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Objective: To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS). Data Sources: PubMed, Cochrane Library and Scopus. Review Methods: Three investigators searched the specified databases for studies investigating the relationship between LPR, GERD and recalcitrant CRS with or without polyposis. The following outcomes were investigated with PRISMA criteria: age; gender; reflux and CRS diagnosis; association outcomes and potential treatment outcomes. The authors performed a bias analysis of papers and provided recommendations for future studies. Results: A total of 17 studies investigated the association between reflux and recalcitrant CRS. According to pharyngeal pH monitoring, 54% of patients with recalcitrant CRS reported hypo or nasopharyngeal acid reflux events. The number of hypo‐ and nasopharyngeal acid reflux events was significantly higher in patients compared to healthy individuals in 4 and 2 studies, respectively. Only one study did not report intergroup differences. The proportion of GERD was significantly higher in CRS patients compared to controls, with a prevalence ranging from 32% to 91% of cases. No author considered nonacid reflux events. There was significant heterogeneity in the inclusion criteria; definition of reflux and association outcomes, limiting the ability to draw clear conclusions. Pepsin was found in sinonasal secretions more frequently in CRS patients than controls. Conclusion: Laryngopharyngeal reflux and GERD may be contributing factors of CRS therapeutic resistance, but future studies are needed to confirm the association considering nonacid reflux events. [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]

Objectives: The objective is to study the usefulness of acoustic measurements as therapeutic outcomes for patients with dysphonia related to laryngopharyngeal reflux (LPR). Methods: From September 2019 to April 2021, 120 patients with LPR at the hypopharyngeal-esophageal multichannel intraluminal impedance pH-monitoring (HEMII-pH) were prospectively recruited from three University Hospitals. They were divided in two groups regarding the presence of dysphonia. The treatment consisted of a combination of diet, proton-pump inhibitors, magaldrate and alginate for 3–6 months. The following clinical and acoustic evaluations were studied regarding groups at baseline, 3- and 6-month posttreatment: reflux symptom score (RSS), reflux sign assessment (RSA), percent jitter, percent shimmer and noise-to-harmonic ratio (NHR). Results: A total of 109 patients completed the evaluations, accounting for 49 dysphonic and 60 non-dysphonic individuals. HEMII-pH, gastrointestinal endoscopy, baseline clinical and acoustic features were comparable between groups. RSS and RSA significantly improved from pre- to 3-month posttreatment in both groups. Jitter, Shimmer and NHR significantly improved from pre- to 3-month posttreatment in dysphonic patients, without additional 3- to 6-month posttreatment changes. Acoustic parameters did not change throughout treatment in patients without dysphonia. Conclusion: Acoustic measurements may be an interesting indicator of treatment in LPR patients who reported dysphonia. In this group of individuals, the evolution of acoustic parameters was consistent with the evolution of symptoms and findings. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to evaluate potential predictive factors of smell recovery in a clinical series of 288 patients presenting olfactory dysfunction (OD) related to coronavirus disease 2019 (COVID‐19). Potential correlations were sought between epidemiological, clinical and immunological characteristics of patients and the persistence of OD at 60 days. Methods: COVID‐19 positive patients presenting OD were prospectively recruited from three European hospitals. Baseline clinical and olfactory evaluations were performed within the first 2 weeks after OD onset and repeated at 30 and 60 days. In a subgroup of patients, anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies were measured in serum, saliva and nasal secretions at 60 days. Results: A total of 288 COVID‐19 patients with OD were included in the study. Two weeks after the onset of the loss of smell, 52.4% of patients had OD on psychophysical tests, including 113 cases (39.2%) of anosmia and 38 cases (13.2%) of hyposmia. At 60‐day follow‐up, 25.4% of the patients presented persistent OD. There was no significant correlation between sex, age, viral load on nasopharyngeal swab or COVID‐19 severity and poor olfactory outcome. In a subgroup of 63 patients, it was demonstrated that patients with poor olfactory outcomes at 60 days had lower levels of salivary and nasal immunoglobulin G (IgG) and IgG1, but similar levels of antibodies in the serum. Conclusions: No clinical markers predicted the evolution of OD at 60 days. Patients with poor olfactory outcome at 60 days had lower saliva and nasal antibodies, suggesting a role for local immune responses in the persistence of COVID‐19 related OD. [ABSTRACT FROM AUTHOR]

