Treatment of medication-related osteonecrosis of the jaw with cell therapy.

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) poses a significant challenge considering the absence of a "gold standard" treatment. Cell-based therapy and tissue engineering offer promising therapeutic alternatives. This study aimed to harness the regenerative properties of adipose-tissue stromal vascular fraction (AT-SVF) and leukocyte-platelet-rich fibrin (L-PRF) for MRONJ treatment. AT-SVF contains mesenchymal stromal cells (MSC) and endothelial progenitor cells (EPC), which promote bone formation, while the L-PRF scaffold can serve as a three-dimensional scaffold for the AT-SVF and support tissue healing through growth factor release. Materials and methods: The protocol involved applying autologous AT-SVF within an L-PRF matrix following surgical debridement. Age, gender, body mass index, comorbidities, underlying oncological condition, prescribed antiresorptive treatment: BP or DMB, antiresorptive treatment duration, antiresorptive treatment potential discontinuation, number of MRONJ lesion, MRONJ location, MRONJ stage, MRONJ trigger factor were assessed for each patient. Patients underwent the procedure and were monitored for a minimum of 6 months based on clinical, biological and medical imaging criteria. Results: Nine patients, with a total of ten MRONJ lesions, participated in the study. Six patients were female, and three were male, with a mean age of 68 ± 8 years. Four patients had multiple myeloma (MM), three had metastatic breast cancer, and two had metastatic prostate cancer. Seven MRONJ cases were classified as stage II, and three were classified as stage III. Soft tissue completely healed within a month after treatment in nine cases, with no clinical improvement observed in the remaining case. During follow-up, no sign of MRONJ recurrence was observed. Tridimensional medical imaging revealed bone healing 6 months after the surgical procedure. Immunophenotyping confirmed the presence of MSC and EPC in the AT-SVF: 12,6 ± 4,5% CD31+, 20.5 ± 7,8% CD34+, 34,4 ± 7,3% CD146+ and 54,6 ± 7,4% CD45+. Conclusion: This prospective study introduces a potential new treatment approach for MRONJ using autologous AT-SVF within an L-PRF scaffold. Our results are encouraging and suggest the need for further investigation with a larger patient cohort to better understand the underlying mechanisms.

Validity and reliability of the Group for Learning Useful and Performant Swallowing (GLUPS) tool.

INTRODUCTION: To validate the Group for Learning Useful and Performant Swallowing (GLUPS), a clinical tool dedicated to videofluoroscopy swallowing study (VFSS). METHODS: Forty-five individuals were recruited from January 2022 to March 2023 from the Department of Otolaryngology Head and Neck Surgery of University Hospital Saint-Pierre (Brussels, Belgium). Subjects underwent VFSS, which was rated with GLUPS tool by two blinded otolaryngologists and one speech-therapist. VFSS were rated twice with GLUPS within a 7-day period to assess test-retest reliability. RESULTS: Twenty-four patients and twenty-one controls completed the evaluations. The internal consistency (α = 0.745) and the test-retest reliability (rs = 0.941; p = 0.001) were adequate. GLUPS reported a high external validity regarding the significant correlation with the Penetration-Aspiration Scale (rs = 0.551; p = 0.001). Internal validity was adequate, because GLUPS score was significant higher in patients compared to controls (6.21 ± 4.42 versus 2.09 ± 2.00; p = 0.001). Interrater reliability did not report significant differences in the GLUPS sub- and total score among the independent judges. The mean GLUPS score of individuals without any evidence of VFSS abnormalities was 2.09/23 (95% CI 1.23-2.95), which supported that a GLUPS score ≥ 3.0 is suggestive of pathological VFSS. CONCLUSIONS: GLUPS is a clinical instrument documenting the abnormal findings of oral and pharyngeal phases at the VFSS. GLUPS demonstrated high reliability and excellent criterion-based validity. GLUPS may be used in clinical practice for the swallowing evaluation at the VFSS.

Having a carotid in the throat: A rare case of internal carotid medialization-induced dysphonia.

