Transoral non-robotic surgery for oropharyngeal squamous cell carcinoma.

PURPOSE: This retrospective cohort study aims to evaluate the clinical, oncological, and functional outcomes of transoral non-robotic surgery for oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Data from 131 patients with surgically treated OPSCC (2010-2022) were analyzed. Patients who underwent exclusively transoral surgery were included in the study. The surgeries were performed under microscopic or endoscopic guidance and either a CO2 laser or an ultrasound/radiofrequency scalpel was used as a cutting instrument, depending on the characteristics and location of the tumor. Functional outcomes were assessed in terms of length of hospital stay, tracheostomy rate, duration of feeding tube dependency and complications. Survival outcomes were assessed in terms of overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: Of 74 included patients, transoral surgery demonstrated safety with no major complications. Tracheotomy was performed in 51.4 % of cases, and was maintained for a median of 10 days. Complete swallowing recovery was restored in 97.3 % of cases, after a median of 5 days. The median length of hospital stay was 12 days. At 5 years, OS was 68.2 %, PFS was 58.2 % and DSS was 83.6 %. CONCLUSION: The study confirms the safety and efficacy of a transoral approach for OPSCC. Having the capability to utilize and access a variety of tools provides the opportunity to tailor the technique to the individual patient and specific circumstances.

MRI and frozen section evaluation of mylohyoid muscle in determining surgical approach for T2-T3 floor of the mouth cancer.

PURPOSE: The choice of surgical approach for floor of the mouth (FOM) cancer, particularly for intermediate-stage tumors (cT2-cT3), remains controversial. This study aims to evaluate a method considering mylohyoid muscle (MM) invasion as a determinant for surgical approach selection, utilizing magnetic resonance imaging (MRI) preoperatively and frozen section (FS) analysis intraoperatively. METHODS: This observational retrospective cohort study analyzed patients undergoing surgical resection of cT2 and cT3 FOM squamous cell carcinoma (SCC) between January 2013 and June 2023. MM infiltration assessed by preoperative MRI determined the surgical approach: clear infiltration led to compartmental surgery (CS), while doubtful or absent infiltration led to transoral surgery (TOS). Conversion from TOS to CS occurred intraoperatively based on macroscopic evidence or positive FS. Data collected included demographic, clinical, surgical, and pathological variables. Survival analysis was conducted using Kaplan-Meier method. RESULTS: Among 44 patients included, majority had cT2 tumors (59.1%). MM resection was necessary in 22.7% of cases. Overall survival (OS) and progression-free survival (PFS) did not significantly differ between TOS and CS groups. Radiological depth of invasion (rDOI) < 10 mm is correlated with MM preservation in 89% of cases, while rDOI > 10 mm is correlated with MM resection only in 23.8% of cases. Pathological depth of invasion (pDOI) discrepancies were observed in the two groups: in CS group is shown a higher pDOI (> 10 mm) confirmation (90%). Surgical complications and functional outcomes differed between TOS and CS groups. CONCLUSION: Considering MM invasion for surgical approach selection in cT2-cT3 FOM tumors appears oncologically safe, with better functional outcomes in muscle preservation. Preoperative MRI for MM assessment combined with intraoperative FS analysis provides reliable guidance for surgical decision-making.

Cochlear implant cost analysis in adults: a European narrative review.

PURPOSE: The aim of this study was to provide an updated European narrative review spanning the last decade, focusing on the cost-effectiveness of cochlear implants (CIs) for adults with severe to profound post-lingual hearing loss. METHODS: This review encompasses both prospective and retrospective approaches, as well as cross-sectional and longitudinal trials conducted on CIs in adults. All studies related to European countries (Austria, Germany, Switzerland, the Netherlands, Sweden, the UK and Poland) were conducted in English and were published between 2012 and June 2023. RESULTS: Nine studies were included in the analysis. The patients' ages ranged from 18 years to over 67 years, with sample sizes ranging from 20 to 100 patients; two of these studies were focused on single-sided deafness in adults. The Markov model was identified as the most commonly utilized analysis method. CONCLUSIONS: This review identified a general consensus on CI cost-effectiveness, despite substantial variability among countries in factors such as observation time horizons, cost-effectiveness thresholds, methods of cost collection, discount rates, CI eligibility criteria and country-specific health systems. Generally, CIs yield positive societal benefits for working-age individuals, potentially less for seniors. Early unilateral CI enhances cost-effectiveness, highlighting the importance of prompt candidate identification. A consistent undersupply of CIs relative to the percentage of potential recipients emerged across countries. Therefore, further investigation into subcategories such as single-sided deafness is warranted, along with country-specific cost analyses. Emphasizing the significance of detailed information on health systems and associated costs and benefits is crucial for facilitating comparisons across different settings.