Background: From the start of the pandemic, many European otolaryngologists observed an unprecendented number of anosmic patients. Early reports proposed that anosmia could be the first or even the only symptom of COVID-19 infection, prompting calls for self-isolation in affected patients. Methods: In the present article, we review the COVID-19 anosmia literature and try to answer the following two questions: first, why is COVID-19 infection responsible for such a high incidence of anosmia? Second, in patients with more severe forms is anosmia really less prevalent and why? Results: In terms of the etiology of olfactory dysfunction, several hypotheses were proposed at the outset of the pandemic; that olfactory cleft inflammation and obstruction caused a localized conductive loss, that there was injury to the sustentacular supporting cells in the olfactory epithelium or, given the known neurotropic potential of coronavirus, that the virus could invade and damage the olfactory bulb. Olfactory cleft obstruction may contribute to the olfactory dysfunction in some patients, perhaps most likely in those that show very early resolution, it cannot account for the loss in all patients. Moreover, disordered regrowth and a predominance of immature neurons have been shown to be associated with parosmia, which is a common finding amongst patients with Covid-related anosmia. A central mechanism therefore certainly seems to be consistent with the group of patients with more prolonged olfactory deficits. Sustentacular cells showing ACE-2 immunohistochemical expression 200 to 700 times greater than nasal or tracheal epithelia seem to be the main SARS-CoV-2 gateway. As the pathophysiology of COVID-19 anosmia seems to be better understood, the question of why patients with a moderate to severe form of COVID-19 infection have less olfactory involvement remains unresolved. Different potential explanations are discussed in this review. Conclusions : The last 5 months have benefited from great international collaborative research, first highlighting and then proving the value of loss of smell and taste as a symptom of COVID-19. Adoption of loss of smell into the case definition by international public health bodies will facilitate control of disease transmission. [ABSTRACT FROM AUTHOR]

The authors investigated the occurrence of dysphonia in COVID-19 patients in Egypt and the videolaryngoscopic findings associated with vocal symptoms. Keywords: Dysphonia; COVID-19; SARS-CoV-2; Voice; Infection; Reflux EN Dysphonia COVID-19 SARS-CoV-2 Voice Infection Reflux 3202 3203 2 11/29/22 20221002 NES 221002 Dear Editor We read the article entitled: " I Vocal Disorders in Patients with COVID 19 in Egypt i " by Aziz Azzam et al. [[1]]. [Extracted from the article]

Objective: To investigate safety, feasibility, and effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of COVID-19 patients with persistent olfactory dysfunction (OD). Methods: From March 2022 to July 2022, COVID-19 patients with persistent OD were consecutively recruited to benefit from PRP injection into the olfactory clefts. Patient pain, annoyance, time of procedure, and adverse events were evaluated. Olfactory function was evaluated at baseline and 2-month post-injection with the olfactory disorder questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test. Results: Eighty-seven patients with anosmia (N = 30), hyposmia (N = 40), or parosmia (N = 17) with a mean OD duration of 15.7 months completed the evaluations. The PRP injection was successfully performed in all patients with a mean procedure time of 18.4 ± 3.4 min. The adverse events included transient epistaxis (N = 31), parosmia related to xylocaine spray (N = 10), and vasovagal episode (N = 2). The injection procedure was evaluated as somewhat or moderately painful by 41 (47%) and 22 (25%) patients, respectively. Thirty-seven patients were assessed after 2 months post-injection. The mean ODQ and TDI scores significantly improved from baseline to 2-month post-injection (p < 0.01). The olfactory improvement occurred after a mean of 3.6 ± 1.9 weeks. Conclusion: The injection of PRP into the olfactory clefts is safe and associated with adequate patient-reported outcomes. The findings of this preliminary study suggest possible efficacy on subjective and psychophysical evaluations, but future randomized controlled studies are needed to determine the superiority of PRP injection over placebo. [ABSTRACT FROM AUTHOR]

Objectives: To investigate effectiveness of olfactory training (OT) in COVID-19 patients with persistent olfactory dysfunction (OD). Methods: From March 2020 to March 2022, COVID-19 patients with OD were prospectively followed in three European medical centers for a period of 18 months. A standardized OT protocol were recommended to patients. Patient-reported outcome questionnaires and psychophysical evaluations were used to evaluate olfaction at baseline, 6, 12, and 18 months after the start of OT. The evolution of olfactory outcome was compared according to the adherence to the OT protocol. Results: Fifty-seven patients completed the evaluations. Thirty-two patients fully adhered to the OT, while 25 did not adhere. The psychophysical scores significantly improved from baseline to 6-month post-infection in both groups. In the OT group, the psychophysical scores continued to significantly improve from 6 to 12 months after the start of OT (p = 0.032). The mean duration of OT was 15.4 weeks. The mean delay of patient recovery perception was comparable between groups (27.4 weeks). The occurrence of cacosmia (35.1%) and parosmia (43.9%) throughout the follow-up period was comparable between groups. There proportion of phantosmia was higher in training (34.4%) compared with no-OT (16.0%; p = 0.007) group. The baseline Sniffin'Sticks tests was positively associated with the 6-month Sniffin'Sticks tests (rs = 0.685; p < 0.001) and negatively associated with the time of recovery (rs = − 0.369; p = 0.034). Conclusions: The adherence to an OT protocol was associated with better mid-term improvement of psychophysical scores. Future large-cohort randomized-controlled studies are needed to confirm the effectiveness of OT in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence and recovery of olfactory dysfunction (OD) in COVID‐19 patients 24 months after the infection. Methods: From 22 March 2020 to 5 June 2022, 251 COVID‐19 patients were followed in three European medical centres. Olfactory function was assessed with subjective patient‐reported outcome questionnaires and odour identification tests at baseline, 6, 12, 18 and 24 months postinfection. The predictive values of epidemiological and clinical data were investigated with multivariate analysis. Results: One hundred and seventy‐one patients completed the evaluations. The odour identification test revealed that 123 patients (50.8%) had OD at baseline. The prevalence of persistent psychophysical abnormalities at 6, 12, 18 and 24 months post‐COVID‐19 was 24.2%, 17.9%, 5.8% and 2.9%, respectively (p = 0.001). Parosmia occurred in 40 patients (23.4%) and lasted 60 ± 119 days. At 2 years, 51 patients (29.8%) self reported that their olfaction was unnormalised. Older patients had better odour identification evaluations at baseline (p < 0.001) but those with OD reported lower odour identification test scores at the end of the follow‐up. Parosmia occurred more frequently in young patients. The olfactory training was significantly associated with higher values of Sniffin' Sticks tests at 18 months postinfection (rs = 0.678; p < 0.001). Conclusion: Two years post‐COVID‐19, 29.8% of patients reported persistent OD, but only 2.9% had abnormal identification psychophysical evaluations. [ABSTRACT FROM AUTHOR]

