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Objective: To investigate the digestive enzymes and biomarkers in the saliva of patients with laryngopharyngeal reflux (LPR) and asymptomatic individuals. Study Design: Prospective controlled study. Setting: Multicenter study. Methods: Patients with LPR at the hypopharyngeal‐esophageal impedance‐pH monitoring (HEMII‐pH) and asymptomatic individuals were consecutively recruited from January 2020 to April 2023 from 2 University Hospitals. The saliva of patients (off PPIs) and asymptomatic individuals was collected to measure pH, elastase, bile salts, cholesterol, gastric, and pancreatic lipases. Anxiety, symptoms, and findings were studied through perceived stress scale (PSS), reflux symptom score (RSS), and reflux sign assessment (RSA). Results: Sixty‐seven LPR patients and 57 asymptomatic individuals completed the evaluations. LPR patients reported higher PSS, RSS, and RSA than asymptomatic individuals. The mean saliva pH was more alkaline in LPR patients (7.23: 95% confidence interval [CI]: 7.08, 7.38) compared to controls (6.13; 95% CI: 5.95, 6.31; P =.001). The mean concentration of elastase was higher in patients (51.65 µg/mL; 95% CI: 44.47, 58.83 µg/mL) versus asymptomatic individuals (25.18 µg/mL; 95% CI: 21.64, 28.72 µg/mL; P =.001). The saliva cholesterol reported higher concentration in healthy individuals (3.43 mg/dL; 95% CI: 3.21, 3.65 mg/dL) compared to patients (1.16 mg/dL; 95% CI: 1.05, 1.27 mg/dL; P =.001). The saliva pH, and elastase concentration were significantly associated with the baseline RSS, while saliva cholesterol was negatively associated with the severity of RSS and RSA. Conclusion: Cholesterol, bile salts, and elastase are biomarkers of LPR and should be considered to develop future non‐invasive saliva device for the detection of LPR. [ABSTRACT FROM AUTHOR]

Objective: The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. Methods: Forty‐eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. Results: After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non‐specific laryngeal and extra‐laryngeal symptoms and signs that can be evaluated with validated patient‐reported outcome questionnaires and clinical instruments. The hypopharyngeal–esophageal multichannel intraluminal impedance–pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. Conclusion: A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. Level of Evidence: 5 Laryngoscope, 134:1614–1624, 2024 [ABSTRACT FROM AUTHOR]

Objective: To develop a French Short Version of the Questionnaire of Olfactory Disorders-Negative Statements (Fr-sQOD) to assess the quality of life impairments of patients with olfactory dysfunction (OD). Methods: Patients with OD and controls were enrolled from 2 academic centers. Individuals completed the Fr-sQOD, an OD visual analog scale severity, and the French version of the sinonasal outcome tool-22 (SNOT-22). Cronbach α was used to measure the internal consistency of Fr-sQOD. The reliability and the external validity of Fr-sQOD were assessed through a test–retest approach and by correlating Fr-sQOD with SNOT-22 scores, respectively. The external validity was assessed by correlation analysis between Fr-sQOD and the result of an assessment of the severity of OD on a visual analog scale. Results: Eighty patients completed the evaluations. The internal consistency was adequate (Cronbach α.96), and the test–retest reliability was high in the entire cohort (rs = 0.877, P <.001). The correlation between Fr-sQOD total scores and the severity of OD was moderate but significant (rs = −0.431; P =.001) supporting an acceptable external validity. Patients with OD had a significantly higher score of Fr-sQOD than healthy individuals (P <.001), indicating a high internal validity. Conclusion: The Fr-sQOD is a reliable and valid self-administered tool in the evaluation of the impact of OD on quality of life of French-speaking patients. [ABSTRACT FROM AUTHOR]

Post-vaccine olfactory and gustatory disorders are very rare and were reported in patients who received influenza vaccines. In this article, we report 6 cases of post-coronavirus disease 2019 (COVID-19) vaccine olfactory and gustatory disorders in patients with negative nasal swabs. Precisely, olfactory and gustatory dysfunctions were reported in 5 and 1 patients, respectively. Sense disorders occurred after the first injection of AstraZeneca (n = 4) or the second injection of Pfizer (n = 2) vaccines. In 4 cases, the olfactory or gustatory disorder was confirmed with psychophysical evaluations. The duration of chemosensory dysfunction ranged from 4 to 42 days. None of the patient reported mid- or long-term olfactory or gustatory disorder. The occurrence of olfactory and gustatory dysfunctions in adults benefiting from COVID-19 vaccines is still rare but has to be known by otolaryngologists. [ABSTRACT FROM AUTHOR]