Reliability of large language models for advanced head and neck malignancies management: a comparison between ChatGPT 4 and Gemini Advanced.

PURPOSE: This study evaluates the efficacy of two advanced Large Language Models (LLMs), OpenAI's ChatGPT 4 and Google's Gemini Advanced, in providing treatment recommendations for head and neck oncology cases. The aim is to assess their utility in supporting multidisciplinary oncological evaluations and decision-making processes. METHODS: This comparative analysis examined the responses of ChatGPT 4 and Gemini Advanced to five hypothetical cases of head and neck cancer, each representing a different anatomical subsite. The responses were evaluated against the latest National Comprehensive Cancer Network (NCCN) guidelines by two blinded panels using the total disagreement score (TDS) and the artificial intelligence performance instrument (AIPI). Statistical assessments were performed using the Wilcoxon signed-rank test and the Friedman test. RESULTS: Both LLMs produced relevant treatment recommendations with ChatGPT 4 generally outperforming Gemini Advanced regarding adherence to guidelines and comprehensive treatment planning. ChatGPT 4 showed higher AIPI scores (median 3 [2-4]) compared to Gemini Advanced (median 2 [2-3]), indicating better overall performance. Notably, inconsistencies were observed in the management of induction chemotherapy and surgical decisions, such as neck dissection. CONCLUSIONS: While both LLMs demonstrated the potential to aid in the multidisciplinary management of head and neck oncology, discrepancies in certain critical areas highlight the need for further refinement. The study supports the growing role of AI in enhancing clinical decision-making but also emphasizes the necessity for continuous updates and validation against current clinical standards to integrate AI into healthcare practices fully.

Validation of the Quality Analysis of Medical Artificial Intelligence (QAMAI) tool: a new tool to assess the quality of health information provided by AI platforms.

BACKGROUND: The widespread diffusion of Artificial Intelligence (AI) platforms is revolutionizing how health-related information is disseminated, thereby highlighting the need for tools to evaluate the quality of such information. This study aimed to propose and validate the Quality Assessment of Medical Artificial Intelligence (QAMAI), a tool specifically designed to assess the quality of health information provided by AI platforms. METHODS: The QAMAI tool has been developed by a panel of experts following guidelines for the development of new questionnaires. A total of 30 responses from ChatGPT4, addressing patient queries, theoretical questions, and clinical head and neck surgery scenarios were assessed by 27 reviewers from 25 academic centers worldwide. Construct validity, internal consistency, inter-rater and test-retest reliability were assessed to validate the tool. RESULTS: The validation was conducted on the basis of 792 assessments for the 30 responses given by ChatGPT4. The results of the exploratory factor analysis revealed a unidimensional structure of the QAMAI with a single factor comprising all the items that explained 51.1% of the variance with factor loadings ranging from 0.449 to 0.856. Overall internal consistency was high (Cronbach's alpha = 0.837). The Interclass Correlation Coefficient was 0.983 (95% CI 0.973-0.991; F (29,542) = 68.3; p < 0.001), indicating excellent reliability. Test-retest reliability analysis revealed a moderate-to-strong correlation with a Pearson's coefficient of 0.876 (95% CI 0.859-0.891; p < 0.001). CONCLUSIONS: The QAMAI tool demonstrated significant reliability and validity in assessing the quality of health information provided by AI platforms. Such a tool might become particularly important/useful for physicians as patients increasingly seek medical information on AI platforms.

Blood Markers Predicting Clinically Occult Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma.