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 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]

The article discusses the importance of personalized medicine in olfactory testing to improve patient compliance. Olfactory disorders (OD) have a significant impact on quality of life, but there is a lack of awareness among medical professionals about this problem. The COVID-19 pandemic has highlighted the importance of the sense of smell, as many patients experience persistent olfactory dysfunctions. Psychophysical tests (PT) are considered the gold standard for evaluating olfaction, but they are not always adjusted to the patient's complaints and wishes. The addition of specific odors from the patient's daily life could improve the accuracy of PT and patient compliance. The use of artificial intelligence (AI) software in olfactory training could also enhance patient adherence and collect important data for research. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Functionalized iron oxide nanoparticles (IONPs) are increasingly being designed as a theranostic nanoplatform combining specific targeting, diagnosis by magnetic resonance imaging (MRI), and multimodal therapy by hyperthermia. The effect of the size and the shape of IONPs is of tremendous importance to develop theranostic nanoobjects displaying efficient MRI contrast agents and hyperthermia agent via the combination of magnetic hyperthermia (MH) and/or photothermia (PTT). Another key parameter is that the amount of accumulation of IONPs in cancerous cells is sufficiently high, which often requires the grafting of specific targeting ligands (TLs). Herein, IONPs with nanoplate and nanocube shapes, which are promising to combine magnetic hyperthermia (MH) and photothermia (PTT), were synthesized by the thermal decomposition method and coated with a designed dendron molecule to ensure their biocompatibility and colloidal stability in suspension. Then, the efficiency of these dendronized IONPs as contrast agents (CAs) for MRI and their ability to heat via MH or PTT were investigated. The 22 nm nanospheres and the 19 nm nanocubes presented the most promising theranostic properties (respectively, r2 = 416 s−1·mM−1, SARMH = 580 W·g−1, SARPTT = 800 W·g−1; and r2 = 407 s−1·mM−1, SARMH = 899 W·g−1, SARPTT = 300 W·g−1). MH experiments have proven that the heating power mainly originates from Brownian relaxation and that SAR values can remain high if IONPs are prealigned with a magnet. This raises hope that heating will maintain efficient even in a confined environment, such as in cells or in tumors. Preliminary in vitro MH and PTT experiments have shown the promising effect of the cubic shaped IONPs, even though the experiments should be repeated with an improved set-up. Finally, the grafting of a specific peptide (P22) as a TL for head and neck cancers (HNCs) has shown the positive impact of the TL to enhance IONP accumulation in cells. [ABSTRACT FROM AUTHOR]

References 1 Vaira LA, De Vito A, Deiana G, Pes C, Giovanditto F, Fiore V. Correlations between IL-6 serum level and olfactory dysfunction severity in COVID-19 patients: a preliminary study. The results of the correlation analysis are confirmed by the analysis of the interleukin-6 (IL-6) median concentration differences between clinical groups of olfactory function, determined on the basis of the olfactory scores (Kruskal-Wallis test I p i = 0.369). The choice of the statistical test for the study of correlations between variables that is burdened by the lowest rate of bias has always been at the centre of a heated debate among biostatisticians. [Extracted from the article]

