Olfactory Neuron Prokineticin-2 as a Potential Target in Parkinson's Disease.

OBJECTIVE: The objective of this study was to outline the dynamics of prokineticin-2 pathway in relation to clinical-pathological features of Parkinson's disease by examining olfactory neurons of patients. METHODS: Thirty-eight patients (26 de novo, newly diagnosed) and 31 sex/age-matched healthy controls underwent noninvasive mucosa brushing for olfactory neurons collection, and standard clinical assessment. Gene expression levels of prokineticin-2, prokineticin-2 receptors type 1 and 2, and prokineticin-2-long peptide were measured in olfactory neurons by real-time polymerase chain reaction (PCR); moreover, the prokineticin-2 protein and α-synuclein species (total and oligomeric) were quantified by immunofluorescence staining. RESULTS: Prokineticin-2 expression was significantly increased in Parkinson's disease. De novo patients had higher prokineticin-2 levels, directly correlated with Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III motor score. In addition, oligomeric α-synuclein was higher in Parkinson's disease and directly correlated with prokineticin-2 protein levels. Total α-synuclein did not differ between patients and controls. INTERPRETATION: Prokineticin-2 is a chemokine showing neuroprotective effects in experimental models of Parkinson's disease, but translational proof of its role in patients is still lacking. Here, we used olfactory neurons as the ideal tissue to analyze molecular stages of neurodegeneration in vivo, providing unprecedented evidence that the prokineticin-2 pathway is activated in patients with Parkinson's disease. Specifically, prokineticin-2 expression in olfactory neurons was higher at early disease stages, proportional to motor severity, and associated with oligomeric α-synuclein accumulation. These data, consistently with preclinical findings, support prokineticin-2 as a candidate target in Parkinson's disease, and validate reliability of olfactory neurons to reflect pathological changes of the disease. ANN NEUROL 2023;93:196-204.

Polycystic Ovary Syndrome and Alteration of Vocal Function: A Systematic Review and Meta-Analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common hormonal disorder among young women, correlated with hyperandrogenism. Among the symptoms of PCOS, vocal alterations are quite unknown. Dysphonia may be related to hyperandrogenism, and there is no consensus about its prevalence and the severity of vocal disorders, which can cause noticeable discomfort. METHODS: A systematic review of the literature was conducted. Four studies on PCOS that evaluated the phonatory system were included for a total of 174 patients (96 PCOS, 78 controls), and a meta-analysis on comparable data was performed. RESULTS: Four studies evaluated parameters related to vocal symptomatology, altered audiometric examination, and findings at the laryngoscopy in patients affected by PCOS versus controls. Although the individual studies showed increased incidence of alterations and a tendency to develop speech fatigue in women with PCOS, when the results of studies were pulled in meta-analysis, the overall difference was not statistically significant. The studies themselves were very different from each other; therefore, it is hard to draw any firm conclusions. DISCUSSION: The aim of this study was to assess the prevalence of vocal alterations, the correlation with hyperandrogenism, the quality of life, and the voice changes after starting a therapy for PCOS. The present meta-analysis failed to find any difference in terms of PCOS and control cohort. However, the lack of high-quality studies makes it difficult to draw firm conclusions. New and larger studies or big population program data are therefore warranted.

Enhancing the therapeutic potential of intravenous glycerol for Meniere's disease: Robust results from an extensive patient cohort.

INTRODUCTION: Meniere's disease (MD) is an idiopatic condition characterized by recurrent attacks of vertigo, hearing loss, tinnitus, and aural fullness, affecting quality of life. Intravenous glycerol has shown potential as a therapeutic option. This study evaluates its efficacy in a larger patient cohort. MATERIALS AND METHODS: Retrospective study with 168 patients having unilateral MD unresponsive to dietary restrictions. Intravenous 10 % glycerol with 0.9 % sodium chloride was administered for six months. Audio-vestibular assessments and questionnaires were used. RESULTS: Significant improvements in vertigo control observed. 7.1 % achieved complete control, and 58.3 % had substantial control. Quality of life measures improved, and audiometry thresholds remained unchanged. No major adverse events reported. DISCUSSION: Intravenous glycerol effectively controlled vertigo and improved MD patients' quality of life. Limitations include lack of a control group and a relatively short-term follow-up. Future prospects include randomized controlled trials and optimization of treatment protocols. CONCLUSION: Intravenous glycerol shows promise as a therapeutic option for MD, with notable improvements in vertigo control and quality of life. Further research is needed for validation and optimization.

