Yüksel Olgun

Objectives: Cisplatin (CDDP) is a potent anticancer agent with significant side effects, including ototoxicity. Capsaicin (CAPS), the active compound in chili peppers, has shown protective effects against CDDP‐induced toxicities. This study aimed to investigate the role of capsaicin in CDDP‐induced ototoxicity via DNA damage and apoptotic cell death pathways in House Ear Institute Organ of Corti 1 (HEI‐OC1) cells and to evaluate its effects on neuroblastoma (KELLY) cells under the same conditions. Methods: HEI‐OC1 and KELLY neuroblastoma cells were treated with CDDP (100 μM), CAPS (5 μM), and CAPS+CDDP combinations for 24 h. Cell viability was assessed using the WST‐1 assay, and apoptosis was evaluated by Annexin V/PI flow cytometry. DNA damage‐related gene expressions were analyzed in HEI‐OC1 cells using a real‐time PCR array. CAPS alone did not alter the viability of HEI‐OC1 or KELLY cells. CDDP significantly reduced the viability of both. Results: CAPS + CDDP combination significantly decreased KELLY cell viability, while only slightly affecting HEI‐OC1 cells. Both CDDP alone and CAPS + CDDP induced similar levels of apoptosis in HEI‐OC1 cells. In KELLY cells, the combination induced greater apoptosis than CDDP alone. CDDP treatment upregulated DNA damage‐related genes and downregulated DNA repair genes in HEI‐OC1 cells. CAPS + CDDP treatment altered expression profiles, suggesting a role in DNA repair modulation. Conclusion: Capsaicin may serve as a moderate protective agent against cisplatin‐induced ototoxicity without compromising cisplatin's cytotoxic effects on neuroblastoma cells. Changes in DNA repair‐related gene expression support capsaicin's involvement in modulating the cellular response to cisplatin.

Background and Objectives: Noise-induced hearing loss (NIHL) is a major cause of sensorineural hearing loss. However, effective pharmacological treatments remain limited. The aim of this study was to investigate the therapeutic effects of allicin on NIHL in a rat model. Materials and Methods: Forty-two female Wistar albino rats were randomly divided into six groups (n= 7 per group): saline (SF), allicin, dimethyl sulfoxide (DMSO), noise+SF, noise+allicin+DMSO, and noise+DMSO. Noise exposure was performed using 4 kHz octave-band noise at a sound pressure level (SPL) of 120 dB for 4 hours. Allicin (20 mg/kg/day, intraperitoneally) was administered for 7 days following noise exposure. Auditory brainstem response (ABR) thresholds (dB SPL) were measured at 8, 12, 16, 20, and 32 kHz at baseline, 24 hours, and day 7. Histopathological evaluation of the cochlea was performed after euthanasia. Results: Noise exposure significantly increased ABR thresholds in all noise-exposed groups. On day 7, the noise+allicin+ DMSO group demonstrated significantly lower ABR thresholds at 16, 20, and 32 kHz compared with the noise+SF group and at 20 and 32 kHz compared with the noise+DMSO group (p<0.05). No significant differences were observed at lower frequencies. Histopathological analysis showed a trend toward reduced cochlear damage in the allicin-treated group; however, the differences were not statistically significant. Conclusions: Allicin treatment improved high-frequency hearing thresholds in rats with NIHL. However, the absence of significant histopathological and mechanistic findings indicates that further molecular and region-specific studies are required.

Labyrinthine fistulas are a common complication of cholesteatomatous chronic otitis media (COM), with the lateral semicircular canal (LSCC) being the most frequently affected site. This retrospective cohort study aims to evaluate the clinical management of cases with LSSC fistula secondary to cholesteatomatous COM in a tertiary care hospital and analyze the obtained results along with the literature. Between January 2009 and June 2024, patients who developed LSSC fistula due to cholesteatomatous COM and underwent surgical treatment at our center were retrospectively analyzed. The study evaluated patients’ demographic data, presenting symptoms, radiological findings, preoperative and postoperative audiological assessments, surgical approaches applied, and postoperative follow-up processes. A total of 36 patients were included in the study. Of these, 21 (58.3%) were male and 15 (41.7%) were female, with a mean age of 49.2 years. Postoperatively, patients were followed up for a minimum of 4 weeks and a maximum of 1 year. LSCC fistulas were classified based on Durko labyrinthine fistula classification, revealing Type I in 31 cases (86%), Type II in 3 cases (8%), and Type III in 2 cases (6%). Canal wall-down mastoidectomy was performed in all patients, transtemporal in 33 (92%) and inside-out mastoidectomy in 3 patients (8%). In 11 patients (31%), the fistula was covered with a temporalis muscle fascia graft, whereas in 25 patients (69%), a combination of bone dust and temporalis fascia was used for repair. No cases of recurrent cholesteatoma were detected during postoperative follow-up. The bone conduction thresholds were preserved in all patients, highlighting the positive postoperative hearing outcomes and the potential for a successful recovery. LSCC fistula is a common complication in COM with cholesteatoma patients. Early diagnosis and complete, atraumatic removal of the cholesteatoma matrix with closure using temporalis fascia and/or bone dust is a safe and effective treatment approach.

