How to manage recurrences after surgery in CRSwNP patients in the biologic era: a narrative review.

Objective: This narrative review analyses factors affecting recurrence of Chronic rhinosinusitis with nasal polyps (CRSwNP) after surgery, such as type, extension and completeness of endoscopic sinus surgery (ESS). We also described new implications in the management of recurrences after the advent of biologics. Methods: We identified four topics: definition of disease state; factors linked to recurrence of polyps; evaluation and management of recurrence in clinical practice. Results: We analysed the differences between exacerbation and recurrence, as well as the concept of "controlled disease". We focused on potential predictors of recurrence after ESS, such as type 2 inflammation, asthma, aspirin-exacerbated respiratory disease, incomplete initial surgery and lack of adherence to long-term post-operative local corticosteroids. We discussed the new aspects of diagnosis and treatment of recurrences after surgery, summarising our suggestions in a detailed algorithm for practical management of patients with recurrent disease. Conclusions: The results emphasised the importance of accurate evaluation of patients with CRSwNP recurrence, focusing on the reasons of failure and risk of disease progression, in order to guide personalised interventions. It is crucial to define the concept of appropriate surgery, which affects the choice between starting a biologic or repeating surgery.

Study of Angiogenic, Pro-Apoptotic, and Pro-Inflammatory Factors in Congenital and Acquired Cholesteatomas.

OBJECTIVES: Despite recent advances in biomolecular research that have improved our knowledge of cholesteatoma pathogenesis, the reasons behind its highly variable clinical course are still not clarified. It has been proposed that biological signaling between peri-matrix and matrix cells could play a critical role in disease homeostasis. The aim of our study was to analyze the expression of inflammatory (IL-1ß), hyper-proliferative (STAT-3, TGF-ß), and angiogenic (VEGF-C, PDGFr) factors in congenital and acquired cholesteatomas (both in adults and children), which might correlate with the clinical features observed. We performed an experimental study on 37 patients (29 males and 8 females, ranging from 4 to 66 years of age) who were diagnosed with cholesteatoma between 2020 and 2021 in our institution. All patients underwent clinical, audiologic, and radiologic assessments. Bone erosion grading and staging of cholesteatoma growth were assessed through preoperative evaluation and intraoperative middle ear findings, according to the PTAM System proposed by the Japan Otological Society (2016). Retro-auricular skin specimens were intraoperatively collected in all patients. Skin and cholesteatoma samples were analyzed through histopathological, western blot, and immunohistochemical evaluations. The expression rate was measured to find out the differences between congenital and acquired cholesteatomas as well as between the adult and pediatric populations. Expression of angiogenic, inflammatory, and proliferative biomarkers is significantly increased in acquired cholesteatomas in children as compared to congenital and acquired forms in adults, in accordance with the higher stage of disease shown by imaging, surgical, and histological features. Our data suggest that pathways already supposed to be involved in the pathogenesis of cholesteatomas could be differently activated in more destructive forms, typically found in children. The identification of potential biomarkers of cholesteatoma aggressiveness could lead to more personalized management (timing of intervention, recurrence prevention) and the future identification of anti-growth/anti-proliferative agents as non-surgery therapeutic options.

Artificial intelligence for the recognition of benign lesions of vocal folds from audio recordings.

Objective: The diagnosis of benign lesions of the vocal fold (BLVF) is still challenging. The analysis of the acoustic signals through the implementation of machine learning models can be a viable solution aimed at offering support for clinical diagnosis. Materials and methods: In this study, a support vector machine was trained and cross-validated (10-fold cross-validation) using 138 features extracted from the acoustic signals of 418 patients with polyps, nodules, oedema, and cysts. The model's performance was presented as accuracy and average F1-score. The results were also analysed in male (M) and female (F) subgroups. Results: The validation accuracy was 55%, 80%, and 54% on the overall cohort, and in M and F, respectively. Better performances were observed in the detection of cysts and nodules (58% and 62%, respectively) vs polyps and oedema (47% and 53%, respectively). The results on each lesion and the different patterns of the model on M and F are in line with clinical observations, obtaining better results on F and detection of sensitive polyps in M. Conclusions: This study showed moderately accurate detection of four types of BLVF using acoustic signals. The analysis of the diagnostic results on gender subgroups highlights different behaviours of the diagnostic model.