Efficacy and preservation of hearing with low-dose gentamicin in unilateral meniere's disease: A clinical symptomatology-based study.

PURPOSE: Meniere's disease (MD), a disorder of the inner ear, presents numerous therapeutic challenges, and intratympanic (IT) gentamicin has been proposed for intractable cases. However, controversy regarding dosage and method persists. The purpose of this study was to assess the efficacy and safety of low-dose IT gentamicin on vertigo attacks in MD using a clinical symptomatology-based method, wherein administration was repeated only if vertigo attacks recurred, with a 2-week interval between injections. MATERIALS AND METHODS: This study included 88 patients with unilateral intractable MD. All patients received one to five IT injections with 0.5 ml of 10 mg of gentamicin (80 mg/2 ml) with an interval of 2 weeks between injections. Vertigo attacks were evaluated before and after therapy and categorized into classes A-F according to the 2015 Equilibrium Committee criteria. Audiovestibular assessments, including Pure Tone Audiometry and Vestibulo-Ocular Reflex evaluations, were performed. RESULTS: Before treatment, patients had an average of 4.4 vertigo attacks/month; after treatment, this average decreased to 0.52. The majority of patients (57 %) reached Class A or B vertigo control with five or fewer gentamicin injections. VOR gain was slightly affected on the healthy side and significantly reduced on the affected side. No hearing deterioration was found in any of the treated patients. CONCLUSIONS: Low-dose IT gentamicin administration based on clinical symptomatology can produce a satisfactory control of vertigo attacks after treatment. This protocol primarily affected the vestibular function, as demonstrated by the significant reduction in VOR gain on the affected side, while avoiding cochlear damage. The lack of adverse events and preservation of hearing underscore the safety and efficacy of this method. These findings have significant clinical implications, suggesting that a low-dose, clinical symptomatology-based gentamicin treatment regimen could be an effective and safe strategy for managing unilateral Meniere's disease in a larger population.

Post-operative radiotherapy in adenoid cystic carcinoma of salivary glands versus surgery alone: what is the evidence about survival and local control? A systematic review and meta-analysis.

BACKGROUND: Adenoid cystic carcinoma of the salivary glands is a relatively rare malignancy characterized by slow growth and a poor prognosis, and effective treatments remain challenging to identify. This systematic review, following the PRISMA guidelines, aimed to analyze the potential benefits of post-operative radiotherapy in terms of local control of recurrences and survival advantages when compared with surgery alone in patients with adenoid cystic carcinoma. METHODS: A comprehensive systematic review was conducted by searching the MEDLINE, Cochrane, EMBASE, and OVID databases from January 1999 to July 2022. The goal was to identify articles comparing surgery alone with surgery plus postoperative radiotherapy for adenoid cystic carcinoma of the salivary glands. Downs and Black Checklist was used to assess the methodological quality and risk of bias of each included study. The data analysis was performed using Review Manager version 5.4.1. RESULTS: This review included 8 studies comprising a total of 3103 patients, divided based on the analyzed outcomes. The pooled odds ratio for overall survival at 5 years was 0.87 (95% confidence interval 0.43-1.76, p = 0.70), and at 10 years was 1.23 (95% confidence interval 0.69-2.16, p = 0.48). In both cases, no statistically significant differences were observed. However, the pooled odds ratio for local control at 5 years was 3.37 (95% confidence interval 1.35-8.42, p = 0.009), providing strong support for the use of post-operative radiation. CONCLUSIONS: The findings from the meta-analysis suggest that post-operative radiotherapy significantly improves local control in patients with adenoid cystic carcinoma. However, there was no statistically significant increase in survival at 5 and 10 years. It is essential to note that the quality of the studies included in this meta-analysis ranged from fair to poor. To better clarify the indications for post-operative radiotherapy, future high-quality research is needed, particularly with improved stratification of patient groups. Additionally, it is important to recognize that achieving local control in adenoid cystic carcinoma is crucial for enhancing the overall quality of life for patients. We acknowledge that this review was not registered in the PROSPERO database, and the data pooling was conducted using a random effects model.

Nerve Growth Factor and Autoimmune Diseases.