INTRODUCTION: The presence of cervical lymph node metastases is an unfavorable prognostic factor in head and neck squamous cell carcinoma (HNSCC) and a potential cause of treatment failure. Occult lymph node metastasis occurs in approximately 15-20% of HNSCC patients with a clinically negative neck (cN0), greatly impacting on their prognosis. The present study aimed to investigate the role of pre-treatment peripheral blood markers in predicting clinically occult cervical lymph node metastasis. METHODS: This multicenter, retrospective study was performed in a cohort of 472 patients diagnosed with cN0 HNSCC who underwent up-front surgery. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated from available blood parameters. RESULTS: Oro-hypopharyngeal and oral cancers, locally advanced stage, moderately (G2), and poorly (G3) differentiated grade were associated with an increased risk of pathological lymph node involvement. NLR, LMR, PLR, SIM, and SII were significantly associated at multivariable analysis. NLR >2.12 was the most reliable at predicting occult lymph node metastasis (OR = 5.22; 95% CI: 2.14-12.75). We describe a predictive score integrating cancer site, local stage, and NLR which is effective at predicting positive lymph node pathological status. CONCLUSIONS: The present study provides evidence that pre-treatment peripheral blood markers, in particular NLR, represent reliable predictors of clinically occult cervical lymph node metastasis in cN0 HNSCC. Therefore, the present study provides a novel useful predictive score for directing the elective management of the neck in patients with cN0 HNSCC.

Impact of time-to-surgery on survival and quality of life in oral cancer.

PURPOSE: To investigate the association between time-to-surgery (TTS) and overall survival (OS), disease specific survival (DSS) and quality of life (QoL) in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: 116 patients with OSCC candidate to surgery were examined. TTS intervals starting from diagnosis (TTS-clinical-based) and from histological reports (TTS-biopsy-based) were calculated. The effects of TTS intervals and prognostic factors on 5-year OS and DSS were explored. RESULTS: In our cohort advanced T-categories OSCCs with TTS < 30 days showed a trend to have higher DSS rate (p = 0.049). Patients with TTS-clinical-based < 30 days showed better postoperative QoL. Positive surgical margins, nodal involvement (pN+), DOI >10 mm, invasive surgery and extra-capsular extension in pN+ were found to be significantly associated with a poor OS and DSS. CONCLUSIONS: TTS ≥ 30 days can adversely affect DSS, especially in the advanced T categories. Short TTS intervals resulted associated with a better postoperative QoL.

Is there a role for tumor volume in prediction of prognosis for oral cancer?

PURPOSE: New prognostic factors in oral squamous cell carcinoma (OSCC) (tumor-, host-, and environment-related) have been introduced recently to complete those traditionally considered. Among them, tumor volume (TV) could be the most interesting and applicable in clinical practice, considering the routine use of computed tomography in tumor staging. In this retrospective study we aimed to investigate whether a correlation exists among these new prognostic factors and survival outcomes. METERIALS AND METHODS: We collected data about 140 patients affected by OSCC who underwent primary surgery. Prognostic factors were collected and Overall Survival (OS), Disease Specific Survival (DSS) and Disease Free Survival (DFS) were estimated using Kaplan-Meier method; the Log-Rank test (Mantel-Cox) and Cox regression models were applied to investigate predictors of survival. RESULTS: The 5-year OS, DSS and DFS were 73.6 %, 89.2 % and 75.2 % respectively. Nodal metastasis (pN+), relapse and American Society of Anesthesiologists ASA-II were found independent prognostic factors for OS, and significantly associated to worst DSS (p < 0.001). TV significantly correlated with higher relapse occurrence (p = 0.03). CONCLUSIONS: In our experience, lymph-node status, ASA classification and relapse significantly influenced DSS on univariate analysis. TV could represent an interesting additional parameter, since it significantly influenced DFS. However, prospective studies with standardized TV measurements and a greater number of patients are needed to validate this result.

Recovery from olfactory and gustatory dysfunction following COVID-19 acquired during Omicron BA.1 wave in Italy.

