Modified screening and management strategies for chronic rhinosinusitis in hematologic patients receiving hematopoietic stem cell transplantation.

OBJECTIVES: Given the lack of consensus on the screening and treatment for chronic rhinosinusitis (CRS) in the patients undergoing hematopoietic stem cell transplantation (HSCT), we reviewed the risk factors for CRS to improve the efficiency of sinonasal screening and analyzed the effect of treating CRS in search of guidance for modifying current management strategies for rhinosinusitis in HSCT patients. METHODS: We conducted a nested case-control study in a retrospective cohort of hematologic patients receiving HSCT from April 2011 to April 2021 and collected data on demographics, smoking/atopic status, hematological diseases, and features of rhinosinusitis for analysis. The associated factors for control of rhinosinusitis and survival were analyzed. RESULTS: Fifty-eight CRS patients were identified, and another 116 age- and sex-matched controls were selected from HSCT patients without CRS. Allergy and smoking were risk factors for CRS in HSCT patients. The multivariable logistic analysis indicated that endoscopic sinus surgery (ESS) was an independent factor for better control of CRS. However, survival was not associated with rhinosinusitis-related factors, but only with hematologic-related factors, including allogenic HSCT, reduced-intensity conditioning, and remission. CONCLUSIONS: Sinonasal evaluation should be targeted to the high-risk group. ESS is effective in managing CRS, while control of CRS is not determinant of overall survival in patients receiving HSCT.

Comprehensive evaluation of type 2 endotype and clinical features in patients with chronic rhinosinusitis with nasal polyps in Taiwan: a cross-sectional study.

PURPOSE: Endotype-driven treatment has been introduced in the management of chronic rhinosinusitis with nasal polyps (CRSwNP), and an understanding of the associations between phenotypes and endotypes of CRSwNP will be beneficial in identifying responders. We aimed to determine the correlations between clinical manifestations and type 2 inflammatory mediators of sinonasal tissues. METHODS: Adult patients undergoing endoscopic sinus surgery for bilateral CRSwNP were prospectively enrolled. Tissue eosinophilia and type 2 mediator expression in tissue homogenates were assessed and correlated with clinical features, including symptoms, comorbidities, blood eosinophil counts, specific allergen immunoglobulin (IgE) testing, computed tomography (CT) scan findings, and Sino-Nasal Outcome Test-22 scores. RESULTS: A total of 93 subjects were recruited in our study. Fifty-nine (63.4%) cases were identified as the eosinophilic endotype, demonstrating with higher rates of comorbidity of asthma, blood eosinophilia and a high ethmoid-maxillary ratio on CT images. To correlate of phenotypes with the inflammatory mediator profile, multivariate analyses revealed the associations of IgE expression in nasal polyp tissues with allergen sensitization (p = 0.042), CT ethmoid-maxillary ratio (p = 0.001) and tissue eosinophil counts (p = 0.022); the association of interleukin (IL-5) expression with the blood eosinophil percentage (p = 0.020); and the association of IL-13 expression with white blood cell count (p = 0.002) and central compartment-type inflammation (p < 0.001). CONCLUSION: We demonstrated associations of IgE and IL-5 expression with clinical features of eosinophilic-type inflammation and a significantly elevated level of IL-13 in patients with central-compartment-type CRSwNP. These observations may be useful when considering the use of type 2 biologic treatment and require further validation studies.

Revision of endoscopic sinus surgery in adults: A population-based study in Taiwan.

