Search

Background: Central compartment atopic disease (CCAD) is a recently described variant of chronic rhinosinusitis (CRS) strongly associated with atopy. The association between central compartment disease (CCD) and inhalant allergy is not well established in South-East Asia, where perennial allergic rhinitis is common. Objectives: The primary objective was to evaluate endoscopic and radiologic CCD as predictors of perennial allergen sensitization in primary CRS. The secondary objective was to compare clinical characteristics of CCAD with other CRS subtypes (CRSwNP and CRSsNP). Methods: A retrospective study of consecutive patients with primary CRS who underwent endoscopic sinus surgery at our institution was performed. Allergen sensitization was confirmed by skin or serum testing. Endoscopy records and computed tomography scans of paranasal sinuses were reviewed for CCD. The diagnostic accuracy of endoscopic and radiologic CCD in predicting atopy was calculated. Results: There were 104 patients (43 CCAD, 30 CRSwNP and 31 CRSsNP). Endoscopic CCD was significantly associated with aeroallergen sensitization (odds ratio (OR) 3.99, 95% confidence interval (CI) 1.65-9.67, P = 0.002). Endoscopic CCD predicted atopy with 57% sensitivity, 72% specificity, 69% positive predictive value and positive likelihood ratio of 2.05. Radiologic CCD was not associated with aeroallergen sensitization (OR 0.728, 95%CI 0.292-1.82, P = 0.496). There were more CCAD patients who reported hyposmia (86% vs 42%, P < 0.001) and had anosmia on olfactory testing than CRSsNP (65% vs 14%, P = 0.015). The prevalence of atopy was significantly higher in CCAD than CRSwNP and CRSsNP (70% vs 37% and 42%, P = 0.015 and P = 0.05, respectively). Median serum total immunoglobulin E was higher in CCAD (283 IU/ml) and CRSwNP (127 IU/ml) than CRSsNP (27 IU/ml, P = 0.006 and P = 0.042, respectively). Conclusions: Endoscopic CCD was a better predictor of inhalant allergy than radiologic CCD in primary CRS, in a locale of perennial allergic rhinitis. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the outcomes of parent artery occlusion (PAO) versus stent‐assisted reconstruction in radiated nasopharyngeal carcinoma (NPC) patients with internal carotid artery (ICA) blowouts. A retrospective review from our institution (2011–2021) and systematic review of Pubmed and Embase (1995–2022) was performed. Twenty‐eight eligible studies were identified. Eighty‐six PAOs and 37 stent‐assisted reconstructions were analyzed, including 11 PAOs and 5 stents from our institution. Stents were associated with significantly higher incidence of overall re‐bleeding (16.2% [95% CI 7.4–31.9] vs. 4.6% [95% CI 1.3–13.5], p = 0.047), delayed stroke (5.4% [95% CI 1.3–19.4] vs. 0%, p = 0.034) and reduced median survival (7.1 [95% CI 3.8–14.0] months vs. 29.0 [95% CI 9.4–63.4] months, p = 0.017) compared to PAO. There were no significant differences in terms of overall stroke, infection, extruded/migrated foreign body, and peri‐procedure death. PAO is preferred over reconstructive treatment in patients with adequate collateral circulation. [ABSTRACT FROM AUTHOR]

Background: Human rhinoviruses (HRVs) are frequently associated with asthma exacerbations, and have been found in the airways of asthmatic patients. While HRV‐induced acute infection is well‐documented, it is less clear whether the nasal epithelium sustains prolonged HRV infections along with the associated activation of host immune responses. Objective: To investigate sustainably regulated host responses of human nasal epithelial cells (hNECs) during HRV persistence. Methods: Using a time‐course study, HRV16 persistence and viral replication dynamics were established using an in vitro infection model of hNECs. RNA sequencing was performed on hNECs in the early and late stages of infection at 3 and 14 days post‐infection (dpi), respectively. The functional enrichment of differentially expressed genes (DEGs) was evaluated using gene ontology (GO) and Ingenuity pathway analysis. Results: HRV RNA and protein expression persisted throughout prolonged infections, even after decreased production of infectious virus progeny. GO analysis of unique DEGs indicated altered regulation of pathways related to ciliary function and airway remodeling at 3 dpi and serine‐type endopeptidase activity at 14 dpi. The functional enrichment of shared DEGs between the two time‐points was related to interferon (IFN) and cytoplasmic pattern recognition receptor (PRR) signaling pathways. Validation of the sustained regulation of candidate genes confirmed the persistent expression of RIG‐I and revealed its close co‐regulation with interferon‐stimulated genes (ISGs) during HRV persistence. Conclusions: The persistence of HRV RNA does not necessarily indicate an active infection during prolonged infection. The sustained expression of RIG‐I and ISGs in response to viral RNA persistence highlights the importance of assessing how immune‐activating host factors can change during active HRV infection and the immune regulation that persists thereafter. [ABSTRACT FROM AUTHOR]

Background: The primary objective is to identify clinical predictors of internal carotid artery (ICA) blowout in radiated nasopharyngeal carcinoma (NPC). Methods: Seventeen ICA blowouts, 14 external carotid artery (ECA) bleeds, and 60 controls were identified from January 1, 2007 to July 31, 2020. Multinomial logistic regression was performed to identify features predictive of ICA blowouts. Results: Headache was significantly more common among ICA blowouts than ECA bleeds and controls (58.8% vs. 7.1% vs. 6.7%, p < 0.001). The petrous skull base and sphenoid sinus lateral wall was eroded in all petrous and cavernous segment blowouts, respectively. Nasoendoscopy showing exposed clivus (OR 20.5, 95%CI 1.3–324.2) and computed tomography demonstrating skull base erosion (OR 17.8, 95%CI 1.0–311.0) were significantly associated with ICA blowouts compared to controls. Conclusions: Findings of headache and skull base erosion on nasoendoscopy or imaging during NPC surveillance warrants prophylactic intervention to avoid an ICA blowout. [ABSTRACT FROM AUTHOR]

