The hippo pathway effector Yes-associated protein promotes epithelial proliferation and remodeling in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Hippo-Yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and development. However, its possible role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. We aim to investigate it on nasal epithelial proliferation and remodeling in CRSwNP. METHODS: The expressions of hippo pathway components as well as Ki-67 and E-cadherin in the sinonasal mucosa and nasal epithelial cells were analyzed in 14 controls, 14 eosinophilic CRSwNP, and 14 noneosinophilic CRSwNP. Nasal epithelial cells from 6 controls, 6 eosinophilic CRSwNP, and 6 noneosinophilic CRSwNP were cultured and treated with lipopolysaccharide (LPS), Poly(I:C), or a selective YAP inhibitor verteporfin (VP). RESULTS: The hippo pathway components MST1, LATS1/2, YAP, and TEAD1 were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells, along with upregulation of Ki-67 and downregulation of E-cadherin. The mRNA levels of YAP positively correlated with the Ki-67 mRNA levels, and negatively associated with the E-cadherin mRNA levels in polyp tissues and epithelial cells from nasal polyps (NPECs). LPS and Poly(I:C) upregulated the YAP expression in nasal epithelial cells accompanied by increased TEAD1 and Ki-67 expression. Conversely, YAP inhibition by VP decreased TEAD1 and Ki-67 expression in NPECs. CONCLUSIONS: Hippo pathway components are abnormally upregulated in NPECs, and its effector YAP promotes nasal epithelial cells proliferation and remodeling in CRSwNP. It provides a rationale to explore inhibition of YAP as a novel therapeutic strategy for reducing the epithelial proliferation and remodeling in CRSwNP.

[Characteristics and therapeutic strategies of Pott's puffy tumor].

Objective:To explore the characteristics and therapeutic strategies of Pott's puffy tumor（PPT）. Methods:The clinical data of two patients with PPT were retrospectively analyzed and combined with the literature, focusing on the comprehensive analysis of perioperative diagnosis and treatment strategies. Both patients underwent muti-disciplinary treatment, including timely administration of sufficient antibiotics capable of penetrating the blood-brain barrier. Early removal of PPT lesions was performed using a combined internal and external approach under nasal endoscopic guidance. Results:After standardized perioperative management, the symptoms of the two patients were completely relieved, with no recurrence after one=year follow=up. Postoperative complications such as frontal pain, numbness, local depression, or scar hyperplasiawere not present. Conclusion:PPT, being relatively rare and severe, requires careful attention. Key strategies for standardized perioperative management include multi-disciplinary consultation, timely and adequate antibiotic administration, and surgical intervention using a combined intranasal and extranasal endoscopic approach for lesion removal.

Refractory Epistaxis: A Map is Enough!

Combined the big data from Chinese researches and our clinical experiences, we drew a concise "distributed map" of intractable epistaxis showing the concealed bleeding regions and offending vessels clearly (Figure 1). The bleeding site was located accurately according to the "distributed map," and bleeding was stopped via bipolar radiofrequency ablation under nasal endoscope without nasal packing, followed by five classic cases (Figure 2). It is our recommended precise mode of diagnosis and treatment of refractory epistaxis.

Advances in Image-Based Artificial Intelligence in Otorhinolaryngology-Head and Neck Surgery: A Systematic Review.

OBJECTIVE: To update the literature and provide a systematic review of image-based artificial intelligence (AI) applications in otolaryngology, highlight its advances, and propose future challenges. DATA SOURCES: Web of Science, Embase, PubMed, and Cochrane Library. REVIEW METHODS: Studies written in English, published between January 2020 and December 2022. Two independent authors screened the search results, extracted data, and assessed studies. RESULTS: Overall, 686 studies were identified. After screening titles and abstracts, 325 full-text studies were assessed for eligibility, and 78 studies were included in this systematic review. The studies originated from 16 countries. Among these countries, the top 3 were China (n = 29), Korea (n = 8), the United States, and Japan (n = 7 each). The most common area was otology (n = 35), followed by rhinology (n = 20), pharyngology (n = 18), and head and neck surgery (n = 5). Most applications of AI in otology, rhinology, pharyngology, and head and neck surgery mainly included chronic otitis media (n = 9), nasal polyps (n = 4), laryngeal cancer (n = 12), and head and neck squamous cell carcinoma (n = 3), respectively. The overall performance of AI in accuracy, the area under the curve, sensitivity, and specificity were 88.39 ± 9.78%, 91.91 ± 6.70%, 86.93 ± 11.59%, and 88.62 ± 14.03%, respectively. CONCLUSION: This state-of-the-art review aimed to highlight the increasing applications of image-based AI in otorhinolaryngology head and neck surgery. The following steps will entail multicentre collaboration to ensure data reliability, ongoing optimization of AI algorithms, and integration into real-world clinical practice. Future studies should consider 3-dimensional (3D)-based AI, such as 3D surgical AI.