OBJECTIVE: This study aimed to elucidate the revision rate, time to revision, and factors associated with revision of endoscopic sinus surgery (ESS) in Taiwan. DESIGN: Retrospective study. SETTING: Population-based analysis. PARTICIPANT: We identified all in-hospital patients, aged >20 years, who underwent ESS between 2000 and 2008 from the Taiwan National Health Insurance Research Database, and followed up with them until 2018. MAIN OUTCOME MEASURES: Factors associated with revision surgery were analyzed using multivariable Cox proportional hazard model. RESULTS: Overall, 66 592 patients were identified (mean age, 46.3 years; 62% males). The revision rate was 14.5% (9644/66 592) and time to revision surgery was 5.9 years. Multivariable Cox proportional hazard model showed that young age, male gender (hazard ratio [HR] = 1.18; 95% confidence interval [CI], 1.13-1.23), having nasal polyposis (HR = 1.17; 95% CI, 1.12-1.22), having allergic rhinitis (HR = 1.08; 95% CI, 1.04-1.13), having asthma (HR = 1.26; 95% CI, 1.14-1.39), and surgical time of >4 h (HR = 1.11; 95% CI, 1.06-1.16) were associated with increased risk of revision surgery. Concurrent septal surgery (HR = 0.81; 95% CI, 0.76-0.87), turbinate surgery (HR = 0.91; 95% CI, 0.85-0.97), or septal and turbinate surgery (HR = 0.68; 95% CI, 0.64-0.73) were associated with decreased risks of revision surgery. CONCLUSION: In Taiwan, risk factors for revision ESS are young age, male gender, having nasal polyposis, having allergic rhinitis, having asthma, and long surgical times. Concurrent septal or turbinate surgery decreases the risk of revision.

Effect of sleep surgery on lipid profiles in adults with obstructive sleep apnea: a meta-analysis.

PURPOSE: The effects of sleep surgery on the lipid profile of adults diagnosed as having obstructive sleep apnea (OSA) remain unclear. This meta-analysis aimed to clarify whether sleep surgeries improve patients' lipid profile. METHODS: The study protocol was registered on PROSPERO (CRD42020154425). Two authors independently searched the PubMed, MEDLINE, EMBASE, and Cochrane review databases up to September 2020 using keywords such as sleep apnea, OSA, sleep apnea syndromes, lipids, and surgery. The effects of sleep surgery on the apnea-hypopnea index (AHI) and lipid profile parameters were evaluated using a random-effects model. RESULTS: Thirteen studies were included, with a total of 710 patients (mean age: 42.0 years; 85% men; mean sample size: 54.6 patients). The summary estimate of AHI change was - 20.6 events/h (95% CI - 25.9 to - 15.3) and the Epworth Sleepiness Scale score was - 4.2 (95% CI - 5.9 to - 2.5). Sleep surgery lowered total cholesterol (mean - 7.7 mg/dL; 95% CI - 12.2 to - 3.2), low-density lipoprotein (mean - 7.2 mg/dL; 95% CI - 11.0 to - 3.3), and triglyceride (mean - 14.0 mg/dL; 95% CI - 22.2 to - 5.8) levels but did not affect high-density lipoprotein (mean 1.5 mg/dL; 95% CI - 0.6 to 3.7) levels. Subgroup analysis revealed that the lipid profile changes were not associated with the surgical procedure but with the degree of OSA improvement. Meta-regression analyses demonstrated that the improvement in the lipid profile was positively correlated with AHI reduction. CONCLUSION: Surgeries for OSA may improve the lipid profile, which is positively correlated with the degree of OSA improvement.

Epstein-Barr Virus Enhances Cancer-Specific Aberrant Splicing of TSG101 Pre-mRNA.

