nasi unter einem Asthmabiologikum.

INTRODUCTION: For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID intolerance (Widal's disease) behaves under biologicals. We therefore describe the case of a patient with both clinical conditions who reacted with a severe intolerance reaction under perioperative metamizole administration.

Somatostatin receptor types 1 and 2 in the developing mammalian cochlea.

The neuropeptide somatostatin (SST) exerts several important physiological actions in the adult central nervous system through interactions with membrane-bound receptors. Transient expression of SST and its receptors has been described in several brain areas during early ontogeny. It is therefore believed that SST may play a role in neural maturation. The present study provides the first evidence for the developmental expression of SST receptors in the mammalian cochlea, emphasizing their possible roles in cochlear maturation. In the developing mouse cochlea, cells immunoreactive to somatostatin receptor 1 (SSTR1) and somatostatin receptor 2 (SSTR2) were located in the embryonic cochlear duct on Kolliker's organ as early as embryonic day (E) 14 (E14). At E17, the expression of both receptors was high and already located at the hair cells and supporting cells along the length of the cochlear duct, which have become arranged into the characteristic pattern for the organ of Corti (OC) at this stage. At birth, SSTR1- and SSTR2-containing cells were only localized in the OC. In general, immunoreactivity for both receptors increased in the mouse cochlea from postnatal day (P) 0 (P0) to P10; the majority of immunostained cells were inner hair cells, outer hair cells, and supporting cells. Finally, a peak in the mRNA and protein expression of both receptors is present near the time when they respond to physiological hearing (i.e., hearing of airborne sound) at P14. At P21, SSTR1 and SSTR2 levels decrease dramatically. A similar developmental pattern was observed for SSTR1 and SSTR2 mRNA, suggesting that the expression of the SSTR1 and SSTR2 genes is controlled at the transcriptional level throughout development. In addition, we observed reduced levels of phospho-Akt and total Akt in SSTR1 knockout and SSTR1/SSTR2 double-knockout mice compared with wild-type mice. We know from previous studies that Akt is involved in hair cell survival. Taken together, the dynamic nature of SSTR1 and SSTR2 expression at a time of major developmental changes in the cochlea suggests that SSTR1 and SSTR2 (and possibly other members of this family) are involved in the maturation of the mammalian cochlea.

Primary Burkitt lymphoma of the thyroid associated with Hashimoto's thyroiditis.

Primary Burkitt lymphoma of the thyroid is an extremely rare entity with only a few reported cases. A female patient in her 70s with Hashimoto's thyroiditis presented with a 2-month history of progressive left-sided neck swelling. Ultrasound examination revealed a multinodular goitre and fine needle aspiration (FNA) showed no signs of malignancy. The rapid growth of the thyroid mass raised the concern of a lymphoproliferative process. After left thyroid lobectomy and histopathological examination, the diagnosis of Burkitt lymphoma was made and the patient was included in a randomised study providing chemotherapy following a dose adjusted EPOCH-R regimen. Clinical remission was reached after 6 cycles of chemotherapy. There were no signs of relapse on follow-up, 1.5 years after the end of the treatment. Fast growing thyroid nodules in HT warrant a high index of suspicion. Despite no signs of malignancy after FNA cytology, these nodules may need further investigations.

The somatostatinergic system in the mammalian cochlea.