Objectives: To investigate usefulness, feasibility, and patient satisfaction of an electronic pre-consultation medical history tool (EPMH) in laryngopharyngeal reflux (LPR) work-up. Methods: Seventy-five patients with LPR were invited to complete electronic medical history assessment prior to laryngology consultation. EPMH collected the following parameters: demographic and epidemiological data, medication, medical and surgical histories, diet habits, stress and symptom findings. Stress and symptoms were assessed with perceived stress scale and reflux symptom score. Duration of consultation, acceptance, and satisfaction of patients (feasibility, usefulness, effectiveness, understanding of questions) were evaluated through a 9-item patient-reported outcome questionnaire. Results: Seventy patients completed the evaluation (93% participation rate). The mean age of cohort was 51.2 ± 15.6 years old. There were 35 females and 35 males. Patients who refused to participate (N = 5) were > 65 years old. The consultation duration was significantly lower in patients who used the EPMH (11.3 ± 2.7 min) compared with a control group (18.1 ± 5.1 min; p = 0.001). Ninety percent of patients were satisfied about EPMH easiness and usefulness, while 97.1% thought that EPMH may improve the disease management. Patients would recommend similar approach for otolaryngological or other specialty consultations in 98.6% and 92.8% of cases, respectively. Conclusion: The use of EPMH is associated with adequate usefulness, feasibility, and satisfaction outcomes in patients with LPR. This software is a preliminary step in the development of an AI-based diagnostic decision support tool to help laryngologists in their daily practice. Future randomized controlled studies are needed to investigate the gain of similar approaches on the traditional consultation format. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus (HPV) has become the major risk factor for the development of oropharyngeal squamous cell carcinomas (OPSCCs), the incidence of which continues to grow in Western countries. Their biological features, associated with a better prognosis as well as a greater response to treatment, has already led to their staging system reclassification and to the development of clinical trials to deintensify the therapeutic approaches. In this context, we proposed to evaluate the recruitment levels of immune cells to ameliorate the classification of some groups of OPSCCs that are always associated with poor outcomes. For this purpose, we scored the density of CD8 and FoxP3 lymphocytes, CD68 macrophages and CD1a Langerhans cells and associated the significant cells with either p16 status or TNM staging to create strong combinations that demonstrated powerful prognostic values in such patients. These results encourage the development of further studies based on the inclusion of immune criteria in the classification of OPSCCs. The incidence of oropharyngeal cancers (OPSCCs) has continued to rise over the years, mainly due to human papillomavirus (HPV) infection. Although they were newly reclassified in the last TNM staging system, some groups still relapse and have poor prognoses. Based on their implication in oncogenesis, we investigated the density of cytotoxic and regulatory T cells, macrophages, and Langerhans cells in relation to p16 status, staging and survival of patients. Biopsies from 194 OPSCCs were analyzed for HPV by RT-qPCR and for p16 by immunohistochemistry, while CD8, FoxP3, CD68 and CD1a immunolabeling was performed in stromal (ST) and intratumoral (IT) compartments to establish optimal cutoff values for overall survival (OS). High levels of FoxP3 IT and CD1a ST positively correlated with OS and were observed in p16-positive and low-stage patients, respectively. Then, their associations with p16 and TNM were more efficient than the clinical parameters alone in describing patient survival. Using multivariate analyses, we demonstrated that the respective combination of FoxP3 or CD1a with p16 status or staging was an independent prognostic marker improving the outcome of OPSCC patients. These two combinations are significant prognostic signatures that may eventually be included in the staging stratification system to develop personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Bufalin is an endogenous cardiotonic steroid, first discovered in toad venom but also found in the plasma of healthy humans, with anti-tumour activities in different cancer types. The current review is focused on its mechanisms of action and highlights its very large spectrum of effects both in vitro and in vivo. All leads to the conclusion that bufalin mediates its effects by affecting all the hallmarks of cancer and seems restricted to cancer cells avoiding side effects. Bufalin decreases cancer cell proliferation by acting on the cell cycle and inducing different mechanisms of cell death including apoptosis, necroptosis, autophagy and senescence. Bufalin also moderates metastasis formation by blocking migration and invasion as well as angiogenesis and by inducing a phenotype switch towards differentiation and decreasing cancer cell stemness. Regarding its various mechanisms of action in cancer cells, bufalin blocks overactivated signalling pathways and modifies cell metabolism. Moreover, bufalin gained lately a huge interest in the field of drug resistance by both reversing various drug resistance mechanisms and affecting the immune microenvironment. Together, these data support bufalin as a quite promising new anti-cancer drug candidate. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To validate a French version of the Olfactory Disorders Questionnaire (Fr-ODQ). Methods: Patients with olfactory disorder (OD) and controls were enrolled from two medical centers. Individuals completed the Fr-ODQ and the French version of the sinonasal outcome tool-22 (SNOT-22). The extended Sniffin'Sticks procedure was used to test odor Threshold, Discrimination, and Identification (TDI). Cronbach's alpha was used to measure the internal consistency of Fr-ODQ. The reliability and the external validity were evaluated through a test–retest approach and by correlating Fr-ODQ and SNOT-22 scores. Results: Eighty-nine patients with OD and 65 healthy individuals completed the evaluations. The Cronbach's alpha was 0.827, reporting adequate internal consistency. The test–retest reliability was high (rs = 0.944, p = 0.001). The external validity was adequate regarding the significant correlation between Fr-ODQ and SNOT-22 (rs = 0.498; p = 0.001). Patients with OD reported a significant higher score of Fr-ODQ than healthy individuals (p < 0.001), indicating a high internal validity. The baseline Fr-ODQ significantly improved after 3-month olfactory training, which corroborated the improvement of TDI scores. Conclusion: The Fr-ODQ is the first patient-reported outcome questionnaire validated for French speaking patients. Fr-ODQ is reliable and valid for the evaluation of the olfactory dysfunction and the related impact on quality of life of French-speaking patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the mid-to-long-term symptom evolution and treatment findings of laryngopharyngeal reflux (LPR) patients. Methods: Patients with LPR and treated between September 2016 and December 2017 were prospectively followed. The diagnosis consisted of > 1 pharyngeal event at the hypopharyngeal–esophageal multichannel intraluminal impedance-pH monitoring. The treatment consisted of 3- to 9-months diet, stress management and medication according to the type of LPR. Reflux symptom score was used to assess the therapeutic response. Patients were surveyed yearly to know the reflux evolution, the potential recurrence(s) of symptoms, and the approaches used to control the disease. Results: A total of 77 patients completed the evaluations (45 females). The initial treatment duration was 3, 6, or 9 months in 25 (32.5%), 23 (29.9%), and 6 (7.7%) cases before weaning, respectively. Twenty-three patients (29.9%) reported chronic course of the disease. According to the reduction of reflux symptom score, symptoms did not change in 11 (14.3%) patients, while the rest of the patients reported symptom reduction or relief (responder rate of 85.7%). Over time, LPR symptoms never relapsed in 31% of cases, while 38% of patients reported one or several recurrences a year. The recurrence episodes of patients were all adequately treated with medication or diet and did not require long-term medication. Conclusion: Chronic course of the disease was observed in 31% of patients who required long-term medication. Preliminary observations reported that LPR may be classified as acute, recurrent, or chronic disease. The medication weaning is possible in most patients, leading to reduction of cost burden related to LPR treatment. [ABSTRACT FROM AUTHOR]