BACKGROUND: Despite alterations in the sense of smell and taste have dominated the symptoms of SARS-CoV-2 infection, the prevalence and the severity of self-reporting COVID-19 associated olfactory and gustatory dysfunction has dropped significantly with the advent of the Omicron BA.1 subvariant. However, data on the evolution of Omicron-related chemosensory impairment are still lacking. OBJECTIVE: The aim of the present study was to estimate the prevalence and the recovery rate of self-reported chemosensory dysfunction 6-month after SARS-CoV-2 infection acquired during the predominance of the Omicron BA.1 subvariant in Italy. METHODS: Prospective observational study based on the sino-nasal outcome tool 22 (SNOT-22), item "sense of smell or taste" and additional outcomes conducted in University hospitals and tertiary referral centers in Italy. RESULTS: Of 338 patients with mild-to-moderate COVID-19 completing the baseline survey, 294 (87.0 %) responded to the 6-month follow-up interview. Among them, 101 (34.4 %) and 4 (1.4 %) reported an altered sense of smell or taste at baseline and at 6 months, respectively. Among the 101 patients with COVID-19-associated smell or taste dysfunction during the acute phase of the disease, 97 (96.0 %) reported complete resolution at 6 months. The duration of smell or taste impairment was significantly shorter in vaccinated patients (p = 0.007). CONCLUSIONS: Compared with that observed in subjects infected during the first wave of the pandemic, the recovery rate from chemosensory dysfunctions reported in the present series of patients infected during the predominance of the Omicron BA.1 subvariant was more favorable with a shorter duration being positively influenced by vaccination.

Aetiology and management options for secondary referred otalgia: a systematic review and meta-analyses.

OBJECTIVES OF REVIEW: To review the literature for the evidence base for the aetiology and management of referred otalgia, looking particularly at non-malignant, neuralgic, structural and functional issues. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: A systematic literature search was undertaken from the databases of EMBASE, CINAHL, MEDLINE®, BNI, and Cochrane Library according to predefined inclusion and exclusion criteria. EVALUATION METHOD: All relevant titles, abstracts and full text articles were reviewed by three authors who resolved any differences by discussion and consultation with senior author. RESULTS: 44 articles were included in our review. The overall quality of evidence was low, with the vast majority of the studies being case-series with three cohort and four randomised-controlled trials included. The prime causes and management strategies were focussed on temporomandibular joint dysfunction (TMJD), Eagle syndrome and neuralgia. Our meta-analyses found no difference on the management strategies for the interventions found. CONCLUSIONS: Referred otalgia is common and treatment should be aimed at the underlying pathology. Potential aetiologies are vast given the extensive sensory innervation of the ear. An understanding of this and a structured approach to patient assessment is important for optimal patient management.

Orthonasal and retronasal odor identification in patients with parosmia.

OBJECTIVE: To compare retronasal and orthonasal perception in parosmic COVID-19 patients, in order to determine whether COVID-19 has a differential effect on these functions. METHODS: Using the Sniffin Sticks test battery orthonasal function was examined for odor threshold, discrimination and identification. Retronasal function was assessed using 20 tasteless aromatized powders. Gustatory function was measured using the Taste Strips test. RESULTS: This study included 177 patients (127 women, 50 men; mean age 45 years), of whom 127 (72%) were hyposmic and 50 (28%) normosmic. Compared to patients without parosmia, parosmic patients performed worse in odor identification for both orthonasal (F = 4.94, p = 0.03) and retronasal tests (F = 11.95, p < 0.01). However, an interaction effect between route of odor identification (orthonasal or retronasal) and parosmia status was found (F = 4.67, p = 0.03): patients with parosmia had relatively lower retronasal scores than patients without parosmia. CONCLUSION: Our results suggest that COVID-19 may affect the olfactory mucosa differently along the anterior-posterior axis, thereby possibly contributing to the pathophysiology of parosmia. Patients with parosmia also exhibit a higher degree of impairment when odors are presented through the retronasal route during eating and drinking.

Comparison of prevalence and evolution of COVID-19 olfactory disorders in patients infected by D614 (wild) and B.1.1.7. Alpha variant: a brief report.

