Validity and Reliability of the Reflux Sign Assessment-10 (RSA-10).

OBJECTIVE: To develop and validate the Reflux Sign Assessment-10 (RSA-10) for documenting the physical findings of laryngopharyngeal reflux disease (LPRD). METHODS: Patients with LPRD at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring and asymptomatic individuals were consecutively recruited from two European hospitals. Three experienced otolaryngologists rated RSA-10 in patients and controls for assessing internal validity. RSA-10 was rated within a 7-day period to assess test-retest reliability. Internal consistency was measured using Cronbach's α in patients and controls. Convergent validity was evaluated through a correlation analysis between RSA-10 and Reflux Finding Score (RFS). Interrater reliability was evaluated by comparing the RSA-10 evaluations of the three otolaryngologists through Fleiss kappa. Pre- to posttreatment change of RSA-10 was evaluated to assess responsiveness to change. The RSA-10 thresholds were examined by receiver operating characteristic analysis. RESULTS: Fifty-five patients completed the pre- to posttreatment evaluations from January 2020 to December 2023. A total of 115 asymptomatic individuals completed the study. RSA-10 reported high internal consistency reliability (α = 0.822) and test-retest reliability (rs = 0.725). The RSA-10 scores of patients were significantly higher than those of controls (p = 0.001), suggesting high internal validity. RSA-10 was significantly correlated with the RFS (rs = 0.771). The interrater reliability was adequate for sub- and total RSA-10 scores (k = 0.708). RSA-10 significantly improved from baseline to 3-month posttreatment (p = 0.001). An RSA-10 > 13 may be suggestive of LPRD. Both RSA-10 > 13 and Reflux Symptom Score-12 > 11 were associated with a sensitivity of 92.7% and a specificity of 97.3%. CONCLUSION: The RSA-10 is a reliable and valid clinical instrument for documenting the most prevalent laryngeal and extra-laryngeal findings associated with LPRD. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3981-3988, 2024.

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.

Management of Laryngopharyngeal Reflux Around the World: An International Study.

OBJECTIVE: To investigate worldwide practices of otolaryngologists in the management of laryngopharyngeal reflux (LPR). METHODS: An online survey was sent on the management of LPR to members of many otolaryngological societies. The following aspects were evaluated: LPR definition, prevalence, clinical presentation, diagnosis, and treatment. RESULTS: A total of 824 otolaryngologists participated, spread over 65 countries. The symptoms most usually attributed to LPR are cough after lying down/meal, throat clearing and globus sensation while LPR-related findings are arytenoid erythema and posterior commissure hypertrophy. Irrespective to geography, otolaryngologists indicate lack of familiarity with impedance pH monitoring, which they attribute to lack of knowledge in result interpretation. The most common therapeutic regimens significantly vary between world regions, with a higher use of H2 blocker in North America and a lower use of alginate in South America. The duration of treatment also significantly varies between different regions, with West Asia/Africa and East Asia/Oceania otolaryngologists prescribing medication for a shorter period than the others. Only 21.1% of respondents are aware about the existence of nonacid LPR. Overall, only 43.2% of otolaryngologists believe themselves sufficiently knowledgeable about LPR. CONCLUSIONS: LPR knowledge and management significantly vary across the world. International guidelines on LPR definition, diagnosis, and treatment are needed to improve knowledge and management around the world. LEVEL OF EVIDENCE: N.A. Laryngoscope, 131:E1589-E1597, 2021.

Are the Acoustic Measurements Reliable in the Assessment of Voice Quality? A Methodological Prospective Study.

OBJECTIVE: Acoustic parameters are widely used as voice quality therapeutic outcomes in many laryngological diseases. The aim of this study is to explore the impact of changes in the nature and duration of the analyzed time interval and the vowel choice on the significance of the acoustic measurements used as therapeutic outcomes in two different diseases. STUDY DESIGN: A prospective case series. MATERIAL AND METHODS: From September 2013 to January 2018, patients with laryngopharyngeal reflux (LPR) disease were recruited and treated with pantoprazole, diet, and behavioral changes for 3 months. The reflux symptom index and reflux finding score were used for both diagnosis and assessment of treatment effectiveness. Simultaneously, patients with early idiopathic Parkinson's disease (IPD) were enrolled and benefited from a levodopa challenge test. An Iowa Oral Performance Instrument was used for objective outcomes in the assessment of levodopa effectiveness on muscular strength of IPD patients. Acoustic measurements were performed in both groups pre- and postmedication intake at different time intervals, including the "most stable" time intervals of 1 second, 2 seconds, 3 seconds, 4 seconds, and 5 seconds and a 1 second-time interval positioned at mid-production. We also measured acoustic parameters on the entire signal of three vowels and on the signal of each vowel being taken separately. RESULTS: A total of 80 LPR and 19 IPD patients met our inclusion criteria and completed the study protocol. LPR and IPD patients had significant clinical improvements throughout treatment, according to reflux symptom index, reflux finding score, and Iowa Oral Performance Instrument scores. The acoustic analysis revealed that acoustic parameters significantly improved from pre- to post-treatment and varied across methods used for measurement. The duration and position of the analyzed time interval in the production and the vowel on which the acoustic measures were made yielded considerable differences in the results. CONCLUSION: Depending on the time interval over which the acoustic parameters are measured, the clinically demonstrated effect of the medication may or may not be statistically demonstrated irrespective of the disease. According to the results of this study and regarding the lack of standardization of acoustic measurement methods, a line of thought is proposed to bypass the interval selection problem.