Chinese Central Compartment Atopic Disease: The Clinical Characteristics and Cellular Endotypes Based on Whole-Slide Imaging.

Purpose: Histopathologic characterizations of central compartment atopic disease (CCAD) by whole-slide imaging remains lacking. We aim to study clinical presentations and cellular endotyping diagnosis of Chinese CCAD using artificial intelligence (AI). Methods: A total of 72 patients diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled. CCAD was defined by positive result of serology specific IgE, endoscopic and radiological findings. The aeroallergen sensitization status, endoscopic results, radiological findings, and symptoms were evaluated and compared between patients with CCAD (n=14), eosinophilic CRSwNP (ENP, n=32) and non-eosinophilic CRSwNP (NENP, n=26). The cellular endotypes including eosinophils, neutrophils, lymphocytes, and plasma cells were analyzed by the AI chronic rhinosinusitis evaluation platform 2.0. Results: CCAD was most common in male (71.43%). The positive rate of aeroallergen in patients with CCAD is 100%, which is much higher than those in patients with ENP (40.63%) and NENP (23.08%). Allergic rhinitis incidence was found to be 57.14% in Chinese CCAD subjects, which is obviously higher when compared with those in patients with ENP (21.88%) or NENP (0.00%). The presence of asthma was not significantly different between groups. Chinese CCAD population demonstrated mild symptoms and lower endoscopic and radiological scores than those in patients with ENP and NENP. For cellular endotypes in CCAD subjects, the median of eosinophils, neutrophils, lymphocytes, and plasma cells was 26.55%, 0.49%, 60.85%, and 7.33%, respectively. The proportion of eosinophils in nasal tissue and peripheral blood mononuclear cells from the CCAD group is between the proportions in those patients with ENP and NENP. Conclusion: Chinese CCAD was associated with aeroallergen sensitivity, and displayed an eosinophil-dominant inflammatory pattern. Thus, proper management with allergy control and topical steroids could be recommended for CCAD treatment.

Mature Cervical Teratoma Extending Into the Anterior Mediastinum of an Adult.

There have been few reports of mature cystic teratoma, also known as a dermoid cyst, in the head and neck. Cervical neck teratoma extending into the mediastinum is also relatively rare. Here, we report a mature teratoma found in a cervical tumor in a 21-year-old man. This is the first reported case of a mature cervical teratoma extending into the anterior mediastinum. A combination of frontal X-ray, ultrasonography, computed tomography, and magnetic resonance imaging indicated a large oval heterogeneous mass surrounding the thyroid gland and trachea, underneath the sternocleidomastoid and sternohyoid, which pressed on the left lobar thyroid and trachea and extended into the anterior mediastinum. Based on preoperative observation, a diagnosis of an embryonal benign tumor was made. Although rare, this case demonstrates that these tumors should be completely removed during workup of cervical tumors.

YAP Promotes Cell Proliferation and Epithelium-Derived Cytokine Expression via NF-κB Pathway in Nasal Polyps.