Tumor viruses gain control of cellular functions when they infect and transform host cells. Alternative splicing is one of the cellular processes exploited by tumor viruses to benefit viral replication and support oncogenesis. Epstein-Barr virus (EBV) participates in a number of cancers, as reported mostly in nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL). Using RT-nested-PCR and Northern blot analysis in NPC and BL cells, here we demonstrate that EBV promotes specific alternative splicing of TSG101 pre-mRNA, which generates the TSG101∆154-1054 variant though the agency of its viral proteins, such as EBNA-1, Zta and Rta. The level of TSG101∆154-1054 is particularly enhanced upon EBV entry into the lytic cycle, increasing protein stability of TSG101 and causing the cumulative synthesis of EBV late lytic proteins, such as VCA and gp350/220. TSG101∆154-1054-mediated production of VCA and gp350/220 is blocked by the overexpression of a translational mutant of TSG101∆154-1054 or by the depletion of full-length TSG101, which is consistent with the known role of the TSG101∆154-1054 protein in stabilizing the TSG101 protein. NPC patients whose tumor tissues express TSG101∆154-1054 have high serum levels of anti-VCA antibodies and high levels of viral DNA in their tumors. Our findings highlight the functional importance of TSG101∆154-1054 in allowing full completion of the EBV lytic cycle to produce viral particles. We propose that targeting EBV-induced TSG101 alternative splicing has broad potential as a therapeutic to treat EBV-associated malignancies.

Dysregulation of Dual-Specificity Phosphatases by Epstein-Barr Virus LMP1 and Its Impact on Lymphoblastoid Cell Line Survival.

The strongest evidence of the oncogenicity of Epstein-Barr virus (EBV) in vitro is its ability to immortalize human primary B lymphocytes into lymphoblastoid cell lines (LCLs). Yet the underlying mechanisms explaining how the virus tempers the growth program of the host cells have not been fully elucidated. The mitogen-activated protein kinases (MAPKs) are implicated in many cellular processes and are constitutively activated in LCLs. We questioned the expression and regulation of the dual-specificity phosphatases (DUSPs), the main negative regulator of MAPKs, during EBV infection and immortalization. Thirteen DUSPs, including 10 typical and 3 atypical types of DUSPs, were tested. Most of them were downregulated after EBV infection. Here, a role of viral oncogene latent membrane protein 1 (LMP1) in limiting DUSP6 and DUSP8 expression was identified. Using MAPK inhibitors, we found that LMP1 activates extracellular signal-regulated kinase (ERK) or p38 to repress the expression of DUSP6 and DUSP8, with corresponding substrate specificity. Morphologically, overexpression of DUSP6 and DUSP8 attenuates the ability of EBV-immortalized LCL cells to clump together. Mechanistically, apoptosis induced by restoring DUSP6 and DUSP8 in LCLs indicated a novel mechanism for LMP1 to provide a survival signal during EBV immortalization. Collectively, this report provides the first description of the interplay between EBV genes and DUSPs and contributes considerably to the interpretation of MAPK regulation in EBV immortalization.IMPORTANCE Infections by the ubiquitous Epstein-Barr virus (EBV) are associated with a wide spectrum of lymphomas and carcinomas. It has been well documented that activation levels of MAPKs are found in cancer cells to translate various external or intrinsic stimuli into cellular responses. Physiologically, the dual-specificity phosphates (DUSPs) exhibit great ability in regulating MAPK activities with respect to their capability of dephosphorylating MAPKs. In this study, we found that DUSPs were generally downregulated after EBV infection. EBV oncogenic latent membrane protein 1 (LMP1) suppressed DUSP6 and DUSP8 expression via MAPK pathway. In this way, LMP1-mediated MAPK activation was a continuous process. Furthermore, DUSP downregulation was found to contribute greatly to prevent apoptosis of EBV-infected cells. To sum up, this report sheds light on a novel molecular mechanism explaining how EBV maintains the unlimited proliferation status of the immortalized cells and provides a new link to understand EBV-induced B cell survival.

The clinical features of endoscopic treated isolated sphenoid sinus diseases.

