Laryngeal Paraganglioma-A Case Report.

Background and Objectives: Paragangliomas of the head and neck are rare neuroendocrine tumors originating from the paraganglia, which might be sympathetic or parasympathetic. Laryngeal paragangliomas are the rarest subtype of these tumors, with only 1.41% of all paragangliomas, arising from the supraglottic or subglottic paraganglia of the larynx. The vast majority of them are benign, but there are some cases in which they turn out to be malignant, and the only way to know with certainty the difference between them is when we identify distant metastases. The aim of this article is to share our experience with a rare case of laryngeal paraganglioma and review the clinical characteristics, methods of diagnostic, necessary investigation prior to the operation, and surgical management of this type of tumor. Materials and Methods: We present the case of a 68-year-old female patient, a non-smoker, who accused dysphagia, dysphonia, foreign body sensation, chronic cough, and hoarseness for six months. We performed a tracheostomy prior to biopsy to secure the airways in case of bleeding and then took a few biopsy samples. The histopathological exam revealed the presence of a laryngeal paraganglioma. An enhanced CT scan was performed in order to describe the localization, size, and invasion of the tumor. We also measured the vanillylmandelic acid from the urine to determine if the tumor produced catecholamines alongside a full cardiology and endocrinology examinations. In order to prevent massive bleeding during the operation, chemoembolization was attempted before surgery, but it was unsuccessful due to an anatomical variation of the left superior thyroid artery. She underwent surgery, first through transoral endoscopic microsurgery; however, we decided to undertake an external approach because of poor bleeding control, even though we had ligated both the superior thyroid artery and the external carotid artery, with a thyrotomy and laryngofissure achieving the complete resection of the tumor. Results: The patient was discharged 10 postoperative days later, with the recommendation of introducing food step-by-step from liquids to solids. She was decannulated after 30 days, with no complications regarding breathing, phonation, or deglutition. Twelve months after the surgery, we did not identify any local relapses of distant metastases. Conclusions: Laryngeal paragangliomas are rare neuroendocrine tumors that arise from the laryngeal paraganglia. Surgery is the best treatment option available, and it can be done by either an external approach or by transoral endoscopy. Enhanced CT or MRI, as well as full cardiological and endocrinological evaluation are mandatory prior to the operation. Measuring the catecholamines levels show the if the tumor is secretory. Controlling the bleeding poses the biggest challenge in performing the resection of the tumor, especially when a transoral endoscopic approach is chosen. Further standardized follow-up guidelines are required in the future.

Vertigo Associated with Otosclerosis and Stapes Surgery-A Narrative Review.

Otosclerosis is a pathological condition affecting the temporal bone, and is characterized by remodelling of the labyrinthine bone tissue through a dynamic process of osteolysis and osteogenesis. This condition progressively leads to hearing loss, tinnitus, and vertigo. Stapedotomy, a surgical procedure involving the removal of the stapes superstructure and its replacement with a prosthesis, is the treatment of choice to improve hearing in individuals with otosclerosis. However, vestibular dysfunction is a significant complication associated with this procedure, which can occur intraoperatively or postoperatively, ranging from the immediate postoperative period to weeks, months, or even years after surgery. This paper aims to provide a comprehensive review of the most important causes of vertigo associated with otosclerosis and stapes surgery with the goal of minimizing the incidence of this complication. Understanding the underlying factors contributing to vertigo in this context is crucial for the prevention and effective management of vertigo in patients undergoing stapedotomy.

Sheep's Head as an Anatomic Model for Basic Training in Endoscopic Sinus Surgery.

Background and Objectives: This study aims to establish the sheep head as a viable anatomical model for training in functional endoscopic sinus surgery through comprehensive anatomical examination and training-based assessment of participants' satisfaction. Materials and Methods: Participants were divided into three groups according to their prior experience in endoscopic sinus surgery; in total, 24 participants were included. Each participant in the study was assigned to perform the designated procedures on a single sheep's head. Following the completion of the procedures, each participant was provided with a 14-item comprehensive satisfaction questionnaire with a scale attributed from 1 to 5. The normality of distribution was checked by applying the Shapiro-Wilk Test. The Kruskal-Wallis test was applied to compare study group sentiment of agreement towards individual procedures. Results: No significant differences were noted between the answers of the different groups. For the resident group, the average satisfaction score was 4.09 ± 0.54; junior specialist group 4.00 ± 0.55; for the senior specialist group overall satisfaction average score was 4.2 ± 0.77. Conclusions: The sheep's head can be successfully used for learning and practicing manual skills and the use of instruments specific to functional endoscopic sinus surgery. Moreover, the sheep head model can be used for training in other diagnostic or surgical procedures in the field of otorhinolaryngology, such as endoscopy of the salivary glands, open laryngotracheal surgery, or in otologic surgery, but also in other different surgical fields such as neurosurgery, ophthalmology or plastic surgery. Despite the differences between the ovine model and human anatomy, it provides a resourceful and cost-effective model for beginners in endoscopic nasal surgery.