BACKGROUND: Hippo-Yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and inflammation development in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the underlying mechanisms remain unclear. OBJECTIVE: This study intends to investigate the role of YAP and the nuclear factor kappa-B (NF-κB) pathway in cell proliferation and the expression of epithelium-derived cytokines in nasal polyps (NP). METHODS: The expression levels of YAP, TEA domain family member 1 (TEAD1), Ki-67, and NF-κB as well as interleukin (IL-) 33, IL-25 and thymic stromal lymphopoietin (TSLP) in sinonasal mucosa, primary nasal epithelial cells (NPECs), and human nasal epithelial RPMI 2650 cells were detected. NPECs were cultured and treated with verteporfin (VP), YAP shRNA or BAY 11-7082. RESULTS: The hippo pathway effector YAP, Ki-67, p65 NF-κB, and cyclin D1 were significantly increased in NP compared with control mucosa, which was accompanied by overexpression of IL-33, IL-25, and TSLP. Pharmaceutical inhibition of YAP by VP suppressed cell proliferation of RPMI 2650 cells by blocking cell cycle progression at G0/G1 without inducing obvious cell apoptosis. Furthermore, lentiviral transfection-mediated knockdown of hippo pathway activity reduced the expression of IL-33, IL-25, TSLP as well as p65 NF-κB in RPMI 2650 cells. Downregulation of NF-κB pathway with BAY 11-7082 in NPECs could decrease the mRNA level of TSLP, IL-33 and IL-25 accordingly. CONCLUSION: Inhibition of hippo pathway suppressed nasal epithelial cell proliferation and declined the expression of epithelium-derived cytokines via the NF-κB pathway in NPECs.

Artificial intelligence for cellular phenotyping diagnosis of nasal polyps by whole-slide imaging.

BACKGROUND: artificial intelligence (AI) for cellular phenotyping diagnosis of nasal polyps by whole-slide imaging (WSI) is lacking. We aim to establish an AI chronic rhinosinusitis evaluation platform 2.0 (AICEP 2.0) to obtain the proportion of inflammatory cells for cellular phenotyping diagnosis of nasal polyps and to explore the clinical significance of different phenotypes of nasal polyps on the WSI. METHODS: a total of 453 patients were enrolled in our study. For the development of AICEP 2.0, 179 patients (WSIs) were obtained from the Third Affiliated Hospital of Sun Yat-Sen University (3HSYSU) from January 2008 to December 2018. A total of 24,625 patches were automatically extracted from the regions of interest under a 400× HPF by Openslide and the number of inflammatory cells in these patches was counted by two pathologists. For the application of AICEP 2.0 in a prospective cohort, 158 patients aged 14-70 years old with chronic rhinosinusitis with nasal polyps (CRSwNP) who had undergone endoscopic sinus surgery at 3HSYSU from June 2020 to December 2020 were included for preoperative demographic characteristics. For the application of AICEP 2.0 in a retrospective cohort, 116 patients with CRSwNP who had undergone endoscopic sinus surgery from May 2016 to June 2017 were enrolled for the recurrence rate. The proportion of inflammatory cells of these patients on WSI was calculated by our AICEP 2.0. FINDINGS: for AICEP 2.0, the mean absolute errors of the ratios of eosinophils, lymphocytes, neutrophils, and plasma cells were 1.64%, 2.13%, 1.06%, and 1.22%, respectively. The four phenotypes of nasal polyps were significantly different in clinical characteristics (including asthma, itching, sneezing, total IgE, peripheral eosinophils%, tissue eosinophils%, tissue neutrophils%, tissue lymphocytes%, tissue plasma cells%, and recurrence rate; P <0.05), but there were no significant differences in age distribution, onset time, total VAS score, Lund-Kennedy score, or Lund-Mackay score. The percentage of peripheral eosinophils was positively correlated with the percentage of tissue eosinophils (r = 0.560, P <0.001) and negatively correlated with tissue lymphocytes% (r = -0.489, P <0.001), tissue neutrophils% (r = -0.225, P = 0.005), and tissue plasma cells% (r = -0.266, P = 0.001) in WSIs.

Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma.

BACKGROUND: Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them. METHODS: We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP's role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP's role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP. RESULTS: The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes. CONCLUSION: Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.

Olfactory Sensitivity Is Related to Erectile Function in Adult Males.