OBJECTIVES: To investigate the prevalence and the evolution of olfactory disorders (OD) related to coronavirus disease 2019 (COVID-19) in patients infected during the first and the second European waves. METHODS: From March 2020 to October 2020, COVID-19 patients with OD were recruited and followed over the 12-month post-infection. The following data were collected: demographic, treatments, vaccination status, and olfactory function. Olfaction was assessed with the Olfactory Disorder Questionnaire (ODQ), and threshold, discrimination, and identification (TDI) test. Outcomes were compared between patients of the first wave (group 1: wild/D614G virus) and the second wave (group 2: B.1.1.7. Alpha variant) at 1-, 3- and 12-month post-infection. RESULTS: Sixty patients completed the evaluations accounting for 33 and 27 patients in group 1 and 2, respectively. The 1-month TDI score (23.7 ± 5.3) was significantly lower in group 2 compared to group 1 (29.8 ± 8.7; p = 0.017). Proportion of normosmic patients at 1-month post-infection was significantly higher in group 1 compared to group 2 (p = 0.009). TDI scores only significantly increased from 1- to 3-month post-infection in anosmic and hyposmic patients. Focusing on There was a negative association between the 1-month ODQ and the 1-month TDI (rs = - 0.493; p = 0.012). ODQ was a significant predictor of TDI scores at 3- and 12-month post-infection. The 12-month prevalence of parosmia was 60.6% in group 1 and 42.4% in group 2, respectively. There was no significant influence of oral corticosteroid treatment, adherence to an olfactory training and vaccination status on the olfactory outcomes. CONCLUSIONS: Patients of the second wave (Alpha B.1.1.7. variant) reported significant higher proportion of psychophysical test abnormalities at 1-month post-infection than patients infected during the first wave (D614G virus).

Evaluating long-term smell or taste dysfunction in mildly symptomatic COVID-19 patients: a 3-year follow-up study.

INTRODUCTION: No studies have reported data on 3-year prevalence and recovery rates of self-reported COVID-19-related olfactory and gustatory dysfunction. The aim of the present study was to estimate the 3-year prevalence and recovery rate of self-reported COVID-19-related chemosensory dysfunction in a cohort of patients with antecedent mild COVID-19. METHODS: This is a prospective observational study, measuring the prevalence of altered sense of smell or taste at follow-up and their variation from baseline, on adult patients consecutively assessed at Treviso and Trieste University Hospitals, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction during March 2020. RESULTS: Overall, out of 403 respondents, 267 patients (66.3%) reported an altered sense of smell or taste (SNOT-22 > 0) at baseline, while 56 (13.9%), 29 (7.2%), and 21 (5.2%) reported such alterations at 6-24 months, 2 years, and 3 years, respectively. Among the 267 patients with COVID-19-associated smell or taste dysfunction at baseline, 246 (92.1%) reported complete resolution at 3 years. Of the patients who still experienced smell or taste dysfunction 2 years after COVID-19, 27.6% and 37.9% recovered completely and partially, respectively, at the 3-year follow-up. CONCLUSION: Among subjects with antecedent mildly symptomatic SARS-CoV-2 infection, the 3-year prevalence and recovery rate of COVID-19-related alteration in sense of smell or taste was 5% and 92%, respectively. In approximately two-thirds of patients experiencing chemosensory dysfunction still 2 years after COVID-19, it is still possible to observe a delayed complete or partial recovery after a period of 3 years, while the remaining one-third of individuals continues to have unchanged persistent chemosensory alteration.

Parosmia as a predictor of a better olfactory function in COVID-19: a multicentric longitudinal study for upper respiratory tract infections.

PURPOSE: This study aimed to evaluate the course of olfactory dysfunction [OD] due to upper respiratory tract infections [URTI] especially for COVID-19 [C19] in a multicentric design and to investigate possible predictors for the outcome. METHODS: In a multicentric study, patients (n = 147, of which 96 were women) with OD due to URTI, including C19 and non-C19 were evaluated at two visits with a standardized medical history and "Sniffin' Sticks" extended psychophysical testing to examine the course and possible predictors for improvement of olfactory function. RESULTS: C19 patients showed better overall olfactory function (p < 0.001) compared to non-C19. Olfactory function (p < 0.001) improved over 3.5 ± 1.2 months in a comparable fashion for C19 and non-C19 comparable over time (p = 0.20) except for a more pronounced improvement of odour threshold (p = 0.03) in C19. C19 patients with parosmia exhibited a higher probability of clinically relevant improvement of odour threshold, a better threshold in the second visit, and tended to have a better TDI-score at the second visit. Further possible predictors for an improving olfactory function were younger age, female gender, and had lower scores in olfactory tests at the first visit. CONCLUSIONS: Patients with C19 and non-C19 URTI exhibit a similar improvement over 3-4 months except for the odour threshold, with a better TDI in both visits for C19. For C19 a better prognosis in terms of olfactory recovery was found for younger patients with parosmia and lower olfactory scores at the first visit. Still, for many patients with olfactory loss, an improvement that is experienced as complete may only occur over months and possibly years.

