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Background: This first prospective study evaluates the efficacy and safety of single-port transoral robotic surgery (SP TORS) for tongue base resection (TBR) in obstructive sleep apnea (OSA) patients., Methods: A single-center, single-surgeon clinical investigation enrolled 25 subjects from April 2021 to September 2022. Pre- and postsurgery polysomnography reports and standardized sleep quality assessments were collected. Surgical parameters and complications were documented., Results: According to Sher's success criteria (50% reduction in AHI and AHI < 20), the success rate was 76% (19/25 patients). Preoperative AHI decreased from 58.56 ± 26.40 to 18.19 ± 22.02 postsurgery. Symptoms such as foreign body sensation and taste dysfunction improved within 3 months. Major complications, including hemorrhage, occurred in two patients (8%)., Conclusions: SP TORS TBR effectively manages OSA, significantly improving AHI outcomes and safety. Its precision and targeted tissue removal highlight its advantages over traditional methods, warranting further clinical investigation. Traial Registration: ClinicalTrials.gov identifier: NCT04795817., (© 2024 Wiley Periodicals LLC.)

Objective: To assess the surgical outcomes and identify predictors of surgical success in patients with positional and non-positional obstructive sleep apnea following multilevel airway surgery., Study Design: Retrospective cohort study., Setting: Singe-tertiary medical center., Methods: This study included 158 patients with obstructive sleep apnea who underwent multilevel airway surgery. Patients were divided into 2 groups according to position dependency: "positional patients" group (n = 100), and "nonpositional patients" group (n = 58). The characteristics and surgical outcomes of the 2 groups were compared., Results: The nonpositional group included younger and more obese patients in comparison to the positional group. Moreover, the nonpositional group had more severe disease than the positional group. Both groups showed overall improvement after surgery, and the surgical success rate did not differ significantly between the 2 groups (nonpositional, 41.4% vs positional, 48.0%; P = .424). Notably, 69.0% of patients belonging to the non-positional group converted to positional group postoperatively. Logistic regression analysis revealed that larger tonsil size, female sex, and higher mean O 2 saturation were associated with higher success rate in the positional group, whereas larger tonsil size was associated with surgical success in the nonpositional group., Conclusion: Both nonpositional and positional groups showed improvements following multilevel airway surgery, and surgery induced a transition from nonpositional to positional group. Given that the factors related to surgical success differed between the two groups, surgeons should consider position dependency and these distinct factors during decision-making., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

To identify the differences between COVID-19-associated and non-COVID-19-associated olfactory dysfunction (OD), we analyzed demographic and clinical characteristics based on the causative virus (COVID versus non-COVID groups) in patients with post-infectious olfactory dysfunction (PIOD) who underwent the olfactory questionnaire and olfactory function test. Out of 169 patients with PIOD, 99 were diagnosed with COVID-19 (COVID group), while 70 were not (non-COVID group). The COVID group was younger and had a higher percentage of male patients as well as patients with parosmia than the non-COVID group. In the initial olfactory function tests, the TDI, discrimination and identification scores were significantly higher in the COVID group than in the non-COVID group. TDI scores were significantly increased in patients with PIOD after treatment, regardless of the group. The threshold score was significantly increased by 1.38 in the COVID group while the identification score was significantly increased by 2.67 in the non-COVID group. Patients with COVID-19-associated OD were younger in age, tended to be male, had a higher incidence of parosmia, and had better initial olfactory function test results compared to those with non-COVID-19-associated OD. Following treatment, odor detection threshold improved in the COVID group, whereas odor identification improved in the non-COVID group., (© 2024. The Author(s).)