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. Abstract: 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.

Preventive and Therapeutic Effect of Metformin in Head and Neck Cancer: A Concise Review.

BACKGROUND: Head and neck cancer (HNC) is a complex affection. Nowadays, conventional treatments are associated with many side effects, reducing the patient's quality of life. Recent studies suggest that metformin, a first-line treatment for diabetes, could decrease cancer incidence and improve cancer-related survival rates. METHODS: This systematic review summarizes important data from studies evaluating metformin's contribution to preventing and treating HNC. RESULTS: The results suggest a protective effect of metformin in HNC. However, no consensus has been found on its therapeutic effects. Metformin seems to confer an improved cancer-related survival rate in a diabetic population, but compared to a non-diabetic population, the review could not identify any advantages. Nevertheless, no studies presented a negative impact. CONCLUSION: In conclusion, the results of this systematic review suggest that HNC patients may benefit from metformin. Indeed, it would reduce the HNC incidence. However, more studies are required to evaluate the effect on cancer-related survival rates.

Antibiotic Use in Patients Undergoing Complex Clean-Contaminated Head and Neck Surgery: A Prospective Study.

Aims and Objectives: Oncological surgery of the upper aerodigestive tract is a complex procedure and often includes neck dissection and flap reconstruction. It can be complicated by severe surgical site infection (SSI) leading to flap necrosis, delayed wound healing, and increasing mortality and morbidity. The purpose of this study is to perform a systematic descriptive analysis and to evaluate the effect of our adapted antibiotic regimen strategy on postoperative outcomes. Materials and Methods: A prospective cohort analysis of 47 patients undergoing major clean-contaminated head and neck surgery was conducted at the Cervicomaxillofacial Surgery Department (Saint-Pierre Hospital), between 2019 and 2022. The patients were divided into two groups: group I, which received a short-term postoperative antibiotic regimen for 24 h, and group II, which received a more extended postoperative antibiotic course for more than 24 h. Antibioprophylaxy amoxicillin and clavulanate were administered intravenously 30-60 min before making the incision. The antibiotic regimen was continued after surgery. The prognostic significance of the antibiotic regimen on postoperative outcomes, including clinical signs of infection and biological markers such as white blood cells count, and C-reactive protein levels was evaluated using univariate analysis. Results: Eighteen patients developed SSIs. All of these infections were grade 2 and were treated with antibiotics. After univariate analysis, only a history of hypothyroidism seems to be a predictor of SSI (P = 0.038). No significant difference was found in terms of onset and hospital stay when we compared the patients who received antibiotics for 24 h or more. Moreover, the rate of multidrug-resistant bacteria was not different in both groups. Conclusions: Our results suggest that postoperative antibiotics for more than 24 h do not confer benefit in terms of SSI. Oncological patients undergoing complex clean-contaminated head and neck surgery are often suffering from infectious complications and, despite the absence of guidelines, practicians should consider these findings in their decision-making.

Macrophage Profiling in Head and Neck Cancer to Improve Patient Prognosis and Assessment of Cancer Cell-Macrophage Interactions Using Three-Dimensional Coculture Models.

Tumor-associated macrophages are key components of the tumor microenvironment and play important roles in the progression of head and neck cancer, leading to the development of effective strategies targeting immune cells in tumors. Our study demonstrated the prognostic potential of a new scoring system (Macroscore) based on the combination of the ratio and the sum of the high and low densities of M1 (CD80+) and M2 (CD163+) macrophages in a series of head and neck cancer patients, including a training population (n = 54) and a validation population (n = 19). Interestingly, the Macroscore outperformed TNM criteria and p16 status, showing a significant association with poor patient prognosis, and demonstrated significant predictive value for overall survival. Additionally, 3D coculture spheroids were established to analyze the crosstalk between cancer cells and monocytes/macrophages. Our data revealed that cancer cells can induce monocyte differentiation into protumoral M2 macrophages, creating an immunosuppressive microenvironment. This coculture also induced the production of immunosuppressive cytokines, such as IL10 and IL8, known to promote M2 polarization. Finally, we validated the ability of the macrophage subpopulations to induce apoptosis (M1) or support proliferation (M2) of cancer cells. Overall, our research highlights the potential of the Macroscore as a valuable prognostic biomarker to enhance the clinical management of patients and underscores the relevance of a spheroid model in gaining a better understanding of the mechanisms underlying cancer cell-macrophage interactions.