NGF plays a crucial immunomodulatory role and increased levels are found in numerous tissues during autoimmune states. NGF directly modulates innate and adaptive immune responses of B and T cells and causes the release of neuropeptides and neurotransmitters controlling the immune system activation in inflamed tissues. Evidence suggests that NGF is involved in the pathogenesis of numerous immune diseases including autoimmune thyroiditis, chronic arthritis, multiple sclerosis, systemic lupus erythematosus, mastocytosis, and chronic granulomatous disease. Furthermore, as NGF levels have been linked to disease severity, it could be considered an optimal early biomarker to identify therapeutic approach efficacy. In conclusion, by gaining insights into how these molecules function and which cells they interact with, future studies can devise targeted therapies to address various neurological, immunological, and other disorders more effectively. This knowledge may pave the way for innovative treatments based on NGF manipulation aimed at improving the quality of life for individuals affected by diseases involving neurotrophins.

Specific local nasal immunotherapy: Single center experience on 324 patients.

OBJECTIVE: To evaluate the efficacy and safety of specific local nasal immunotherapy (LNIT) in patients with allergic rhinitis. MATERIALS AND METHODS: A retrospective single-center study of 324 patients with allergic rhinitis (191 allergic to mites, 133 allergic to Grarninaceae or Parietaria pollen) treated with specific LNIT was carried out. As control group, 158 patients without allergic rhinitis were enrolled. All patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. RESULTS: Clinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test and the rhinomanometric analysis confirm the result with a difference statistically significant. No differnces in mucociliary clearance time were found. CONCLUSIONS: Specific LNIT is a valide alternative to subcutaneous and sublingual administration. It is effective, safe, well tolerated by the patient, it can be done at home with fewer systemic reactions.

Clinico-histopathological review of 255 patients who underwent parotidectomy for pleomorphic adenoma: a 10-year retrospective study-a proposal for an optimal diagnostic and therapeutic algorithm for patients with recurrent pleomorphic adenoma.

PURPOSE: Pleomorphic adenoma (mixed tumor) is the most common neoplasm of the parotid gland and one of the most frequent types of salivary gland tumor, generally with benign behavior and relatively slow growing. The adenomas could arise from the superficial, deep or from both superficial and deep parotid's lobes. METHODS: The aim of this review is to retrospectively analyze the surgical management of patients with pleomorphic adenoma of the parotid gland performed at the Department of Otorhinolaryngology (Department of Sense Organs of "Azienda Policlinico Umberto I" in Rome), from 2010 to 2020, with a focus on the percentage of recurrence and on the complication related to surgery to suggest an optimal diagnostic and therapeutic algorithm for patients with recurrent pleomorphic adenoma. The analysis of the complications observed in case of different surgical approaches was performed using the X2 test. RESULTS: The choice of a surgical approach (superficial parotidectomy-SP, total parotidectomy-TP, extracapsular dissection-ECD) depends on several elements, such as the location and the size of the adenoma, the availability of existing technical facilities and the professional experience of the surgeon. A transient facial palsy was present in 37.6%, 2.7% reported a permanent facial nerve palsy, 1.6% developed a salivary fistula, 1.6% a post-operative bleeding and 2.3% showed Frey Syndrome. CONCLUSION: The surgical management of this benign lesion is required, even in asymptomatic cases, to prevent the progressive growing and to reduce the risk of malignant transformation. The goal of surgical excision is to obtain the complete resection to minimize the risk of tumor recurrence and avoiding facial nerve disability. Therefore, an accurate preoperative study of the lesion and the choice of the most appropriate surgical treatment are essential to minimize the rate of recurrence.

Neoadjuvant chemotherapy and transoral robotic surgery for the posterior pharyngeal wall carcinoma.