Impact of lymph node ratio and number of lymph node metastases on survival and recurrence in laryngeal squamous cell carcinoma.

INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. METHODS: This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. RESULTS: We observed a significant decrease in NPS from a median value of 6 (IQR 5-6) at baseline to 1.0 (IQR 0.0-2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49-70) at baseline to 11 (IQR 6-21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. CONCLUSIONS: Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell.

Noise-induced auditory damage affects hippocampus causing memory deficits in a model of early age-related hearing loss.

Several studies identified noise-induced hearing loss (NIHL) as a risk factor for sensory aging and cognitive decline processes, including neurodegenerative diseases, such as dementia and age-related hearing loss (ARHL). Although the association between noise- and age-induced hearing impairment has been widely documented by epidemiological and experimental studies, the molecular mechanisms underlying this association are not fully understood as it is not known how these risk factors (aging and noise) can interact, affecting memory processes. We recently found that early noise exposure in an established animal model of ARHL (C57BL/6 mice) accelerates the onset of age-related cochlear dysfunctions. Here, we extended our previous data by investigating what happens in central brain structures (auditory cortex and hippocampus), to assess the relationship between hearing and memory impairment and the possible combined effect of noise and sensory aging on the cognitive domain. To this aim, we exposed juvenile C57BL/6 mice of 2 months of age to repeated noise sessions (60 min/day, pure tone of 100 dB SPL, 10 kHz, 10 consecutive days) and we monitored auditory threshold by measuring auditory brainstem responses (ABR), spatial working memory, by using the Y-maze test, and basal synaptic transmission by using ex vivo electrophysiological recordings, at different time points (1, 4 and 7 months after the onset of noise exposure, corresponding to 3, 6 and 9 months of age). We found that hearing loss, along with accelerated presbycusis onset, can induce persistent synaptic alterations in the auditory cortex. This was associated with decreased memory performance and oxidative-inflammatory injury in the hippocampus, the extra-auditory structure involved in memory processes. Collectively, our data confirm the critical relationship between auditory and memory circuits, suggesting that the combined detrimental effect of noise and sensory aging on hearing function can be considered a high-risk factor for both sensory and cognitive degenerative processes, given that early noise exposure accelerates presbycusis phenotype and induces hippocampal-dependent memory dysfunctions.

Real-Life Experience in the Management of Sinonasal Complications of Dental Disease or Treatments.

Diagnosis and management of sinonasal complications of dental diseases or treatment (SCDDT) may be challenging. We aimed to report our real-life experience in patients treated with endoscopic endonasal approach describing data about symptoms, etiology, extension of the disease and success rate. We evaluated retrospectively data about 262 patients diagnosed as SCDDT and managed from August 2015 to May 2022. In 44.65% cases, maxillary sinus complications were determined by a dental disorder; the remaining 55.34% of cases were iatrogenic. Patients were managed according to our multidisciplinary protocol including ENT, dental, and radiological evaluation. Treatments were planned with a personalized approach, based on the patient's clinical characteristics; all patients were treated with an endonasal endoscopic mini-invasive conservative approach. Combined dental treatment was performed simultaneously in 152/262 (58%) of patients; in the remaining cases, it was postponed after surgery. The overall treatment success rate (symptom resolution and endoscopically observed maxillary sinus healing) was 96.5%. At 15 days after surgery, we observed a significant improvement in the quality of life. The mean post-operative Sinonasal outcome test-22 (SNOT-22) score was significantly lower compared to baseline (6 versus 43.4; p < 0.05). Our study showed that endoscopic sinus surgery can be a successful procedure for treatment of SCDDT, leading to fast resolution of sinonasal symptoms and improving the quality of life. Furthermore, the technique allows removal of migrated dental material or dental implants even in challenging cases.

Posturographic Analysis in Patients Affected by Central and Peripheral Visual Impairment.

