Elevated body mass index increased the risk of recurrence in Chinese patients with chronic rhinosinusitis.

BACKGROUND: Elevated body mass index (BMI) has been associated with an increased prevalence of chronic rhinosinusitis (CRS). However, the impact of BMI on the risk of recurrence of CRS is unknown. This study aimed to investigate the association between BMI and the risk of CRS recurrence. MATERIAL AND METHODS: A retrospective cohort study was conducted and recruited 1057 CRS patients who underwent functional endoscopic sinus surgery (FESS). All subjects were classified into four groups: "underweight", "normal weight", "overweight", and "obese". Multivariate regression analysis was performed to examine the associations between BMI categories and other factors and the risk of CRS recurrence. RESULTS: The rate of recurrent CRS was significantly higher in the overweight group and obese group than in the normal weight group (P < 0.05). Unadjusted and adjusted logistic regression analyses demonstrated that overweight and obesity exhibited an increased risk of CRS recurrence as compared to patients with normal weight (P < 0.05). Furthermore, all patients were divided into primary CRS group and recurrent CRS group, and the BMI, duration of disease and rate of allergic rhinitis were vastly increased in the recurrent group than in the primary group (P < 0.05). Univariate and multivariate regression analysis showed that BMI and duration of disease were the dominant risk factors of CRS recurrence (P < 0.05). CONCLUSION: Overweight and obesity presented significant impacts on the CRS recurrence, and elevated BMI were associated with an increased risk of CRS recurrence independently from traditional risk factors. A longer duration of disease was correlated with a higher risk of CRS recurrence.

Significance of leukocyte-specific transcript 1 levels in nasal mucosal tissue to predict recurrence of nasal polyps.

OBJECTIVE: Chronic Rhinosinusitis with Polyps (CRSwNP) is characterized by high heterogeneity and postoperative recurrence rate. This study aims to explore the clinical significance of tissue Leukocyte-Specific Transcript 1 (LST1) in predicting CRSwNP recurrence. METHODS: We enrolled 62 CRSwNP patients including 30 primary CRSwNP and 32 recurrent CRSwNP patients, and 40 Healthy Controls (HC). Tissue samples were collected. Tissue LST1 expression was assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western Blotting (WB) and Immunofluorescence (IF) staining. The predictive values of LST1 expression for CRSwNP postoperative recurrence were assessed through the Receiver Operating Characteristic (ROC) curves. RESULTS: The tissue levels of LST1 were significantly increased in the CRSwNP group than the HC group, especially in the recurrent group, and the elevated LST1 mRNA levels were positively correlated with the peripheral eosinophil percentages, tissue eosinophil counts and percentages. IF staining results showed that the LST1 protein levels were higher in CRSwNP patients, especially in the recurrent patients than in the HC group. ROC curves highlighted that tissue LST1 levels were associated with recurrent CRSwNP and exhibited a higher predictive ability for postoperative CRSwNP recurrence. CONCLUSION: This was the first report suggesting that LST1 expression was upregulated and associated with mucosal eosinophil infiltration and CRSwNP recurrence. Tissue LST1 could be a promising biomarker for predicting postoperative recurrence in CRwNP patients. LEVEL OF EVIDENCE: Level 5.

Improvements and challenges of tissue preparation for spatial transcriptome analysis of skull base tumors.