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. Level of evidence: 4 [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.

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. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to appreciate the tolerance and convenience of a new FFP2 mask allowed the realization of nasal examination in period of pandemic. Methods: Fifty-one patients were prospectively recruited from two European hospitals to test the FFP2 mask prototype. The following outcomes were evaluated in patients after the clinical examination: fear about coronavirus disease 2019 (COVID-19) infection; easiness of mask placement; tolerability; reassurance; and overall satisfaction about the use of this kind of mask in a pandemic context. Seven otolaryngologists evaluated the mask acceptance and usefulness in patients through a standardized physician-reported outcome questionnaire. Results: Fifty patients completed the evaluation. There were 25 males and 25 females. The mean age of patients was 41 years. Ninety percent of patients considered that the use of the mask reduced the risk to be infected during the examination. Seventy percent of patients reported high or very high satisfaction and should recommend mask to other patients in pandemic period. The realization of nasal examination was easier with optic compared with flexible trans-nasal examination (p = 0.001), which significantly impacted the satisfaction level of physician (p = 0.001). The physician difficulty to perform the examination significantly impacted the satisfactory of patient (p = 0.033). Conclusion: The new bioserenity FFP2 mask allows the realization of the trans-nasal endoscopic examination during a pandemic. The use of this mask requires little training period of physician. The use of this mask prototype is well received by patients who reported better perception of self-protection against the virus. [ABSTRACT FROM AUTHOR]

The head and neck tumor microenvironment (TME) is highly infiltrated with macrophages. More specifically, tumor-associated macrophages (TAM/M2-like) are one of the most critical components associated with poor overall survival in head and neck cancers (HNC). Two extreme states of macrophage phenotypes are described as conducting pro-inflammatory/anti-tumoral (M1) or anti-inflammatory/pro-tumoral (M2) activities. Moreover, specific metabolic pathways as well as oxidative stress responses are tightly associated with their phenotypes and functions. Hence, due to their plasticity, targeting M2 macrophages to repolarize in the M1 phenotype would be a promising cancer treatment. In this context, we evaluated macrophage infiltration in 60 HNC patients and demonstrated the high infiltration of CD68+ cells that were mainly related to CD163+ M2 macrophages. We then optimized a polarization protocol from THP1 monocytes, validated by specific gene and protein expression levels. In addition, specific actors of glutamine pathway and oxidative stress were quantified to indicate the use of glutaminolysis by M2 and the production of reactive oxygen species by M1. Finally, we evaluated and confirmed the plasticity of our model using M1 activators to repolarize M2 in M1. Overall, our study provides a complete reversible polarization protocol allowing us to further evaluate various reprogramming effectors targeting glutaminolysis and/or oxidative stress in macrophages. [ABSTRACT FROM AUTHOR]