Background: Epithelial cytokines including IL-25, IL-33 and thymic stromal lymphopoietin (TLSP) are recently established as drivers of type 2 chronic inflammatory diseases such as chronic rhinosinusitis with nasal polyps (CRSwNP). Here, we further confirmed the increased expression of IL-25 in CRSwNP and investigated potential contributors of IL-25 in CRSwNP epithelium. Methods: Sixty CRSwNP, 25 CRSsNP and 15 healthy control tissues were examined for IL-25 expression and for the accompanying type 2 inflammatory cytokines. We then tested different respiratory virus infections on human nasal epithelial cells (hNECs) for their ability to trigger IL-25 expression. In addition, we subjected hNECs generated from CRSwNP tissues to pretreatment with recombinant interferon-alpha (IFN-α) prior to viral infection to evaluate IFN effects on IL-25 induction. Results: We confirmed that significantly enhanced levels of IL-25 were observed in CRSwNP tissues, and that IL-25 expression correlated with type 2 inflammatory cytokine expression. In vitro, we observed significantly elevated IL-25 in hNECs infected with influenza A virus as early as 24 hours post-infection (hpi), regardless of tissue origin, and IL-25 correlated positively with viral load. While other respiratory viruses exhibited increasing trends of IL-25, these were not significant at the time-points tested. IFN-α treatment of CRSwNP epithelium was found to exert bimodal effects, ie IFN-α treatment alone induced moderate IL-25 expression, whereas IFN-α pretreatment of hNECs before influenza infection significantly diminished IL-25 induction by active influenza virus infection. Conclusion: We have authenticated the observation of elevated IL-25 in CRSwNP, which is correlated with type 2 inflammatory cytokines. Notably, we identified influenza virus infection as a potential contributor of IL-25 in both control and CRSwNP epithelium during active infection. This IL-25 induction can be abated by IFN-α pretreatment which ameliorated active influenza infection. Trial Registration: Chictr.org.cn ChiCTR-BON-16010179, Registered 18 December 2016, http://www.chictr.org.cn/showproj.aspx?proj=17331. The authors agree on the sharing of deidentified participant data where it pertains to request directly related to the data in this article when contacted (Haiyu Hong; [email protected]). [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To describe the magnetic resonance imaging (MRI) characteristics of the pericranial flap, changes in the pericranial flap thickness over time, presence of frontal sinus opacification, and presence of frontal lobe herniation into the nasal cavity.Study Design: Retrospective case series.Methods: Seventeen consecutive endoscopic craniofacial resections with pericranial flap reconstruction performed at a tertiary hospital from 2010 to 2019 were reviewed. Sixty-eight serial MRI scans were evaluated.Results: All pericranial flaps consistently featured a homogenous appearance on T1-weighted sequence and enhanced with contrast. On T2-weighted sequence, the skull base reconstruction demonstrated four layers of alternating hypo- and hyperintensity, which corresponded with the inlay synthetic graft or neodura (hypointense), loose areolar tissue (hyperintense), fibrous pericranium (hypointense), and nasal mucosa or granulation tissue (hyperintense). The mean pericranial flap thickness was 9.9 mm. In thicker flaps, the loose areolar layer contributed the bulk of the thickness. Of 13 patients who underwent three or more serial MRI scans, 11 flaps (84.6%) were stable and two (15.4%) had >50% reduction in their original thickness over time. Thirteen of 17 (76.5%) patients had frontal sinus opacification on follow-up. None developed frontal sinus mucoceles or frontal lobe herniation.Conclusions: The pericranial flap has a distinctive MRI appearance, especially on T2-weighted sequence. The thickness of the flap remains relatively stable over time for most patients even following radiotherapy. It is a sturdy flap that is able to support the frontal lobe. Frontal sinus obstruction is common, although complications from this appear to be rare.Level Of Evidence: 4 Laryngoscope, 131:E90-E97, 2021. [ABSTRACT FROM AUTHOR]

