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Objective To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. Methods Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). Results A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders ( p  < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals ( p  = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males ( p  = 0.001). Conclusion Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.

Purpose To evaluate the evolution of chemosensation via extended psychophysical testing in patients who suffered from sudden chemosensory loss due to coronavirus disease 2019 (COVID-19). Additionally, this study sought to determine whether odor threshold testing provided additional information on olfactory loss due to COVID-19 compared to the more common odor identification testing. Methods Prospective cohort study of patients with sudden chemosensory loss since February 2020 and confirmed COVID-19 infection via RT-PCR or serology testing. Olfactory function was tested extensively using the “Sniffin Sticks” test battery. In addition, we screened gustatory perception and nasal cooling sensations using psychophysical tests. Results Seventy-two patients completed the study. After a mean of 37 days, 37% of patients showed olfactory dysfunction, 7% were dysgeusic, and 48% showed signs of low sensitivity for cooling sensation. A longer duration of anosmia before smell improvement was correlated with lower olfactory function at 5 weeks. Odor threshold detection was more affected by COVID-19 compared to odor identification. Conclusion Five weeks after developing sudden chemosensory loss due to COVID-19, a high proportion of patients were dysosmic and showed signs of low nasal cooling sensitivity, whereas most of them had normal taste function. SARS-CoV-2 affected mainly odor thresholds, possibly suggesting that the major cause of loss of smell lies at the level of the olfactory neuroepithelium, rather than in the central nervous system.

Head and neck squamous cell carcinomas (HNSCC) are one of the most prevalent cancers worldwide. Active human papillomavirus (HPV) infection has been identified as an important additional risk factor and seems to be associated with a better prognosis in non-drinker and non-smoker young patients with oropharyngeal SCC. The better response of the immune system against the HPV-induced HNSCC is suspected as a potential explanation for the better prognosis of young patients. To further assess this hypothesis, our review aims to shed light the current knowledge about the impact of HPV infection on the immune response in the context of HNSCC, focusing on the innate immune system, particularly highlighting the role of macrophages, Langerhans and myeloid cells, and on the adaptative immune system, pointing out the involvement of T regulatory, T CD8 and T CD4 lymphocytes. In addition, we also review the preventive (HPV vaccines) and therapeutic (checkpoint inhibitors) strategies against HPV-related HNSCC, stressing the use of anti-CTLA4, PD-L1, PD-L2 antibodies alone and in combination with other agents able to modulate immune responses.

Bone regeneration is a complex, well-orchestrated process based on the interactions between osteogenesis and angiogenesis, observed in both physiological and pathological situations. However, specific conditions (e.g., bone regeneration in large quantity, immunocompromised regenerative process) require additional support. Tissue engineering offers novel strategies. Bone regeneration requires a cell source, a matrix, growth factors and mechanical stimulation. Regenerative cells, endowed with proliferation and differentiation capacities, aim to recover, maintain, and improve bone functions. Vascularization is mandatory for bone formation, skeletal development, and different osseointegration processes. The latter delivers nutrients, growth factors, oxygen, minerals, etc. The development of mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) cocultures has shown synergy between the two cell populations. The phenomena of osteogenesis and angiogenesis are intimately intertwined. Thus, cells of the endothelial line indirectly foster osteogenesis, and conversely, MSCs promote angiogenesis through different interaction mechanisms. In addition, various studies have highlighted the importance of the microenvironment via the release of extracellular vesicles (EVs). These EVs stimulate bone regeneration and angiogenesis. In this review, we describe (1) the phenomenon of bone regeneration by different sources of MSCs. We assess (2) the input of EPCs in coculture in bone regeneration and describe their contribution to the osteogenic potential of MSCs. We discuss (3) the interaction mechanisms between MSCs and EPCs in the context of osteogenesis: direct or indirect contact, production of growth factors, and the importance of the microenvironment via the release of EVs.

