Abstract Objective Nasopharyngeal Carcinoma (NPC) is a tumor with ethnic and geographic distribution characteristics. HOXA Transcript at the distal Tip (HOTTIP) has been confirmed to have cancer-promoting effects in various tumors. The aim of this study was to investigate the clinical significance of HOTTIP in the development of NPC and its role in prognostic assessment. Methods Reverse transcription real-time PCR was used to analyze the expression of HOTTIP in the serum of 122 NPC patients before treatment, 35 controls and 30 NPC patients after treatment, and the relationship between HOTTIP expression and the clinicopathological features and prognosis of NPC patients was analyzed. The NPC cell lines CNE1 and HNE1 stably overexpressing HOTTIP were constructed using the retroviral method. Plate clone formation assays, MTT assays, flow cytometry, and Transwell migration and invasion assays were used to investigate the effects of HOTTIP overexpression on the colony-formation ability, cell proliferation ability, apoptosis, and migration and invasion abilities of CNE1 and HNE1 cells, respectively. Results HOTTIP was highly expressed in NPC serum and cells compared with the control group; serum HOTTIP expression in NPC patients after treatment was significantly lower than that before treatment; Kaplan-Meier survival curve revealed that the Progression-Free Survival (PFS) and Overall Survival (OS) of the HOTTIP low-expression group were both better than those of the HOTTIP high-expression group; COX proportional hazard models showed that high HOTTIP expression was an independent risk factor for PFS in NPC patients. The overexpression of HOTTIP promoted the proliferation, migration and invasion abilities of CNE1 and HNE1 NPC cells and inhibited cell apoptosis in vitro cell experiments. Conclusion Increased HOTTIP expression in serum indicates a poor prognosis and may be used as a molecular marker and therapeutic target in NPC. Level of Evidence: 4.

Abstract Since we published the “IV Brazilian Consensus on Rhinitis”, in 2017, several advances have been achieved and have enabled a further understanding of the different aspects of “Rhinitis”. This new guideline, developed jointly by ASBAI, SBP and SBORL, represents a relevant milestone in the updated and integrated management of the different forms of the disease, and it aims to unify evidence-based approaches to improve the diagnosis and treatment of this common and often underestimated condition. The document covers a wide range of topics, including clear definitions of the different phenotypes and endotypes of rhinitis, risk factors, updated diagnostic criteria, and recommended methods for clinical and laboratory investigation. We stress the importance of detailed clinical history and objective assessment, as well as tools for control and assessing severity tools an accurate diagnostic approach to the disease. Regarding treatment, it emphasizes the treatment customization, considering the severity of symptoms, the presence of comorbidities and the impact on the patient's quality of life. We discuss different drug treatment, in addition to non-pharmacological measures, such as environmental control and specific immunotherapy; and the possible role of immunobiological agents. Furthermore, the consensus addresses issues related to patient education, prevention and management of special situations, such as rhinitis in children, in pregnant women and in the elderly. In short, the “V Brazilian Consensus on Rhinitis” represents a comprehensive and updated guide for healthcare professionals involved in the diagnosis and management of rhinitis, aiming to improve patients' quality of life through an integrated and evidence-based approach.

Abstract Objectives Several studies have evaluated the prognostic significance of Perineural Invasion (IPN) in laryngeal cancer; however, the results are non-conclusive. Therefore, we conducted a meta-analysis aiming to identify the prognostic value of IPN in laryngeal cancer. Methods A literature review was performed, searching MedLine via PubMed, Scielo, Lilacs, Cochrane and Websco. RevMan 5.4 was used for the statistical analysis. Results A total of 19 laryngeal cancer studies were included. The results indicate that IPN in laryngeal cancer shows 2-year survival with RR 0.71 (0.59‒0.86); disease-free survival RR 0.51 (0.14-1.95); and locoregional recurrence RR 1.71 (1.25-2.35). Conclusion IPN is a negative prognostic factor in laryngeal cancer.