Background: Spatial transcriptome (ST) provides molecular profiles of tumor cells at the spatial level, which brings new progress to the research of tumors and the tumor microenvironment. This study summarizes the experiences and lessons learned in the spatial section preparation of two different pathological types of nose and skull base tumors at our institution, with the aim of offering guidelines to researchers to avoid wasting precious samples and provide a basis for the application of ST in clinical practice. Methods: Frozen tissue blocks from patients with squamous cell carcinoma and adenocarcinoma of the nose and skull base diagnosed at our institution were prepared. The effects of different procedures and pathological tissue types on slide quality were explored and evaluated using RNA integrity number (RIN) and HE scores as criteria. The effects of different RIN values on ST sequencing data were explored. Results: A total of 43 samples were obtained from 26 patients, including 22 with squamous carcinomas and 21 with adenocarcinomas. Thirteen samples with satisfactory RNA quality control and good histological morphology were sequenced for ST. Sample isolation time <15 min and abandonment of snap-frozen isopentane significantly improved RNA quality (p = 0.004, p < 0.0001) and histomorphological integrity (p = 0.02, p = 0.02). Selection of a suitable tissue RNA extraction kit was critical for RNA quality (p < 0.0001). No difference between 6 ≤ RIN <7 and RIN >7 in ST sequencing results was found, indicating that RIN ≥6 can be used as a criterion for qualified RNA quality control. Therefore, fresh tissues washed as soon as possible with cold PBS and then dried using OCT for snap freezing are currently the best method for preparing spatial sections of nose and skull base tumor tissues of different pathological types. Conclusion: This study is the first to investigate the feasibility of applying ST to different pathological types of nose and skull base tumors and to demonstrate the widespread application of ST in tumors. Rational optimization of spatial slide preparation procedures and exploration of individualized pre-sequencing protocols are used as the first stage to ensure the quality of spatial sequencing and lay the foundation for subsequent spatial analysis.

Susceptibility of immature spiral ganglion neurons to aminoglycoside-induced ototoxicity is mediated by the TRPV1 channel in mice.

Aminoglycoside antibiotics are among the most common agents that can cause sensorineural hearing loss. From clinical experience, premature babies, whose inner ear is still developing, are more susceptible to aminoglycoside-induced ototoxicity, which is echoed by our previous study carried out in organotypic cultures. This study aimed to investigate whether a nonselective cation channel, TRPV1, contributes to the susceptibility of immature spiral ganglion neurons (SGNs) to the damage caused by aminoglycosides. Through western blotting and immunofluorescence, we found that the TRPV1 expression levels were much higher in immature SGNs than in their mature counterparts. In postnatal day 7 cochlear organotypic cultures, AMG-517 reduced reactive oxygen species generation and inhibited SGN apoptosis under aminoglycoside challenge. However, in adult mice, AMG-517 did not ameliorate the ABR threshold increase at high frequencies (16 kHz and 32 kHz) after aminoglycoside administration, and the SGNs within the cochleae had no morphological changes. By further regulating the function of TRPV1 in primary cultured SGNs with its inhibitor AMG-517 and agonist capsaicin, we demonstrated that TRPV1 is a major channel for aminoglycoside uptake: AMG-517 can significantly reduce, while capsaicin can significantly increase, the uptake of GTTR. In addition, TRPV1 knockdown in SGNs can also significantly reduce the uptake of GTTR. Taken together, our results demonstrated that aminoglycosides can directly enter immature SGNs through the TRPV1 channel. High expression of TRPV1 contributes to the susceptibility of immature SGNs to aminoglycoside-induced damage. The TRPV1 inhibitor AMG-517 has the potential to be a therapeutic agent for preventing aminoglycoside-induced ototoxicity in immature SGNs.

Circulating C-X-C Motif Ligand 13 as a Biomarker for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With Chronic Allergic Rhinitis.

Background: C-X-C motif ligand 13 (CXCL13) and B cell-activating factor (BAFF) are proven to be involved in inflammatory diseases, but their role in allergic rhinitis (AR) remains unclear. The aim of this study was to investigate the role of serum CXCL13 and BAFF in AR and their clinical values as objective biomarkers to predict the efficacy of subcutaneous immunotherapy (SCIT). Methods: We prospectively recruited 90 children with AR treated with SCIT and collected their serum specimens before SCIT. One-year follow-up was conducted for all patients, and they were categorized into effective and ineffective groups based on efficacy. The serum concentrations of CXCL13 and BAFF were detected and compared between the two groups. A validation cohort of 52 responders and 26 non-responders were further assessed for both cytokines and serum CXCL13 and BAFF levels were assayed by enzyme-linked immunosorbent assay (ELISA). Results: Eighty children completed the follow-up schedule, and 56 children were categorized into the effective group and 24 children into the ineffective group. The serum levels of CXCL13 in the effective group were clearly higher than those in the ineffective group (P < 0.05). Receiver operating characteristic (ROC) curves revealed the potential values of CXCL13 as a biomarker in predicting the response of SCIT. Further, in the validation cohort, ELISA results demonstrated that serum CXCL13 levels were increased in responders than non-responders (P < 0.05). ROC curves showed good accuracy of serum CXCL13 in predicting the efficacy of SCIT. Conclusion: Our discovery-validation study demonstrated that circulating CXCL13 might serve as a novel biomarker to predict the outcome of SCIT in childhood AR. The findings indicated that CXCL13 was involved in the pathological mechanisms of AR and made help to the fundamental therapeutic mechanism of SCIT.