BACKGROUND: The olfactory system influences human social behavior, in particular the selection of a spouse. However, there is currently a lack of clinical research on the relationship between the olfactory system and erectile dysfunction (ED) in adult males. AIM: We explored the association between olfactory sensitivity and erectile function and its possible mechanisms. RESULTS: A total of 574 patients, adult males aged between 19 and 42 years, diagnosed with ED in the Department of Infertility and Sexual Medicine of the Third Affiliated Hospital of Sun Yat-sen University from 2015 to 2018 were analyzed retrospectively. Among them, 115 patients (20.03%) had rhinologic diseases (RDs). In addition, in 201 adult male patients who underwent nasal surgery in the ENT department from 2012 to 2016, including 29 (14.43%) with ED, nasal congestion, nasal discharge, and hyposmia were the most common complaints based on the numerical rating scale (NRS). Furthermore, a prospective study was performed in a total of 102 sequential outpatients (male adults) with RD only (n = 46), ED only (n = 42) and both RD and ED (n = 14) in 2019, together with 40 healthy (male adults) volunteers as controls. The results showed that ED patients with RD had severe nasal discomfort and decreased erectile function (P < 0.0001). The olfactory sensitivity of patients with ED was lower than that of the controls, and patients with both ED and RD had the worst olfactory sensitivity (P < 0.0001). Spearman correlation analyses showed that sense of smell was positively correlated with the International Index of Erectile Function-5 score (R = 0.507, P ≤ 0.0001) and the Erection Hardness Scale score (R = 0.341, P < 0.0001). Logistic regression analyses showed that having an olfactory disorder (OD), RD, age, and visual analog scale (VAS, over 5) score were risk factors for ED outcome, indicating that OD patients had a 16.479-fold increased risk for an ED outcome (P < 0.05). CONCLUSION: A significant correlation was detected between olfactory sensitivity and erectile function in adult males. In particularly, impairment of olfactory sensitivity is more common in patients with both ED and RD than in patients suffering from a single disease.

Infiltration pattern of gammadelta T cells and its association with local inflammatory response in the nasal mucosa of patients with allergic rhinitis.

BACKGROUND: gammadelta (γδ) T cells play important roles in allergic lower airway inflammation. However, little is known about their infiltration pattern in the nasal mucosa during upper airway inflammation. This study investigated γδ T cell distribution in nasal tissues of allergic rhinitis (AR) patients and the relationship between γδ T cells and other inflammatory cell types. METHODS: A total of 30 patients with septal deviation were examined, including 22 with and 8 without AR. The localization of γδ T cells and other cells (eosinophils, neutrophils, mast cells, macrophages, B cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, regulatory T cells [Tregs], interferon [IFN]-γ+ cells, interleukin [IL]17+ cells, and IL10+ cells) was evaluated by histological analysis and immunohistochemistry. T helper cell (Th)1/Th2/Th17 and Treg gene expression was analyzed by quantitative polymerase chain reaction (PCR). RESULTS: γδ T cells were localized in the epithelium or subepithelial region of nasal mucosa, and their infiltration was higher in AR patients relative to control subjects. The number of γδ T cells was associated with the presence of eosinophils, macrophages, mast cells, B cells, CD8+ T cells, Forkhead box (Fox)p3+ Tregs, IL17+ cells, and IL10+ cells but not of neutrophils or IFN-γ+ cells. The messenger RNA (mRNA) level of a γδ T cell subunit was positively correlated with those of Th1 genes (T-bet and IFN-γ), Th2 cytokine (C-C motif chemokine ligand 18), and Treg genes (Foxp3 and IL10). CONCLUSION: γδ T cells play multiple roles in mucosal inflammation in AR including immune surveillance and adaptive and innate immune responses.

[Diagnostic performance of prospective versus retrospective electrocardiogram-gated 64-slice computed tomography coronary angiography].