An Unusual Case of Primary Hyperparathyroidism: Case Report of a Bifocal Intrathyroidal Parathyroid Carcinoma.

Intrathyroidal parathyroid carcinoma is an extremely rare cause of primary hyperparathyroidism. We reported a 51-year old woman who presented symptoms of hypercalcemia. 99mTc sestamibi single-photon emission computed tomography/computed tomography (CT) revealed a large hypermetabolic nodule in the left thyroid lobe suggestive of hyperfunctioning parathyroid tissue. 11C-methionine positron emission tomography/computed tomography (PET/CT) and 18F-fluorocholine PET/CT confirmed the nodule in the left thyroid lobe and also revealed a hypermetabolic activity on the posterior surface of the lower left pole. The patient underwent a total thyroidectomy and parathyroidectomy, and a diagnosis of bifocal intrathyroidal parathyroid carcinoma was confirmed. We present the first reported case of bifocal intrathyroidal carcinoma and discuss the discordant imaging results.

Chronic Course, Weaning, and Awareness of Patients With Reflux Toward Proton Pump Inhibitor Therapy.

OBJECTIVES: To assess the feasibility of middle-term proton pump inhibitor (PPI) weaning in patients with laryngopharyngeal reflux (LPR) and evaluate patient awareness of PPI adverse events. METHODS: We conducted a cross-sectional study of 100 LPR patients treated with an association of diet, PPIs, and alginate. Patients were followed from September 2016 to May 2020. At the end of the initial 3-to-6 months therapeutic period, LPR patients were weaned from PPIs and instructed to respect diet and stress management over the long-term. The 3-year symptom recurrence rate, PPI use, and patient awareness of PPI adverse events were assessed. RESULTS: Sixty-seven patients completed the evaluation. Twenty-seven patients (40.3%) reported a chronic course of LPR-symptoms, requiring chronic or occasional PPI use. LPR symptom recurrence occurred 1-to-2 or 3-to-5 times yearly in 8.9% and 20.9% of patients, respectively. Recurrences were managed by short-term diet, alginate, or PPI intake. The remaining patients (29.9%) did not report middle-term LPR recurrence. The 3-year weaning rate of occasional or chronic use of PPIs was 64.2%. Among participants, 26.8% were aware of PPI-related adverse events, most frequently through physicians (33%), online sources (17%), and friends or family (17%). Nonresponder patients were significantly more aware of PPI adverse events than responders (P = 0.029). PPI-attributed adverse events occurred in 29.8% of patients. CONCLUSION: Sixty-four percent of LPR patients treated with PPIs were weaned at 3-year posttreatment time. Different forms of LPR may exist regarding symptom relief, recurrences, and chronic course.

Patient-reported outcomes in terms of swallowing and quality of life after prophylactic versus reactive percutaneous endoscopic gastrostomy tube placement in advanced oropharyngeal cancer patients treated with definitive chemo-radiotherapy: Swall PEG study.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is often used to provide nutritional support in locally advanced head and neck cancer patients undergoing multimodality treatment. However, there is little published data on the impact of prophylactic versus reactive PEG. PEG placement may affect swallowing-related physiology, function, and quality of life. The Swall PEG study is a randomized controlled phase III trial testing the impact of prophylactic versus reactive PEG on patient-reported outcomes in terms of swallowing and quality of life in oropharyngeal cancer patients. METHODS: Patients with locally advanced oropharyngeal cancer receiving chemo-radiotherapy will be randomized to either the prophylactic or reactive PEG tube group. Randomization will be stratified by human papillomavirus (HPV) status and unilateral versus bilateral positive neck lymph nodes. The primary objective of the study is the patient's reported outcome in terms of swallowing (MD Anderson Dysphagia Inventory (MDADI)) at 6 months. Secondary objectives include health-related quality of life, dosimetric parameters associated with patient-reported outcomes, chemo-radiation toxicities, PEG tube placement complications, the impact of nutritional status on survival and toxicity outcomes, loco-regional control, overall survival, the impact of HPV and tobacco smoking on survival outcomes and toxicities, and the cost-effectiveness of each treatment strategy. DISCUSSION: Findings from this study will enhance clinical evidence regarding nutritional management in oropharyngeal cancer patients treated by concurrent chemo-radiation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04019548, study protocol version 2.0_08/08/2019. Registered on 15 July 2019.