The novel coronavirus SARS-CoV-2 is the causative agent of Coronavirus Disease 2019 (COVID-19), a global healthcare and economic catastrophe. Understanding of the host immune response to SARS-CoV-2 is still in its infancy. A 382-nt deletion strain lacking ORF8 (Δ382 herein) was isolated in Singapore in March 2020. Infection with Δ382 was associated with less severe disease in patients, compared to infection with wild-type SARS-CoV-2. Here, we established Nasal Epithelial cells (NECs) differentiated from healthy nasal-tissue derived stem cells as a suitable model for the ex-vivo study of SARS-CoV-2 mediated pathogenesis. Infection of NECs with either SARS-CoV-2 or Δ382 resulted in virus particles released exclusively from the apical side, with similar replication kinetics. Screening of a panel of 49 cytokines for basolateral secretion from infected NECs identified CXCL10 as the only cytokine significantly induced upon infection, at comparable levels in both wild-type and Δ382 infected cells. Transcriptome analysis revealed the temporal up-regulation of distinct gene subsets during infection, with anti-viral signaling pathways only detected at late time-points (72 hours post-infection, hpi). This immune response to SARS-CoV-2 was significantly attenuated when compared to infection with an influenza strain, H3N2, which elicited an inflammatory response within 8 hpi, and a greater magnitude of anti-viral gene up-regulation at late time-points. Remarkably, Δ382 induced a host transcriptional response nearly identical to that of wild-type SARS-CoV-2 at every post-infection time-point examined. In accordance with previous results, Δ382 infected cells showed an absence of transcripts mapping to ORF8, and conserved expression of other SARS-CoV-2 genes. Our findings shed light on the airway epithelial response to SARS-CoV-2 infection, and demonstrate a non-essential role for ORF8 in modulating host gene expression and cytokine production from infected cells. Author summary: Airway epithelial cells are one of the earliest cell types infected in COVID-19 patients. We show that differentiated NECs are a suitable model for studying the dynamics of SARS-CoV-2 infection in vitro, and that the immune response from infected NECs is surprisingly limited. This limited early response to SARS-CoV-2 infection could impair viral clearance, and prolong the duration of infection. This further implies that infiltrating immune cells are the likely source of pro-inflammatory cytokines such as IL-6 and TNFα reported to be elevated in patient sera later during infection. CXCL10 production could represent a major therapeutic node for limiting immune cell infiltration and subsequent cytokine production. The similarities in host-response between SARS-CoV-2 and Δ382 infection in-vitro highlight the plasticity of CoV genomes, and implicate a post-translational (and not a transcriptional) role for ORF8 in modulating the host-response. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study are to describe the levator veli palatini (LVP) as a landmark for the parapharyngeal internal carotid artery (pICA) and the endoscopic course of the pICA. Methods: Cadaver dissection and illustrative case study. Results: Seven cadaveric heads (12 sides) were dissected. In all 12 sides, the LVP was consistently located between the Eustachian tube and the pICA near the skull base, making the LVP just anterior to and the closest structure to the pICA. The distance between the pICA and the nares ranged from 9.0 to 12.7 cm. The distance between the pICA and the midpoint of the nasopharynx ranged from 1.9 to 3.7 cm. The case study illustrated the applicability of these findings. Conclusion: The LVP is a reliable and precise landmark for the pICA. A safe working distance to the pICA is 1.9 cm from the midpoint of the nasopharynx and 9.0 cm from the nares. [ABSTRACT FROM AUTHOR]

Our understanding of the pathophysiology of chronic rhinosinusitis (CRS) is continuously evolving. The traditional description of CRS in terms of two phenotypes based on the presence or absence of nasal polyps belies the underlying intricate immunopathophysiological processes responsible for this condition. CRS is being increasingly recognized as a disease spectrum encompassing a range of inflammatory states in the sinonasal cavity, with non‐type 2 inflammatory disease on one end, type 2 inflammatory, eosinophil‐heavy disease on the other and an overlap of both in different proportions in between. Abundance in research on the immune mechanisms of CRS has revealed various new endotypes that hold promise as biomarkers for the development of targeted therapies in severe, uncontrolled CRS. The introduction of precision medicine to manage this chronic, complex condition is a step forward in providing individualized care for all patients with CRS. In this review, the latest research on the pathophysiology of CRS with a focus on potential novel biomarkers and treatment options over the last 2 years are summarized and integrated into a suggested model of precision medicine in CRS. [ABSTRACT FROM AUTHOR]

We report a case of a 2-year-old female who presented with bilateral progressive proptosis, visual loss, nasal obstruction, and breathing difficulty. Magnetic resonance imaging revealed a large sino-orbital mass that was extending to the orbital apex and skull base. An initial diagnosis of rhabdomyosarcoma was made elsewhere on the basis of the presence of round and spindle cell tumor. Subsequent biopsy with immunohistochemical staining was positive for nuclear staining with β-catenin, shifting the diagnosis to a myofibroblastic tumor, favoring desmoid-type fibromatosis. With image guidance, near complete excision of tumor was performed by a multidisciplinary team, while respecting danger zones such as the skull base and the optic nerve. Following a recurrence over 2 months, additional excision was performed with a 6-month treatment of methotrexate and vinblastine. Desmoid tumor is a rare form of soft tissue tumor uncommonly seen in the orbital area. Although benign, it is known to be recurrent and infiltrative. Few data are known and further information will aid in the management of these tumors. [ABSTRACT FROM AUTHOR]

Background: Nasal polyp (NP) is a chronic upper airway inflammatory disease that is frequently triggered by defective host-defense. However, the mechanisms underlying the impaired barrier function such as cilia-mediated mucociliary clearance remain poorly understood. Objective: To assess ciliary ultrastructural and ciliogenesis marker expression and the phenotypes of ciliated cells in NP. Methods: NP biopsy samples were obtained from 97 NP patients and inferior turbinate from 32 healthy controls. Immunofluorescence staining, quantitative polymerase chain reaction, and single-cell cytospin staining were performed. We classified the patterns of radial spoke head protein (RSPH) 1, 4A (RSPH4A), 9 (RSPH9), and dynein axonemal heavy chain 5 (DNAH5) localization. A semi-quantitative scoring system was developed to assess their expression patterns and associations with ciliogenesis markers [centrosomal protein 110 (CP110) and forkhead box j1 (FOXJ1)]. Results: Median scores of RSPH1 , RSPH4A , RSPH9, and DNAH5 were significantly higher in NP than in healthy controls, particularly in eosinophilic NPs. Expression pattern scores of RSPH1 , RSPH4A , RSPH9, and DNAH5 correlated positively with each other in both groups. In primary-cell specimens, abnormal expression patterns were significantly more common in NP. The total fluorescence intensity of CP110 and FOXJ1 was significantly higher in NPs and correlated positively with expression pattern scores of RSPH1 , RSPH4A , RSPH9, and DNAH5. A trend towards lengthened cilia was observed in NP. Conclusion: In the chronic airway inflammatory milieu, the up-regulated ciliogenesis correlates with the abnormal expression of ciliary ultrastructural markers (i.e., DNAH5) in NP (particularly eosinophilic NP). [ABSTRACT FROM AUTHOR]