Do Polymorphisms of the TERT, GSTM1, and GSTT1 Genes Increase Laryngeal Cancer Susceptibility in Smokers of Romanian Descent?

Background and Objectives: The aim of this study was to investigate the association between smoking status and single-nucleotide polymorphism in candidate genes that had a known association with smoking-related tumors in previous studies and to explore their link to laryngeal cancer risk in a population of northern Romanian descent. The genes selected have key functions in xenobiotic metabolism (GSTs: the glutathione S-transferases family: GSTM1 and GSTT1) and chromosomal management (TERT). Materials and Methods: The genotype frequencies of TERTRs2736100 and the GST subfamilies (GSTM1 and GSTT1) were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The relationship between the polymorphisms and the risk of laryngeal cancer was analyzed in a retrospective case-control study of 92 laryngeal cancer cases and 101 controls, all of whom were smokers. Results: Subjects presenting the GSTT1-null variant had a two-fold increase in risk (OR = 2.05, 95% CI = 1.07-3.95, p = 0.02). While no individual risk was observed for the TERTRs2736100 polymorphism, stratification based on gender revealed a nine-fold increase in risk for carriers of the "C" allele in the heterozygote variant who were male (OR = 9, 65% CI = 3.51-26.51, p = 0.0000). Conclusions: The results showed that the GSTT1-null genotype and the mutant heterozygote variant of TERTRs2736100 genes may play a significant role in laryngeal cancer susceptibility in subjects of northern Romanian descent. There may be no association between the susceptibility to laryngeal carcinoma and the GSTM1 polymorphism. The results could not confirm the carcinogenic influence smoking has on laryngeal cancer development for the studied polymorphisms.

The Effect of Platelet-Rich Plasma Injection on Short Term Vocal Outcomes Following Phonosurgery-A Pilot Study.

Background and Objectives: The efficiency and optimal voice rest period following phonosurgery remains debatable. Platelet-rich plasma (PRP) is a safe and cheap alternative to many bioactive agents being studied on animal models, and is already in use in many medical areas. We investigate the short-term effects of PRP and voice rest on voice outcomes following phonosurgery as an alternative to voice rest alone. Materials and Methods: A prospective single-blinded pilot study was conducted. Sixteen patients with a diagnosis of vocal fold cyst and polyps were included, forming equal groups (PRP and voice rest vs. voice rest alone). Voice analysis was carried out on the preoperative day, day three, and week three following surgery. The measured parameters were fundamental frequency (F0), noise-signal ratio (NSR), harmonic poverty (HP), attack alteration (AL), pitch instability (PI), and amplitude instability (AI).VHI(Voice Handicap Index)-30 questionnaires were carried out before surgery and three weeks following surgery to assess the impact of subjective voice change on quality of life. PRP was obtained using commercial kits with separator gel. Results: An average 3.68-fold increase in platelets was obtained with PRP. No side effects were noted after injection. All voice parameters improved on day three and week three following surgery. Statistical significance was noted only in the fundamental frequency of male patients (p = 0.048) in favor of the PRP-voice rest group. In addition, the VHI- 30 questionnaire results between preoperative and postoperative assessments showed statistically significant differences in total VHI score (p = 0.02) as well as the physical (p = 0.05) and emotional (p = 0.02) scale in favor of the PRP-voice rest group. Conclusions: PRP presents short term safety in patients who undergo phonosurgery, although long-term outcomes are unknown. PRP and voice rest are superior to voice rest alone when considering subjective assessment of the voice. When analyzing acoustic parameters, PRP and voice rest are not superior to voice rest alone.

Current Concepts and Future Trends in Increasing the Benefits of Cochlear Implantation: A Narrative Review.