BACKGROUND: Isolated sphenoid sinus disease (ISSD) is a rare clinical entity with potentially serious complications. The etiological distribution of ISSD varies among different areas and ethnicities. We aimed to investigate the clinical features of patients with endoscopic treated ISSD. METHODS: We retrospectively reviewed all patients with ISSD who had undergone endoscopic surgery between April 2013 and May 2019. The patient records were reviewed for demographic data, clinical presentations, endoscopic and imaging study findings, surgical outcomes and complications. RESULTS: A total of 37 patients with ISSD who underwent surgery were recruited. We divided patients into three groups according to etiology, including inflammatory diseases (78.4%), neoplasms (13.5%) and spontaneous cerebrospinal fluid (CSF) leaks (8.1%); fungal ball (62.2%) constituted the major cause of ISSD. Overall, the most common presenting symptom was headache or facial pain (65.5%). The endoscopic findings of bloody discharge and tumor lesions were mainly from the neoplasm group. Bony defects were more obvious on computed tomography in the neoplasm and CSF leak groups. Magnetic resonance imaging revealed a higher rate of involvement of the cavernous sinus (40.0%) and intracranial extensions (40.0%) in the neoplasm group. To summarize the surgical outcomes, the success rate was 97.1%, and the major complication rate was 5.4%. CONCLUSION: ISSD represents a variety of etiologies, mostly comprising fungal ball in our area, while there is still a considerable proportion of ISSDs attributed to neoplasm and CSF leak. Untreated ISSD can result in serious complications. We recommend early surgical intervention for all patients with ISSD.

Ear, nose, and throat foreign bodies in adults: A population-based study in Taiwan.

BACKGROUND/PURPOSE: This study performed a population-based analysis in the managements of adult ear, nose, and throat FBs in Taiwan. METHODS: The Taiwan Longitudinal Health Insurance Database 2000 were used, which comprises 1,000,000 beneficiaries randomly sampled in 2000 with a follow-up period from 2000 to 2013. Patients aged >18 years with ear, nose, or throat FB were identified according to the International Codes of Diseases. RESULTS: In total, 94,312 adults with ear (n = 21,786), nose (n = 1007), throat (n = 62,986), airway (n = 419), or esophageal (n = 8114) FB were identified. Emergency department visits were most common among patients with esophageal or airway FB (33.3% and 25.1%, respectively). X-rays were most commonly performed for patients with esophageal FB (44.8%), and computed tomography (CT) was most commonly used for those with airway FB (4.3%). Hospitalization rate was the highest among patients with airway FB (7.4%), followed by those with esophageal (3.0%) and nose (0.7%) FB. Patients with airway FBs corresponded with the highest rate of intensive care unit stay (58.1%), longest hospital stay (10.5 days), and highest in-hospital mortality rate (25.8%). A multiple logistic regression model indicated that old age, medical comorbidities, undergoing CT, and airway or esophageal FB were associated with hospitalization among adults with FB. CONCLUSION: Disparities were identified in the treatment of ear, nose, and throat FB in adults. This study provides population-based data that may serve as a reference for otolaryngologists in clinical FB management.

Cancer-Specifically Re-Spliced TSG101 mRNA Promotes Invasion and Metastasis of Nasopharyngeal Carcinoma.

TSG101 (Tumor susceptibility 101) gene and its aberrantly spliced isoform, termed TSG101∆154-1054, are tightly linked to tumorigenesis in various cancers. The aberrant TSG101∆154-1054 mRNA is generated from cancer-specific re-splicing of mature TSG101 mRNA. The TSG101∆154-1054 protein protects the full-length TSG101 protein from ubiquitin-mediated degradation, implicating TSG101∆154-1054 protein in the progression of cancer. Here, we confirmed that the presence of TSG101∆154-1054 mRNA indeed caused an accumulation of the TSG101 protein in biopsies of human nasopharyngeal carcinoma (NPC), which was recapitulated by the overexpression of TSG101∆154-1054 in the NPC cell line TW01. We demonstrate the potential function of the TSG101∆154-1054 protein in the malignancy of human NPC with scratch-wound healing and transwell invasion assays. By increasing the stability of the TSG101 protein, TSG101∆154-1054 specifically enhanced TSG101-mediated TW01 cell migration and invasion, suggesting the involvement in NPC metastasis in vivo. This finding sheds light on the functional significance of TSG101∆154-1054 generation via re-splicing of TSG101 mRNA in NPC metastasis and hints at its potential importance as a therapeutic target.