Abstract Objective The Interleukin-1 (IL-1) family plays an important regulatory role in the development of tumors, but its function is still unclear in head and neck squamous cell carcinoma (HNSCC). Analyzing the IL-1 family can help to understand the tumor mechanism. Methods Using GEPIA2, UALCAN, cBioprotocol and HPA databases, the IL-1 family and related genes (IL-1α, IL-1β, IL1RN, IL1R1, IL1R2, IL1RL1, IL1RL2, IL1RAP, IL1RAPL1, IL1RAPL2, IL1F10, IL18, IL18BP, IL18R1, IL18RAP, IL36A, IL36B, IL36G, IL36RN, IL33, IL37, SIGIRR, CASP1, AIM2) were analyzed for their expression and prognostic relevance in HNSCC. The Kaplan-Meier, log-rank test and Spearman correlation were used to analysis. Results In tumors, IL-1α, IL-1β, IL1R1, IL1RL1, IL1F10, IL33, CASP1, and AIM2 are highly expressed, while IL1RN, IL1RAPL1, IL1RAPL2, IL18BP, IL18R1 and IL18RAP are poorly expressed. IL-1α, IL1RAP, and IL1RAPL2 were prognostic risk factors in at least two databases, while IL18RAP, IL36A, and SIGIRR were prognostic protective factors. SIGIRR was confirmed in all three databases. Compared to HPV- tumors, IL18RAP and SIGIRR are highly expressed in HPV+ tumors. In addition, IL-1α, IL-1β, IL1RL2, IL1RAP were negatively correlated with CD8A/B expression, while IL1R2, IL18R1, IL18RAP, IL33, SIGIRR, CASP1, AIM2 were positively correlated with CD8A/B expression. Conclusion The differential expression of the IL-1 family and related genes affects the microenvironment changes and survival prognosis of HNSCC patients. Among them, IL-1α, IL1RAP, IL18RAP, and SIGIRR may affect the prognosis of patients by affecting local CD8+ T cell infiltration in the tumor. Level of evidence: 3.

Abstract Objectives The present study aims to characterize immunohistochemical features of markers associated with Epithelial-Mesenchymal Transition (EMT) and proliferative activity that could lead to death in Papillary Thyroid Cancer (PTC). Methods Clinical data and tumor material were retrospectively collected. The patients were separated into death from PTC (Group 1), metastatic cases with indolent behavior (Group 2) and non-metastatic indolent PTC (Group 3). Immunohistochemical assessment of E-cadherin, β-catenin, Vimentin, ZEB-1 and Ki-67 was performed in each tumor and a semiquantitative estimation of the percentage of expression was fulfilled on the best marking area at high of the tumor invasion front. Results 31 patients were included, 15 that died from PTC (Group 1), 6 in Group 2 and 10 in Group 3. The proliferative marker Ki-67 showed a significant difference in its expression in the tumor invasion front between the groups, specifically between groups 1 and 3 (p= 0.006). On the other hand, EMT-related immunohistochemical markers did not show significant difference in their percentage of expression, since loss of E-cadherin, β-catenin and Vimentin was observed in most cases at the invasion front. Conclusion Patients that died from PTC had a significantly higher Ki-67 labelling index compared to patients with indolent disease (cutoff of 11%). Ki-67 may have a role as a prognostic marker and could be considered for routine use in PTC. Level of evidence: 4.