Hearing loss is the most common neurosensory disorder, and with the constant increase in etiological factors, combined with early detection protocols, numbers will continue to rise. Cochlear implantation has become the gold standard for patients with severe hearing loss, and interest has shifted from implantation principles to the preservation of residual hearing following the procedure itself. As the audiological criteria for cochlear implant eligibility have expanded to include patients with good residual hearing, more attention is focused on complementary development of otoprotective agents, electrode design, and surgical approaches. The focus of this review is current aspects of preserving residual hearing through a summary of recent trends regarding surgical and pharmacological fundamentals. Subsequently, the assessment of new pharmacological options, novel bioactive molecules (neurotrophins, growth factors, etc.), nanoparticles, stem cells, and gene therapy are discussed.

Zeaxanthin-Rich Extract from Superfood Lycium barbarum Selectively Modulates the Cellular Adhesion and MAPK Signaling in Melanoma versus Normal Skin Cells In Vitro.

The concern for implementing bioactive nutraceuticals in antioxidant-related therapies is of great importance for skin homeostasis in benign or malignant diseases. In order to elucidate some novel insights of Lycium barbarum (Goji berry) activity on skin cells, the present study focused on its active compound zeaxanthin. By targeting the stemness markers CD44 and CD105, with deep implications in skin oxidative stress mechanisms, we revealed, for the first time, selectivity in zeaxanthin activity. When applied in vitro on BJ human fibroblast cell line versus the A375 malignant melanoma cells, despite the moderate cytotoxicity, the zeaxanthin-rich extracts 1 and 2 were able to downregulate significantly the CD44 and CD105 membrane expression and extracellular secretion in A375, and to upregulate them in BJ cells. At mechanistic level, the present study is the first to demonstrate that the zeaxanthin-rich Goji extracts are able to influence selectively the mitogen-activated protein kinases (MAPK): ERK, JNK and p38 in normal BJ versus tumor-derived A375 skin cells. These results point out towards the applications of zeaxanthin from L. barbarum as a cytoprotective agent in normal skin and raises questions about its use as an antitumor prodrug alone or in combination with standard therapy.

Effects of family environment features on cochlear-implanted children.

PURPOSE: The role of cochlear implant in deaf children development is well-known. However, the results are highly variable and depend on several factors. The most important role belongs to the family, family environment in which the child develops. The aim of the study was to evaluate the features of the family environment in which cochlear-implanted children develop. METHODS: The questionnaire "Family Environment Scale" was sent to 108 families who had cochlear-implanted child with more than 6 months of experience. One of the parents was asked to fill out the questionnaire which also included general information about the child and the family. RESULTS: A total of 58 families responded to the questionnaire and accepted to participate in the study. Mean values were higher compared with normal families in the areas of cohesion, expressiveness, intellectual-cultural orientation and organization, but the cohesion and organization score mean value exceeded the normal values (between 40 and 60). The independence and the conflict areas had lower values than normal families but did not exceed the lower limit of normal (40). CONCLUSIONS: The relationship between the family and the auditory-verbal development potential of the cochlear-implanted child is obvious. However, further studies are needed to establish correlations between the characteristics of the family environment and the level of auditory-verbal and psycho-cognitive development of the cochlear-implanted child so we can act on the family environment through education or therapy, to get maximum benefit with these children.

Exploring the Ovine Anatomy: A Comprehensive Study of the Sheep's Head for Basic Training in Functional Endoscopic Sinus Surgery.