Epstein-Barr virus LMP2A suppresses MHC class II expression by regulating the B-cell transcription factors E47 and PU.1.

Oncogenic Epstein-Barr virus (EBV) uses various approaches to escape host immune responses and persist in B cells. Such persistent infections may provide the opportunity for this virus to initiate tumor formation. Using EBV-immortalized lymphoblastoid cell lines (LCLs) as a model, we found that the expression of major histocompatibility complex (MHC) class II and CD74 in B cells is repressed after EBV infection. Class II transactivator (CIITA) is the master regulator of MHC class II-related genes. As expected, CIITA was downregulated in LCLs. We showed that downregulation of CIITA is caused by EBV latent membrane protein 2A (LMP2A) and driven by the CIITA-PIII promoter. Furthermore, we demonstrated that LMP2A-mediated E47 and PU.1 reduction resulted in CIITA suppression. Mechanistically, the LMP2A immunoreceptor tyrosine-based activation motif was critical for the repression of E47 and PU.1 promoter activity via Syk, Src, and the phosphatidylinositol 3-kinase/Akt pathway. Elimination of LMP2A in LCLs using a shLMP2A approach showed that the expression levels of E47, PU.1, CIITA, MHC class II, and CD74 are reversed. These data indicated that the LMP2A may reduce MHC class II expression through interference with the E47/PU.1-CIITA pathway. Finally, we demonstrated that MHC class II may be detected in tonsils and EBV-negative Hodgkin disease but not in EBV-associated posttransplant lymphoproliferative disease and Hodgkin disease.

Role of the Frontal Sinus in Mediating Ocular Vestibular-Evoked Myogenic Potentials by Bone Vibration Stimuli Applied to the Forehead.

This study investigated ocular vestibular-evoked myogenic potential (oVEMP) tests via Fpz and Fz taps to assess the role of the frontal sinus in mediating oVEMP elicitation. Forty healthy subjects and 80 patients with Ménière disease (MD) underwent a series of oVEMP tests via a minishaker tapping at the Fpz and Fz sites in a randomized order. Response rates of oVEMP test via various tapping sites were compared. Dimensions of the frontal sinus were measured via CT scan. A significantly negative correlation between the age and height of the frontal sinus was noted, and the cutoff age for discriminating present and absent Fpz oVEMPs in MD patients was 52 years. Additionally, oVEMPs by Fpz tapping were more efficiently presented in males than females, likely because of the greater resonance by the larger height of the frontal sinus in males (3.88 ± 0.68 cm) than females (3.42 ± 0.67 cm). In conclusion, the height of the frontal sinus plays a role in mediating the elicitation of oVEMPs. The oVEMPs could be easily elicited by the first-order bone vibration (Fpz/Fz tapping) coupled with the second-order resonance effect (with a high extent of the frontal sinus). Thus, initial tapping at the Fpz site is suggested. If it fails, try the Fz site for screening the oVEMPs.

Revision adenoidectomy in children: a population-based cohort study in Taiwan.

There is a lack of population-level analysis of revision adenoidectomy in children. This study reveals the revision rates and factors associated with paediatric revision adenoidectomy in Taiwan. From the Taiwan National Health Insurance Research Database, we identified all in-hospital children (age <18 years) who underwent adenoidectomy between 2000 and 2007. All children had received at least 5 years of follow-up from the index date, and the clinical records until 2012 were examined. Factors affecting the paediatric revision adenoidectomy were analysed using the multivariable Cox proportional hazards model. A total of 10,396 children were enrolled (mean age 7.3 years; 66% boys; mean follow-up period 8.7 years). Two hundred and seventy-five children underwent revision adenoidectomy, and the mean interval between primary adenoidectomy and revision surgery was 2.97 years. Only 58.5% of children underwent revision surgery at the initial hospital. The incidence of revision surgery was highest in the second year (0.69%), followed by the third year (0.53%) after primary adenoidectomy. The multivariable Cox proportional hazards model revealed that young age [hazard ratio (HR) = 0.8], male gender (HR = 1.57), surgery at an eastern hospital (HR = 2.08), surgical indication of adenoid hypertrophy (HR = 1.51), and concurrent ventilation tube insertion (HR = 2.61) or nasal surgeries (HR = 4.84) were associated with revision adenoidectomy. The incidence of revision adenoidectomy in Taiwan was 2.6%. Male gender, young age, concurrent nasal or ventilation tube insertion, and surgery at an eastern hospital increased the risk of revision.