BACKGROUND: The squamous cell carcinoma (SCC) of the posterior pharyngeal wall (PPW) is associated with poor oncological outcomes based on current literature data. We reported the preliminary outcomes of a potential new treatment protocol based on neoadjuvant chemotherapy (NCT) and transoral robotic surgery (TORS). METHODS: A retrospective single-center case series was performed including a total of 20 patients diagnosed with a SCC of the PPW between October 2010 and September 2021. All patients successfully completed TORS with neck dissection after NCT. Adjuvant treatment was performed in the presence of adverse pathologic features. Loco-regional control (LRC), overall survival (OS), and disease-specific survival (DSS) were defined as the time from surgery to tumor recurrence or death, as appropriate. Survival estimates were calculated by Kaplan-Meier analysis. Surgical data and post-operative functional outcomes were also reported. RESULTS: Estimated 3-year LRC, OS, and DSS rates (95% Confidence interval) were 59.7% (39.7-89.6), 58.6% (38.7-88.8), and 69.4% (49.9-96.6). The median hospital stay was 21 days (IQR 17.0-23.5). Oral diet and decannulation were achieved after a median of 14 days (IQR 12.0-15.0). Feeding tube and tracheostomy dependence after 6 months was observed in 3 (15%) and 2 (10%) patients, respectively. CONCLUSIONS: The use of NCT followed by TORS for PPW SCC treatment appears to have good oncological and functional outcomes for both early and locally advanced cancers. Further randomized trials and site-specific guidelines are needed.

The RNA-Binding Protein SMN as a Novel Player in Laryngeal Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here, we focus on the SMN in the cancer context. We conducted a pilot study in a total of 20 patients with LSCC where the SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that the SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between the SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumors. This study proposes the SMN protein as a novel therapeutic target in LSSC and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of the SMN in human cancer.

Barbed reposition pharyngoplasty (BRP) in obstructive sleep apnea treatment: State of the art.

PURPOSE: In this paper, we perform a systematic review that discusses the state of the art and evolution on the barbed reposition pharyngoplasty (BRP) in the velo-pharyngeal surgery. Clinical evidence and published outcomes of this surgical technique are reported and discussed. MATERIALS AND METHODS: We performed a systematic review of the current literature through the analysis of the last 10 years of literature on barbed palate surgery. Study design, number of patients enrolled, inclusion criteria, pre- and posttreatment outcomes (AHI, ODI), surgical success rate, follow-up time and complication has been collected and reported. RESULTS: 15 studies for a total of 1531 patients, out of which 1061 underwent barbed reposition pharyngoplasty. Five trials were uncontrolled prospective studies (215 patients, 14% of total), nine were retrospective studies (1266 patients, 82,6% of total), and one randomized prospective clinical trial (RCT) (50 patients, 3,32% of total). All analyzed studies reported good outcomes after BRP surgery. Average preoperative values of AHI and ODI reduced in all studies considered with a significative statistical difference between preoperative and postoperative values (p < 0.05 in all cases). The postoperative surgical success rate ranged between 65.4 and 93% of cases. There were no significant intra-operative or post-operative complications in all studies considered in this systematic review. CONCLUSIONS: Barbed reposition pharyngoplasty has proven to be an easy to learn, quick, safe and effective new palatopharyngeal procedure, that can be used in a single level surgery or as a part of multilevel procedures.

Voice quality after transoral CO2 laser microsurgery (TOLMS): systematic review of literature.

PURPOSE: Transoral laser microsurgery (TOLMS) with carbon dioxide is a safe approach for laryngeal carcinoma. In literature there are three main methods for evaluating speech outcomes: acoustic and aerodynamics analysis, perceptual evaluation and patient-reported outcomes (PROs). The aim of this study was to systematically review the literature about the voice quality outcomes of TOLMS according to type of cordectomy. METHODS: A systematic literature review was performed and all the results until December 2021 were extrapolated. We evaluated the acoustic and aerodynamics parameters (fundamental frequency, harmonics to noise ratio, jitter, shimmer and maximum phonation time), perceptual data (GRBAS scale) and patient-related outcomes (VHI scale). RESULTS: 24 studies met the inclusion criteria for a total number of 1207 patients enrolled. The number for each type of cordectomy are: 287 type I (23.78%), 311 type II (25.78%), 328 type III (27.14%), 129 type 4 (10.69%) and 152 type V (12.60%). Patients are grouped according to the type of cordectomy in: limited cordectomy (type I and II) and extended cordectomy (types III-IV-V). The difference between two groups is statistically significative in terms of acoustic analysis, perceptual data and patient-related outcomes (p < 0.05). CONCLUSIONS: Patients who underwent type I or II cordectomy have significantly better quality of voice in terms of VHI, perceptual voice quality evaluations and acoustic parameters compared to type III, IV and V cordectomies. The effect of TOLMS on the voice should depend from the extent of the resection and in particular from the scar of the vocal muscle.