OBJECTIVE: To compare the diagnostic performance of prospective electrocardiogram (ECG)-triggered computed tomography coronary angiography (CTCA) versus retrospective ECG-gated CTCA. METHODS: Patients with suspected coronary artery disease divided into two groups which underwent 64-slice CTCA with prospective ECG-triggered or retrospective ECG-gated scanning (n = 100 each, HR < or = 65 bpm). Multi-planar reconstruction (MPR), curved-planar reconstruction (CPR), maximum intensity projection (MIP) and volume rendering (VR) were made to demonstrate the coronary arteries. The image quality was defined as excellent, good and poor by motion and stair-step artifacts. Individual radiation exposure dose was estimated from the dose-length product. RESULTS: The mean effective radiation dose of prospective ECG-triggered CTCA [(2.81 +/- 0.48) mSv] was significantly lower than that of retrospective ECG-gated CTCA [(10.16 +/- 1.09) mSv, P < 0.01]. Segments of diagnostic image quality (95.2%, 1165/1224) and non-diagnostic coronary segments (4.8%, 59/1224) in prospective ECG-triggered group were similar as those of retrospective ECG-gated group (94.1%, 1186/1261 and 5.9%, 75/1261, all P > 0.05). CONCLUSION: Though the radiation exposure dose required is significantly lower, the diagnostic performance of prospective ECG-triggered 64 slice CTCA is comparable with that of retrospective ECG-gated 64 slice CTCA on patients with stable heart rates up to 65 bpm.

Effect of continuous positive airway pressure on allergic rhinitis in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: The effect of continuous positive airway pressure (CPAP) on nasal symptoms in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) remains controversial. In addition, possible mechanism(s) remains unclear. OBJECTIVE: To examine whether CPAP contributes to the onset and exacerbation of allergic rhinitis (AR) in OSAHS patients based on patient-reported changes in nasal symptoms with and without CPAP therapy and the detection of house dust mites (HDMs) in CPAP filters and household environments. MATERIALS AND METHODS: In a cohort of OSAHS patients, 350 patients who were undergoing CPAP therapy and 100 patients who declined CPAP therapy were retrospectively analyzed. These patients were contacted by telephone and asked to compare their nasal symptoms before and after CPAP therapy. HDMs in air conditioner and CPAP device filters and in household dust samples were detected using enzyme-linked immunosorbent assays. RESULTS: The prevalence of AR was higher in the CPAP group vs the non-CPAP group (15.8% vs 7.0%, respectively; P = 0.025). The onset of AR among the OSAHS patients with no previous history of AR significantly increased within the first year of CPAP therapy compared with the control group (5.7% vs 0%, respectively; P = 0.031). Meanwhile, the patients with a history of AR were more likely to experience exacerbated rhinitis symptoms within the second year of treatment compared with the control group (7.5% vs 0%, respectively; P = 0.005). There was no significant difference in HDM concentrations between the CPAP and air conditioner filters, yet the concentrations in both the filters were higher than the concentrations in the bedroom dust samples (all P < 0.05). CONCLUSION: CPAP is associated with the onset and exacerbation of AR in OSAHS patients. Long-term exposure to high concentrations of HDM allergens may be a significant factor.

Comparative Study of Recessive Spherical Headed Silicone Intubation and Endonasal Dacryocystorhinostomy under Nasal Endoscopy for Nasolacrimal Duct Obstruction.

Between July 2014 and November 2015, we compared the curative effects and cost-effectiveness of two kinds of nasal endoscopic surgery for nasolacrimal duct obstruction (NLDO) in a single-centre, two-armed clinical trial with a 1-year follow-up. We included two groups: a recessive spherical headed silicone intubation (RSHSI) group and an endonasal dacryocystorhinostomy (En-DCR) group; both received nasal endoscopy. Patients were recruited from the Otorhinolaryngology and Ophthalmology departments. The main outcome measures were epiphora improvement (classified as cure, effective, or invalid), cost-effectiveness, visual analogue scale (VAS) intraoperative pain score, bleeding volume, operating time, hospitalisation time, total cost, and VAS postoperative epiphora score. No significant group difference was identified in postoperative epiphora VAS scores (P > 0.050) or success rate (P = 0.406). However, average VAS intraoperative pain score, operating time, bleeding volume, hospitalisation time and total cost in the RSHSI group were clearly lower to those in the En-DCR group (P = 0.000). In conclusion, RSHSI under nasal endoscopy can provide similar treatment outcomes to En-DCR. RSHSI has advantages including minimal invasiveness, reduced risk, shorter duration of surgery and hospitalisation, reduced intraoperative discomfort, and lower financial burden, which is more acceptable to patients. Thus, RSHSI may be the preferred option for NLDO.