Current opinions on diagnosis and treatment of adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a rare malignant tumor derived mainly from the salivary glands, representing approximately 1% of all headandneck carcinomasand 10% of all salivary gland neoplasms. ACC displays a paradoxical behavioral combination of an indolent growth pattern but an aggressive progression, with local recurrence and distant metastasis. The propensity of ACC of the head and neck (ACCHN) for perineural invasion and its anatomical location, especially if it extends to the nasal cavity and paranasal sinuses, facilitates tumor involvement in the surrounding structures, such as the orbit, pterygopalatine fossa, Meckel'scave, and cavernous sinus, which can lead to skull base involvement and intracranial extension. Despite advances in molecular mechanisms and diagnostic imaging, ACC treatment remainschallenging due to the lack ofconsensuson treatment patterns. In this review, we aimed toprovideanupdatedinsight intothe understanding of ACCHN by focusing on clinical behavior, imaging diagnosis, pathological features, and therapeutic strategies. We reviewed the molecular mechanisms, especially in ACCHN with perineural invasion, and elaborated on treatment options, including chemotherapy, targeted therapies, and immunotherapy, to establish a comprehensive understanding of ACC to arrive at a policy for proper diagnosis, preoperative evaluation, and therapeutic strategies.

Treatment of Recurrent Nasopharyngeal Carcinoma: A Sequential Challenge.

Recurrent nasopharyngeal carcinoma (NPC), which occurs in 10-20% of patients with primary NPC after the initial treatment modality of intensity-modulated radiation therapy (IMRT), is one of the major causes of death among NPC patients. Patients with recurrent disease without distant metastases still have a chance to be saved, but re-treatment often carries more serious toxicities or higher risks. For this group of patients, both otolaryngologists and oncologists are committed to developing more appropriate treatment regimens that can prolong patient survival and improve survival therapy. Currently, there are no international guidelines for the treatment of patients with recurrent NPC. In this article, we summarize past publications on clinical research and mechanistic studies related to recurrent NPC, combined with the experience and lessons learned by our institutional multidisciplinary team in the treatment of recurrent NPC. We propose an objective protocol for the treatment of recurrent NPC.

Exosomes Derived hsa-miR-4669 as a Novel Biomarker for Early Predicting the Response of Subcutaneous Immunotherapy in Pediatric Allergic Rhinitis.

Purpose: Subcutaneous immunotherapy (SCIT) is an effective treatment for pediatric allergic rhinitis (AR), but its efficacy fluctuates among individuals. This study aims to identify the profile of serum exosomes derived microRNAs (miRNAs) and evaluate their capacities to early predict SCIT efficacy in pediatric AR. Patients and Methods: High-throughput sequencing was applied to identify the miRNA of serum exosomes in AR children. GO enrichment and KEGG pathway analysis were performed to enrich the biological annotations of target mRNAs of miRNAs. Then we validated differentially expressed miRNAs in two independent cohorts by RT-qPCR. Logistic regression and receiver operating characteristic curve (ROC) were applied to evaluate the abilities of identified miRNAs in predicting the efficacy of SCIT in AR children. Results: A total of 812 miRNAs were detected in the serum exosomes, including 16 upregulated and 14 downregulated. Differentially expressed genes are enriched in the biological process of developmental process and regulation of cellular process, and gathered in pathways such as the signaling pathways regulating pluripotency of stem cells and the Wnt signaling pathway. In the first validation cohort, hsa-miR-4669 (P=0.009) and hsa-miR-4686 (P=0.032) were significantly downregulated in the effective group than the ineffective group, while hsa-miR-3196 (P=0.015) was upregulated. In the second cohort, hsa-miR-4669 level (P<0.0001) was downregulated in the effective group than the ineffective group. In addition, logistic regression revealed that hsa-miR-4669 level was correlated with the visual analogue scale (r=0.323, P=0.001) and total nasal symptoms score (r=0.269, P =0.007). ROC curve highlighted that hsa-miR-4669 level exhibited a reliable accuracy in predicting SCIT efficacy in pediatric AR (AUC=0.785). Conclusion: Serum exosomes derived miRNA were associated with the efficacy of SCIT. Serum exosomes derived hsa-miR-4669 might serve as a novel biomarker for early predicting the response of SCIT in AR children.