Despite advancements in treating metastatic melanoma, many patients exhibit resistance to targeted therapies. Our study focuses on ATP1A1, a sodium pump subunit associated with cancer development. We aimed to assess ATP1A1 prognostic value in melanoma patients and examine the impact of its ligand, bufalin, on melanoma cell lines in vitro and in vivo. High ATP1A1 expression (IHC) correlated with reduced overall survival in melanoma patients. Resistance to BRAF inhibitor was linked to elevated ATP1A1 levels in patient biopsies (IHC, qPCR) and cell lines (Western blot, qPCR). Additionally, high ATP1A1 mRNA expression positively correlated with differentiation/pigmentation markers based on data from The Cancer Genome Atlas (TCGA) databases and Verfaillie proliferative gene signature analysis. Bufalin specifically targeted ATP1A1 in caveolae, (proximity ligation assay) and influenced Src phosphorylation (Western blot), thereby disrupting multiple signaling pathways (phosphokinase array). In vitro, bufalin induced apoptosis in melanoma cell lines by acting on ATP1A1 (siRNA experiments) and, in vivo, significantly impeded melanoma growth using a nude mouse xenograft model with continuous bufalin delivery via an osmotic pump. In conclusion, our study demonstrates that ATP1A1 could serve as a prognostic marker for patient survival and a predictive marker for response to BRAF inhibitor therapy. By targeting ATP1A1, bufalin inhibited cell proliferation, induced apoptosis in vitro, and effectively suppressed tumor development in mice. Thus, our findings strongly support ATP1A1 as a promising therapeutic target, with bufalin as a potential agent to disrupt its tumor-promoting activity. [ABSTRACT FROM AUTHOR]

Olfactory dysfunction (OD) was one of the most common symptom of infection with the Wuhan strain of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and could persist for several months after symptom onset. The pathogenesis of prolonged OD remains poorly understood but probably involves sustained viral replication associated with limited mucosal immune response to the virus. This prospective study was conducted to investigate the potential relationship between nasal SARS‐CoV‐2 viral load and antibody levels in patients with loss of smell. One hundred and five patients were recruited 2 weeks after presenting with confirmed coronavirus disease 2019 associated OD. Based on the identification sniffing test performed at enrollment, 52 patients were still anosmic or hyposmic and 53 were normosmic. SARS‐CoV‐2 was detectable in nasal wash of about 50% of anosmic and normosmic patients. Higher viral load was detected in anosmic patients with lower levels of SARS‐CoV‐2 specific nasal immunoglobulins (Ig) IgG and IgA. This association was not observed in normosmic patients. No relationship between nasal viral load and antibodies to endemic coronaviruses was observed. SARS‐CoV‐2 replication in the nasal cavity may be promoted by defective mucosal antibody responses in patients with OD. Boosting mucosal immunity may limit nasal SARS‐CoV‐2 replication and thereby help in the control of persistent OD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of platelet‐rich plasma (PRP) injection into the olfactory clefts of coronavirus disease 2019 (COVID‐19) patients with persistent olfactory dysfunction (OD). Study Design: Controlled study. Setting: Multicenter study. Methods: From March 2022 to November 2022, COVID‐19 patients with persistent OD were recruited from three European hospitals to undergo PRP injections into the olfactory clefts. Olfactory function was evaluated at baseline and 10 weeks postinjection with the Olfactory Disorder Questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test. Data were compared with a control group of untreated patients. Results: Eighty‐one patients who underwent PRP injection and 78 controls were included. Sixty‐five PRP patients (80.3%) experienced subjective smell improvement after a mean duration of 3.4 ± 1.9 weeks. The parosmia, life quality statement, and ODQ sub‐ and total scores significantly decreased from pre‐ to 10‐week postinjection in the PRP group. The TDI sub‐ and total scores significantly increased 10 weeks postinjection. In controls, the ODQ score did not change over time, while the discrimination, identification, and total TDI scores significantly increase after 10 weeks of follow‐up. The 10‐week TDI and ODQ scores were significantly better in the PRP group compared with the controls. Conclusion: Patients who underwent PRP injection reported better 10‐week subjective and objective smell outcomes than controls. Future randomized‐controlled studies using saline injection into the olfactory cleft of controls are needed to determine the superiority of PRP over placebo. [ABSTRACT FROM AUTHOR]