Key Clinical Message Positional anomalies of the internal carotid artery are common. Often asymptomatic, they can cause dysphagia or dysphonia and can represent an important surgical risk. Knowing their existence is, therefore, essential for the ENT specialist. Aberrant positions of the extracranial internal carotid artery (eICA) affect between 10 and 40% of the population and can present several forms that can bring them close to the pharyngeal walls. Although usually asymptomatic, some aberrant positions of eICA may cause symptoms such as cough or dysphagia but rarely dysphonia. Depending on their location, they can also represent a great risk during oro/hypopharyngeal interventions or intubations. We report here the case of a 72‐year‐old patient who presented for a first consultation with a little progressive chronic dysphonia without associated dysphagia or cough. The nasofibrostroboscopy revealed a pulsatile retrocricoid mass pushing the right arytenoid forward. Otherwise, the clinical examination of the ENT sphere was normal. A cervicofacial CT scan revealed a major medialization of the right carotid bifurcation and the eICA located within the retropharyngeal fatty space and causing a mass effect pushing forward and downward the right arytenoid and the piriform sinus, resulting in a loss of horizontality of the glottic plane. Given the absence of life‐threatening complications and the associated risk of surgery, no treatment was proposed. A follow‐up was established after discussion with the patient. The aim of this study was to describe a rare case of isolated dysphonia caused by right internal carotid medialization with mass effect on the arytenoid cartilage. It seems important for ENT to know these rare causes of dysphonia and/or dysphagia due to anatomical variations of eICA in order to avoid the operative risks associated with possible future therapeutic procedures in these patients. Fibroscopic view of the larynx. Bulging of the posterior pharyngeal wall (red arrow) due to abnormal position of the internal carotid artery pushing the right arytenoid (white arrow). The right vocal cord (green arrow) is not damaged.

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that is strongly associated with oxidative damage and oxidative stress. Tobacco and alcohol - sources of massive quantities of reactive oxygen species (ROS) - have been clearly identified as etiologic factors that contribute to these malignancies. Considering the role of glutathione (GSH) in ROS detoxification, we hypothesized that potential biological markers can be found in addition to the parameters of oxidative stress. In line with previous studies that emphasized the accumulation of GSH in tumor cells, in this study, we have reported a lower ratio of oxidized versus reduced GSH in head and neck tumors. The aim of the paper was to evaluate the prognostic and clinical significance of the ratio of oxidized versus reduced GSH in patients with head and neck cancers. Thirty-six patients with HNSCC were included in this study. The tumoral redox status was determined by measuring the ratio of oxidized/reduced GSH (GSSG/GSH) by capillary electrophoresis. Statistical analysis was performed to assess the correlation between patient, clinical factors and the redox status. The results showed a low tumoral ratio of GSSG/GSH and a better locoregional control. Moreover, a significant correlation between the tumoral redox status ratio (GSSG/GSH) and nodal stage (N0 versus N1, N2 and N3) was also observed. A higher tumoral redox status ratio was found to be associated with the presence of lymph node metastasis (N1, N2 and N3). A strong correlation was observed between the oxidative status and locoregional control of the tumors. Moreover, a higher basal tumoral redox status ratio was found to be correlated with the presence of lymph node metastasis.

We assessed immune cell infiltrates to develop an immunoscore for prognosis and to investigate its correlation with the clinical data of patients with head and neck cancer. CD8, FoxP3, and CD68 markers were evaluated by immunohistochemistry in 258 carcinoma samples and positive cells were counted in stromal and intra-tumoral compartments. The RStudio software was used to assess optimal cut-offs to divide the population according to survival while the prognostic value was established by using Kaplan–Meier curves and Cox regression models for each immune marker alone and in combination. We found with univariate analysis that the infiltration of immune cells in both compartments was predictive for recurrence-free survival and overall survival. Multivariate analysis revealed that CD8+ density was an independent prognostic marker. Additionally, the combination of CD8, FoxP3, and CD68 in an immunoscore provided a significant association with overall survival (p = 0.002, HR = 9.87). Such an immunoscore stayed significant (p = 0.018, HR = 11.17) in a multivariate analysis in comparison to tumor stage and histological grade, which had lower prognostic values. Altogether, our analysis indicated that CD8, FoxP3, and CD68 immunoscore was a strong, independent, and significant prognostic marker that could be introduced into the landscape of current tools to improve the clinical management of head and neck cancer patients.