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite-Induced Allergic Rhinitis.

Background: Macrophage migration inhibitory factor (MIF) is described as a pro-inflammatory cytokine involved in many inflammatory and allergic disorders, but the role of MIF in allergic rhinitis (AR) remains poorly clarified. The aim of this study was to investigate the association between circulating MIF levels and house dust mite (HDM)-induced AR, and evaluate MIF as a potential biomarker in reflecting disease severity and predicting the clinical response of sublingual immunotherapy (SLIT) in HDM-induced AR patients. Methods: In this study, we enrolled 160 persistent HDM-induced AR patients (AR group), including 48 mild AR patients (MAR group) and 112 moderate-severe AR patients (MSAR group), and 77 healthy controls (HC group). Circulating levels of MIF were measured by ELISA, and the relationship between MIF concentrations and disease severity was assessed. In the MSAR group, 106 patients were assigned to receive SLIT for 3 years. At the end of the study, patients were categorized into good response group and poor response group, and associations between clinical variables or biomarkers and clinical response were analyzed by the multivariate regression analysis. Results: The concentrations of serum MIF were significantly higher in AR patients than in HCs, especially in those with MSAR. Moreover, circulating MIF levels were positively correlated with TNSS, VAS, serum HDM-specific IgE, total IgE, blood eosinophil count, and blood eosinophil percentage (all p < 0.05). Eighty MSAR patients finally completed SLIT, 45 patients obtained good response, and 35 patients resulted in poor response. The serum levels of MIF were significantly lower in the good-response group than in the poor-response group (p < 0.001). The receiver operating characteristic analysis for MIF showed good accuracy for predicting clinical response of SLIT (area under the curve = 0.877, p < 0.001). The multivariate regression analysis demonstrated that serum MIF was an independent factor for SLIT responsiveness. Conclusion: Serum MIF appeared to be an important biological indicator in reflecting disease severity and an independent predictor for clinical responsiveness of SLIT in HDM-induced AR patients.

Comparing the Effectiveness of Endoscopic Surgeries With Intensity-Modulated Radiotherapy for Recurrent rT3 and rT4 Nasopharyngeal Carcinoma: A Meta-Analysis.

BACKGROUND: This meta-analysis aimed to compare the efficacy of intensity-modulated radiotherapy (IMRT) and endoscopic surgery (ES) for high T-stage recurrent nasopharyngeal carcinoma (NPC). METHODS: Relevant studies were retrieved in six databases from 02/28,2011 to 02/28,2021. The 2-year, 3-year, 5-year overall survival (OS) rates and 2-year disease-free survival (DFS) rates were calculated to compare the survival outcomes of the two treatments of IMRT and ES. Combined odds ratios (ORs) and 95% confidence interval (C Is) were measured as effect size on the association between high T-stage and 5-year OS rates. RESULTS: A total of 23 publications involving 2,578 patients with recurrent NPC were included in this study. Of these, 1611 patients with recurrent rT3-4 NPC were treated with ES and IMRT in 358 and 1,253 patients, respectively. The combined 2-year OS and 5-year OS rates for the two treatments were summarized separately, and the 2-year OS and 5-year OS rate for ES were 64% and 52%, respectively. The 2-year OS and 5-year OS rate for IMRT were 65% and 31%, respectively. The combined 2-year DFS rates of IMRT and ES were 60% and 50%, respectively. Combined ORs and 95% confidence intervals for 5-year survival suggest that ES may improve survival in recurrent NPC with rT3-4. In terms of complications, ES in the treatment of high T-stage recurrent NPC is potentially associated with fewer complications. CONCLUSIONS: The results of our study suggest that ES for rT3-4 may be a better treatment than IMRT, but the conclusion still needs to be sought by designing more studies.