Keywords: Xerostomia; Otolaryngology; Laryngopharyngeal; Gastroesophageal; Reflux; Laryngology; Voice; Dysphonia EN Xerostomia Otolaryngology Laryngopharyngeal Gastroesophageal Reflux Laryngology Voice Dysphonia 5147 5148 2 10/11/23 20231101 NES 231101 This comment refers to the article available online at https://doi.org/10.1007/s00405-023-07941-x. Xerostomia, Otolaryngology, Gastroesophageal, Laryngopharyngeal, Reflux, Laryngology, Voice, Dysphonia Interestingly, the prevalence of LPR-related symptoms and findings may reach 50% of outpatients in laryngology office [[5]]. [Extracted from the article]

Background: Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19) Methods: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19. Results: Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups. In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7–18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (rs = 0.182) and not significant (p = 0.12). Conclusions: In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions. [ABSTRACT FROM AUTHOR]

Introduction: Olfactory dysfunction (OD) is a well know symptom of coronavirus disease 2019 (COVID-19), accounting for 48 to 85% of patients. In 1 to 10% of cases, patients develop a chronic olfactory dysfunction (COD), lasting more than 6 months. Recently, platelet-rich plasma (PRP) was used in patients with non-COVID-19 COD and authors reported encouraging results. Methods: In the present study, we investigated the usefulness and safety of PRP injection in 56 patients with COVID-19 COD by the Sniffing Stick test (TDI score) and a linker-scale from 0 (none) to 3 (strong) and we compare the result to a control group. Results: At 1 month post-PRP injection, the mean TDI scores significantly improved by 6.7 points in the PRP group (p < 0,001), the mean self-assessment of improvement in smell function was 1.8 (mild-to-moderate) in the PRP group, which was significantly higher than the score (0.3) in the control group (p < 0,001). Conclusion: Our results showed that PRP in the olfactory cleft can increase the olfactory threshold 1 month after the injection. Moreover, our results suggest that timing of treatment may be an important factor and that PRP is a safe treatment, because no adverse effects were reported throughout the study. Trial registration number: NCT05226546. [ABSTRACT FROM AUTHOR]

Keywords: anosmia; chest CT; coronavirus; COVID-19; hyposmia; olfactory; pneumonia; recovery; SARS-CoV-2; smell EN anosmia chest CT coronavirus COVID-19 hyposmia olfactory pneumonia recovery SARS-CoV-2 smell 103 107 5 12/31/21 20220101 NES 220101 INTRODUCTION The prognostic value of olfactory dysfunction (OD) in coronavirus disease 2019 (COVID-19) remains controversial, with conflicting reports of the association between OD and COVID-19 severity.1 Many of the prognostic studies published so far have important drawbacks that limit the reliability of the results; most are anamnestic studies that do not formally evaluate olfactory function with risk of recall bias, and use "need for hospitalization" alone to determine COVID-19 severity. Coronavirus, COVID-19, hyposmia, pneumonia, anosmia, chest CT, olfactory, recovery, SARS-CoV-2, smell At baseline, 35 patients (76.1%) had OD: 12 cases of anosmia (26.1%), severe hyposmia in 10 (21.7%), and moderate hyposmia in 13 cases (28.3%). [Extracted from the article]

Chemosensitive dysfunctions are now considered as frequent and early symptoms of coronavirus disease 2019 (COVID-19). In the last few weeks, researchers' greatest efforts have been focusing mainly on the analysis of olfactory disorders, neglecting taste dysfunctions. According to our psychophysical evaluations, it can be inferred that the pathogenesis of taste disorders in COVID-19 patients is largely smell-independent. Moreover, isolated gustatory disorders are highly specific of SARS-CoV-2 infection. For these reasons, it is essential that gustatory dysfunctions, like olfactory disorders, are included in the COVID-19 guidelines. [ABSTRACT FROM AUTHOR]