Background: Forkhead box J1 (FOXJ1) plays pivotal roles in motile cilia formation. However, it remains unclear whether abnormal expression or localization of FOXJ1 in nasal mucosa tissues is associated with allergic rhinitis (AR), in which impaired mucociliary clearance is implicated. Objective: We sought to investigate the expression and localization of FOXJ1 in inferior turbinate from patients with AR and controls. Methods: We assayed mRNA levels of FOXJ1, DNAI1, DNALI1, and DNAH9 by using whole-genome expression array and quantitative real-time polymerase chain reaction. We elucidated the localization of FOXJ1 by using immunofluorescence assays in paraffin sections and primary single cells. Four patterns of FOXJ1 localization (normal, N; intermediate, I; mislocalization, M; absence, A) were defined. We developed a semiquantitative scoring system to elucidate their localization in 5 areas per paraffin section, with individual sections being assigned a score between 0 and 2. Results: The mRNA levels of FOXJ1, DNAI1, DNALI1, and DNAH9 were significantly reduced in patients with AR compared with controls (all p < 0.05). The median (1st and 3rd quartile) of the FOXJ1 score was 0.4 (0.0 and 0.85) in patients with AR, and 0.2 (0.0 and 0.4) in controls (p < 0.05). For primary cytospin samples, the mean percentages of FOXJ1 localization patterns N, I, M, and A were 46.7, 10.0, 30.0, and 26.7% in patients with AR, and 82.5, 5.0, 5.0, and 7.5% in controls, respectively (p < 0.05). Conclusion: Downregulation and aberrant localization of FOXJ1 may be crucial characteristics of the allergic nasal mucosa. [ABSTRACT FROM AUTHOR]

Human rhinoviruses (HRVs) are the commonest cause of the common cold. While HRV is less pathogenic than other respiratory viruses, it is frequently associated with exacerbation of chronic respiratory diseases such as rhinosinusitis and asthma. Nasal epithelial cells are the first sites of viral contact, immune initiation, and airway interconnectivity, but there are limited studies on HRV infection of nasal epithelial cells. Hence, we established a model of HRV infection of in vitro-differentiated human nasal epithelial cells (hNECs) derived from multiple individuals. Through HRV infection of hNECs, we found that HRV mainly targeted ciliated cells and preferentially induced type I and III interferon antiviral pathways. Quantitative polymerase chain reaction analysis of inflammatory genes suggested predominant type 1 immunity signaling and recruitment, with secreted CXCL9, IP-10, CXCL11, and RANTES as likely initiators of airway inflammatory responses. Additionally, we further explored HRV bidirectional release from the hNECs and identified 11 associated genes. Other HRV interactions were also identified through a systematic comparison with influenza A virus infection of hNECs. Overall, this in vitro hNEC HRV infection model provides a platform for repeatable and controlled studies of different individuals, thus providing novel insights into the roles of human nasal epithelium in HRV interaction and immune initiation. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to determine the prognostic value of relapse status (recurrent vs residual disease) in patients receiving surgical salvage for nasopharyngeal carcinoma (NPC). Methods Retrospective review was conducted on 52 patients who underwent salvage surgery for locoregional relapse of NPC. Univariate and multivariate analyses were used to investigate the prognostic value of relapse status. Results Median follow-up duration was 44.4 months. Mean overall survival (OS) and disease-free survival (DFS) for patients with NPC with residual and recurrent disease after surgical salvage were 107.4 and 54.4 months, and 83.6 and 34.6 months, respectively ( p < .001). This improved survival was demonstrated regardless whether the relapse was at the primary or nodal site. Multivariate analysis revealed that recurrent disease status and nodal disease relapse were independent poor prognostic factors for survival in patients receiving salvage surgery for NPC. Conclusion In patients undergoing surgical salvage for NPC relapse, residual disease carries a better prognosis than recurrent disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1393-1400, 2016 [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal cancer (NPC) is endemic among Chinese populations in Southeast Asia. However, the outcomes of non-Chinese NPC patients in Singapore are not well reported. Aim: To determine if non-Chinese NPC patients have a different prognosis and examine the clinical outcomes of NPC patients in a multi-ethnic society. Methods: Retrospective chart review of 558 NPC patients treated at a single academic tertiary hospital from 2002 to 2012. Survival and recurrence rates were analysed and predictive factors identified using the Kaplan-Meier method and Cox regression model. Results: Our cohort comprised 409 males (73.3%) and 149 females (26.7%) with a median age of 52 years. There were 476 Chinese (85.3%), 57 Malays (10.2%), and 25 of other ethnic groups (4.5%). Non-Chinese patients were more likely to be associated with advanced nodal disease at initial presentation (p = 0.049), compared with the Chinese. However, there were no statistical differences in their overall survival (OS) or disease specific survival (DSS) (p = 0.934 and p = 0.857 respectively). The 3-year and 5-year cohort OS and DSS rates were 79.3%, 70.7%, and 83.2%, 77.4% respectively. Advanced age (p<0.001), N2 disease (p = 0.036), N3 disease (p<0.001), and metastatic disease (p<0.001) at presentation were independently associated with poor overall survival. N2 disease (p = 0.032), N3 disease (p<0.001) and metastatic disease (p<0.001) were also independently associated with poor DSS. No predictive factors were associated with loco-regional recurrence after definitive treatment. Advanced age (p = 0.044), N2 disease (p = 0.033) and N3 disease (p<0.001) were independently associated with distant relapse. Conclusion: In a multi-ethnic society in Singapore, non-Chinese are more likely to present with advanced nodal disease. This however did not translate into poorer survival outcomes. Older patients with N2 or N3 disease are associated with a higher risk of distant relapse and poor overall survival. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The operative management of infratemporal skull base lesions is challenging. Expanded endonasal approaches to this area can decrease surgical morbidity. Access lateral to the natural nasal corridor can be achieved via a middle meatal antrostomy, medial maxillectomy complemented by a septotomy, or anteromedial maxillotomy (i.e., Denker's approach). We sought to compare the access to the infratemporal fossa offered by these endoscopic endonasal approaches. Study Design: Software-enabled CT scan measurements. Methods: Axial CT scans obtained with submillimeter cuts through the skull base were examined. All calculations were performed on axial images obtained at the level of the sphenoid floor using Kodak Carestream Image Software (Rochester, NY) measuring tools. Results: Fifty sides were examined. A medial maxillectomy increased the exposure on average by 18.5 degrees (SD = 4.28), when compared to maxillary antrostomy. When we augmented the access with an ipsilateral Denker's approach, an additional 33.5 degrees (SD = 4.81) of exposure were obtained ( P < .0001). The addition of a 1-cm anteromedial maxillotomy accessed the entire posterior maxillary wall in 54% of cases. Equivalent access was obtained via a contralateral approach with a septotomy at 1.56 cm from the columella. To access the entire posterior maxillary wall the average anterior maxillotomy should be 1.1 cm (SD = 0.42). In contrast, to access the entire posterior maxillary wall using a contralateral approach the average septotomy position should be 1.52 cm (SD = 0.39) from the columella. Conclusions: This radioanatomic study provides objective support for the use of an ipsilateral Denker's approach to augment an endoscopic endonasal approach to the infratemporal fossa. [ABSTRACT FROM AUTHOR]