Immune Microenvironment Change and Involvement of Circular RNAs in TIL Cells of Recurrent Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma is a malignant tumor that is highly prevalent in southern China and the Southeast Asian belt. Recent studies have shown that the T cells play important regulatory roles in tumorigenesis and progression. We test TIL cell of recurrent nasopharyngeal carcinoma and primary nasopharyngeal carcinoma cell. We found that T cell change in recurrent nasopharyngeal carcinoma and primary nasopharyngeal carcinoma cell. Based on GEO database, we selected differently expressed circRNAs in nasopharyngeal carcinoma tissues. qRTPCR show that some circRNAs also highly expressed in TIL cells. In conclusion, immune microenvironment changed in recurrent nasopharyngeal carcinoma. There is involvement of circular RNAs in this progress, with should be researched further.

Identification of Novel Biomarkers for Evaluating Disease Severity in House-Dust-Mite-Induced Allergic Rhinitis by Serum Metabolomics.

The aim of this study was to identify differences in serum metabolomics profiles of house-dust-mite (HDM)-induced allergic rhinitis (AR) patients compared to controls and to explore novel biomarkers reflecting disease severity. Serum samples were collected from 29 healthy controls and HDM-induced 72 AR patients, including 30 mild patients (MAR) and 42 moderate to severe AR patients (MSAR). Metabolomics detection was performed, and orthogonal partial least square discriminate analysis was applied to assess the differences between AR patients and controls and for subgroups based on disease severity. These analysis results successfully revealed distinct metabolite signatures which distinguished MAR patients and MSAR patients from controls. MSAR patients also could be discriminated from MAR patients based on their metabolic fingerprints. Most observed metabolite changes were related to glycine, serine, and threonine metabolism, pyrimidine metabolism, sphingolipid metabolism, arginine and proline metabolism, and fatty acid metabolism. Levels of sarcosine, sphingosine-1-phosphate, cytidine, and linoleic acid significantly correlated with the total nasal symptom score and visual analogue scale in AR patients. These results suggest that metabolomics profiling may provide novel insights into the pathophysiological mechanisms of HDM-induced AR and contribute to its evaluation of disease severity.

Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling.

Background: Subcutaneous immunotherapy (SCIT) is an effective treatment for children with allergic rhinitis (AR), but its efficacy fluctuates among patients. There are no reliable candidate biomarkers for monitoring and predicting the response to SCIT. The present study aims to identify novel biomarkers for early predicting the efficacy of SCIT in pediatric AR patients based on multiple cytokine profiling. Methods: We prospectively recruited 72 children with house dust mite (HDM)-induced AR who were assigned to receive SCIT. The serum samples were collected and multiple cytokine profiling was conducted by Luminex assay at baseline. All patients were followed-up for 1 year and then categorized into effective and ineffective group based on their efficacy, and levels of 48 selected cytokines were tested and compared between the two groups. The potential cytokines were further validated by enzyme-linked immunosorbent assay (ELISA) in a cohort with 54 responders and 26 non-responders. Results: Sixty-nine of 72 children completed one-year follow-up schedule with 46 included in effective group and 23 in ineffective group. The results of multiple cytokine profiling showed that 15 cytokines (eotaxin, G-CSF, GM-CSF, IFN-γ, IL-12(p40), IL-13, IL-15, IL-16, IL-4, MIF, MIP-1α, RANTES, SCF, SDF-1α and VEGF) were dysregulated between effective and ineffective group (all P < 0.05). Unadjusted and adjusted multivariate analysis models highlighted that serum eotaxin, IFN-γ, IL-4 and MIF levels closely associated with the efficacy of SCIT in pediatric HDM-induced AR patients. In addition, receiver operating characteristic (ROC) curves revealed potential values of these four biomarkers in predicting the response to SCIT. Further ELISA validation results in the cohort of 80 pediatric patients demonstrated that serum eotaxin and IL-4 levels were elevated in responders while IFN-γ levels decreased in responders (all P < 0.05). ROC curves demonstrated that serum IL-4 exhibited more reliable accuracy in predicting SCIT efficacy than eotaxin and IFN-γ. Conclusion: Our discover-validation study suggested that cytokines including IL-4, eotaxin and IFN- γ may serve as robust biomarkers for early predicting response of SCIT in children with HDM-induced AR. These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms.