COVID-19-Related Quantitative and Qualitative Olfactory and Gustatory Dysfunction: Long-Term Prevalence and Recovery Rate.

INTRODUCTION: No studies have reported data on 2-year prevalence and recovery rates of self-reported COVID-19-related quantitative and qualitative olfactory and gustatory dysfunction. The aim of the present study was to estimate the 2-year prevalence and recovery rate of self-reported COVID-19-related olfactory and gustatory dysfunction in a cohort of patients with antecedent mild-to-moderate disease. METHODS: This is a prospective observational study, measuring the prevalence of altered sense of smell or taste at follow-up and their variation from baseline, on adult patients consecutively assessed at Trieste University Hospital, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction during March 2020. RESULTS: Overall, 174 (68.8%), 53 (20.9%), and 36 (14.2%) of 253 responders reported an altered sense of smell or taste (SNOT-22 >0) at baseline, 12 months, and 24 months, respectively. Among the 174 patients who have complained a COVID-19-associated olfactory or gustatory dysfunction at baseline, 138 (79.3%) reported complete resolution of smell or taste impairment with 17 subjects (9.8%) recovering after more than 1 year after the initial infection, 33 (19.0%) reported a decrease in the severity, and only 3 (1.7%) reported that the symptom was unchanged at the 24-month interview. Twenty subjects (7.9%) complained of at least one qualitative long-term symptom. CONCLUSION: Two years after the infection, most patients experience a favourable evolution of COVID-19-related olfactory or gustatory dysfunction. A late recovery was observed in 10% of subjects.

A narrative review of the management of pars flaccida tympanic membrane retractions without cholesteatoma.

OBJECTIVE: Review the effectiveness of surgical and non-surgical management strategies for isolated pars flaccida and combined pars tensa and flaccida tympanic membrane retractions in preventing progression or recurrence, improving hearing and preventing development of cholesteatoma. DESIGN: Narrative review. SETTING: ENT and otology services worldwide. PARTICIPANTS: Patients with non-cholesteatoma tympanic membrane retractions. MAIN OUCTOME MEASURE: Changes in retraction (progression or resolution, or development of a known sequela such as perforation). RESULTS: Eight full text papers are included: three randomised controlled trials and five case series or cohort studies of more than five patients (a total of 238 ears). Data exists for the use of conservative management, ventilation tubes, laser tympanoplasty, cartilage and fascia tympanoplasty, lateral attic reconstruction as well as mastoid procedures. CONCLUSION: Few high-quality studies on the management of isolated and combined pars flaccida retractions exist. For isolated pars flaccida retractions deemed to require surgical intervention, this review suggests that lateral attic reconstruction and cartilage tympanoplasty carries least risk of recurrence.

Supporting Cells of the Human Olfactory Epithelium Co-Express the Lipid Scramblase TMEM16F and ACE2 and May Cause Smell Loss by SARS-CoV-2 Spike-Induced Syncytia.

BACKGROUND/AIMS: Quantitative and qualitative alterations in the sense of smell are well established symptoms of COVID-19. Some reports have shown that non-neuronal supporting (also named sustentacular) cells of the human olfactory epithelium co-express ACE2 and TMPRSS2 necessary for SARS-CoV-2 infection. In COVID-19, syncytia were found in many tissues but were not investigated in the olfactory epithelium. Some studies have shown that syncytia in some tissues are formed when SARS-CoV-2 Spike expressed at the surface of an infected cell binds to ACE2 on another cell, followed by activation of the scramblase TMEM16F (also named ANO6) which exposes phosphatidylserine to the external side of the membrane. Furthermore, niclosamide, an approved antihelminthic drug, inhibits Spike-induced syncytia by blocking TMEM16F activity. The aim of this study was to investigate if proteins involved in Spike-induced syncytia formation, i.e., ACE2 and TMEM16F, are expressed in the human olfactory epithelium. METHODS: We analysed a publicly available single-cell RNA-seq dataset from human nasal epithelium and performed immunohistochemistry in human nasal tissues from biopsies. RESULTS: We found that ACE2 and TMEM16F are co-expressed both at RNA and protein levels in non-neuronal supporting cells of the human olfactory epithelium. CONCLUSION: Our results provide the first evidence that TMEM16F is expressed in human olfactory supporting cells and indicate that syncytia formation, that could be blocked by niclosamide, is one of the pathogenic mechanisms worth investigating in COVID-19 smell loss.