Although vision loss is known to affect equilibrium maintenance, postural control in patients affected by low vision has been poorly investigated. We evaluated postural stability and the ability to use visual, proprioceptive and vestibular information in different low vision patterns. Ten adults with normal vision (NC), fourteen adults affected by central visual impairment (CLV) and eight adults affected by peripheral visual impairment (PLV) were enrolled in our study. Patients underwent visual, vestibular and postural evaluation (bedside examination, Computed Dynamic Posturograophy). Motor Control Tests were performed to analyze automatic postural adaptive responses elicited by unexpected postural disturbances. Clinical evaluations did not show abnormality in all patients. In the Sensory Organization Test, CLV and PLV patients performed more poorly in conditions 3-6 and 3-4, as compared to NC subjects. The condition 5 score was significantly lower in the CLV group with respect to the PLV patients. Composite equilibrium scores demonstrated significant differences between low-vision subjects vs. NC subjects. No differences were found for somatosensorial contribution. Visual afferences showed lower values in all visually impaired subjects, while vestibular contribution was lower in the CLV patients as compared to the NC and PLV patients. MCT latencies were significantly worse in the CLV subjects. In the low-vision patients, postural control was modified with a specific pattern of strategy adaptation. Different modulations of postural control and different adaptive responses seemed to characterize CLV patients as compared to PLV subjects.

Bioradiotherapy with Cetuximab May Reduce the Risk of Neck Node Relapse in Locoregionally Advanced Laryngeal Glottic Carcinoma: May HER1-Profile Be Useful in the Bioselection of Patients?

The aim of the study was to evaluate survival in patients with advanced glottic laryngeal squamous cell carcinoma treated by bioradiotherapy (BioRT) with cetuximab and eventual salvage surgery (group A, n = 66) or upfront surgery (total laryngectomy or near-total laryngectomy) with or without postoperative radiotherapy (PORT) (group B, n = 66). The predictive role of HER1 expression in the bioselection of tumors was evaluated. Relapse-free (RFS), metastasis-free (MFS), overall (OS) survivals, salvageability, and rates of larynx preservation were analyzed. The two groups were balanced by propensity score method on their baseline characteristics. No significant differences in RFS and OS were found, while MFS results were significantly higher in group A (p = 0.04). Group A showed a 22% reduction in the probability of nodal metastasis (p = 0.0023), mostly in tumors with higher HER1 expression. The salvageability with TL at 3 years was 54% after prior BioRT and 18% after prior upfront NTL (p < 0.05). BioRT with cetuximab showed a reduction in the risk of lymph node relapse, particularly in the case of HER1 positive tumors, and it allowed to achieve a higher rate of functional larynx preservation and a higher salvageability compared with upfront surgery. HER1 analysis could be clinically useful in the bioselection of tumors that may benefit from BioRT with cetuximab, particularly in those with neck node metastatic propensity.

ORIFICE (Interventional Radiotherapy for Face Aesthetic Preservation) Study: Results of Interdisciplinary Assessment of Interstitial Interventional Radiotherapy (Brachytherapy) for Periorificial Face Cancer.

(1) Background: Periorificial face cancer (PFC), defined as both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) arising around the eyelids, the nose vestibule and the lips, has very high incidence rates worldwide. The aim of our retrospective analysis, focusing on local control (LC) and patients' degree of satisfaction with the cosmetic outcome, is to present the results of a single institutional series of patients affected by PFC and treated by interventional radiotherapy (brachytherapy-IRT). (2) Methods: We retrospectively evaluated patients affected by PFC who were treated at our Interventional Oncology Center (IOC) with interstitial IRT from 2012 to 2021 with doses and volumes specific for each subsite considered. (3) Results: We report the results of 40 patients affected by PFC and treated by HDR interstitial IRT. The median follow-up was 24 months. The actuarial 3-year LC was 94%. Regarding patients' satisfaction, we found that 93% of patients were satisfied and only 7% of patients were not completely satisfied with the final cosmetic result. (4) Conclusions: Interstitial HDR IRT could be an effective therapeutic option providing adequate disease control and preventing potentially disfiguring surgical approaches. More numerous and standardized studies are warranted to confirm the available evidence.

Mometasone Furoate in Non-Allergic Rhinitis: A Real-Life Italian Study.