Preliminary Efficacy Report and Prognosis Analysis of Endoscopic Endonasal Nasopharyngectomy for Recurrent Nasopharyngeal Carcinoma.

Background: Compared with radiotherapy, endoscopic endonasal nasopharyngectomy (EEN) is increasingly used to treat recurrent nasopharyngeal carcinoma (NPC) because of its good prognosis and mild complications. This study aims to investigate the efficacy of EEN in the treatment of recurrent NPC and factors affecting prognosis. Methods: This study included all patients who received EEN for recurrent nasopharyngeal carcinoma from April 2016 to April 2020. All operations were performed in Xiangya Hospital Central South University. The patient's 2-year overall survival (OS) rate, disease-free survival (DFS) rate and significant prognostic factors are reported. Results: There were 38 (67.9%) males and 28 (32.1%) females, with a median age of 43 (range, 24-69 years).43 (76.8%) of the patients in our study were in advanced rT3-rT4 stage and 32 (74.4%) of the patients in the advanced stage had tumor growth closely related to the internal carotid artery (ICA). During a mean follow up period of 44 month (range 1-65 months) post-surgery. The 2-year OS rate was 48.6%, 2-year DFS rate was 42.6%. The 2-year OS rates of rT1-2 and rT3-4 recurrent NPC were 83.9 and 35.6%, respectively. The 2-year DFS rates of rT1-2 and rT3-4 recurrent NPC 76.2 and 56.3%. The advanced T stage were associated with a poor prognosis in terms of OS and DFS. Conclusions: Data indicate that T staging may be an independent prognostic factor for OS and DFS. Through proper preoperative evaluation, EEN is an alternative treatment option for advanced recurrent NPC that ensures a certain level of efficacy and is relatively safe with few complications. However, additional studies with long-term follow-up and a larger sample size are required.

Prediction of sublingual immunotherapy efficacy in allergic rhinitis by serum metabolomics analysis.

BACKGROUND: Allergen-specific immunotherapy (ASIT) is currently the only therapy for allergic rhinitis (AR) that can induce immune tolerance to allergens. However, the course of ASIT is long and there is no objective biomarker to predict treatment efficacy. The present study aimed to explore potential biomarkers predictive of efficacy of AIT based on serum metabolomics profiles. METHODS: This prospective study recruited 72 consecutive eligible patients who were assigned to receive sublingual immunotherapy (SLIT). Serum samples were collected prior to SLIT and utilized to obtain metabolomics profiling by applying ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Treatment response was determined 3 years after SLIT, and patients were divided into effective group and ineffective group. Orthogonal partial least square-discriminate analysis (OPLS-DA) was performed to evaluate the metabolite differences between two groups. RESULTS: Sixty-eight patients completed the whole SLIT, 39 patients were categorized into effective group and 29 patients were classified into ineffective group. A total of 539 metabolites were obtained, and 197 of which were identified as known substances. Using these 197 known metabolites, the OPLS-DA results showed that effective group and ineffective group exhibited distinctive metabolite signatures and metabolic pathways. Six metabolites including lactic acid, ornithine, linolenic acid, creatinine, arachidonic acid and sphingosine were identified to exhibit good performance in predicting the efficacy of SLIT, and these metabolite changes mainly involved glycolysis and pyruvate metabolism, arginine and proline metabolism and fatty acid metabolism pathways. CONCLUSION: By metabolomics analysis, we identified several serum biomarkers that can reliably and accurately predict the efficacy of SLIT in AR patients. The discriminative metabolites and related metabolic pathways contributed to better understand the mechanisms of SLIT in AR patients.