Ethyl alcohol threshold test: a fast, reliable and affordable olfactory Assessment tool for COVID-19 patients.

OBJECTIVE: COVID-19 patients may present mild symptoms. The identification of paucisymptomatic patients is paramount in order to interrupt the transmission chain of the virus. Olfactory loss could be one of those early symptoms which might help in the diagnosis of COVID-19 patients. In this study, we aim to develop and validate a fast, inexpensive, reliable and easy-to-perform olfactory test for the screening of suspected COVID-19 patients. STUDY DESIGN: Phase I was a case-control study and Phase II a transversal descriptive study. SUBJECTS AND METHODS: Olfaction was assessed with the ethyl alcohol threshold test and symptoms with visual analogue scales. The study was designed in two phases: In Phase I, we compared confirmed COVID-19 patients and healthy controls. In Phase II, patients with suspected COVID-19 infection referred for testing were studied. RESULTS: 275 participants were included in Phase I, 135 in Phase II. The ROC curve showed an AUC of 0.749 in Phase I, 0.737 in Phase II. The cutoff value which offered the highest amount of correctly classified patients was ≥ 2 (10% alcohol) for all age intervals. The odds ratio was 8.19 in Phase I, 6.56 in Phase II with a 75% sensitivity. When cases report normal sense of smell (VAS < 4), it misdiagnoses 57.89% of patients detected by the alcohol threshold test. CONCLUSION: The olfactory loss assessed with the alcohol threshold test has shown high sensitivity and odds ratio in both patients with confirmed COVID-19 illness and participants with suspected SARS-CoV-2 infection.

Validity and Reliability of the Reflux Sign Assessment.

OBJECTIVE: To develop and validate the Reflux Sign Assessment (RSA), a clinical instrument evaluating the physical findings of laryngopharyngeal reflux (LPR). METHODS: A total of 106 patients completed a 3-month treatment based on the association of diet, pantoprazole, alginate, or magaldrate with the LPR characteristics (acid, nonacid, mixed). Forty-two asymptomatic individuals completed the study (control group). The RSA results and reflux finding score (RFS) were documented for the LPR patients at baseline and after treatment. Intrarater reliability was assessed through a test-retest blinded evaluation of signs (7-day intervals). Interrater reliability was assessed by comparing the RSA evaluations of three blinded otolaryngologists through Kendall's W. Responsiveness to change was evaluated through a comparison of the baseline and 3-month posttreatment findings. The RSA cutoffs for determining the presence and absence of LPR were examined by receiver operating characteristic (ROC) analysis. RESULTS: A total of 102 LPR patients completed the study (68 females). The mean age was 53 years. The mean RSA at baseline was 25.95 ± 9.58; it significantly improved to 18.96 ± 7.58 after 3 months of therapy (P < .001). RSA exhibited good intra- (r = 0.813) and interrater (Kendall's W = 0.663) reliabilities (N = 56). There was no significant association between the RSA, gastrointestinal endoscopy findings, and the types of reflux (acid, nonacid, or mixed) according to impedance-pH monitoring. An RSA >14 may be suggestive of LPR. CONCLUSION: The RSA is a complete clinical instrument evaluating both laryngeal and extralaryngeal findings associated with LPR. The RSA demonstrated high intra- and interrater reliabilities and responsiveness to change.

In vivo assessment of temozolomide local delivery for lung cancer inhalation therapy.

The aim of this study was to compare the efficacy of local drug delivery by inhalation to intravenous delivery in a B16F10 melanoma metastatic lung model. Temozolomide was formulated as a suspension, which was elaborated and evaluated in terms of particle size, shape and agglomeration. An endotracheal administration device was used to aerosolise the suspension. This mode of delivery was evaluated at different temozolomide concentrations and was optimized for the uniformity of delivered dose, the droplet size distribution and the distribution of droplets in vivo. Of the particles in the stabilised suspension, 79% were compatible with the human respirable size range, and this formulation retained 100% in vitro anticancer activity as compared to temozolomide alone in three distinct cancer cell lines. The pulmonary delivery device provided good reproducibility in terms of both the dose delivered and the droplet size distribution. Most of the lung tissues that were exposed to aerosol droplets contained the particles, as revealed by fluorescent microscopy techniques. The global in vivo antitumour activity of the inhaled temozolomide provided a median survival period similar to that for intravenous temozolomide delivery, and three out of 27 mice (11%) survived with almost complete eradication of the lung tumours. The present study thus shows that inhalation of a simple liquid formulation is well tolerated and active against a very biologically aggressive mouse melanoma pulmonary pseudo-metastatic model. This inhalation delivery could be used to deliver other types of anticancer drugs.