The human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies. Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways. Here, we elucidated the global transcriptomic changes during H3N2 infection of human nasal epithelial cells from multiple individuals. Using RNA sequencing, we characterized the differentially-expressed genes and pathways associated with changes occurring at the nasal epithelium following infection. We used in vitro differentiated human nasal epithelial cell culture model derived from seven different donors who had no concurrent history of viral infections. Statistical analysis highlighted strong transcriptomic signatures significantly associated with 24 and 48 h after infection, but not at the earlier 8-h time point. In particular, we found that the influenza infection induced in the nasal epithelium early and altered responses in interferon gamma signaling, B-cell signaling, apoptosis, necrosis, smooth muscle proliferation, and metabolic alterations. These molecular events initiated at the infected nasal epithelium may potentially adversely impact the airway, and thus the genes we identified could serve as potential diagnostic biomarkers or therapeutic targets for influenza infection and associated disease management. [ABSTRACT FROM AUTHOR]

Abstract Tight junctions (TJs) alteration is commonly seen in airway inflammatory diseases. Oncostatin M (OSM) is an inflammatory mediator associated with chronic rhinosinusitis with nasal polyps (CRSwNP). We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for influenza A virus (IAV). However, its role in TJs alteration and the effects of IAV on inducing OSM expression in nasal epithelium remains to be further investigated. In this study, OSM and TJs expression was measured and compared between inferior turbinate from healthy controls and nasal polyps from CRSwNP. Additionally, hNECs cultured at air-liquid interface (ALI) were infected with H3N2 influenza virus to study the role of influenza virus in inducing epithelial OSM expression as a possible means of exacerbation. The expression of ZO-1, claudin-1, and occludin was markedly decreased and correlated negatively with that of OSM in CRSwNP. By using the in vitro hNEC model, H3N2 infection resulted in significantly increased OSM expression (2.2-, 4.7- and 3.9-fold higher at 8, 24, and 48 h post-infection vs. mock infection). Furthermore, OSM is found to co-localize with ciliated and goblet cells in hNECs infected with H3N2 influenza virus. Our findings demonstrated that increased OSM expression is implicated in CRSwNP as a possible mechanism of TJs’ impairment, which can be further augmented following influenza infection via epithelial OSM expression, possibly contributing to exacerbations. [ABSTRACT FROM AUTHOR]

Background: SWI/SNF complex-deficient sinonasal carcinomas are rare, genetically distinct, and aggressive entities., Methods: SMARCB1 and SMARCA4 immunohistochemistry was retrospectively performed on a cohort of undifferentiated, poorly differentiated, and poorly defined sinonasal carcinomas. Survival outcomes were compared between SMARCB1/SMARCA4 (SWI/SNF complex)-deficient and -retained groups., Results: Eight SWI/SNF complex-deficient (six SMARCB1-deficient, two SMARCA4-deficient) cases were identified among 47 patients over 12 years. Triple-modality treatment was more frequently utilized in SWI/SNF complex-deficient carcinomas than in SWI/SNF complex-retained carcinomas (71.4% vs. 11.8%, p = 0.001). After a median follow-up of 21.3 (IQR 9.9-56.0) months, SWI/SNF complex-deficient sinonasal carcinomas showed comparable recurrence rates (57.1% vs. 52.9%, p = 0.839), time-to-recurrence (7.3 [IQR 6.6-8.3] vs. 9.1 [IQR 3.9-17.4] months, p = 0.531), and overall survival (17.7 [IQR 11.8-67.0] vs. 21.6 [IQR 8.9-56.0] months, p = 0.835) compared to SWI/SNF complex-retained sinonasal carcinomas., Conclusion: Triple-modality treatment may improve survival in SWI/SNF complex-deficient sinonasal carcinomas., (© 2024 Wiley Periodicals LLC.)