Different inflammatory blood markers correlate with specific outcomes in incident HPV-negative head and neck squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes. METHODS: This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated. RESULTS: The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients' survival was found for SIM (10-year OS = 53.2% for SIM < 1.40 and 40.9% for SIM ≥ 2.46; c-index = 0.569) and LMR (10-year OS = 60.4% for LMR ≥ 3.76 and 40.5% for LMR < 2.92; c-index = 0.568). While LMR showed the strongest association with local failure (HR = 2.16; 95% CI:1.22-3.84), PLR showed the strongest association with regional (HR = 1.98; 95% CI:1.24-3.15) and distant failure (HR = 1.67; 95% CI:1.08-2.58). CONCLUSION: Different inflammatory blood markers may be useful to identify patients at risk of local, regional, or distant recurrences who may benefit from treatment intensification or intensive surveillance programs.

The CO2 waveguide laser with flexible fiber in transoral resection of oral and oropharyngeal cancers: a retrospective cohort study on postoperative and quality of life outcomes.

The aim of this study was to evaluate the CO2 waveguide laser (WG CO2 laser) with flexible fiber (Lumenis Ltd., Yokneam, Israel) in the treatment of oral and oropharyngeal cancers, specifically focusing on postoperative outcomes, pain, and quality of life (QoL). Eighty-one patients, 43 women and 38 men, with oral or oropharyngeal cancer who consecutively underwent transoral resection by WG CO2 laser from August 2015 to April 2020 were retrospectively enrolled. Resections were performed in super pulsed mode with a power setting ranging between 3 and 10 W. Data about frozen sections, reconstruction, complication rate, length of hospital stay, tracheostomy rate and time to decannulation, nasogastric feeding tube rate and time to oral feeding, pain, and QoL were reviewed. Continuous variables were presented as mean and standard deviation. Concordance between intraoperative frozen section examination and definitive histology was calculated using Cohen's K test of agreement. The mean length of hospital stay was 13 days. The feeding tube rate was 81%; the tracheostomy rate was 35%; the feeding tube was left in place for 8 days on average, and the time to decannulation was 9 days. The only complication was a postoperative bleeding in 4 patients. The median postoperative pain score measured by the Numeric Pain Rating Scale on postoperative days 1, 3, and 5 was 0 and there was a constant decrease in painkiller use over the days. The overall mean composite QoL score was 77 ± 14, with excellent results in saliva, taste, pain, and speech domains. Frozen section evaluation had a specificity of 99% and a negative predictive value of 98%. WG CO2 laser is a good and safe tool for transoral tailored resection of oral and oropharyngeal cancers. It ensures a good overall QoL and guarantees fast recovery and a very low postoperative pain.

Relevance of perimarginal nodes for head and neck cancer.

OBJECTIVE: To estimate the prevalence of metastasis in the perimarginal nodes (PMNs) (also known as perifacial, preglandular and retroglandual nodes) in head and neck cancer. METHODS: We recruited 136 patients affected by cancers of the oral cavity, lip, oropharynx, skin and by cáncer of unknown primary (CUP), who were candidates for level IB dissection. PMNs were identified and sent separately for histological analysis. Correlation between metastasis to the PMNs and characteristics of the primary tumour were reported. RESULTS: The incidence of metastasis was 17% from oral cancer, 50% from lip cancer and 12.5% from skin cancer. No metastases were reported for oropharynx cancer or CUP. The only factor that correlated with the incidence of metastases was origin of the tumour from the upper part of oral cavity. CONCLUSION: PMNs represent a frequent site of metastasis in oral and lip cancers. In cancer of the oropharynx, their involvement has not been not reported, while their role in skin cancers remains to be clarified.