Clinical Characteristics and Prognosis of Sudden Sensorineural Hearing Loss in Post-irradiated Nasopharyngeal Carcinoma Survivors.

OBJECTIVES: Sudden sensorineural hearing loss (SSNHL) may occur in post-irradiated nasopharyngeal carcinoma (NPC) survivors with a rare rate. This study was conducted to evaluate the clinical characteristics and prognosis of this population. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary otology referral center. PATIENTS: Five hundred ninety nine SSNHL patients were recruited between January 2010 and January 2019. Patients were divided into two groups: NPC group (n = 24) and non-NPC group (n = 575). INTERVENTIONS: All SSNHL patients were diagnosed by pure tone audiometry and treated with steroids, blood flow promoting agents, and hyperbaric oxygen therapy. MAIN OUTCOME MEASURES: We evaluated the clinical characteristics and prognosis of post-irradiated SSNHL and identified prognostic factors by logistic regression analysis. RESULTS: In the NPC group, the initial hearing threshold, contralateral hearing threshold, rate of vertigo, rate of profound hearing loss were all higher than in the non-NPC group (p < 0.05). Hearing gains and the rate of good recovery (both complete recovery and partial recovery) were lower in the NPC group than in the non-NPC group (p < 0.05). Logistic regression analysis revealed that NPC was significantly associated with poor hearing recovery (OR = 3.499, p = 0.040), and that a higher initial hearing threshold and longer treatment delay time were related to a poor prognosis (p < 0.05). CONCLUSIONS: SSNHL occurred in post-irradiated NPC survivors often suffered a severe hearing loss with a high rate of accompanying vertigo. NPC may have an adverse impact on the prognosis of SSNHL, and higher initial hearing threshold and longer treatment delay time were indicators of poor hearing recovery.

The Role of Serum Metabolomics in Distinguishing Chronic Rhinosinusitis With Nasal Polyp Phenotypes.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by different clinical features and treatment responsiveness. This study aimed to compare the serum metabolomics profiles between eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP) and healthy controls (HC) and explore objective biomarkers for distinguishing eCRSwNP before surgery. Methods: Serum samples were collected from 33 neCRSwNP patients, 37 eCRSwNP patients, and 29 HC. Serum metabolomics profiles were investigated by ultra-high-performance liquid chromatography-mass spectrometry. Results: The analysis results revealed that neCRSwNP, eCRSwNP, and HC exhibited distinctive metabolite signatures. In addition, eCRSwNP could be distinguished from neCRSwNP referring to their serum metabolic profiles, and the top ten different metabolites were citrulline, choline, linoleic acid, adenosine, glycocholic acid, L-serine, triethanolamine, 4-guanidinobutyric acid, methylmalonic acid, and L-methionine, which were related to several most important pathways including arginine and proline metabolism; glycine, serine, and threonine metabolism; linoleic acid metabolism; and purine metabolism. Among these distinctive metabolites, citrulline, linoleic acid, adenosine, and 4-guanidinobutyric acid showed good predictabilities, and the serum levels of citrulline, linoleic acid, and adenosine were significantly correlated with tissue eosinophil (T-EOS) percentage and T-EOS count. Conclusion: eCRSwNP patients exhibited discriminative serum metabolic signatures in comparison with neCRSwNP patients and HC. These results suggested that metabolomics profiles contributed to understanding the pathophysiological mechanisms of CRSwNP and distinguishing its phenotypes.

Activated leukocyte cell adhesion molecule as a biomarker for disease severity and efficacy of sublingual immunotherapy in allergic rhinitis.