Background/Objectives: This study aimed to evaluate factors necessitating alternative techniques during cochlear implant (CI) surgery and to compare outcomes with standard procedures. Methods: Patients of all ages who underwent CI at our center between January 2003 and January 2024 were included. Alternative methods were defined as removal of external auditory canal/posterior canal wall, removal of ossicles to enhance surgical view, use of an endoscope for round window visualization, or similar approaches. Results: A total of 404 patients (mean age 13 ± 19.7 years) were analyzed. Preoperative imaging revealed inner ear anomalies in 44 patients (10.9%). Alternative methods were used in 41 patients (10.1%), including incus removal (n = 16), endoscopic assistance (n = 14), posterior canal wall removal (n = 4), incus buttress removal (n = 3), combined ossicle removal (n = 3), and one canal wall down mastoidectomy with fat graft obliteration and blind pouch closure. Alternative methods were significantly more frequent in patients with inner ear anomalies or additional otologic disease (p = 0.01 and p < 0.01, respectively), but not across age groups (p = 0.65). Partial electrode insertion occurred in 17 cases. Electrode insertion and complication rates were comparable between groups (p = 0.08 and p = 0.99, respectively). Bony cochleostomy was significantly more common in the alternative methods group (p = 0.01). Conclusions: Inner ear anomalies and additional otologic diseases may necessitate alternative CI techniques. These methods achieve electrode insertion and complication rates comparable to standard approaches, supporting their effectiveness in selected cases.

Cisplatin is an alkylating chemotherapeutic drug used in the treatment of many pediatric solid tumors, and cisplatin ototoxicity is characterized by sensorineural, bilateral, irreversible, and progressive hearing loss. The aim of this study is to identify biomarkers that may serve as predictors of cisplatin-induced ototoxicity in pediatric cancers. In our preliminary study, patients with severe hearing loss were analyzed using the comparative genomic hybridization (CGH) method. Mutations were identified in the following genes: ADAM6, SIX3, GNAS, NDUFV1, H19, DEFA4, and ZIM2. Based on these data, we aimed to investigate the mutation status of these candidate genes in a larger population of pediatric cancer patients treated with cisplatin. DNA samples were extracted from the mononuclear cells of peripheral blood samples obtained from 82 patients. These genes were analyzed using the RT-PCR technique, and ototoxicity was assessed using the Brock and Muenster classifications. Hearing loss was detected in 28% of patients; 76.8% and 23.2% had mild and severe hearing loss, respectively. A significant correlation was found between ZIM2 gene amplification and the presence of ototoxicity (rho = 0.461, p = 0.003), especially in advanced-stage cancer patients with severe hearing loss (rho = 0.38, p = 0.017). Our findings suggest that ZIM2 is a promising biomarker for predicting cisplatin ototoxicity.