Maintenance of Epstein-Barr Virus Latent Status by a Novel Mechanism, Latent Membrane Protein 1-Induced Interleukin-32, via the Protein Kinase Cδ Pathway.

UNLABELLED: Epstein-Barr virus (EBV), an oncogenic herpesvirus, has the potential to immortalize primary B cells into lymphoblastoid cell lines (LCLs) in vitro. During immortalization, several EBV products induce cytokines or chemokines, and most of these are required for the proliferation of LCLs. Interleukin-32 (IL-32), a recently discovered proinflammatory cytokine, is upregulated after EBV infection, and this upregulation is detectable in all LCLs tested. EBV latent membrane protein 1 (LMP1) is responsible for inducing IL-32 expression at the mRNA and protein levels. Mechanistically, we showed that this LMP1 induction is provided by the p65 subunit of NF-κB, which binds to and activates the IL-32 promoter. Furthermore, the short hairpin RNA (shRNA)-mediated depletion of endogenous LMP1 and p65 in LCLs suppressed IL-32 expression, further suggesting that LMP1 is the key factor that stimulates IL-32 in LCLs via the NF-κB p65 pathway. Functionally, knockdown of IL-32 in LCLs elicits viral reactivation and affects cytokine expression, but it has no impact on cell proliferation and apoptosis. Of note, we reveal the mechanism whereby IL-32 is involved in the maintenance of EBV viral latency by inactivation of Zta promoter activity. This atypical cytoplasmic IL-32 hijacks the Zta activator protein kinase Cδ (PKCδ) and inhibits its translocation from the cytoplasm to the nucleus, where PKCδ binds to the Zta promoter and activates lytic cycle progression. These novel findings reveal that IL-32 is involved in the maintenance of EBV latency in LCLs. This finding may provide new information to explain how EBV maintains latency, in addition to viral chromatin structure and epigenetic modification. IMPORTANCE: EBV persists in two states, latency and lytic replication, which is a unique characteristic of human infections. So far, little is known about how herpesviruses maintain latency in particular tissues or cell types. EBV is an excellent model to study this question because more than 90% of people are latently infected. EBV can immortalize primary B cells into lymphoblastoid cell lines in vitro. Expression of IL-32, a novel atypical cytoplasmic proinflammatory cytokine, increased after infection. The expression of IL-32 was controlled by LMP1. In investigating the regulatory mechanism, we demonstrated that the p65 subunit of NF-κB is required for this upregulation. Of note, the important biological activity of IL-32 was to trap protein kinase Cδ in the cytoplasm and prevent it from binding to the Zta promoter, which is the key event for EBV reaction. So, the expression of LMP1-induced IL-32 plays a role in the maintenance of EBV latency.

Associations between allergic diseases and attention deficit hyperactivity/oppositional defiant disorders in children.