The dynamics of SARS-CoV-2 infection in COVID-19 patients are highly variable, with a subset of patients demonstrating prolonged virus shedding, which poses a significant challenge for disease management and transmission control. In this study, the long-term dynamics of SARS-CoV-2 infection were investigated using a human well-differentiated nasal epithelial cell (NEC) model of infection. NECs were observed to release SARS-CoV-2 virus onto the apical surface for up to 28 days postinfection (dpi), further corroborated by viral antigen staining. Single-cell transcriptome sequencing (sc-seq) was utilized to explore the host response from infected NECs after short-term (3-dpi) and long-term (28-dpi) infection. We identified a unique population of cells harboring high viral loads present at both 3 and 28 dpi, characterized by expression of cell stress-related genes DDIT3 and ATF3 and enriched for genes involved in tumor necrosis factor alpha (TNF-α) signaling and apoptosis. Remarkably, this sc-seq analysis revealed an antiviral gene signature within all NEC cell types even at 28 dpi. We demonstrate increased replication of basal cells, absence of widespread cell death within the epithelial monolayer, and the ability of SARS-CoV-2 to replicate despite a continuous interferon response as factors likely contributing to SARS-CoV-2 persistence. This study provides a model system for development of therapeutics aimed at improving viral clearance in immunocompromised patients and implies a crucial role for immune cells in mediating viral clearance from infected epithelia. IMPORTANCE Increasing medical attention has been drawn to the persistence of symptoms (long-COVID syndrome) or live virus shedding from subsets of COVID-19 patients weeks to months after the initial onset of symptoms. In vitro approaches to model viral or symptom persistence are needed to fully dissect the complex and likely varied mechanisms underlying these clinical observations. We show that in vitro differentiated human NECs are persistently infected with SARS-CoV-2 for up to 28 dpi. This viral replication occurred despite the presence of an antiviral gene signature across all NEC cell types even at 28 dpi. This indicates that epithelial cell intrinsic antiviral responses are insufficient for the clearance of SARS-CoV-2, implying an essential role for tissue-resident and infiltrating immune cells for eventual viral clearance from infected airway tissue in COVID-19 patients.

Chronic rhinosinusitis (CRS) is a clinical syndrome stemming from persistent inflammation of the sinonasal mucosa. Phenotypically, it is traditionally and widely described according to the presence or absence of polyps. While this distinction is simple to use, it has little bearing on prognosis and treatment, for CRS is essentially an inflammatory disease resulting from dysregulated interaction between a multitude of host and environmental factors. Allergy is merely one of them and, like many of the proposed aetiologies, has been subject to much debate which will be discussed here. As our understanding of CRS continues to evolve, previous so-called conventional wisdom about phenotypes (e.g. CRS with nasal polyps is associated with Type 2 inflammation) is being challenged, and new phenotypes are also emerging. In addition, there is growing interest in defining the endotypes of CRS to deliver precise and personalised treatment, especially pertaining to the development of biologics for the group of severe, difficult-to-treat CRS patients. A proposed model of precision medicine tailored to management of CRS will also be introduced to readers, which can be continually modified to adapt to new discoveries about this exciting condition., (© 2021. Springer Nature Switzerland AG.)

The early interactions between the nasal epithelial layer and the innate immune cells during viral infections remains an under-explored area. The significance of innate immunity signaling in viral infections has increased substantially as patients with respiratory infections who exhibit high innate T cell activation show a better disease outcome. Hence, dissecting these early innate immune interactions allows the elucidation of the processes that govern them and may facilitate the development of potential therapeutic targets and strategies for dampening or even preventing early progression of viral infections. This protocol details a versatile model that can be used to study early crosstalk, interactions, and activation of innate immune cells from factors secreted by virally infected airway epithelial cells. Using an H3N2 influenza virus (A/Aichi/2/1968) as the representative virus model, innate cell activation of co-cultured peripheral blood mononuclear cells (PBMCs) has been analyzed using flow cytometry to investigate the subsets of cells that are activated by the soluble factors released from the epithelium in response to the viral infection. The results demonstrate the gating strategy for differentiating the subsets of cells and reveal the clear differences between the activated populations of PBMCs and their crosstalk with the control and infected epithelium. The activated subsets can then be further analyzed to determine their functions as well as molecular changes specific to the cells. Findings from such a crosstalk investigation may uncover factors that are important for the activation of vital innate cell populations, which are beneficial in controlling and suppressing the progression of viral infection. Furthermore, these factors can be universally applied to different viral diseases, especially to newly emerging viruses, to dampen the impact of such viruses when they first circulate in naïve human populations.