The effect of female hormone in otosclerosis. A comparative study and speculation about their effect on the ossicular chain based on the clinical results.

PURPOSE: This study aimed at identifying gender differences in the hearing thresholds in a sample of patients with otosclerosis before and after surgery to understand the impact of female hormones on auditory thresholds. METHODS: This retrospective study analyzed 184 patients (123 women and 61 men) affected by otosclerosis. All the patients were affected by conductive hearing loss and treated by stapedoplasty. Auditory thresholds at the baseline (T0) and one month after surgery (T30) were collected. Air and bone thresholds and Air Bone Gap (ABG) were compared between females and males using one-way ANOVA. RESULTS: Statistically significant differences were observed comparing the air threshold at T0 vs T30 both in women and men (p < 0.0001). No statistically significant differences were observed in the bone conduction thresholds before and after surgery. The comparison between females and males showed statistically significant differences both at T0 (p < 0.01) and T30 (p < 0.05) for air conduction thresholds and ABG at 4000 Hz. CONCLUSION: Although stapedoplasty reduced the difference between females and males in the air conduction thresholds and ABG, women showed better recovery of their middle ear function with better auditory thresholds and ABG. The female hormones might positively impact the ligaments of the incudostapedial joint improving chain flexibility. This benefit might explain the statistically significant difference observed in women at 4000 Hz before and after surgery.

Carcinosarcomas of the larynx: systematic review of the literature of a rare nosologic entity.

PURPOSE: Carcinosarcoma, also known as Spindle Cell Carcinoma (SpCC), is a rare type of malignant tumor. Generally, this type of pathology occurs in the urogenital tract, the gastrointestinal tract, respiratory tract and mammary gland; in the larynx, SpCC represents only 2-3% of all malignancies. Due to its rarity, there is currently no generally acceptable treatment guideline for this disease. The aim of this study was to systematically review the literature of SpCC of larynx and report epidemiologic, clinicopathologic and main therapeutic approaches for this entity. METHODS: A systematic literature review was performed using MEDLINE, EMBASE, PubMed and Scopus databases. For this review, the results were extrapolated in the period between January 1990 to September 2020. Data extraction was performed using a standard registry database. The clinical and pathological staging were recalculated according to the Eight Edition of AJCC Cancer Staging Manual and statistical analyses were performed using SPSS Version 25.0. RESULTS: A total of 111 patients affected by laryngeal carcinosarcoma were included. From our review arises that surgery is the main treatment for primary laryngeal carcinosarcoma. In this way, various techniques such as minimally invasive laryngoscopy excision, laser CO2 cordectomy, partial laryngectomy (vertical and horizontal) and total laryngectomy. The role of radiotherapy is still controversial. The overall survival (OS) for T1 stage tumor at 5 years of follow-up is 82.9%, the OS for T2 and T3 tumor is 74% and 73.4%. The OS at 5 years of follow-up is 91.7% for supraglottic tumor, 69.3% for glottic tumor and 50% for transglottic site. Subglottic site is described in only 2 cases [12-13], so the OS at 5 years is not statistically significant. The 5-year overall survival in patients without lymph nodes involvement (N0) is 90.2%, 66.7% and 50%, respectively, for N1 and N2 lesions. CONCLUSION: Primary laryngeal carcinosarcoma is a very rare malignancy. There are no clear guidelines in the management but in the literature, surgery is described as the best modality of therapy; radiation only can be a reasonable alternative with controversial efficacy. The most important prognostic factor is the nodal metastasis.

Partial intracapsular tonsillectomy in the treatment of pediatric obstructive sleep apnea/hypopnea syndrome: a prospective study with 5-year follow-up.