Abstract Objective The aim of this study was to construct a prognostic model based on the TP53 mutation to calculate prognostic risk scores of patients with HPSCC. Methods TP53 mutation and transcriptome data were downloaded from the TCGA databases. Gene expression data from GSE65858, GSE41613, GSE3292, GSE31056, GSE39366, and GSE227156 datasets were downloaded from the GEO database. GSEA, univariate, multivariate Cox analyses, and LASSO analysis were employed to identify key genes and construct the prognostic model. ROC curves were utilized to validate the OS and RFS results obtained from the model. The associations between risk scores with various clinicopathological characteristics and immune scores were analyzed via ggplot2, corrplot package, and GSVA, respectively. Single-cell sequencing data was analyzed via unbiased clustering and SingleR cell annotations. Results Initially, two key genes, POLD2 and POLR2G, were identified and utilized to construct the prognostic model. Samples were divided into different risk groups via the risk scores obtained from the model, with high-risk group samples exhibiting poorer prognosis. Furthermore, the risk score exhibited a positive correlation with lymphatic metastasis in patients and the immune scores of CD4+ T, CD8+ T, dendritic cell, macrophage, and neutrophil. The immune responses also exhibited notable disparities between the high- and low-risk groups. The results of single-cell sequencing analysis demonstrated that epithelial cells and macrophages were relatively abundant in HPSCC samples. POLD2 and POLR2G exhibited higher expressions in epithelial cells, with most of the identified pathways also enriched in epithelial cells. Conclusion The prognostic model exhibited a significant capacity for predicting the prognosis of HSPCC samples based on the TP53 mutation conditions and may also predict the cancer characteristics and immune infiltration scores of samples via different risk scores obtained from the model. Level of evidence: Level 5.

Abstract Objective To investigate, through a systematic review of the literature, whether there are differences in the results of otoacoustic emissions suppression tests in individuals with and without central auditory processing disorder. Methods Searches were carried out in the scientific databases Latin American and Caribbean Health Sciences Literature, PubMed, Scientific Electronic Library Online, Web of Science, Scopus, Science Direct and Cochrane, as well as the databases of gray literature British Library, OpenGrey.eu and Object View and Interaction Design. A systematic review of the literature was carried out, with the descriptors otoacoustic emissions and auditory perceptual disorders and their synonyms, combined by the Boolean operators AND and OR. The reading of the studies was done by peers independently and in case of disagreement in the inclusion of studies, a third researcher was consulted. Original cross-sectional articles with a comparison group that suppressed transient evoked otoacoustic emissions in individuals with and without central auditory processing disorder were included. Results Seven studies that evaluated children aged between 7 and 14 years old were included, with methodological variability in the performance and analysis of the exam, the contralateral noise was the most used to elicit suppression. In only three studies did the group with central auditory processing disorder show lower suppression values, however the meta-analysis shows significant differences between the groups, with lower suppression values in the study groups. Conclusion This study points the need for a protocol that standardizes the measurement of OAE suppression and its findings, aiming to reduce the inclusion of results unrelated to the olivocochlear system.