Contribution of Antiangiogenic Agents to the Risk of Medication-related Osteonecrosis of the Jaw in Combination with Antiresorptive Agents: Preliminary Results in a Comparative Prospective Report of 59 Oncologic Cases.

Aim: The aim of this preliminary study was to evaluate in an oncological population the association risk of antiangiogenic (AA) agents to antiresorptive (AR) agents on the incidence and the severity of medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: In this prospective study, we reviewed the medical records and clinical variables of 59 consecutive oncologic patients who developed MRONJ. For all patients, we retrieved the following variables: age, gender, alcohol and tobacco use, type of cancer, use of corticosteroids for >3 months, history of diabetes, MRONJ staging, combination of AR and AA agents, dental history (surgery, prosthesis) or spontaneous, site of MRONJ, delay between AR and AA first intake, and MRONJ development. Patients were divided into two groups according to drugs therapy they underwent: group 1 (G1) including patients treated with AR agents alone and group 2 (G2) including patients receiving antiresorptive-antiangiogenic drugs (AR+AA). The degree and the therapeutical success were defined as primary outcomes and the number, the localization, and the delay in onset of the lesions as secondary outcomes. In order to identify predictive factors of osteonecrosis-free interval time, univariate and multivariate Cox regression was performed. Statistical tests were carried out using the IBM® SPSS® Statistics software. All reported P-values are two-tailed and were considered to be significant when less than 0.05. Results: Among the 47 patients who received AR agent alone (group 1), the mean treatment duration before diagnosis of MRONJ was 39.2 months. In the second group (n = 12), patients developed MRONJ with a comparable mean time of 55 months (P = 0.16). According to the staging of MRONJ at the time of diagnosis, no significant difference (P = 0.736) was observed between the two groups. Moreover, the treatment applied was not statistically different in both the groups and was successful in 36.17% of the patients in group 1 and 58.33% of the patients in group 2. No statistically difference was reported in both the groups (P = 0.16). After statistical analysis, no significant difference in terms of MRONJ localization (P = 0.13) was observed. Finally, the incidence of spontaneous MRONJ was comparable in both the groups. Statistical analysis revealed that total time of treatment was the only factor associated with poor osteonecrosis-free interval time (hazard ratio 0.99; P = 0.001). Interestingly, the combination of an AA and AR agent was not a significant predictor factor of the interval time before the diagnosis of osteonecrosis. Additionally, corticosteroid use, diabetes mellitus, and dental consultation before treatment were not statistically related to poorer osteonecrosis-free interval time rates. Conclusion: In our preliminary study, neither the mean treatment time duration before the diagnosis of MRONJ nor the dose delivered was different in both the groups (AR vs. AR+AA). Moreover, no significant difference was observed between both the groups regarding the localization and the staging of MRONJ at the time of diagnosis. Interestingly, our results demonstrated that the risk of spontaneous MRONJ is statistically comparable in the AR and AR-AA groups. Additionally, the addition of an AA agent did not influence the treatment applied in the two groups of patients.

Papillary Thyroid Carcinoma Metastatic to the Frontal Sinus and Frontal Recess: Case Report.