INTRODUCTION: Training young doctors in functional endoscopic sinus surgery requires dedicated centers for cadaveric dissections. However, ethical constraints have limited cadaver availability. Alternative anatomical models, like the ovine model, are being explored for effective training, offering easier procurement and resembling human head anatomy. This study aims to demonstrate that the ovine model is useful for endoscopic sinus surgery training, highlighting the anatomical, imaging, histological, and endoscopic aspects. METHODS: Three adult Native Romanian Turcana sheep's heads were obtained fresh and frozen from a local slaughterhouse. Using a helical scanner, CT scans were performed, and anatomical structures in the images were carefully labeled. Two heads frozen at -20°C were serially sectioned, with one cut sagittally, dividing the skull, and the other head sectioned transversely with 2.5 cm thickness. Sectional photographs were taken. The third sheep's head underwent endoscopy, and samples from the septal mucosa and inferior turbinate were collected for histopathology examination. The specimens were processed, stained, and examined by a pathologist. RESULTS: The study successfully highlighted the gross anatomy, CT imaging aspects, histological characteristics of sheep nasal mucosa, and endoscopic features, demonstrating the similarity of the sheep's head to human anatomy, making it a suitable anatomical training model for endoscopic sinus surgery. CONCLUSION: The use of sheep's heads as substitutes for human cadaver heads in nasal surgery simulations presents a promising avenue for research. The anatomical similarities and cost-effectiveness make sheep's heads a practical choice for certain aspects of nasal surgery investigation. However, researchers must approach this methodology with a thorough understanding of its limitations, including anatomical and biomechanical differences. Validation studies comparing outcomes with human models are crucial to establishing reliability. The sheep's head anatomical model provides a highly valuable experience for young trainees in endoscopic sinus surgery. Despite encountering several challenges, including some anatomical differences, considering its advantageous attributes renders it an ideal material for mimicking surgical procedures in functional endoscopic sinus surgery.

Hand Motion Analysis Using Accelerometer-Based Sensors and Sheep's Head Model for Basic Training in Functional Endoscopic Sinus Surgery.

INTRODUCTION:  Motion analysis, the study of movement patterns to evaluate performance, plays a crucial role in surgical training. It provides objective data that can be used to assess and improve trainee's precision, efficiency, and overall surgical technique. The primary aim of this study is to employ accelerometer-based sensors placed on the wrist to analyze hand motions during endoscopic sinus surgery training using the sheep's head. By capturing detailed movement data, the study seeks to quantify the motion characteristics that distinguish different levels of surgical expertise. This approach seeks to quantify motion characteristics indicative of surgical expertise and enhance the objectivity and effectiveness of surgical training feedback mechanisms. MATERIALS AND METHODS:  Twenty-four participants were divided into three groups based on their experience with endoscopic endonasal surgery. Each participant was tasked with performing specified procedures on an individual sheep's head, concentrating on exploring both nasal passages. A single Bluetooth Accelerometer WitMotion sensor was mounted on the dorsal surface of each hand. This facilitates the evaluation of efficiency parameters such as time, path length, and acceleration during the training procedures. Accelerometer data were collected and imported in CSV format (comma-separated values) for each group of surgeons-senior, specialist, and resident-mean values and standard deviations were computed. The Shapiro-Wilk Test assessed the normality of the distribution. The Kruskal-Wallis test was employed to compare procedural time, acceleration, and path length differences across the three surgeon experience levels. RESULTS:  For the procedural time, statistical significance appears in all surgical steps (p<0.001), with the biggest difference in the septoplasty group in favor of the senior group. A clear difference can be observed between the resulting acceleration of the dominant hands (instrument hand) and the non-dominant hand (endoscopic hand) and between the study groups. The difference between groups reaches statistical significance with a p-value <0.001. A statistically significant difference can be seen between the paths covered by each hand of every participant (p<0.001). Also, senior doctors covered significantly less movement with both hands than the specialists and the resident doctors (p<0.001). CONCLUSIONS:  The data show a clear learning curve from resident to senior, with residents taking more time and using more hand movements to complete the same tasks. Specialists are in the intermediate phase, showing signs of honing their technique towards efficiency. This comprehensive data set can help tailor training programs to focus on both efficiency (quicker procedures) and economy of motion (reduced path length and acceleration), especially in more complex procedures where the difference in performance is more pronounced.

Rapid progressive bilateral hearing loss due to granulomatous otitis media in Lyme disease.

We report on a patient with Lyme disease who presented with chronic bilateral otitis media and cranial neuropathy with rapid progressive hearing loss. After ceftriaxone and high-dose intravenous immunoglobulins, the disease was controlled only with methylprednisolone and cyclophosphamide. The relationship between Lyme disease and granulomatous vasculitis is discussed. Lyme disease should be kept in mind in the differential diagnosis of various otolaryngological and neurological presentations.

Technical and functional hearing results after unilateral stapes surgery for otosclerosis at Cluj-Napoca University Hospital.