Abstract Objectives To clarify the hearing outcomes after endoscopic type I tympanoplasty for medium and large perforations due to chronic otitis media. Methods We examined the clinical records of patients who underwent endoscopic type I tympanoplasty for medium and large perforations of the eardrum resulting from chronic otitis media between January 2019 and December 2021. We analyzed the changes in hearing pre- and post-operation in patients with healed eardrums and assessed the impact of tympanosclerosis on hearing. Patients with incomplete follow-up data, middle ear cholesteatoma, stapes fixation, severe lesions in the tympanic antrum and mastoid necessitating mastoidectomy and/or ossicular chain reconstruction were excluded. Results A total of 156 patients underwent analysis for audiological outcomes. Among them, 63 had medium tympanic membrane perforations, with 18 cases showing calcification of the tympanic membrane and 20 cases with calcification in the tympanic cavity. Additionally, 93 cases had large tympanic membrane perforations, with 25 cases showing tympanic membrane calcification and 32 cases with tympanic cavity calcification. Prior to surgery, the Air Conduction threshold (AC) in the large perforation group was higher than in the medium perforation group, particularly at low frequencies, measuring (47.4 ± 13.3 dB) and (41.2 ± 14.7 dB), respectively (p-value < 0.05). Following surgery, both groups experienced an improvement in AC, measuring (33.6 ± 13.9 dB) and (32.6 ± 12.8 dB), respectively, with no significant difference noted (p-value > 0.05). There was no significant change in Bone Conduction threshold (BC) before and after surgery in either the large or medium perforation groups (all p-values > 0.05). Except for 4000 Hz an increase, bone conduction did not increase post-surgery, instead showing further improved. Pre-surgery, the Air-Bone Gap (ABG) in the large and medium perforation groups was (27.7 ± 8.5 dB) and (21.8 ± 8.3 dB), respectively, mainly affecting low frequencies, with a statistically significant difference noted (p-value < 0.05). Following surgery, ABG in both groups improved to (16.3 ± 7.6 dB) and (15.7 ± 8.4 dB), respectively, with no significant difference observed (p-value > 0.05). There was no significant difference in hearing pre-surgery among the groups with No calcification (No), Tympanic Membrane Calcification (TM), and Tympanic Cavity Calcification (TC). However, TC significantly impacted low frequency (250-500 Hz) AC and ABG. The differences in AC and ABG pre-surgery between TC and No group, and TC and TM group (at 250-500 Hz) were statistically significant (all p-values < 0.05). Preoperative ABG in TM group was better than in No group and TC group, suggesting minimal impact of tympanic membrane calcification on hearing. No interaction was observed between tympanic membrane perforation size and tympanosclerosis on hearing. Post-surgery, both large and medium tympanic membrane perforation groups, regardless of tympanosclerosis presence, showed good AC and ABG, with no statistically significant difference in △ABG (all p-values > 0.05). Conclusion Preoperative AC and ABG were increase in cases of large tympanic membrane perforations and medium tympanic membrane perforations with tympanic cavity calcification. Surgical intervention led to more significant hearing improvement in these patients. However, irrespective of tympanic membrane perforation size and the presence of tympanosclerosis, as long as the ossicular chain remains intact and functional, postoperative AC and ABG outcomes are satisfactory. Endoscopic type I tympanoplasty proves effective in achieving improved hearing outcomes for patients with medium to large tympanic membrane perforations and tympanosclerosis, provided there is no ossicle chain fixation. Level of evidence: Level 4.

Abstract Objectives This study aimed to clarify the impact of hypertonic solutions on various outcomes, including persistence or reduction of nasal crusts, polypoid edema, and postoperative inflammatory symptoms. Methods We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for studies comparing hypertonic with isotonic saline irrigation after FESS in adult patients with Chronic Rhinosinusitis (CRS). Outcomes were polypoid mucosa, nasal crusts, and variation from the baseline of Sino-Nasal Outcome Test (SNOT) 20/22 and Visual Analog Scale (VAS). For statistical analysis, we used RevMan 5.4.1, and assessed heterogeneity with I2 statistics. Results We included a total of 479 patients from 7 studies. In the hypertonic saline group, there was a reduction in the nasal crust Risk Ratio (RR) (RR = 0.65; 95% CI 0.49 to 0.87; p= 0.004; I2 = 0%) after 30-45 days and severe crusts at 14-21 days (RR = 0.59; 95% CI 0.38 to 0.91; p= 0.02; I2 = 0%). Additionally, the persistence of polypoid mucosa was lower in the intervention arm (RR = 0.53; 95% CI 0.43 to 0.65; p< 0.00001; I2 = 0%) after 14-21 days. In the symptomatic evaluation hypertonic saline group showed an improvement in postoperative symptoms by a VAS Mean Difference (MD) (MD = −5; 95% CI −5.77 to −4.24; p< 0.00001; I2 = 0%) and a SNOT 20/22 Standard Mean Difference (SMD) (SMD = −1.65; 95% CI −2.7 to −0.61; p= 0.002; I2 = 93%) reduction from baseline in 30-45 days after the surgery. Conclusion Hypertonic saline showed a superior improvement in postoperative evaluation by means of nasal crusting, mucosal healing aspect, and nasal inflammatory symptoms compared with isotonic saline irrigation.