Background: This study aims to present our experiences regarding otitis media (OM) complications in a tertiary hospital and discuss them in light of the literature. Methods: In our study, the demographic information, findings at admission, radiological examinations, treatment approaches, and follow-up periods of the patients treated for OM complications at Dokuz Eylül University Hospital Ear Nose and Throat Clinic between January 2010 and January 2024 were retrospectively analyzed. Complications were grouped as acute otitis media (AOM), chronic otitis media (COM), and extracranial and intracranial complications. Results: In the study, 74 complications were observed in 67 patients, 44 of which were due to AOM and 30 due to COM. Thirty-nine patients were male (58.2%) and 28 were female (41.8%). The mean age was 28.7 years (2 months-78 years). Twenty-eight of the COM complications were extracranial, and 2 were intracranial. Extracranial complications consisted of 14 perilymphatic fistula (PLF), 11 cases of peripheral facial paralysis (PFP), 2 subperiosteal abscesses, and 1 Citelli abscess. There was a temporal lobe abscess and a sigmoid sinus thrombosis as intracranial complications. More than 1 complication was observed in 3 patients. A patient treated for temporal lobe abscess underwent radical mastoidectomy along with neurosurgery and intracranial abscess drainage. In 14 patients with PLF, the fistula was repaired with bone pates and soft tissues after the appropriate removal of the cholesteatoma. We managed to preserve hearing in all of these patients. While complete recovery was observed in 6 of the 11 PFP patients who underwent surgery, 3 patients had grade 2 PFP and 1 patient had grade 3 PFP according to the House–Brackmann staging system at the last follow-up. One patient voluntarily lost follow-up after the first month of the operation. Modi!ed radical mastoidectomy and medical treatment were applied to the patient who was diagnosed with sigmoid sinus thrombosis. At the second-month follow-up, it was observed that the thrombosed segment in the sinus was recanalized. Forty-four AOM complications were treated in 40 patients. Extracranial complications were listed as 14 subperiosteal abscesses, 10 cases of mastoiditis, 6 cases of labyrinthitis, and 4 PFP. Among the intracranial complications, sigmoid sinus thrombosis was observed in 6 patients, epidural abscess was observed in 3 patients, and otitic hydrocephalus was observed in 1 patient. All patients with subperiosteal abscesses underwent abscess drainage and a ventilation tube in addition to intravenous antibiotic therapy. Patients with PFP and labyrinthitis were treated with a ventilation tube, and patients were also given antibiotics and oral steroids. Intravenous antibiotics, abscess drainage, mastoidectomy, and anticoagulant treatment were applied to patients presenting with epidural abscess and sigmoid sinus thrombosis. Another remarkable situation is that after the emergence of the COVID-19 pandemic, AOM was the increase in complications. Eleven cases of AOM complications in 10 years before the pandemic. Thirty-three cases of AOM complications were observed after the emergence of the pandemic. Three of these 33 cases were diagnosed during the period when pandemic measures were implemented, including curfew, personal hygiene, wearing masks, and closing schools, while 30 were diagnosed after September 2021, when schools reopened after the pandemic and the measures were reduced. It is attractive. Conclusion: Otitis media complications are pathologies in which signi!cant morbidity and mortality can be prevented thanks to early diagnosis and treatment. In addition, these complications increased after the COVID-19 pandemic. For this reason, early diagnosis and treatment are important, as they are lifesaving. Cite this article as: Öncül EC, Olgun Y, Savaş Ö, Çakır Çetin A, Güneri EA. Our 14 years of clinical experience in otitis media complications. Balkan ORL-HNS 2025;2(1):15-21.

Background: This study was designed to assess if thiol-disulfide homeostasis could be used as diagnostic biomarker in noise-induced hearing loss (NIHL) in a laboratory animal model. Methods: The study was carried out with a total of 28 female albino rats in 4 groups: group 1 (control group) included rats that were not exposed to noise or any study treatment; in group 2, following noise exposure, rats received 2 mg of dexamethasone per kilogram of body weight via the intramuscular route for 5 days; in Group 3, rats were exposed to noise and received a saline solution for 5 days, in a volume (0.15 cc) matched to that of dexamethasone administered in group 2; and in group 4, rats were exposed to noise, and blood samples were collected during the early phase to assess thiol-disulfide homeostasis without administering any treatment. Rats in groups 2, 3, and 4 were exposed to 120 dB noise in the 4 kHz octave band for 4 hours. The auditory brainstem response (ABR) test was performed in all groups on day 1 after noise exposure and was repeated in groups 1, 2, and 3 on day 5. Auditory brainstem response thresholds were recorded at 8, 12, 16, 20, and 32 kHz frequencies. Groups 1, 2, and 3 rats were sacrificed on day 5, and group 4 rats were sacrificed by exsanguination on day 1 after noise exposure. Venous blood samples collected from the caudal vena cava were centrifuged and sent to the corresponding laboratory for thiol-disulfide homeostasis studies. After sacrificing the rats, the right and left temporal bones of each rat were removed and stained with hematoxylin eosin for histological studies to explore any pyknotic changes in spiral ganglion cells. Results: Intergroup comparisons by frequency on day 5 of noise exposure showed statistically significantly lower responses in ABR measurements at 8 kHz, 12 kHz, and 16 kHz in group 2 compared to group 3 (P = .003, P=.006, and P=.002). Improvements were observed with dexamethasone administered for therapeutic purposes, particularly if the hearing loss was induced by low-frequency noise. In the assessment of the parameters of thiol-disulfide homeostasis, disulfide/native thiol and disulfide/total thiol ratios and ischemia-modified albumin (IMA) levels were higher in group 4 than in other groups, although only the differences between group 1 and group 4 reached statistical significance. Conclusion: According to this study, thiol-disulfide homeostasis and IMA can be shown as diagnostic biomarkers in NIHL, especially in the early period. The results from our study suggest that these markers may be used as adjunctive diagnostic tools in NIHL, in addition to audiological studies. However, this issue can be clarified with further clinical studies. Cite this article as: Aydın E, Mungan Durankaya S, Yilmaz O, et al. Thiol-disulfide homeostasis in noise-induced hearing loss in rats. J Int Adv Otol. 2024;20(6):466-471.