Making scents of loss of taste in COVID-19: Is self-reported loss of taste due to olfactory dysfunction? Three clinical presentations were accepted for patient eligibility: isolated sudden loss of smell, isolated sudden loss of taste, or concomitant sudden loss of smell and taste. These results support the idea that most patients with COVID-19 tend to unconsciously conflate taste loss and olfactory loss, even when taste function is clearly defined to them beforehand as only referring to the perception of sweet, salty, sour, and bitter tastes. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Objective: To study the profile and the therapeutic response of patients with laryngopharyngeal reflux (LPR) at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) according to the initial pepsin saliva concentration. Methods: From January 2018 to January 2020, patients with positive LPR diagnosis at the HEMII-pH were consecutively recruited from 3 European Hospitals. Saliva pepsin concentration (Peptest™) was measured during the HEMII-pH testing period and patients were classified into 2 groups: negative versus positive Peptest. The clinical outcomes, that is, gastrointestinal and HEMII-pH findings, reflux symptom score-12 (RSS-12), and 3-month therapeutic response, were compared between groups. Results: A total of 124 patients completed the study. Among them, 30 patients had negative Peptest. Pharyngeal reflux events occurred outside 1-hour post-meal time in 74.0%, after the meals in 20.5% and nighttime in 5.5%. The pepsin saliva level was not significantly associated with the reflux events preceding the sample collection. Patients with positive Peptest had better improvement of RSS-12 digestive and respiratory subscores and oral, pharyngeal, and laryngeal findings compared with patients with negative Peptest. Conclusion: Patients with high saliva pepsin concentration had no stronger gastrointestinal, HEMII-pH, or clinical outcomes compared with those with low or undetectable saliva pepsin concentration. [ABSTRACT FROM AUTHOR]

Objective: To investigate prevalence and epidemiological and clinical factors associated with olfactory dysfunction (OD) and gustatory dysfunction (GD) in COVID-19 patients according to the disease severity. Study design: Cross-sectional study. Methods: A total of 2579 patients with a positive diagnosis of COVID-19 were identified between March 22 and June 3, 2020 from 18 European hospitals. Epidemiological and clinical data were extracted. Otolaryngological symptoms, including OD and GD, were collected through patient-reported outcome questionnaire and Sniffin'Sticks tests were carried out in a subset of patients. Results: A total of 2579 patients were included, including 2166 mild (84.0%), 144 moderate (5.6%) and 269 severe-to-critical (10.4%) patients. Mild patients presented an otolaryngological picture of the disease with OD, GD, nasal obstruction, rhinorrhea and sore throat as the most prevalent symptoms. The prevalence of subjective OD and GD was 73.7 and 46.8%, and decreases with the severity of the disease. Females had higher prevalence of subjective OD and GD compared with males. Diabetes was associated with a higher risk to develop GD. Among the subset of patients who benefited from psychophysical olfactory evaluations, there were 75 anosmic, 43 hyposmic and 113 normosmic patients. The prevalence of anosmia significantly decreased with the severity of the disease. Anosmia or hyposmia were not associated with any nasal disorder, according to SNOT-22. Conclusion: OD and GD are more prevalent in patients with mild COVID-19 compared with individuals with moderate, severe or critical diseases. Females might have a higher risk of developing OD and GD compared with males. [ABSTRACT FROM AUTHOR]

Objective: To study the profile of patients with obstructive sleep apnoea syndrome (OSAS) and laryngopharyngeal reflux (LPR) at the hypopharyngeal‐oesophageal multichannel intraluminal impedance‐pH monitoring (HEMII‐pH) and to compare their reflux findings with LPR patients without OSAS. Design: Prospective controlled study. Methods: Patients with LPR and OSAS were prospectively recruited from August 2019 to June 2020. The profile of hypopharyngeal reflux events (HREs) of patients was studied through a breakdown of the HEMII‐pH findings over the 24 hours of testing. Reflux symptom score (RSS), and gastrointestinal and HEMII‐pH outcomes were compared between LPR patients and patients with LPR and OSAS. Multivariate analysis was used to study the relationship between reflux data and the following sleep outcomes: Apnea Hypopnea Index, Epworth Sleepiness Scale (ESS) and paradoxical sleep data. Results: A total of 89 patients completed the study. There were 45 patients with LPR and 44 subjects with both OSAS and LPR. The numbers of upright and daytime HREs and the otolaryngological RSS were significantly higher in patients with LPR compared with those with OSAS and LPR. There was a significant positive association between RSS quality‐of‐life score and ESS (P =.001). The occurrence of HREs in the evening was associated with higher ESS (P =.015). Patients with OSAS, LPR and GERD had higher number of nocturnal HREs compared with those without GERD (P =.001). Conclusion: The presence of OSAS in LPR patients is associated with less severe HEMII‐pH and ear, nose and throat symptoms. There may have different OSAS patient profiles according to the occurrence of GERD. [ABSTRACT FROM AUTHOR]

The most reliable psychophysical test remains the threshold, discrimination, and identification (TDI), and the TDI results may provide substantial differences between the three components (T, D, and I) among COVID-19 patients [[8]]. Keywords: COVID-19; SARS-CoV-2; Olfaction; Smell; Otolaryngology; Head-neck surgery; Olfactory; Variant EN COVID-19 SARS-CoV-2 Olfaction Smell Otolaryngology Head-neck surgery Olfactory Variant 5469 5470 2 09/30/22 20221101 NES 221101 This comment refers to the article available online at https://doi.org/10.1007/s00405-022-07431-6. In this paper, Hintschich et al. investigated the olfactory dysfunction (OD) in COVID-19 patients according to the variant (alpha B.1.1.7. versus B.1617.2). [Extracted from the article]