BACKGROUND: Little is known about expression and function of the somatostatinergic system in the mammalian cochlea. We have previously shown that somatostatin administration may have a protective effect on gentamicin-induced hair cell loss. In this study, we have analyzed the cochlear expression of somatostatin receptor 1 (SST1) and somatostatin receptor 2 (SST2) at both the mRNA and the protein level in wild-type mice, as well as in SST1 and SST2 knock-out (KO) mice and in cultivated neurosensory cells. RESULTS: We demonstrate that the somatostatin receptors SST1 and SST2 are specifically expressed in outer and inner hair cells (HCs) of the organ of Corti (OC), as well as in defined supporting cells. The expression of SST1 and SST2 receptors in cultivated P5 mouse OC explants was similar to their expression in inner and outer hair cells. Somatostatin itself was not expressed in the mammalian cochlea, suggesting that somatostatin reaches its receptors either through the blood-labyrinthine barrier from the systemic circulation or via the endolymphatic duct from the endolymphatic sac. We used mice with a deletion of either SST1 or SST2 to learn more about the regulation of SST1 and SST2 receptor expression. We demonstrate that in SST1 KO mice, SST2 was expressed in outer HCs and Deiters' cells, but not in pillar cells or inner HCs, as compared with wild-type mice. In contrast, in SST2 KO mice, the expression pattern of the SST1 receptor was not altered relative to wild-type mice. CONCLUSIONS: These findings reveal that somatostatin receptors demonstrate specific expression in HCs and supporting cells of the mouse cochlea, and that absence of SST1 alters the expression of SST2. This specific expression pattern suggests that somatostatin receptors may have important functional roles in the inner ear.

Simvastatin protects auditory hair cells from gentamicin-induced toxicity and activates Akt signaling in vitro.

BACKGROUND: Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, known as statins, are commonly used as cholesterol-lowering drugs. During the past decade, evidence has emerged that statins also have neuroprotective effects. Research in the retina has shown that simvastatin, a commonly used statin, increases Akt phosphorylation in vivo, indicating that the PI3K/Akt pathway contributes to the protective effects achieved. While research about neuroprotective effects have been conducted in several systems, the effects of statins on the inner ear are largely unknown. RESULTS: We evaluated whether the 3-hydroxy-3-methylglutaryl-coenzyme A reductase is present within the rat cochlea and whether simvastatin is able to protect auditory hair cells from gentamicin-induced apoptotic cell death in a in vitro mouse model. Furthermore, we evaluated whether simvastatin increases Akt phosphorylation in the organ of Corti. We detected 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in organ of Corti, spiral ganglion, and stria vascularis by reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, we observed a dose-dependent and significant reduction of hair cell loss in organs of Corti treated with simvastatin in addition to gentamicin, as compared to samples treated with gentamicin alone. The protective effect of simvastatin was reversed by addition of mevalonate, a downstream metabolite blocked by simvastatin, demonstrating the specificity of protection. Finally, Western blotting showed an increase in organ of Corti Akt phosphorylation after simvastatin treatment in vitro. CONCLUSION: These results suggest a neuroprotective effect of statins in the inner ear, mediated by reduced 3-hydroxy-3-methylglutaryl-coenzyme A reductase metabolism and Akt activation.

Late prosthetic knee joint infection with Staphylococcus xylosus.

Prosthethic Joint Infection (PJI) is a severe complication following joint replacement. Late PJI can occur years after implantation by hematogenous seeding of a microbial agent. Staphylococcus xylosus is a coagulase-negative commensal of the human skin and rarely associated with opportunistic human infections. We report the rare case of a 70-year old Patient suffering from knee pain 18 years after primary Total Knee Arthroplasty. Microbiological sampling detected S. xylosus as causative agent. The patient was successfully treated with a two-stage implant exchange and antibiotic therapy using co-amoxicillin and rifampicin/cotrimoxazol. This case illustrates the ability of S. xylosus to cause late PJI and the importance of not letting coagulase-negative Staphylococci be routinely categorized as contaminants of microbiological samples.

Case Report: Petrous Apicitis and Otogenic Thrombosis of the Cavernous Sinus in a 10-Year-Old Boy.

Background: Petrous apicitis and cavernous sinus thrombosis are exceedingly rare complications of acute otitis media with only few reported cases in the post-antibiotic era. Especially in children, the appropriate management is a subject of controversy. Case Presentation: We report the case of a 10-year-old boy who presented to the emergency department with left-sided otalgia, otorrhea, and hearing loss, accompanied by somnolence and high spiking fevers. CT and MRI revealed partially obstructed mastoid air cells including a pneumatized petrous apex. Furthermore, thrombosis of the cavernous sinus and vasculitis of the internal carotid artery on the left side were present. The patient was treated with antibiotics for 6 weeks and anticoagulant therapy for 3 months. Follow-up carried out 3 months post-admission showed complete recanalization of the cavernous sinus on MRI and fatigue as the only remaining symptom. Conclusion: A complicated otitis media with petrous apicitis and cavernous sinus thrombosis in a child can in some cases be managed without a surgical intervention.