Objectives: To review the current knowledge regarding the involvement of human papilloma virus (HPV) infection and the immune system in the development of head and neck squamous cell carcinoma (HNSCC). Methods: An electronic literature search was conducted to identify articles published between 1990 and 2019 pertaining to tumor-infiltrating immune cells (TICs) in HNSCC using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Issues of clinical relevance, including tumor location, the number of tumor samples, the inclusion of additional specimens (dysplastic or normal mucosa), tumor size, methods used for HPV detection, relationship between antigen expression and patient characteristics (age, gender, smoking, alcohol consumption, etc.), and prognostic data (overall survival (OS) and recurrence-free survival (RFS)) were assessed by four blinded investigators. Results: The search identified 335 relevant studies, of which 41 met the inclusion criteria. Of these, 7 studies focused on the peripheral blood immune cell concentration in patients with HNSCC according to HPV status, and 36 studies investigated TICs in the intraepithelial and/or stromal compartment(s) according to HPV status. The immune cells studied were CD8+ T cells (N = 19), CD4+ T cells (N = 7), regulatory T cells (Tregs, N = 15), macrophages (N = 13), myeloid-derived suppressor cells (MDSCs, N = 4), and Langerhans cells (LCs, N = 2). Conclusions: Irrespective of tumor location, CD8+ and CD4+ T cells appear to play a key role in the development of HPV−related HNSCC, and their infiltration is likely associated with a significant impact on OS and RFS. To date, the roles and prognostic value of Tregs, macrophages, DCs and MDSCs remain unclear.

Introduction: To assess the impact of total thyroidectomy on thyroid function. Methods: Monocentric observational prospective study. Patients who benefited from a total thyroidectomy in the Department of Otolaryngology-Head and Neck Surgery between September 2017 and July 2019 were included. Three blood samples were taken from each patient during the perioperative period: preoperatively (T0), intraoperatively (T1), and postoperatively (T2). Changes in TSH, T4, T3, and thyroglobulin levels were evaluated from T0 to T2. Epidemiological data were retrieved from the medical charts. Statistical analyses were performed for the entire cohort and subgroups regarding preoperative treatment and type of disease. Results: Seventy-seven patients were included in the study. T4 and thyroglobulin levels increased significantly from T0 to T1. TSH, T4, T3, and thyroglobulin levels decreased significantly from T1 to T2. Conclusions: Our study confirmed the hypothesis of variable kinetics of thyroid hormone levels associated with the manipulation of the thyroid gland during surgery, but none of these changes resulted in clinical effects, including thyrotoxicosis.

Background/Objectives: Recent studies suggest Metformin could be a potential anti-tumoral agent. This review aims to understand the biological anti-tumoral mechanisms of Metformin in head and neck cancer squamous cell carcinomas (HNSCC) both in vitro and in vivo. Methods: Two investigators screened publications on the biological anti-tumoral effects of Metformin in HNSCC. The literature search was conducted on PubMed, Cochrane Library, and Scopus using PICOTS and PRISMA statements. Results: A total of 30 papers were identified, including 18 studies exploring the effect of Metformin alone and 12 studies exploring its effect in association with another drug or therapy for HNSCC lines. The results suggest that Metformin decreases the proliferation rate of HNSCC through inhibition of cell proliferation by the induction of G0/G1 cell cycle arrest and activation of apoptosis, by regulating proteins involved in carcinogenesis pathways, and also affects the tumor microenvironment by switching the metabolism and activating immune cells. In addition, Metformin can potentiate the efficiency and/or sensibility of other anti-tumoral treatments. The present systematic review highlights the biological anti-tumoral effects of Metformin used alone or in combination with traditional therapies for HNSCC. Conclusions: This review of the literature summarizes the biological anti-tumoral effects associated with Metformin alone or in combination with other therapies. While the molecular effects of Metformin on signaling pathways are different when used alone than in combination, they converge in a decreased proliferation of tumor cells and/or a sensitization of HNSCC to other anti-cancer therapies.