OBJECTIVE: To assess efficacy and safety of tonsil reduction with bipolar forceps electrocautery as treatment of paediatric obstructive sleep apnea/hypopnea syndrome (OSAHS). STUDY DESIGN: Prospective interventional study. METHODS: Two hundred and sixty-three children aged 4-10 years with OSAHS and an apnea hypopnea index (AHI) > 3 were enrolled from March 2013 to January 2016. Pre-operative evaluation included oropharyngeal clinical examination with fiberoptic nasopharyngoscopy, OSA-18 questionnaire and overnight sleep study. All children were treated with adenoidectomy and tonsillotomy with bipolar forceps. OSA-18 questionnaire and overnight sleep study were performed 30 days after surgery. RESULTS: Pre-operative average of the OSA-18 questionnaires was of 70.3 (SD = 9.7); 30-day post-operative score was 23.15 (SD = 8.2; p = 0.045). Pre-operative average Apnea Hypopnea Index (AHI) score was 9.41 (SD = 4.1); 30-day post-operative average of AHI score was of 1.75 (SD = 0.8; p = 0.012). Oxygen Desaturation Index (ODI) rate changed from 7.39 (SD = 4) to 1.34 (30-day post-operative) (SD = 4.7; p = 0.085). NADIR rate changed from 79% (SD = 6.32) to 90% (30-day post-operative) (SD = 5.18; p = 0.00012). Peri- and post-operative complications in our sample were mainly pain (average 75 doses of paracetamol), while bleeding did not occur (0%). All patients received a follow-up examination 5 years after surgery to evaluate tonsil size; at this time-point, a reduction in tonsil size from 3.6 (3-4; SD = 4.2) to 1.3 (1-2; SD = 5.5) was found, while tonsil regrowth was observed in five children (2%). CONCLUSION: This study showed that partial tonsillotomy with bipolar forceps electrocautery associated to adenoidectomy is an effective technique in treating OSAHS symptoms in children and ensures less complications in terms of hemorrhage, postoperative pain and infections compared to traditional adenotonsillectomy. The very low tonsillar regrowth rate reported in this study may support the routine use of this technique.

Comparison of different oval window sealing materials in stapes surgery: systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy and safety characteristics of different materials used for oval window sealing during stapedotomy. METHODS: A systematic review was conducted according to the PRISMA guidelines. Published international English literature from January 1, 2000 to December 2021 was screened, checking for studies that compared different materials utilization in patients undergoing stapedotomy surgery for otosclerosis or congenital stapes fixation. Data related to the efficacy and safety of each material were extracted. The primary outcome measure was the air-bone gap (ABG) closure after surgical intervention. RESULTS: Six studies were included in the metanalysis. Because of the heterogeneity of the treatments adopted, we assessed the use of the fat compared to all other treatments, and the use of the gelfoam compared to all other treatments. In the former analysis (fat vs others) we did not identify differences in ABG closure between the groups (p = 0.74), with a low heterogeneity of the results (I2 = 28.36%; Hedge's g = 0.04, 95% CI - 0.19 0.27); similarly, we did not identify differences between the use of gelfoam and other treatments (p = 0.97), with a low heterogeneity of the results (I2 = 28.91%; Hedge's g = 0.00, 95% CI - 0.20 0.21). CONCLUSIONS: Numerous options are available for oval window sealing during stapedotomy, with acceptable safety and effectiveness profiles. Based on the current data, no definitive recommendation can be made regarding the choice of one material over another, and the convenience of sealing over no sealing at all.

Open partial horizontal laryngectomy for T2-T3-T4a laryngeal cancer: oncological outcomes and prognostic factors of two Italian hospitals.

PURPOSE: The purpose of this study was to analyse the oncologic results of open partial horizontal laryngectomy (OPHL) and to assess the prognostic factors that could affect the survival of patients affected by T2, T3 and T4a laryngeal cancer. Using this data, we aim to identify clinical criteria to select patients amenable to conservative surgery, and to facilitate a more targeted approach in the management of advanced laryngeal cancer. METHODS: A retrospective study was performed in patients who underwent OPHL type II for laryngeal squamous cell carcinoma from January 2005 to December 2018. We analysed a total of 170 patients; 21(12.36%) cases were staged as pT2, 116 (68.23%) as pT3 and 33 (19.41%) as pT4a. RESULTS: Five-year overall survival (OS) was 80.9%, 79.3%, 70.4% for T2, T3 and T4 respectively. Disease-specific survival (DSS) was 90.4%, 85.3% and 77.4%. Posterior tumour extension, perineural invasion and N status showed to considerably influence survival in both uni- and multivariate analyses. CONCLUSION: The oncological outcomes from our study show that OPHL for advanced laryngeal cancer can guarantee a high percentage of success. Accurate patient selection is of utmost importance to differentiate advanced disease amenable to conservative surgery, and treatment options should consider selected criteria based on tumour and patient features.