Abstract Objectives Postoperative chemoradiotherapy has arisen as an adjuvant option for head and neck cancers, but its superiority to radiotherapy alone in patients with adverse pathologic factors is not yet well defined. We aimed to perform an updated meta-analysis comparing outcomes in head and neck cancer patients with adverse pathologic factors who underwent postoperative chemoradiotherapy and radiotherapy alone. Methods We systematically searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials for Randomised Controlled Trials (RCTs) in patients submitted to postoperative adjuvant therapy with radiotherapy alone or chemoradiotherapy. Results We included 8 studies with a total of 2376 patients, of whom 1183 (49.8%) underwent postoperative chemoradiotherapy. In pooled analysis, overall survival (HR = 0.86; 95% CI 0.76‒0.98; p = 0.64; I2 = 0%) and disease-free survival (HR = 0.85; 95% CI 0.75‒0.96; p = 0.64; I2 = 0%) were shown to be superior in patients undergoing combined therapy. Chemoradiotherapy was also associated with significantly lower locoregional recurrence. However, there was no significant difference in distant metastasis occurrence between both groups. In an analysis of the extracapsular extension subgroup, the overall survival (OR = 3.12; 95% CI 1.76-5.51; p = 0.78; I2 = 0%), disease-free survival (OR = 3.44; 95% CI 2.00‒5.91; p = 0.68; I2 = 0%), and locoregional control (OR = 1.86; 95% CI 1.16‒2.99; p = 0.98; I2 = 0%) were better in the postoperative adjuvant chemoradiotherapy branch over radiotherapy alone. Conclusion The results of our meta-analysis suggest that postoperative adjuvant chemoradiotherapy in patients with head and neck cancer with adverse pathologic factors favors a superior survival and a better locoregional control compared to postoperative radiotherapy alone, despite not affecting the ocurrence of distant metastasis.

Abstract Objective To analyze the correlation between caloric testing response patterns with respect to cochlear impairment in individuals with unilateral Ménière's disease. Methods In this observational cross-sectional study, the factor under study was Ménière's disease and the outcome was cochleovestibular function, evaluated through caloric stimulation using videonystagmography and four-frequency averages in pure tone audiometry. Results A total of 187 patients (equal sex distribution) who met the inclusion criteria were included. In impairment analysis of the affected ear, 17 patients had only vestibular impairment, 56 had only cochlear impairment, and 114 had cochleovestibular impairment. The distribution of Ménière's disease stages according to four-frequency average was grade I: 23.53%, grade II: 16.04%, grade III: 42.25%, and grade IV: 18.18%. There was a significant association (p< 0.001) between the affected ear and labyrinthine preponderance. The Spearman correlation between four-frequency average and labyrinth preponderance (r = 0.326) indicated a moderate correlation, considering p < 0.01. Conclusion Our results show that the greater the cochlear damage due to Ménière's disease, the more impaired the vestibular function in the affected ear. Level of evidence: Level 2 - Individual cross-sectional studies with consistently applied reference standard and blinding

Abstract Objective To make evidence-based recommendations for the indications and complications of Cochlear Implant (CI) surgery in adults and children. Methods Task force members were educated on knowledge synthesis methods, including electronic database search, review and selection of relevant citations, and critical appraisal of selected studies. Articles written in English or Portuguese on cochlear implantation were eligible for inclusion. The American College of Physicians’ guideline grading system and the American Thyroid Association’s guideline criteria were used for critical appraisal of evidence and recommendations for therapeutic interventions. Results The topics were divided into 2 parts: (1) Evaluation of candidate patients and indications for CI surgery; (2) CI surgery - techniques and complications. Conclusions CI is a safe device for auditory rehabilitation of patients with severe-to-profound hearing loss. In recent years, indications for unilateral hearing loss and vestibular schwannoma have been expanded, with encouraging results. However, for a successful surgery, commitment of family members and patients in the hearing rehabilitation process is essential.