We describe an extremely rare papillary thyroid carcinoma metastasic to the paranasal sinuses and our surgical management. A 39-year-old patient with a history of papillary thyroid carcinoma diagnosed five years earlier who presented with symptoms of chronic sinusitis. Medical imaging demonstrated opacification of the frontal sinuses and the anterior ethmoid sinus without signs of angiogenesis, bone destruction or calcification. Biopsy under general anesthesia revealed presence of papillary thyroid carcinoma cells. Treatment consisted in sinus endoscopic surgery with Draf III procedure followed by 131I therapy. To our best knowledge, this is the first described case of papillary thyroid carcinoma metastatic to the frontal sinus and frontal recess.

Platelet-Rich Plasma, an Innovative and Noninvasive Technique for Closure of Tracheoesophageal Fistula After Laryngectomy, Report of 2 Cases.

An innovative and noninvasive technique for closure of persistent tracheoesophageal fistula after total laryngectomy is described. In our preliminary study, two patients were included. No clinical and radiological signs of locoregional recurrence prior to treatment were diagnosed. We performed local injections of autologous platelet-rich plasma (PRP) according to our protocol. Complete closure of the fistula was observed in both patients who were able to take normal feeding. No side effects associated with the procedure were observed. These preliminary results are encouraging to consider PRP injection before more invasive surgical techniques in the treatment of persistent tracheoesophageal fistulas after total laryngectomy.

Immunoscore Combining CD8, FoxP3, and CD68-Positive Cells Density and Distribution Predicts the Prognosis of Head and Neck Cancer Patients.

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.

Changes in TSH, T4, T3 and Thyroglobulin Levels throughout Total Thyroidectomy.

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.

Laryngopharyngeal Reflux: Evolution and Predictive Value of Symptoms and pH-Impedance Features on Clinical Evolution.

OBJECTIVES: To investigate the features of patients with laryngopharyngeal reflux (LPR) who did not respond to medical treatment. STUDY DESIGN: Prospective uncontrolled study. SETTING: Multicenter study. METHODS: Patients with LPR at 24-hour HEMII-pH monitoring (hypopharyngeal-esophageal multichannel intraluminal impedance-pH) were prospectively recruited from 3 European university centers. Patients were treated with 3- to 6-month medication (proton pump inhibitor and alginate) and categorized as mild to moderate responders, high responders, or nonresponders according to Reflux Symptom Score (RSS) changes at 6 months posttreatment. The predictive value of the following outcomes was studied: epidemiologic data, HEMII-pH, gastrointestinal endoscopy findings, baseline RSS and Reflux Sign Assessment, and early therapeutic response (6-week RSS). RESULTS: A total of 148 patients completed the evaluations, accounting for 40 mild to moderate responders (20%-60% RSS changes), 76 high responders (>60% RSS changes), and 32 nonresponders. Nonresponders presented more often with hiatal hernia and lower esophageal sphincter insufficiency when compared with mild to moderate and high responders (P = .032). Baseline otolaryngologic, digestive, and respiratory RSS and the number of pharyngeal reflux events at the HEMII-pH were predictive of the 6-month therapeutic response (P < .05). The early therapeutic response (6 weeks posttreatment) was predictive of the 6-month treatment response. CONCLUSION: Hiatal hernia and baseline and 6-week RSS were the most predictive indicators of therapeutic effectiveness in patients with LPR.