In this paper, we described technique of platelet rich plasma injection into the olfactory cleft in a 22-year-old female with 24-month post–COVID-19 anosmia. The technique starts with the blood extraction and the isolation of PRP through a 10-min centrifugation. The supernatant was injected in nasal regions after a local anesthesia through a 0° rigid optic. Several points of.2–.5 mL were performed in the nasal septum in regard of the head of the middle turbine and in the head of the middle turbine in both sides. The baseline threshold, discrimination, and identification scores were 1, 8, and 0, and the Olfactory Disorder Questionnaire score was 51, respectively. The injection of PRP in olfactory cleft was done without complication and mild pain. The patient perception of recovery of smell sense occurred at 3-week post-injection. From this time, the smell sense progressively improved to the 2-month consultation. At 2-month post-injection, the TDI scores reached 16, 16, and 16 (48), while the Olfactory Disorder Questionnaire was 73. The injection of PRP into the olfactory cleft appears to be a safe and easiness new approach that may improve the recovery of smell sense. Future controlled studies are needed. [ABSTRACT FROM AUTHOR]

The article proposes a potential hypothesis about the pathophysiological mechanism of olfactory dysfunction (OD) based on some clinical observations. Topics include observation on some patients with persistent COVID-19 OD since the development of vaccination in Western countries, observation on olfactory region abnormalities in imaging study several months after the onset of OD, and analysis of the persistence of OD in COVID-19 patients.

Tumor-associated macrophages are key components of the tumor microenvironment (TME) and have been shown to play important roles in the progression of head and neck cancer. As a result, novel treatment approaches are focused on reprogramming M2 macrophages to adopt the M1 phenotype. A 3D coculture model was established to analyze the influence of cancer cells on monocyte recruitment and their polarization. Macrophages phenotypes were determined by immunofluorescence, western blot and RT-QPCR. Interleukines were analyzed by using CBA array. First, a scoring system based on the high or low density of M1 CD80+ and M2 CD163+ macrophages and on the tumor-infiltrated phenotype was developed in a clinical series of 54 head and neck squamous cell carcinoma patients. Interestingly, this macroscore was found to be more powerful than TNM criteria and p16 status and also significantly associated with poor prognosis for these patients. In vitro, the 3D model demonstrated that cancer cells are responsible for monocyte recruitment and M2 polarization, resulting in an immunosuppressive microenvironment with an increased production of IL8 and IL10 cytokines.Finally, we focused on a new compound found in toad venom. Bufalin is an endogenous cardiotonic steroid with reported anti-cancer and immunomodulatory properties. Our data indicated that bufalin reprogram M2 macrophages towards the M1 phenotype underlining its potential as an antitumor immune modulator. Overall, this research highlights the power of the macroscore as a new valuable prognostic biomarker and sheds light on the immunosuppressive tumor microenvironment. Moreover, it indicates that modulating macrophages in the tumor microenvironment using bufalin could be a promising immunotherapeutic strategy for the treatment of cancer. [ABSTRACT FROM AUTHOR]

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 (r s  = 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 (r s  = 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, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To develop a French Short Version of the Questionnaire of Olfactory Disorders-Negative Statements (Fr-sQOD) to assess the quality of life impairments of patients with olfactory dysfunction (OD)., Methods: Patients with OD and controls were enrolled from 2 academic centers. Individuals completed the Fr-sQOD, an OD visual analog scale severity, and the French version of the sinonasal outcome tool-22 (SNOT-22). Cronbach α was used to measure the internal consistency of Fr-sQOD. The reliability and the external validity of Fr-sQOD were assessed through a test-retest approach and by correlating Fr-sQOD with SNOT-22 scores, respectively. The external validity was assessed by correlation analysis between Fr-sQOD and the result of an assessment of the severity of OD on a visual analog scale., Results: Eighty patients completed the evaluations. The internal consistency was adequate (Cronbach α .96), and the test-retest reliability was high in the entire cohort (r s = 0.877, P < .001). The correlation between Fr-sQOD total scores and the severity of OD was moderate but significant (r s = -0.431; P = .001) supporting an acceptable external validity. Patients with OD had a significantly higher score of Fr-sQOD than healthy individuals ( P < .001), indicating a high internal validity., Conclusion: The Fr-sQOD is a reliable and valid self-administered tool in the evaluation of the impact of OD on quality of life of French-speaking patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Post-vaccine olfactory and gustatory disorders are very rare and were reported in patients who received influenza vaccines. In this article, we report 6 cases of post-coronavirus disease 2019 (COVID-19) vaccine olfactory and gustatory disorders in patients with negative nasal swabs. Precisely, olfactory and gustatory dysfunctions were reported in 5 and 1 patients, respectively. Sense disorders occurred after the first injection of AstraZeneca (n = 4) or the second injection of Pfizer (n = 2) vaccines. In 4 cases, the olfactory or gustatory disorder was confirmed with psychophysical evaluations. The duration of chemosensory dysfunction ranged from 4 to 42 days. None of the patient reported mid- or long-term olfactory or gustatory disorder. The occurrence of olfactory and gustatory dysfunctions in adults benefiting from COVID-19 vaccines is still rare but has to be known by otolaryngologists., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.