The aim of this study was to assess the hearing results after unilateral stapes surgery for otosclerosis at Cluj-Napoca University Hospital, and to evaluate surgical trauma to the inner ear in these patients. The medical records of 387 consecutive patients who underwent unilateral stapes surgery were reviewed. Hearing results were evaluated according to the 1995 American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines and the Glasgow benefit plot. In addition we used Amsterdam plot to give an overview on air conduction gain and bone-conduction differences on an individual level. Results were analyzed separately for patients with preoperative unilateral, bilateral asymmetrical, and bilateral symmetrical hearing loss. Despite good technical hearing results after surgery (closure of the air-bone gap to ≤20 dB in 92% of patients, air conduction gain of 24 ± 10.00 dB), only 37% of patients achieved functionally normal, symmetrical hearing. Our results indicated that the pattern of preoperative hearing impairment in patients with otosclerosis can predict postoperative functional hearing results. The type of preoperative hearing impairment had.

Laser nasal surgery (Review).

Laser nasal surgery has been an elusive subject in the last 10 to 15 years It was considered as a potential surgical staple for nasal surgery in the 1980s; however, it did not become one due to technical difficulties. Laser therapy has reemerged as an alternative to classical endoscopic surgery, and otorhinolaryngology surgeons are considering the benefits that it can offer. The advantages of this procedure are shorter hospitalization time, lack of nasal packing, high procedural precision with tissue sparing, and the unique capability of reducing both bacterial and fungal colonization at the level of the paranasal sinus. Therefore, laser therapy appears to be an invaluable tool for clinical practice. Due to the absence of a guaranteed cure for reoccurring nasal polyposis, laser therapy is worth investigating. For this therapy to evolve, an improved understanding of laser types and the effects that they produce is required. By investing in further developments of the equipment, the technique may become more widely used. With the current accelerated rate of technological evolution and robotic capabilities, laser nasal surgery may become a gold standard in future years. The aim of the present review is to evaluate whether it is worth investing in nasal laser surgery as a future alternative to current treatment standards.

Can Non-Virtual Reality Simulation Improve Surgical Training in Endoscopic Sinus Surgery? A Literature Review.

Simulation in endoscopic sinus surgery allows residents to learn anatomy, to achieve the correct handling of various rhinological instruments, and to practice different surgical procedures. Physically or non-virtual reality models are the main items in endoscopic sinus surgery simulation. The objective of this review is to identify and make a descriptive analysis of non-virtual endoscopic sinus surgery simulators which have been proposed for training. As a new state of the art, surgical simulators are developed continuously, so they can be used to learn basic endoscopic surgery skills by repetitive maneuvers, permitting detection of surgical error and incidents without risk for the patient. Of all training physical models, the ovine model stands out because of the similarities of the sinonasal pathways, the wide availability, and the low costs. Considering the similar nature of the tissues involved, the techniques and surgical instruments can be used almost interchangeably with minimal differences. Every surgical technique studied until now has a degree of risk and the only aspects that consistently reduced the number of complications are training, repetition, and hands-on experience.

Analysis of TERT Rs2736100 genotype distribution in laryngeal squamous cell carcinoma patients.

The applicability of the telomerase reverse transcriptase (TERT) gene Rs2736100 polymorphism in cancer research has been well documented for various malignancies except for head and neck cancers, where data is sparse. This study aimed to analyze this polymorphism with the pathological characterizers of laryngeal squamous cell carcinoma (LSCC) patients. Genetic testing was performed using the Real-time PCR technique on 56 paired samples of biological material (blood and tissue). Data were analyzed using Epi info 7 software. The subjects were predominantly male (95% vs. 5%), with a median age of 62 years, and smokers (89%). The primary tumor origin site was the glottic region (34%), and the advanced clinical stages III-IV were more common (46% vs. 18%). Results show high frequencies for the mutated variants of Rs2736100 (CC 36%>AC 34%>AA 30%), while distribution according to tumor classification criteria leaned towards moderately differentiated carcinoma specimens in T3-T4 stages for the AC/CC variants (P-value without statistical significance) but positively favored the relationship between the AA variant and lack of lymph node metastasis (P=0.0106). The genotypes tend to associate themselves with a better histological presentation regarding the pattern of tumor invasion and, thus, better prognostic values for LSCC. Results suggest that the wild-type genotype of TERT Rs2736100 may be a protective factor for lymph node metastasis and histological pattern of tumor invasion in LSCC. Results regarding the synergistic relationship between cancer and smoking corroborate literature data for moderate to severe smokers regardless of the genetic variant.

Vocal fold injury models in rats: a literature review on techniques and methodology.