Neutrophil-to-lymphocyte ratio as a prognostic marker for head and neck cancer with lung metastasis: a retrospective study.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is the most widely biomarker used to assess the inflammatory system in various solid cancers. An elevated NLR has been reported to be associated with worse outcomes in head and neck squamous cell cancers (HNSCC). However, questions remain about the prognostic value of these findings in HNSCC patients with lung metastasis. This study aims to quantify the prognostic impact of NLR on HNSCC patients with lung metastasis. METHODS: A retrospective chart review of 169 HNSCC patients was performed at the Otorhinolaryngology and the Stomatology and Maxillofacial Surgery Department (Saint-Pierre Hospital), between 2000 and 2017. All patients were divided into two subgroups. Patients who developed lung involvement were assigned to the lung-metastasis-group (LM-group) in contrast to no-lung-metastasis-group patients (NLM-group). The prognostic significance of NLR was evaluated using multivariable analysis adjusting for overall-survival (OS) and lung-metastasis-free-survival (LMFS). RESULTS: 95 patients were enrolled in the NLM-group while 74 were in the LM-group. Multivariable analysis highlights that patients with a higher NLR value had shortened OS in the NLM subgroup (HR 1.3; p = 0.024). However, this association was not found in the LM subgroup. When considering both subgroups, an elevated NLR was reported as a prognostic factor of poor LMFS (HR 1.65; p = 0.047). CONCLUSION: Our data revealed that pretreatment NLR is an independent prognostic factor of mortality and lung metastasis development. However, the prognostic value of NLR is not confirmed in patients who suffered from lung metastasis. Physicians should integrate these findings in their treatment algorithm approach.

Features of Mild-to-Moderate COVID-19 Patients With Dysphonia.

INTRODUCTION: To explore the prevalence of dysphonia in European patients with mild-to-moderate COVID-19 and the clinical features of dysphonic patients. METHODS: The clinical and epidemiological data of 702 patients with mild-to-moderate COVID-19 were collected from 19 European Hospitals. The following data were extracted: age, sex, ethnicity, tobacco consumption, comorbidities, general, and otolaryngological symptoms. Dysphonia and otolaryngological symptoms were self-assessed through a 4-point scale. The prevalence of dysphonia, as part of the COVID-19 symptoms, was assessed. The outcomes were compared between dysphonic and nondysphonic patients. The association between dysphonia severity and outcomes was studied through Bayesian analysis. RESULTS: A total of 188 patients were dysphonic, accounting for 26.8% of cases. Females developed more frequently dysphonia than males (P = 0.022). The proportion of smokers was significantly higher in the dysphonic group (P = 0.042). The prevalence of the following symptoms was higher in dysphonic patients compared with nondysphonic patients: cough, chest pain, sticky sputum, arthralgia, diarrhea, headache, fatigue, nausea, and vomiting. The severity of dyspnea, dysphagia, ear pain, face pain, throat pain, and nasal obstruction was higher in dysphonic group compared with nondysphonic group. There were significant associations between the severity of dysphonia, dysphagia, and cough. CONCLUSION: Dysphonia may be encountered in a quarter of patients with mild-to-moderate COVID-19 and should be considered as a symptom list of the infection. Dysphonic COVID-19 patients are more symptomatic than nondysphonic individuals. Future studies are needed to investigate the relevance of dysphonia in the COVID-19 clinical presentation.

Influence of Age and Sex on Clinical and Therapeutic Features of Laryngopharyngeal Reflux.

OBJECTIVE: To explore the influence of age and sex on the clinical presentation and therapeutic response of patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Prospective study. SETTING: Prospective multicenter study of 271 patients with a diagnosis of LPR confirmed by impedance-pH monitoring. METHODS: Patients were prescribed 6 months of diet changes and a combination of pantoprazole and/or alginate depending on the results of their impedance-pH results. The Reflux Symptom Score (RSS) and Reflux Sign Assessment (RSA) were collected at baseline and at 3 and 6 months posttreatment. Data were explored according to sex and age. RESULTS: A total of 237 patients completed the evaluations (138 females). On the RSS, patients of the oldest group (>60 years) had lower symptom scores (throat pain, ear pain, odynophagia, chest pain, tongue burning, nausea, halitosis, and indigestion) and lower quality-of-life scores than younger individuals. RSS and RSA outcomes significantly improved from pretreatment to 3 months posttreatment in all groups. Scores on the RSS and RSA continued to improve from 3 to 6 months posttreatment in the elderly group. Females with LPR had a higher score on the RSS at baseline as compared with males. On the RSS, scores significantly improved after 3 months in males and females; however, they continued to improve from 3 to 6 months in the female group. CONCLUSION: Age and sex may influence the clinical presentation and pre- to posttreatment evolution of symptoms and findings. Age and sex differences could be considered in future therapeutic approaches to guide more effective personalized treatment plans for patients with LPR.