Background: Respiratory viral infections are one of the main drivers of development and exacerbation for chronic airway inflammatory diseases. Increased viral susceptibility and impaired mucociliary clearance are often associated with chronic airway inflammatory diseases and served as risk factors of exacerbations. However, the links between viral susceptibility, viral clearance, and impaired mucociliary functions are unclear. Therefore, the objective of this study is to provide the insights into the effects of improper clearance of respiratory viruses from the epithelium following infection, and their resulting persistent activation of antiviral response, on mucociliary functions., Methods: In order to investigate the effects of persistent antiviral responses triggered by viral components from improper clearance on cilia formation and function, we established an in vitro air-liquid interface (ALI) culture of human nasal epithelial cells (hNECs) and used Poly(I:C) as a surrogate of viral components to simulate their effects toward re-epithelization and mucociliary functions of the nasal epithelium following damages from a viral infection., Results: Through previous and current viral infection expression data, we found that respiratory viral infection of hNECs downregulated motile cilia gene expression. We then further tested the effects of antiviral response activation on the differentiation of hNECs using Poly(I:C) stimulation on differentiating human nasal epithelial stem/progenitor cells (hNESPCs). Using this model, we observed reduced ciliated cell differentiation compared to goblet cells, reduced protein and mRNA in ciliogenesis-associated markers, and increased mis-assembly and mis-localization of ciliary protein DNAH5 following treatment with 25 μg/ml Poly(I:C) in differentiating hNECs. Additionally, the cilia length and ciliary beat frequency (CBF) were also decreased, which suggest impairment of ciliary function as well., Conclusion: Our results suggest that the impairments of ciliogenesis and ciliary function in hNECs may be triggered by specific expression of host antiviral response genes during re-epithelization of the nasal epithelium following viral infection. This event may in turn drive the development and exacerbation of chronic airway inflammatory diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Chen, Tan, Liu, Ong, Zhou, Huang, Chen, Ong, Thong, Chow, Qiu and Wang.)

Allergic rhinitis (AR) is prevalent in Singapore, with a significant disease burden. Afflicting up to 13% of the population, AR impairs quality of life, leads to reduced work productivity and is an independent risk factor for asthma. In the last 2 decades, local studies have identified patient and physician behaviours leading to suboptimal control of the disease. Yet, there is an overall lack of attention to address this important health issue. Allergic Rhinitis and its Impact on Asthma (ARIA) is a European organisation aimed at implementing evidence-based management for AR worldwide. Recent focus in Europe has been directed towards empowering patients for self-management, exploring the complementary role of mobile health, and establishing healthcare system-based integrated care pathways. Consolidation of these ongoing efforts has led to the release of the 2019 ARIA care pathways. This review summarises the ARIA update with particular emphasis on the current status of adult AR in Singapore. In addition, we identify unmet needs and future opportunities for research and clinical care of AR in the local context.

The pericranial flap is a well-vascularized, robust flap that is used to reconstruct anterior skull base defects following resection of skull base tumors. Failure of this flap is uncommon. However when it occurs, the consequences are potentially disastrous and it poses a challenge to further reconstruction. The authors report the first patient of onlay pericranial flap breakdown following endoscopic craniofacial resection. Possible contributing factors are identified and further management is discussed. With the endoscopic approach being increasingly utilized for craniofacial resection, it is imperative to be mindful of these factors to minimize the risks of onlay pericranial flap failure.

Nasopharyngeal mucoepidermoid carcinoma is a rare entity, for which surgical resection is the treatment of choice. The open technique is considered the standard approach, but this often results in significant morbidities such as trismus, dysphagia, and neurologic deficits. The advent of endoscopic endonasal techniques has made endoscopic resection a viable alternative to the open approach in terms of access, adequacy of resection, and lesser surgical morbidity. The authors describe a patient of recurrent nasopharyngeal mucoepidermoid carcinoma that was resected entirely endoscopically. The authors also present a literature review of this little-known disease and a comparison between the endoscopic and open approach.

Background: Nasopharyngeal carcinoma (NPC) patients have a 19%-56% locoregional recurrence rate after primary therapy. For those recurrent NPC (rNPC) patients, re-irradiation may cause some complications. In recent years, endoscopic endonasal nasopharyngectomy (EEN) has become a surgical option for rNPC patients. Here we introduce the concept of en bloc excision (EBE) technique for EEN, including the surgical technique and clinical outcomes., Methods: A retrospective study was conducted covering September 2009 to May 2013, involving the collection of locoregional rNPC cases from two institutions (Kuang-Tien General Hospital (KTGH) in Taiwan and National University Health System (NUHS) in Singapore). These patients failed prior therapy and then underwent EEN. We reported the 2-year overall survival rate, the 2-year disease-free survival rate, and related complications., Results: Nine patients (five from KTGH and four from NUHS) completed this study, with five, two, and two patients of recurrence tumors (rT1), rT2, and rT3, respectively. The mean age was 46.4 years (range 32-63); the mean follow-up period was 24.9 months (range 10-45). The 2-year survival rate and the 2-year disease-free rate were 100% and 80%, respectively, in five patients. No significant complications or cases of mortality occurred., Conclusions: The EBE concept of EEN is suitable for early rT1 and has relatively encouraging short-term outcomes. In selected rT2, careful EBE can be performed by expanding the surgical field. A clear view of the internal carotid artery-related anatomy is indispensable. In the future, more series may be needed to determine the role of EEN in rNPC patients.

Local recurrence after primary radiation of nasopharyngeal carcinoma (NPC) remains an important cause of morbidity and mortality. Salvage treatment using reirradiation or surgery has been shown to improve survival over nontreatment. Surgery is traditionally performed using an open approach. Advances in endoscopic approaches for resection of paranasal sinus tumors have been extended to NPC. This article reviews the treatment options, in particular the role of endoscopic nasopharyngectomy in the management of recurrent NPC. The endoscopic anatomy, surgical principles, and published results on endoscopic nasopharyngectomy are presented. Short-term outcomes for early-stage recurrences are promising but long-term follow-up is needed., (Copyright © 2011. Published by Elsevier Inc.)

In the past 2 decades, endoscopic sinus surgery has been widely used as a safe and effective treatment for disorders of the paranasal sinuses that are refractory to medical therapy. Advances in surgical technique, including powered instrumentation and stereotactic image-guided surgery, have improved the efficiency and safety of this procedure. These techniques have been further expanded to manage skull base pathologies. This expansion has been facilitated by a better understanding of the endonasal skull base anatomy. Despite these advances, complications are still encountered. Vascular injuries are particularly troublesome. Interior ethmoid artery injuries during sinus surgery that led to orbital hematoma were discussed extensively in a recent issue of this journal. Therefore, this article focuses mainly on inadvertent carotid artery injuries during routine sinus surgery and vascular injuries during endoscopic skull base surgery.