Impact of COVID-19 pandemic on the incidence of otitis media with effusion in adults and children: a multicenter study.

PURPOSE: To compare and analyze the incidence of otitis media with effusion (OME), before and during the COVID-19-related pandemic period, to evaluate the effects of the social changes (lockdown, continuous use of facial masks, social distancing, reduction of social activities) in the OME incidence in children and adults. METHODS: The number of diagnosed OME in e five referral centers, between 1 March 2018 and 1 March 2021, has been reviewed and collected. To estimate the reduction of OME incidence in children and adults during the COVID-19 pandemic period the OME incidence in three period of time were evaluated and compared: group 1-patients with OME diagnosis achieved between 1/03/2018 and 01/03/2019 (not pandemic period). Group 2-patients with OME diagnosis achieved between 1/03/2019 and 1/03/2020 (not pandemic period). Group 3-patients with OME diagnosis achieved between 1/03/2020 and 1/03/2021 (COVID-19 pandemic period). RESULTS: In the non-pandemic periods (group 1 and 2), the incidence of OME in the five referral centers considered was similar, with 482 and 555 diagnosed cases, respectively. In contrast, the OME incidence in the same centers, during the pandemic period (group 3) was clearly reduced with a lower total number of 177 cases of OME estimated. Percentage variation in OME incidence between the first non-pandemic year considered (group 1) and the pandemic period (group 3) was-63, 3%, with an absolute value decrease value of-305 cases. Similarly, comparing the second non-pandemic year (group 2) and the pandemic year (group 3) the percentage variation of OME incidence was-68, 1% with an absolute value of-305 cases decreased. CONCLUSIONS: Our findings showed a lower incidence of OME during the pandemic period compared with 2 previous non pandemic years. The drastic restrictive anti-contagion measures taken by the Italian government to contain the spread of COVID-19 could have had a positive impact on the lower OME incidence during the last pandemic year.

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol.

Both physiological and pathological aging processes induce brain alterations especially affecting the speed of processing, working memory, conceptual reasoning and executive functions. Many therapeutic approaches to reduce the impact of brain aging on cognitive functioning have been tested; unfortunately, there are no satisfactory results as a single therapy. As aging is partly contributed by free radical reactions, it has been proposed that exogenous antioxidants could have a positive impact on both aging and its associated manifestations. The aim of this report is to provide a summary and a subsequent review of the literature evidence on the role of antioxidants in preventing and improving cognition in the aging brain. Manipulation of endogenous cellular defense mechanisms through nutritional antioxidants or pharmacological compounds represents an innovative approach to therapeutic intervention in diseases causing brain tissue damage, such as neurodegeneration. Coherently with this notion, antioxidants, especially those derived from the Mediterranean diet such as hydroxytyrosol and resveratrol, seem to be able to delay and modulate the cognitive brain aging processes and decrease the occurrence of its effects on the brain. The potential preventive activity of antioxidants should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability, able to bypass the blood-brain barrier limitation, and that are well standardized.

Programmed Cell Death-Ligand 1 in Head and Neck Squamous Cell Carcinoma: Molecular Insights, Preclinical and Clinical Data, and Therapies.

Aberrant expression of the programmed cell death protein ligand 1 (PD-L1) constitutes one of the main immune evasion mechanisms of cancer cells. The approval of drugs against the PD-1-PD-L1 axis has given new impetus to the chemo-therapy of many malignancies. We performed a literature review from 1992 to August 2022, summarizing evidence regarding molecular structures, physiological and pathological roles, mechanisms of PD-L1 overexpression, and immunotherapy evasion. Furthermore, we summarized the studies concerning head and neck squamous cell carcinomas (HNSCC) immunotherapy and the prospects for improving the associated outcomes, such as identifying treatment response biomarkers, new pharmacological combinations, and new molecules. PD-L1 overexpression can occur via four mechanisms: genetic modifications; inflammatory signaling; oncogenic pathways; microRNA or protein-level regulation. Four molecular mechanisms of resistance to immunotherapy have been identified: tumor cell adaptation; changes in T-cell function or proliferation; alterations of the tumor microenvironment; alternative immunological checkpoints. Immunotherapy was indeed shown to be superior to traditional chemotherapy in locally advanced/recurrent/metastatic HNSCC treatments.