BACKGROUND: We aim to investigate the detailed associations between allergic diseases with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) among children. METHODS: Clinical information from 2,896 children enrolled in the Taiwan Children Health Study was obtained for analyses. Allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis, have been evaluated based on the questions adjusted from International Study of Asthma and Allergies in Childhood. The Swanson, Nolan, and Pelham questionnaire was used to assess symptoms of ADHD and ODD. Symptoms of depression, stress, and poor sleep quality were evaluated as the interactive risk factors. RESULTS: Children having symptoms of allergic diseases within the past 1 y were associated with having all dimensions of symptoms of ADHD and ODD. Children with ever having a physician-diagnosed atopic dermatitis were associated with inattentive and hyperactive-impulsive symptoms of ADHD. Ever diagnosed asthma was associated with ADHD and ODD. Ever diagnosed allergic rhinitis was associated with inattentive and combined symptoms of ADHD and ODD. CONCLUSION: Children with allergic diseases, such as atopic dermatitis, asthma, and allergic rhinitis, were associated with exhibiting ADHD and ODD.

Autocrine CCL3 and CCL4 induced by the oncoprotein LMP1 promote Epstein-Barr virus-triggered B cell proliferation.

Epstein-Barr virus (EBV) alters the regulation and expression of a variety of cytokines in its host cells to modulate host immune surveillance and facilitate viral persistence. Using cytokine antibody arrays, we found that, in addition to the cytokines reported previously, two chemotactic cytokines, CCL3 and CCL4, were induced in EBV-infected B cells and were expressed at high levels in all EBV-immortalized lymphoblastoid cell lines (LCLs). Furthermore, EBV latent membrane protein 1 (LMP1)-mediated Jun N-terminal protein kinase activation was responsible for upregulation of CCL3 and CCL4. Inhibition of CCL3 and CCL4 in LCLs using a short hairpin RNA approach or by neutralizing antibodies suppressed cell proliferation and caused apoptosis, indicating that autocrine CCL3 and CCL4 are required for LCL survival and growth. Importantly, significant amounts of CCL3 were detected in EBV-positive plasma from immunocompromised patients, suggesting that EBV modulates this chemokine in vivo. This study reveals the regulatory mechanism and a novel function of CCL3 and CCL4 in EBV-infected B cells. CCL3 might be useful as a therapeutic target in EBV-associated lymphoproliferative diseases and malignancies.

Validation of the Chinese version OSA-18 quality of life questionnaire in Taiwanese children with obstructive sleep apnea.

BACKGROUND/PURPOSE: The OSA-18 questionnaire is one of the most widely-used sleep quality measurements in children. We tested the applicability and cross-cultural validation of the traditional Chinese version OSA-18 questionnaire. METHODS: This cross-sectional study was conducted in a tertiary medical referral center. The translation and cultural adaptation of the OSA-18 questionnaire were performed based on Brislin's revised model. A total of 109 children aged 2-18 years old with sleep problems were recruited. Overnight polysomnography and the OSA-18 questionnaire were administered. The reliability and validity of the traditional Chinese version of OSA-18 questionnaire were verified. RESULTS: Excellent test-retest reliability and good internal consistency were achieved, and the validity of OSA-18 with overnight polysomnography was confirmed. The domain of sleep disturbance, daytime function, caregiver concerns, and the OSA-18 total scores were significantly higher in sleep apnea patients. The domain of caregiver concern had the highest score, while those of emotional distress had the lowest scores. The optimal cut-off point of the OSA-18 total scores for detecting obstructive sleep apnea was 67. CONCLUSION: The traditional Chinese version of OSA-18 demonstrated high reliability and good validity in our study. The domain of caregiver concern is the major element in Taiwanese children with sleep-disordered breathing.