Hearing loss significantly affects communication, social interactions, and the overall quality of life. The bone-anchored hearing aid (BAHA) is an implantable system that bypasses the outer and middle ear to directly stimulate the cochlea through bone conduction. This study aimed to compare hearing performance and subjective auditory ability improvements between transcutaneous and percutaneous BAHA devices using audiological assessments and Speech, Spatial and Qualities of Hearing Scale. This cross-sectional prospective study included 29 participants aged 14 to 69 years who had used BAHA for at least 6 months. Both Cochlear Baha System’s percutaneous (connect) and transcutaneous (attract) implants were evaluated. Audiological assessments involved pure-tone audiometry, speech recognition threshold, and free-field (FF) audiometry, while subjective auditory ability was measured using the Turkish Speech, Spatial and Qualities of Hearing scale (Tr-SSQ). Significant improvements in FF audiometry averages and speech recognition thresholds were observed with BAHA compared to without BAHA (P < .001). Both implant types provided similar FF averages, speech audiometry results, and Tr-SSQ outcomes, with no significant differences between them. Tr-SSQ scores showed substantial satisfaction, indicating significant improvements in speech perception, spatial perception, and hearing quality with BAHA (P < .001). The findings align with previous research, demonstrating that BAHA is a reliable and effective solution for hearing rehabilitation. The study also emphasized the importance of using both audiological test results and daily hearing function scales to comprehensively evaluate the benefits of hearing rehabilitation in real-world environments. In conclusion, BAHA, regardless of the implant type, can provide predictable and lasting improvements in hearing thresholds and daily hearing abilities, making it a valuable option for patients with conductive hearing loss.

BACKGROUND: Different organs respond differently to cisplatin (CDDP)-induced toxicity. Oleuropein (OLE) is a natural phenolic antioxidant. The purpose of this study was to determine the potential protective effect of OLE against CDDP-induced ototoxicity by evaluating expression of genes associated with deoxyribonucleic acid (DNA) damage and repair in cochlear cells. METHODS: House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated using CDDP, OLE, and OLE–CDDP. The water-soluble tetrazolium salt assay was used for monitoring cell viability. Deoxyribonucleic acid damage in cells due to the CDDP, OLE, and combination treatments was determined using a flow-cytometric kit. The change in the expression of 84 genes associated with CCDP, OLE, and OLE–CDDP treatments that induced DNA damage was tested using the reverse transcription polymerase chain reaction array. Changes ≥3-fold were considered significant. RESULTS: House Ear Institute-Organ of Corti 1 cell viability was significantly reduced by CDDP. The OLE–CDDP combination restored the cell viability. Cisplatin increased the H2AX ratio, while OLE–CDDP combination decreased it. Some of the DNA damage-associated genes whose expression was upregulated with CDDP were downregulated with OLE–CDDP, while the expression of genes such as Gadd45g and Rev1 was further downregulated. The expression of DNA repair-related Abl1, Dbd2, Rad52, and Trp53 genes was downregulated with CDDP, whereas their expression was upregulated with OLE–CDDP treatment. CONCLUSION: In cochlear cells, the OLE–CDDP combination downregulated DNA damage-associated gene expression relative to that upregulated mainly by CDDP. The results revealed that OLE has a potential protective effect on CDDP-induced ototoxicity in cochlear cells by altering the expression of DNA damage-related genes. Cite this article as: Olgun Y, Altun Z, Tütüncü M, Kum Özşengezer S, Aktaş S, Güneri EA. The impact of oleuropein on cisplatin-induced toxicity in cochlear cells in relation to the expression of deoxyribonucleic acid damage-associated genes. J Int Adv Otol. 2024;20(3):189-195.