BACKGROUND: Activated leukocyte cell adhesion molecule (ALCAM) plays an important role in T cell activation and immune response, but the role of ALCAM in allergic rhinitis (AR) remains unclear. The objective of the current study was to validate serum ALCAM as a biomarker in assessing disease severity and predicting the efficacy of sublingual immunotherapy (SLIT) in AR patients. METHODS: We recruited 40 healthy controls (HC group), 38 mild AR patients (MAR group) and 80 moderate-severe AR patients (MSAR group) in this study. Serum levels of ALCAM were determined by ELISA, and the association between ALCAM levels and disease severity was evaluated. In the MSAR group, 68 patients underwent and finished 3-years of SLIT, and were divided into effective group and ineffective group, the relationship between ALCAM levels and efficacy of SLIT was exampled. RESULTS: ALCAM levels were elevated in the serum of AR patients in comparison with HC. Moreover, serum ALCAM concentrations were higher in MSAR group than in MAR group and HC group, and levels of ALCAM significantly correlated with AR total nasal symptom score (TNSS) (r = 0.330, P < 0.001), visual analogue scale (VAS) (r = 0.387, P < 0.001) and serum total IgE levels (r = 0.442, P < 0.001). In the effective group, the ALCAM levels were significantly lower than in the ineffective group. Receiver operating characteristic (ROC) curve exhibited good accuracy for predicting clinical efficacy of SLIT (area under the curve = 0.805, P < 0.001). CONCLUSIONS: The serum ALCAM maybe a novel biomarker for assessing disease severity and predicting clinical efficacy of SLIT in AR patients.

Significance of leukocyte-specific transcript 1 levels in nasal mucosal tissue to predict recurrence of nasal polyps

Abstract Objective: Chronic Rhinosinusitis with Polyps (CRSwNP) is characterized by high heterogeneity and postoperative recurrence rate. This study aims to explore the clinical significance of tissue Leukocyte-Specific Transcript 1 (LST1) in predicting CRSwNP recurrence. Methods: We enrolled 62 CRSwNP patients including 30 primary CRSwNP and 32 recurrent CRSwNP patients, and 40 Healthy Controls (HC). Tissue samples were collected. Tissue LST1 expression was assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western Blotting (WB) and Immunofluorescence (IF) staining. The predictive values of LST1 expression for CRSwNP postoperative recurrence were assessed through the Receiver Operating Characteristic (ROC) curves. Results: The tissue levels of LST1 were significantly increased in the CRSwNP group than the HC group, especially in the recurrent group, and the elevated LST1 mRNA levels were positively correlated with the peripheral eosinophil percentages, tissue eosinophil counts and percentages. IF staining results showed that the LST1 protein levels were higher in CRSwNP patients, especially in the recurrent patients than in the HC group. ROC curves highlighted that tissue LST1 levels were associated with recurrent CRSwNP and exhibited a higher predictive ability for postoperative CRSwNP recurrence. Conclusion: This was the first report suggesting that LST1 expression was upregulated and associated with mucosal eosinophil infiltration and CRSwNP recurrence. Tissue LST1 could be a promising biomarker for predicting postoperative recurrence in CRwNP patients.

Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons.

Although aminoglycoside antibiotics such as kanamycin are widely used clinically to treat life-threatening bacterial infections, ototoxicity remains a significant dose-limiting side effect. The prevailing view is that the hair cells are the primary ototoxic target of aminoglycosides and that spiral ganglion neurons begin to degenerate weeks or months after the hair cells have died due to lack of neurotrophic support. To test the early developmental aspects of this issue, we compared kanamycin-induced hair cell and spiral ganglion pathology in rat postnatal day 3 cochlear organotypic cultures with adult whole cochlear explants. In both adult and postnatal day 3 cultures, hair cell damage began at the base of the cochleae and progressed toward the apex in a dose-dependent manner. In postnatal day 3 cultures, spiral ganglion neurons were rapidly destroyed by kanamycin prior to hair cell loss. In contrast, adult spiral ganglion neurons were resistant to kanamycin damage even at the highest concentration, consistent with in vivo models of delayed SGN degeneration. In postnatal day 3 cultures, kanamycin preferentially damaged type I spiral ganglion neurons, whereas type II neurons were resistant. Spiral ganglion degeneration of postnatal day 3 neurons was associated with upregulation of the superoxide radical and caspase-3-mediated cell death. These results show for the first time that kanamycin is toxic to postnatal day 3 spiral ganglion neurons, but not adult neurons.