Stress and survival pathways in the mammalian cochlea.

Studies conducted over the last few years demonstrated that signaling pathways that operate in the organs of Corti (OC) play a central role in survival and death of hair cells. An important goal of molecular otology is to characterize these signaling pathways in normal inner ears and inner ears exposed to a variety of different forms of stress, such as ototoxic substances and noise overexposure. In this study, we used high-performance reverse protein microarray technology and phospho-specific antibodies to examine the activation status of defined molecules involved in cellular signaling. We demonstrate that reverse protein microarrays based on the highly sensitive planar-waveguide technology provide an effective and high-throughput means to assess the activation state of key molecules involved in apoptotic and prosurvival signaling in microdissected OC explants over time. In this study, we show that gentamicin and a specific NF-kappaB inhibitor increase the ratio of phospho-c-Jun/c-Jun in OC explants of postnatal rats soon after exposure to these drugs. In addition, we found a decrease in the phospho-Akt/Akt ratio in OC explants early after NF-kappaB inhibition. Finally, we observed an early and consistent decrease in the phospho-p38/p38 ratio in OC explants exposed to the NF-kappaB inhibitor and only a transient decrease in this ratio in OC examples after gentamicin exposure.

Sodium-hydrogen exchanger 6 (NHE6) deficiency leads to hearing loss, via reduced endosomal signalling through the BDNF/Trk pathway.

Acid-base homeostasis is critical for normal growth, development, and hearing function. The sodium-hydrogen exchanger 6 (NHE6), a protein mainly expressed in early and recycling endosomes, plays an important role in regulating organellar pH. Mutations in NHE6 cause complex, slowly progressive neurodegeneration. Little is known about NHE6 function in the mouse cochlea. Here, we found that all NHE isoforms were expressed in wild-type (WT) mouse cochlea. Nhe6 knockout (KO) mice showed significant hearing loss compared to WT littermates. Immunohistochemistry in WT mouse cochlea showed that Nhe6 was localized in the organ of Corti (OC), spiral ganglion (SG), stria vascularis (SV), and afferent nerve fibres. The middle and the inner ears of WT and Nhe6 KO mice were not different morphologically. Given the putative role of NHE6 in early endosomal function, we examined Rab GTPase expression in early and late endosomes. We found no change in Rab5, significantly lower Rab7, and higher Rab11 levels in the Nhe6 KO OC, compared to WT littermates. Because Rabs mediate TrkB endosomal signalling, we evaluated TrkB phosphorylation in the OCs of both strains. Nhe6 KO mice showed significant reductions in TrkB and Akt phosphorylation in the OC. In addition, we examined genes used as markers of SG type I (Slc17a7, Calb1, Pou4f1, Cal2) and type II neurons (Prph, Plk5, Cacna1g). We found that all marker gene expression levels were significantly elevated in the SG of Nhe6 KO mice, compared to WT littermates. Anti-neurofilament factor staining showed axon loss in the cochlear nerves of Nhe6 KO mice compared to WT mice. These findings indicated that BDNF/TrkB signalling was disrupted in the OC of Nhe6 KO mice, probably due to TrkB reduction, caused by over acidification in the absence of NHE6. Thus, our findings demonstrated that NHEs play important roles in normal hearing in the mammalian cochlea.

Evolving Strategies for Resection of Sellar/Parasellar Synchronous Tumors via Endoscopic Endonasal Approach: A Technical Case Report and Systematic Review of the Literature.