This study reviewed the current literature on technical aspects regarding controlled vocal fold injuries in the rat model. Data from PubMed, Embase, and Scopus database for English language literature was collected to identify methodological steps leading to a controlled surgical injury of the rat vocal fold. Inclusion criteria: full disclosure of anesthesia protocol, positioning of the rat for surgery, vocal fold visualization method, instrumentation for vocal fold injury, vocal fold injury type. Articles with partial contribution were evaluated and separately included due to the limited number of original methodologies. 724 articles were screened, and eleven articles were included in the analysis. Anesthesia: ketamine hydrochloride and xylazine hydrochloride varied in dose from 45 mg/kg and 4.5 mg/kg to 100 mg/kg and 10 mg/kg. Visualization: The preferred method was the 1.9 mm, 25-30 degree endoscopes. The widest diameter endoscope used was 2.7 mm with a 0 or 30 degree angle of view. Instruments for lesion induction range from 18 to 31G needles, microscissors, micro forceps to potassium titanyl phosphate, and blue light lasers. Injury types: vocal fold stripping was the main injury type, followed by vocal fold scarring and charring. One article describes scaffold implantation with injury to the superior aspect of the vocal fold. Rats are good candidates for in vivo larynx and vocal folds research. A more standardized approach should be considered regarding the type of vocal fold injury to ease data comparison.

Experimental model for controlled endoscopic subepithelial vocal fold injury in rats.

PURPOSE: To present a detailed, reproducible, cost-efficient surgical model for controlled subepithelial endoscopic vocal fold injury in the rat model. METHODS: Six male Sprague Dawley rats were enrolled in the experiment. The left vocal folds were used to carry out the injury model, and the right vocal fold served as control. After deep sedation, the rats were placed on a custom operating platform. The vocal fold injury by subepithelial stripping was carried out using custom-made microsurgical instruments under endoscopic guidance. Data were analyzed for procedural time and post-procedural pain. Microcomputed tomography (micro-CT) scan and histologic images were obtained to assess the length, area, and depth of injury to the vocal fold. RESULTS: The mean procedural time was 112 s. The mean control vocal fold length was 0.96 ± 0.04 mm. The mean vocal fold injury length was 0.53 ± 0.04 mm. The mean vocal fold surface was 0.18 ± 0.01 mm2 with a mean lesion area of 0.05 ± 0.00 mm2. Mean vocal fold injury depth was 375.4 ± 42.8 µm. The lesion length to vocal fold length ratio was 0.55 ± 0.03, as well as lesion area to vocal fold surface area was 0.29 ± 0.02. CONCLUSIONS: Our described experimental vocal fold injury model in rats is found to be fast, safe, cost-efficient, and reproducible with a rapid learning curve.

The Effect of Pluronic-Coated Gold Nanoparticles in Hearing Preservation Following Cochlear Implantation-Pilot Study.

Introduction: During cochlear implantation, electrode insertion can cause cochlear damage, inflammation, and apoptosis, which can affect the residual hearing. Nanoparticles are increasingly studied as a way to increase the availability of inner ear protective factors. We studied the effect on rats of Pluronic-coated gold nanoparticles (Plu-AuNPs) containing dexamethasone, which were applied locally in the rat's middle ear following the implant procedure. Methods: Seven rats were used in the study. The right ear served as a model for the Dex-Plu-AuNP group. Following the intracochlear dummy electrode insertion through the round window, Dex-Plu-AuNPs were placed in the round window niche. In the right ear, following the same insertion procedure, free dexamethasone (Dex) was placed in the same manner. Auditory brainstem response thresholds (click stimulus, pure tones at 8 kHz, 16 kHz, 24 kHz, and 32 kHz) were measured before and one week after the procedure. A two-tailed T-test was used for the variables. Statistical significance was set as p < 0.05. Results: In the Dex-Plu-AuNP group, the threshold shift was less than that in the free dexamethasone group, but no statistical significance was noted between the groups. When compared individually, only the 8 kHz frequency showed statistically significant, better results after one week, in favor of the Dex-Plu-AuNP group. The mean postoperative 8 kHz threshold in the Dex-Plu-AuNPs was significantly lower than that of the control group (p = 0.048, t-test). For the other frequencies, statistical analysis showed no significant differences between the mean threshold shifts of the two cohorts. Conclusions: The local application of Plu-AuNPs containing dexamethasone following cochlear implantation may better protect the residual hearing than dexamethasone alone, but a larger sample size is needed to reach a possible statistical significance. Dex-Plu-AuNPs do not seem to cause ototoxicity and may be used as a carrier for other agents. In a clinical setting, Dex-Plu-AuNPs may have the effect of protecting lower frequencies in patients with partial deafness who are candidates for electric acoustic stimulation (EAS). If we consider this tendency, Dex-Plu-AuNPs may also be beneficial for patients with Ménière's disease.