Impact of Acid, Weakly Acid and Alkaline Laryngopharyngeal Reflux on Voice Quality.

OBJECTIVES: To analyze pre to posttreatment voice changes regarding the type of reflux in patients with acid, weakly acid or alkaline laryngopharyngeal reflux (LPR). METHODS: Patients with LPR, diagnosed using hypopharyngeal-esophageal multichannel intraluminal impedance pH-monitoring (HEMII-pH), were prospectively recruited from three University Hospitals. Patients were treated with a combination of diet, proton pump inhibitors, magaldrate and alginate for 3 months. The following clinical and voice quality outcomes were studied pre to posttreatment according to the type of reflux (acid, weakly acid, nonacid): HEMII-pH, gastrointestinal endoscopy features, reflux symptom score (RSS), reflux sign assessment (RSA), voice handicap index (VHI), perceptual voice assessment (grade of dysphonia and roughness), aerodynamic and acoustic measurements. RESULTS: From December 2018 to March 2021, 160 patients completed the evaluations, accounting for 60 acid, 52 weakly acid, and 48 alkaline cases of LPR. There were no baseline differences in clinical and voice quality outcomes between groups. RSS and RSA significantly improved from pre to posttreatment in the entire cohort and in all patient groups. VHI, dysphonia and roughness, maximum phonation time, Jitter, Shimmer and noise to harmonic ratio significantly improved from pre to posttreatment. Individuals with alkaline reflux reported better voice quality improvements as compared to acid and weakly acid reflux patients. CONCLUSION: Patients with acid and alkaline reflux reported better posttreatment voice quality outcomes as compared to weakly acid reflux patients. Future basic science and clinical studies are needed to better understand the histological changes of the vocal folds due to reflux of varying pH types and gastroduodenal enzyme content.

Prognostic Significance of a Scoring System Combining p16, Smoking, and Drinking Status in a Series of 131 Patients with Oropharyngeal Cancers.

BACKGROUND: Tobacco and alcohol are two main risk factors associated with head and neck squamous cell carcinoma (HNSCC). Studies showed that human papillomavirus (HPV) plays a role in the etiology of this cancer. HPV-positive oropharyngeal squamous cell carcinoma (OSCC) patients present in general a better response to conventional therapy and better overall survival (OS). However, OSCC is a heterogeneous disease regarding treatment. This study aimed to identify more effective prognostic factors associated with a poor clinical outcome for OSCC patients to improve treatment selection. MATERIALS AND METHODS: OSCC patients diagnosed between 2007 and 2017, in two Belgian hospitals, were included. Demographic and clinicopathologic data were extracted from medical records. HPV status was determined through p16 immunohistochemistry. Univariable and multivariable Cox proportional hazard regression analyses allowed to identify variables prognostic for OS and recurrence-free survival (RFS). Kaplan-Meier survival curves have been assessed for survival. RESULTS: The study included 131 patients. Statistics showed that monotherapies were significantly associated with a shorter OS; p16 overexpression was significantly associated with a weak consumption of tobacco or alcohol, and a high p16 expression was significantly associated with both longer RFS and OS. The study validated that tobacco and alcohol consumption were significantly correlated with poorer RFS and poorer OS. Only p16 expression trended to be significant for RFS when compared to smoking and drinking habits, while p16 upregulation and alcohol use were both vital for OS indicating that p16 is an independent and significant prognostic factor in OSCC patients. Finally, a scoring system combining p16, tobacco, and alcohol status was defined and was significantly associated with longer RFS and longer OS for nonsmoker and nondrinker p16-positive OSCC patients. CONCLUSIONS: This study confirmed that the overexpression of the p16 protein could be viewed as a factor of good prognosis for RFS and OS of OSCC patients. The prognostic significance of a scoring system combining p16 expression, smoking, and drinking status was evaluated and concluded to be a more effective tool to determine therapeutic orientations based on the risk factors for better treatment relevance and survival.