BACKGROUND: In order to evaluate the efficacy of intranasal mometasone furoate in patients with non-allergic rhinitis (NAR), a real-life, observational, prospective study is performed. METHODS: Thirty-one patients (age 18-64 years) receive intranasal (mometasone furoate, 200 µg b.i.d. for 15 consecutive days per month for 6 consecutive months), plus isotonic nasal saline. The cytologic pattern of local inflammation, nasal airflow, through peak nasal inspiratory flow (PNIF), quality of life (QoL), through the rhinitis quality of life questionnaire (RQLQ), the sinonasal outcome test (SNOT-22), the short-form 36-item health survey (SF-36v2), and the combined symptom medication score (CSMS), and, finally, olfactory function, through Sniffin' sticks-16 identification test (SSIT-16), are evaluated at baseline and after treatment. RESULTS: NARNE is the most frequent cytological pattern (48% of the total sample). The therapeutic response shows improvement in olfactory function and QoL. CONCLUSIONS: The results of this study confirm that intranasal mometasone furoate is an effective treatment for patients with NAR.

The Effectiveness of Targeted Electrical Stimulation via Cochlear Implant on Tinnitus-Perceived Loudness.

Introduction: The cause of tinnitus improvement in cochlear implant (CI) users is not understood. On the basis that a spatially limited dysfunction in the auditory pathway could cause tinnitus, we used single-channel stimulation to evaluate any variation of tinnitus-perceived loudness and identify the cochlear regions involved. Materials and Methods: It was an observational prospective case-crossover study. After the first mapping, 21 adults with unilateral CI and chronic tinnitus expressed their tinnitus loudness based on the Visual Analog Scale (VAS) score (0-10) at baseline (L0), during a 10 s single-channel stimulation with C-level of electric current (L1) and 30 min after CI activation (L2). Tinnitus reduction [R T = (L0 - L1) × 100/L0] > 50% was considered significant. VAS outcomes were compared between baseline (L0) and (each) single-channel stimulation (L1) to find the channel with the greatest R T (suppressive channel-SC), whose frequency range revealed the cochlear region involved. Seven patients with asymmetric hearing loss underwent the pitch-matching test to identify the actual frequency evoked by the SC. We compared selective (L1) and non-selective (L2) intracochlear stimulation using paired t-test. Preoperative Tinnitus Handicap Inventory (THI) score was compared with those at 1, 6, and 12 months with paired t-tests to evaluate long-term tinnitus perception. Results: We observed a significant reduction of tinnitus loudness during the experimental procedure [L0 (6.4 ± 2.4) vs. L1 (1.7 ± 2.7), p = 0.003]. A total of 15/21 patients (71.4%) had a significant (R T > 50%) and selective improvement, reporting a mean L1 of 0.4 ± 2.0 (p = 0.0001). In 10/15 (66.6%) patients, the SC was in the apical turn, within 1,000 Hz; in 5/15 patients (33.4%) within 4,000 Hz. The cochlear region 125-313 Hz was the most affected by tinnitus improvement (p = 0.0074). Targeted stimulation was more effective than non-selective stimulation [L1 vs. L2 (4.3 ± 2.5), p = 0.0022]. In 3/7 patients, the perceived pitch did not fall within the SC frequency ranges. All patients with selective attenuation described tinnitus as monotone. Patients with non-selective attenuation had polyphonic tinnitus and better THI results after 1 year. Conclusion: Targeted intracochlear electrical stimulation improved chronic tinnitus perception, especially in monotone tinnitus, and the apical region was mainly involved. Our results provide new insights into the pathophysiological mechanisms of tinnitus and targets for innovative therapeutic strategies.

Survey on Use of Local and Systemic Corticosteroids in the Management of Chronic Rhinosinusitis with Nasal Polyps: Identification of Unmet Clinical Needs.

Background: Local and systemic corticosteroids have long been the workhorse in management of chronic rhinosinusitis with nasal polyps (CRSwNP), although there is no universally accepted modality of prescription. We carried out a survey in Italy to capture current trends in the use of topical and systemic corticosteroids in patients with CRSwNP. Methods: A survey was set up on Survey Monkey®. Each author distributed the link to the survey in an ad hoc manner and a total of 437 participants filled out the survey. Results: Mometasone furoate (79.3%) was the most frequently prescribed, administered daily by 61.9% of participants; the remaining preferred to discontinue treatment for brief periods to reduce side effects or to modulate the therapy in mild cases. The majority believe that a short cycle of systemic steroids should be prescribed for re-exacerbation of symptoms and that the number of cycles in the previous year should be evaluated to define control of the disease even if international guidelines do not provide clear indications on this topic. A certain degree of divergence emerged from responses regarding how long and the maximal dose of systemic steroids which place patients at high risk for adverse events. Finally, systemic corticosteroids seem to offer only temporary benefit on recovery of smell without guaranteeing long-term control even if the patient is adherent to topical corticosteroids. Conclusions: Our results highlight the need for clear guidelines on oral steroids, which could help supporting the use of a precision medicine approach, including indications for new biological agents.