Biopolymer Lipid Hybrid Microcarrier for Transmembrane Inner Ear Delivery of Dexamethasone.

Dexamethasone is one of the most often used corticosteroid drugs for sensorineural hearing loss treatment, and is used either by intratympanic injection or through systemic delivery. In this study, a biopolymer lipid hybrid microcarrier was investigated for enhanced local drug delivery and sustained release at the round window membrane level of the middle ear for the treatment of sensorineural hearing loss (SNHL). Dexamethasone-loaded and dexamethasone-free microparticles were prepared using biopolymers (polysaccharide and protein, pectin and bovine serum albumin, respectively) combined with lipid components (phosphatidylcholine and Dimethyldioctadecylammonium bromide) in order to obtain a biopolymer-liposome hybrid system, with a complex structure combining to enhance performance in terms of physical and chemical stability. The structure of the microparticles was evaluated by FTIR, XRD, thermal analysis, optical microscopy, and scanning electron microscopy (SEM). The encapsulation efficiency determination and the in vitro Dexamethasone release study were performed using UV-Vis spectroscopy. The high value of encapsulation efficiency and the results of the release study indicated six days of sustained release, encouraging us to evaluate the in vitro cytotoxicity of Dexamethasone-loaded microparticles and their influence on the cytotoxicity induced by Cisplatin on auditory HEI-OC1 cells. The results show that the new particles are able to protect the inner ear sensory cells.

The expression of copper transporters associated with the ototoxicity induced by platinum-based chemotherapeutic agents.

BACKGROUND: Antitumor agents based on platinum have gained a well-established place in the treatment of several forms of cancer. Their efficiency is hampered by serious toxic effects against healthy tissues as well. Ototoxicity is a serious side effect leading to hearing impairment and represents an important issue affecting the patients' quality of life. The currently used platinum chemotherapeutics exert different toxicity towards cochlear cells. The aim of our study was to answer some questions regarding the differential uptake and cellular pharmacodynamics of Cisplatin (CDDP), Carboplatin (CBDCA) and Oxaliplatin (L-OHP) in the HEI-OC1 cochlear cell line. METHODS: We studied the expression of copper transporters CTR1, ATP7A and ATP7B which are presumably involved in the uptake, cellular transport and efflux of platinum compounds by immunofluorescence microscopy and flow-cytometry. The cellular uptake of the compounds was evaluated through the determination of intracellular platinum concentration by atomic absorption spectroscopy. The effects of the treatment of HEI-OC1 cells with platinum compounds were also evaluated: cytotoxicity with the Cell Titer Blue viability test, formation of reactive oxygen species with 2',7' -dichlorofluorescein diacetate, genotoxicity with the comet assay and apoptosis with the cleaved PARP ELISA test. RESULTS: CTR1, ATP7A and ATP7B were all expressed by HEI-OC1 cells. The treatment with the platinum compounds led to a modulation of their expression, manifested in a differential platinum uptake. Treatment with Cisplatin led to the highest intracellular concentration of platinum compared to Oxaliplatin and Carboplatin at the same dose. Treatment with CuSO4 reduced platinum uptake of all the compounds, significantly in the case of Cisplatin and Carboplatin. CDDP was the most cytotoxic against HEI-OC1 cells, with an IC50 = 65.79  µM, compared to 611.7 µM for L-OHP and 882.9 µM for CBDCA, at the same molar concentration. The production of ROS was the most intense after CDDP, followed by L-OHP and CBDCA. In the comet assay, at the 100 µM concentration, L-OHP and CBDCA induced DNA adducts while CDDP induced adducts as well as DNA strand breaks. CBDCA and L-OHP lead to a significant increase of cleaved PARP at 24h (p < 0.001), suggesting an important apoptotic process induced by these compounds at the used concentrations. CONCLUSIONS: The results obtained in the current study suggest that the modulation of copper transporters locally may represent a new strategy against platinum drugs ototoxicity.