Tumours affecting the nose, paranasal sinuses and adjacent skull base are fortunately rare. However, they pose significant problems of management due their late presentation and juxtaposition to important anatomical structures such eye and brain. The increasing application of endonasal endoscopic techniques to their excision offers potentially similar scales of resection but with reduced morbidity. The present document is intended to be a state-of-the art review for any specialist with an interest in this area 1. to update their knowledge of neoplasia affecting the nose, paranasal sinuses and adjacent skull base; 2. to provide an evidence-based review of the diagnostic methods; 3. to provide an evidence-based review of endoscopic techniques in the context of other available treatments; 4. to propose algorithms for the management of the disease; 5. to propose guidance for outcome measurements for research and encourage prospective collection of data. The importance of a multidisciplinary approach, adherence to oncologic principles with intent to cure and need for long-term follow-up is emphasised.

Purpose of Review: Technological advances and technical innovations have spearheaded an expansion in the indications for endoscopic sinonasal surgery, which now extend to the resection of sinonasal and skull base malignancies. This review examines recent advances that have contributed to make this technique feasible and reviews the basis of adopting an endonasal approach., Recent Findings: Oncologic goals developed for traditional skull base surgery can be safely applied to endoscopic skull base surgery. This has been made possible with the advent of better understanding of skull base anatomy from the endonasal perspective, as well as the development of better instrumentation, better hemostatic materials and more reliable reconstructive techniques. Recent publications have reported similar short-term outcomes for endoscopic skull base resection as compared with traditional approaches with lower complication rates., Summary: Transnasal endoscopic surgery is an important part of the surgical armamentarium for the treatment of sinonasal and skull base malignancies. New technologies will further expand the limits of what can be achieved endoscopically. Collaborative multiinstitutional studies with long-term follow-up are crucial in defining the role of endoscopic resection in the treatment of skull base malignancies.

Purpose of Review: Endoscopic skull base surgery has significantly revolutionized the management of skull base disease. Our review focuses on the recent literature relating to endoscopic skull base surgery emphasizing its limitations., Recent Findings: Current literature continues to expand the indications for endoscopic approaches to the skull base. Experience in endoscopic techniques continues to grow across the world. This is due in part to advances in instrumentation and technology, improvements in technique and, more importantly, an increase in the number of surgeons with training in endoscopic techniques. Long-term outcome data remain sparse., Summary: The limitations in endoscopic skull base surgery have not been reached. Increasing experience and improvement in technology will likely expand current indications. Future studies should focus on outcome analysis.

Introduction: Combined-modality treatment is considered standard of care in the treatment of stage III non-small-cell lung cancer (NSCLC). This study was designed to assess the efficacy and tolerability of induction paclitaxel/carboplatin followed by concurrent thoracic radiotherapy and weekly paclitaxel., Materials and Methods: Patients with unresectable stage III NSCLC were treated prospectively with two cycles of paclitaxel (175 mg/m2) and carboplatin (area under the curve of 6) followed by radiotherapy (60-66 Gy) concurrent with 6 weekly doses of paclitaxel (60 mg/m2). Response was determined 8 weeks after the completion of treatment and treatment-related toxicities were assessed at each visit during treatment and follow-up., Results: Sixty-three patients were treated, 5 had complete response and 33 had partial response, giving a response rate of 60%. Thirty-seven percent of patients developed grade 3 or 4 neutropenia; 48% had significant esophagitis requiring the use of narcotic analgesics. Two patients developed esophageal stricture subsequently. The median survival was 51 months and 12 months for stage IIIA and IIIB patients, respectively. Progression-free survival was 16 months and 11 months respectively., Conclusions: The response rate was encouraging. Esophagitis was a significant morbidity and should prompt modification of treatment regimen, either in the chemotherapy schedule or by adjusting the radiotherapy treatment planning.

Objective: A review of suppurative intracranial complications of sinusitis in children., Methods: Case series review over a two-year period from 1998 to 1999 in a children's hospital, Singapore., Results: There were seven cases, all male, and age range 9 to 14. Six had subdural empyemas and one had meningitis. The most common presenting symptoms included fever, headache and vomiting. Sinusitis was suspected as the cause in only one patient initially. The intracranial infections were not apparent from the initial brain CT of two patients and were only confirmed later on repeated imaging. Four patients had lumbar punctures without any adverse effects. All seven children had infections involving the frontal, ethmoid and maxillary sinuses and two also had sphenoid involvements. All were treated with high-dose intravenous antibiotics together with drainage of both the intracranial (n=six) and sinus (n=seven) suppurations. Five needed repeated intracranial drainages. Streptococcus species were isolated in five cases. Three patients developed seizures post-operatively which resolved on follow-up. One patient needed a ventriculo-peritoneal shunt for hydrocephalus. All patients had a good Glasgow Outcome Score. The hospital stay ranged from 30 to 89 days with a median of 43 days., Conclusions: Only males were identified in this review, collaborating the feeling that teenage males are at greatest risk of developing intracranial infections from sinusitis. We recommend that radiologic imaging of the brain for suspected intracranial infection should always include the sinuses as this aids early identification of actual cause. Initial CT imaging may be negative and hence repeated scans are warranted if the index of suspicion is high. The successful outcome of the children in this series supports the opinion that combined aggressive surgical and medical treatment is preferable in this patient population.