Effectiveness of Dupilumab in the Treatment of Patients with Severe Uncontrolled CRSwNP: A "Real-Life" Observational Study in the First Year of Treatment.

The aim of this study was to evaluate the efficacy of dupilumab in the treatment of severe uncontrolled Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), with or without asthma as add-on therapy with intra-nasal corticosteroids in a real-life setting over the first year of treatment. Our data demonstrated that subcutaneous 300 mg dupilumab administered at home via a pre-filled auto-injector every two weeks, based on indications set by the Italian Medicines Agency, was rapidly effective in reducing the size of polyps, decreasing symptoms of disease, improving quality of life, and recovering olfaction. Significant improvement was observed after only 15 days of treatment, and it progressively increased at 6 and 12 months. Dupilumab was also effective in reducing the local nasal eosinophilic infiltrate, in decreasing the need for surgery and/or oral corticosteroids, and in improving control of associated comorbidities such as chronic eosinophilic otitis media and bronchial asthma. After 12 months of treatment, 96.5% of patients had a moderate/excellent response. From our data, it was evident that there was a group of patients that showed a very early response within one month of therapy, another group with early response within six months from baseline, and a last group that improved later within 12 months. The results of this study support the use of dupilumab as an effective option in the current standard of care for patients affected by severe uncontrolled CRSwNP.

Development of a prognostic model of overall survival in oropharyngeal cancer from real-world data: PRO.M.E.THE.O.

Objective: The PRO.M.E.THE.O. study (PredictiOn Models in Ent cancer for anti-EGFR based THErapy Optimization) aimed to develop a predictive model (PM) of overall survival (OS) for patients with locally advanced oropharyngeal cancer (LAOC) treated with radiotherapy (RT) and cetuximab (Cet) from an Italian dataset. Methods: We enrolled patients with LAOC from 6 centres treated with RT-Cet. Clinical and treatment variables were collected. Patients were randomly divided into training (TS) (80%) and validation (VS) (20%) sets. A binary logistic regression model was used on the TS with stepwise feature selection and then on VS. Timepoints of 2, 3 and 5 years were considered. The area under the curve (AUC) of receiver operating characteristic of 2, 3 and 5 year and confusion matrix statistics at 5-threshold were used as performance criteria. Results: Overall, 218 patients were enrolled and 174 (79.8%) were analysed. Age at diagnosis, gender, ECOG performance, clinical stage, dose to high-risk volume, overall treatment time and day of RT interruption were considered in the final PMs. The PMs were developed and represented by nomograms with AUC of 0.75, 0.73 and 0.73 for TS and 0.713, 0.713, 0.775 for VS at 2, 3 and 5 years, respectively. Conclusions: PRO.M.E.THE.O. allows the creation of a PM for OS in patients with LAOC treated with RT-Cet.

Elective Neck Dissection during Salvage Total Laryngectomy: Personal Experience.

The role of elective neck dissection during salvage surgery in patients with a clinically negative neck (cN0) is still discussed. The main objective of this work was to estimate the prevalence and predictive factors of occult neck nodes metastasis; we therefore aimed to evaluate the survival rate and the main oncologic outcomes of cN0 patients who underwent salvage total laryngectomy and elective bilateral neck dissection. In this retrospective observational study, we enrolled 80 cN0 patients affected by recurrent laryngeal cancer and who underwent salvage total laryngectomy and bilateral selective elective neck dissection. Several parameters were collected in order to find prognostic factors; finally, postoperative complications were reviewed and survival analysis was performed. Occult lymph node metastases were reported in 18 out of 80 patients (22.5%). Significant statistical correlation between lymphovascular invasion (p = 0.007), perineural invasion (p = 0.025) and occult nodal metastasis was found. Other variables (glottic subsite of recurrence, clinical T, pathological T, previous chemotherapy) were not significantly predictive of occult nodal metastasis. The 5-year OS, DSS, and RFS were 50.4%, 64.7%, and 63.4%, respectively. In conclusion, our single-institution data on a large cohort of patients, suggest performing routinely elective selective bilateral neck dissection during salvage total laryngectomy in cN0 patients due to the biological attitude of the tumor to spread to cervical nodes, considering an acceptable complications rate.