Management of chronic rhinosinusitis with nasal polyps in the Asia-Pacific region and Russia: Recommendations from an expert working group.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition of the nasal and paranasal tissues, characterized by the presence of bilateral nasal polyps. An expert panel of specialists from the Asian-Pacific region and Russia was convened to develop regional guidance on the management of CRSwNP through a consensus approach. The present article presents the chief observations and recommendations from this panel to provide guidance for clinicians in these areas. Etiology and pathogenetic mechanisms in CRSwNP are heterogeneous and complex. In many patients, CRSwNP is primarily driven by type 2 inflammation, although this may be less important in Asian populations. Frequent comorbidities include asthma and other inflammatory diseases such as non-steroidal anti-inflammatory drug (NSAID)/aspirin-exacerbated respiratory disease or atopic dermatitis. Clinical management of CRSwNP is challenging, and a multidisciplinary approach to evaluation and treatment is recommended. While many patients respond to medical treatment (topical irrigation and intranasal corticosteroids, and adjunctive short-term use of systemic corticosteroids), those with more severe/uncontrolled disease usually require endoscopic sinus surgery (ESS), although outcomes can be unsatisfactory, requiring revision surgery. Biological therapies targeting underlying type 2 inflammation offer additional, effective treatment options in uncontrolled disease, either as an alternative to ESS or for those patients with persistent symptoms despite ESS.

Craniofacial and olfactory sensory changes after long-term unilateral nasal obstruction-an animal study using MMP-3-LUC transgenic rats.

Nasal obstruction exerts considerable physiological effects on the respiratory system and craniofacial morphology during the developmental stage. This study used MMP-3-LUC transgenic rats for in vivo tracking of long-term expression in the rat nasal region after unilateral nasal obstruction. Skeletal changes of the craniofacial, nasal, and sinus regions were measured through micro-computed tomography examination and analysis with 3D image processing and calculation. Matrix metalloproteinase-3 and olfactory marker protein expression were also investigated through immunohistochemistry (IHC). Unilateral nasal obstruction significantly reduced the MMP-3 signal in the nasal region of MMP-3-LUC transgenic rats, which was mainly expressed in the respiratory epithelium. Long-term obstruction also caused morphological changes of the craniofacial hard tissue, such as nasal septal deviation, longer inter-jaw distance, and increased maxillary molar dental height. It also caused compensatory growth in olfactory nerve bundles and the olfactory epithelium, as confirmed by IHC. In our study, long-term unilateral nasal obstruction caused nasal septal deviation toward the unobstructed side, hyper divergent facial development including longer molar dental height, and reduced MMP-3 production. However, further investigation is necessary to explore the mechanism in depth.

Multiple instance learning for eosinophil quantification of sinonasal histopathology images: A hierarchical determination on whole slide images.

KEY POINTS: We proposed a hierarchical framework including an unsupervised candidate image selection and a weakly supervised patch image detection based on multiple instance learning (MIL) to effectively estimate eosinophil quantities in tissue samples from whole slide images. MIL is an innovative approach that can help deal with the variability in cell distribution detection and enable automated eosinophil quantification from sinonasal histopathological images with a high degree of accuracy. The study lays the foundation for further research and development in the field of automated histopathological image analysis, and validation on more extensive and diverse datasets will contribute to real-world application.

Involvement of recepteur d'origine nantais receptor tyrosine kinase in Epstein-Barr virus-associated nasopharyngeal carcinoma and its metastasis.

Nasopharyngeal carcinoma (NPC) is characteristic for its strong association with Epstein-Barr virus (EBV) and high metastatic rate. Recently, overexpressed recepteur d'origine nantais (RON) (MST1R), receptor tyrosine kinase has been reported in human cancers and tumor metastasis. Therefore, the role of RON in EBV-associated NPC and its metastasis was investigated. Here we show that RON was found in NPC but not in control tissues. A significant correlation of latent membrane protein 1 (LMP1) and RON expression was found in NPC (Pearson's χ(2) test; P = 0.0023). At the molecular level, LMP1 stimulates nuclear factor-κB binding to the RON promoter through its carboxyl-terminal activation region 1 to induce expression of RON. Knockdown of RON in cells expressing LMP1 significantly reverses LMP1-induced epithelial-mesenchymal transition and suppresses LMP1-induced cell migration and invasion. These results suggest an important role of RON in the tumorigenesis and metastasis of NPC and RON may be a novel therapeutic target for EBV-associated NPC.