Keywords: Covid-19; Anosmia; Smell disorders; Corticosteroids; Coronavirus; SARS-CoV-2; Therapy EN Covid-19 Anosmia Smell disorders Corticosteroids Coronavirus SARS-CoV-2 Therapy 3102 3103 2 11/29/22 20221002 NES 221002 Dear Editor, We enjoyed reading the article by Borah et al. [[1]], recently published in your journal. However, these recent pathogenic findings have provided the rationale for the use of systemic and local corticosteroids for the treatment of persistent COVID-19 related olfactory disorders [[5]]. [Extracted from the article]

The lack of reliability of RSI was supported in a recent study where it was compared with reflux symptom score that considers both severity and frequency of the most prevalent LPR symptoms [[4]]. Moreover, RFS was not assessed in a blind manner regarding the patient symptoms, leading to a potential bias because the sign evaluation may be influenced by the knowledge of symptoms [[6]]. Moreover, RSI does not consider the symptom frequency because it focuses only on symptom severity, which may bias the assessment of the patient clinical picture. [Extracted from the article]

The article discusses two cases of patients who experienced episodes of olfactory and gustatory dysfunctions after COVID-19 reinfection. Topics mentioned include the prevalence of loss of smell and taste senses in COVID-19 patients, the impact of COVID-19 on the quality of life, the definition of gustatory function, and other symptoms of COVID-19.

[Display omitted] A major challenge in nanomedicine is designing nanoplatforms (NPFs) to selectively target abnormal cells to ensure early diagnosis and targeted therapy. Among developed NPFs, iron oxide nanoparticles (IONPs) are good MRI contrast agents and can be used for therapy by hyperthermia and as radio-sensitizing agents. Active targeting is a promising method for selective IONPs accumulation in cancer tissues and is generally performed by using targeting ligands (TL). Here, a TL specific for the epidermal growth factor receptor (EGFR) is bound to the surface of dendronized IONPs to produce nanostructures able to specifically recognize EGFR-positive FaDu and 93-Vu head and neck cancer cell lines. Several parameters were optimized to ensure a high coupling yield and to adequately quantify the amount of TL per nanoparticle. Nanostructures with variable amounts of TL on the surface were produced and evaluated for their potential to specifically target and be thereafter internalized by cells. Compared to the bare NPs, the presence of the TL at the surface was shown to be effective to enhance their internalization and to play a role in the total amount of iron present per cell. [ABSTRACT FROM AUTHOR]

The authors performed hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) in patients with vocal fold leukoplakia (VFL) to evaluate the prevalence of laryngopharyngeal reflux (LPR). The detection of pepsin and other gastroduodenal enzymes in VFL is the missing element to really support more than a simple association between pharyngeal reflux events and the development of VFL. [Extracted from the article]

(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up. [ABSTRACT FROM AUTHOR]

Objectives: To compare the 2 long-term medical strategies in chronic rhinosinusitis without nasal polyps (CRSnNP) and to identify the role of gastroesophageal reflux disease (GERD) and Helicobacter pylori as factors of treatment failure. Material and Methods: Fifty-seven patients with CRSnNP were randomized into 2 therapeutic groups. The first group was treated with 4 weeks of amoxicillin/clavulanate and a short course of oral steroids. The second group received 8 weeks of clarithromycin. Sinonasal Outcome Test-20 (SNOT-20) and Lund and Mackay scores were assessed at baseline and after treatment, and GERD Health-Related Quality of Life (GERD-HRQL) questionnaire was evaluated in all patients. Patients with a GERD-HRQL score >8 received esogastroscopy and H pylori detection. Patients were followed during a 10-year period for clinical course and GERD evolution. The 10-year evolution of patients was described in terms of recurrence, medical, and surgical treatments. Results: Thirty-seven patients completed the study; SNOT-20 and Lund and Mackay scores similarly improved in both groups. Amoxicillin/clavulanate group had significantly more adverse reactions than the clarithromycin group (P =.03). After the therapeutic course, 35% (amoxicillin/clavulanate) and 41% (clarithromycin) of patients needed functional endoscopic sinus surgery (FESS). During the long-term follow-up, 54% (amoxicillin/clavulanate) and 40% (clarithromycin) of patients had late CRSnNP recurrence; FESS was performed in less than 15% of cases of recurrence. Gastroesophageal reflux disease complaint's severity was associated with late recurrence of CRSnNP. Conclusion: Amoxicillin/clavulanate and clarithromycin would be competitive treatments for CRSnNP. Gastroesophageal reflux disease seems to be a negative factor for treatment response and recurrence. [ABSTRACT FROM AUTHOR]

In the original publication of the article, one of the co-author's name was published incorrectly as "Liugi A. Varia". The correct name should read as "Luigi A. Vaira". [ABSTRACT FROM AUTHOR]

In the original publication of the article, one of the author's first and family name was published incorrectly. [ABSTRACT FROM AUTHOR]