Long-term voice outcomes and quality of life after open partial horizontal laryngectomy type II vs. total laryngectomy: A cross-sectional study.

OBJECTIVES: We aim to analyse long-term voice outcomes and quality of life (QoL) in patients undergoing open partial horizontal laryngectomy type II (OPHL type II) and to compare them to those obtained by patients undergoing total laryngectomy (TL) with voice prosthesis (VP). DESIGN: Cross-sectional cohort study. SETTING: Patients undergoing surgery for advanced laryngeal cancer, assessed during the usual follow-up consultations at the Phoniatric Unit (February 2020-December 2020). PARTICIPANTS: Forty-five patients were enrolled and divided into two groups: OPHL group and TL group. MAIN OUTCOMES MEASURES: Acoustic analysis, maximum phonation time, INFV0  scale, I-SECEL, UW-QoL-V4 and MDADI questionnaires were used to assess the long-term outcomes. RESULTS: Voices of patients undergoing OPHL Type II were worse than those of laryngectomised patients with VP. Nevertheless, scores in voice and dysphagia-related QoL were comparable and scores in the social domain of QoL were higher in OPHL group. CONCLUSIONS: Open partial horizontal laryngectomy Type II allows an acceptable voice recovery and a satisfactory QoL.

Efficacy of Biologics on Refractory Eosinophilic Otitis Media Associated with Bronchial Asthma or Severe Uncontrolled CRSwNP.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is resistant to conventional treatments and strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of our study is to evaluate the effectiveness of biologics drugs in the control of EOM. This is a retrospective no-profit real-life observational study, involving patients affected by refractory EOM and in treatment with different biologics for concomitant severe eosinophilic asthma or severe uncontrolled CRSwNP (Dupilumab: n = 5; Omalizumab: n = 1; Mepolizumab: n = 1; Benralizumab: n = 1). We analyzed data at baseline and at the 6-month follow-up, including specific nasal and otological parameters. We observed an improvement of all nasal outcomes, including NPS, SNOT-22, VAS, and smell function. Regarding specific otological parameters, we observed a significant reduction in the mean value of COMOT-15 score and of Otitis Severity Score at 6-month follow-up compared to baseline (p < 0.05). Finally, we observed an improvement in terms of air conduction hearing levels during the treatment. Our results demonstrated that anti type-2 inflammatory pathway biologics can be effective in improving symptoms control and in reducing the severity of eosinophilic otitis media when treating coexisting type-2 diseases, such as asthma and or CRSwNP.

Early Noise-Induced Hearing Loss Accelerates Presbycusis Altering Aging Processes in the Cochlea.

Several studies identified hearing loss as a risk factor for aging-related processes, including neurodegenerative diseases, as dementia and age-related hearing loss (ARHL). Although the association between hearing impairment in midlife and ARHL has been widely documented by epidemiological and experimental studies, the molecular mechanisms underlying this association are not fully understood. In this study, we used an established animal model of ARHL (C57BL/6 mice) to evaluate if early noise-induced hearing loss (NIHL) could affect the onset or progression of age-related cochlear dysfunction. We found that hearing loss can exacerbate ARHL, damaging sensory-neural cochlear epithelium and causing synaptopathy. Moreover, we studied common pathological markers shared between hearing loss and ARHL, demonstrating that noise exposure can worsen/accelerate redox status imbalance [increase of reactive oxygen species (ROS) production, lipid peroxidation, and dysregulation of endogenous antioxidant response] and vascular dysfunction [increased expression of hypoxia-inducible factor-1alpha (HIF-1α) and vascular endothelial growth factor C (VEGFC)] in the cochlea. Unveiling the molecular mechanisms underlying the link between hearing loss and aging processes could be valuable to identify effective therapeutic strategies to limit the effect of environmental risk factors on age-related diseases.