BACKGROUND: Data on the endonasal endoscopic approach (EEA) to treat sellar/parasellar synchronous tumors remain sparse. This work aims to describe a minimally invasive approach with intraoperative magnetic resonance imaging (MRI) to remove a large sellar/parasellar synchronous tumor, and presents a systematic literature review. METHODS: The preoperative MRI of a 54-year-old woman revealed a sellar lesion (28 × 19 × 16 mm), presumably a pituitary macroadenoma, and a second extra-axial lesion (22 × 36 × 20 mm) expanding from the tuberculum sellae to the planum sphenoidale with encasement of the anterior communicating complex, presumably a meningioma. We used intraoperative MRI to assess the extent of the resection before reconstructing the large skull base defect. Furthermore, we systematically reviewed pertinent articles retrieved by a PubMed/Embase database search between 1961 and December 2018. RESULTS: Out of 63 patients with synchronous tumors reported in 43 publications, we found 3 patients in which the tumor was removed by EEA. In these 3 patients and the presented case, the resection of both lesions was successful, without major approach-related morbidity or mortality. More extensive removal of endonasal structures to gain an adequate tumor exposure was not necessary. We did not find any previous reports describing the benefits of intraoperative MRI in the presented setting. CONCLUSIONS: In the rare case of a synchronous meningioma and pituitary adenoma of the sellar region, intraoperative MRI might be beneficial in confirming residual disease before skull base reconstruction, and therefore radiologic follow-up.

Paediatric oropharyngeal tularaemia requiring surgical intervention.

Tularaemia is a rare infectious disease endemic in most European countries caused by the bacterium Francisella tularensis 1 Patients often show acute non-specific symptoms, which causes a delay in diagnosis and proper treatment, potentially resulting in significant morbidities such as deep neck abscess, meningitis, endocarditis and septic shock. The authors present a case of a 5-year old boy with a 4-day history of fever, sore throat and painful cervical lymphadenopathy, whose clinical progression worsened despite being treated with recommended antibiotics as per WHO guidelines once the diagnosis of Tularaemia was confirmed by serologic tests. He developed a parapharyngeal abscess and a persistent left necrotic cervical lymph node, which both were surgically drained and excised, respectively, and an extended course of antibiotic was given. Subsequently, the patient fully recovered from the illness and the follow-up was negative for relapse.

Induction of mitophagy in the HEI-OC1 auditory cell line and activation of the Atg12/LC3 pathway in the organ of Corti.

Autophagy is a highly evolutionary conserved quality control defense mechanism within cells, which has also been implicated in cell death processes. In the mammalian inner ear, autophagy has been shown to play a role during early morphogenesis as well as in adult cochlear hair cells exposed to ototoxic insults. Mitophagy, a selective autophagic cell process targeting mitochondria, hasn't been studied in the inner ear so far. On this work, we searched for molecular indicators of mitophagy within House Ear Institute-Organ of Corti-1 (HEI-OC1) cells as well as in the organ of Corti (OC). We first tested for the expression of Pink1/Park2 mRNA in 5-day-old C57BL/6 mice's cochleae using RT-PCR. We focused on the induction of mitophagy in HEI-OC1 cells as well as in the OC and investigated a possible mitophagic potential of the aminoglycoside agent gentamicin. The induction of mitophagy in HEI-OC1 cells was detected by objectivizing the translocation of fluorescence-tagged LC3 to mitochondria using confocal microscopy after a 6-h incubation with a well-described mitochondrial uncoupler and mitophagy-inducing agent: carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Incubation with gentamicin generated no mitochondrial translocation of LC3. Protein levels of COXIV, Atg5/12 and LC3 were evaluated by an immunoblot analysis after a 24-h CCCP treatment as well as gentamicin. We demonstrated mitophagy after CCCP exposure in HEI-OC1 cells by showing a downregulation of COXIV. A downregulation of COXIV could also be visualized in the OC after CCCP. A significant oxygen consumption rate (OCR) changed in cells treated with CCCP as well as significant morphological changes of mitochondria by electron microscopy (EM) strengthen this assumption. Gentamicin exposure generated no impact on OCR or mitochondrial morphological changes by EM. Finally, we demonstrated changes in the expression of Atg12 and LC3 proteins in both the OC and HEI-OC1 cells after CCCP exposure but not after gentamicin. Our data indicate that gentamicin had no impact in the activation of mitophagy-neither in the HEI-OC1 cell line nor in the OC. Therefore, we speculate that mitophagic-independent mechanisms may underly aminoglycoside ototoxicity.