Background: Chronic inflammation triggers tissue remodeling in human nasal epithelial (HNE) cells. S100A9, a protein secreted by inflammatory cells, exhibits potent proinflammatory activity. However, its effect on HNE cell remodeling, such as squamous metaplasia, remains unclear. Therefore, this study aimed to determine the effects and underlying pathways of S100A9 on HNE cell remodeling and investigate its clinical implications in chronic rhinosinusitis (CRS)., Methods: Cultured HNE cells were treated with S100A9. Bulk RNA sequencing was performed to analyze gene ontology (GO). Ingenuity pathway analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also analyzed. Additionally, immunohistochemistry and multiplex immunofluorescence were performed on tissue samples obtained from 60 patients, whose clinical informations were also reviewed., Results: GO enrichment analysis indicated that S100A9 induced tissue remodeling in HNE cells toward squamous metaplasia. IPA and KEGG commonly showed that S100A9 affected HNE cells associated with the IL-17 signaling pathway, including target molecules such as matrix metalloproteinase 1 (MMP1) and small proline-rich protein 2A (SPRR2A). Squamous metaplasia with a marked expression of S100A9 was observed in 50% of CRS with nasal polyps (CRSwNPs). In addition, in multiplex immunofluorescence, the S100A9 in sub-epithelium was co-expressed with myeloperoxidase, a neutrophil marker, and MMP1 and SPRR2A were strongly expressed in epithelial remodeling. Clinically, the expression of S100A9 correlated with sino-nasal outcome test-22 (r = 0.294, p = 0.022) and Lund-Mackay scores (r = 0.348, p = 0.006)., Conclusion: S100A9 induces tissue remodeling in HNE cells. Its increased expression in CRSwNP, particularly squamous epithelium, correlates with disease severity. This suggests the clinical potential of S100A9 as a biomarker for CRS severity., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Purpose: This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs)., Methods: Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature., Results: Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996)., Conclusion: Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Virus-specific nasal resident T cells are important for protection against subsequent infection with a similar virus. Here we examine the phenotypes and functions of SARS-CoV-2-specific T cells in the nasal mucosa of vaccinated individuals with breakthrough infection (BTI) or without infection. Nasal tissues are obtained from participants during sinus surgery. Analysis of activation-induced markers implicates that a considerable proportion of spike (S)-reactive nasal CD8 + T cells express CD103, a tissue-resident marker. MHC-I multimer staining is performed to analyze the ex vivo phenotype and function of SARS-CoV-2 S-specific CD8 + T cells. We detect multimer + CD8 + T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer + CD8 + T cells remain present in nasal tissues over one year after the last exposure to S antigen, although the frequency decreases. Upon direct ex vivo stimulation with epitope peptides, nasal multimer + CD8 + T cells-particularly the CD49a + subset-exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM + CD8 + T cells confirms the enhanced effector function of the CD49a + subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a + CD8 + memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection., (© 2024. The Author(s).)

This study aimed to investigate the impact of different types of nasal inflammation on the regulation of entry-associated genes of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus 229E (HCoV-229E), and influenza virus, in the nasal epithelium. Subjects were classified into three groups: control, eosinophilic chronic rhinosinusitis (ECRS), and noneosinophilic CRS (NECRS) groups. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), alanyl aminopeptidase (ANPEP), dipeptidyl peptidase 4 (DPP4), and beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1), and beta-galactoside alpha-2,3-sialyltransferase 4 (ST3GAL4) were selected as key entry-associated genes for SARS-CoV-2, HCoV-229E, MERS-CoV, and influenza, respectively, and were evaluated. Brushing samples obtained from each group and human nasal epithelial cells cultured using an air-liquid interface system were treated for 7 days with typical inflammatory cytokines and analyzed using real-time polymerase chain reaction. Western blot analysis and confocal microscopy were performed. The entry-associated genes showed distinct regulation patterns in response to each interleukin-4 (IL-4), interleukin-13 (IL-13), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Specifically, ACE2 significantly decreased in type 2 cytokines (IL-4 and IL-13), while TMPRSS2 significantly decreased in type 1 cytokines (TNF-α and IFN-γ). ANPEP significantly decreased in both types of cytokines. Remarkably, DPP4 significantly increased in type 2 cytokines and decreased in type 1 cytokines. Moreover, ST6GAL1 and ST3GAL4 significantly increased in type 2 cytokines and decreased in type 1 cytokines, particularly IFN-γ. These findings were supported by western blot analysis and confocal imaging results, especially for ACE2 and DPP4. The findings regarding differential regulation suggest that patients with ECRS, primarily mediated by type 2 inflammation, may have lower susceptibility to SARS-CoV-2 and HCoV-229E infections but higher susceptibility to MERS-CoV and influenza infections., (© 2024 Wiley Periodicals LLC.)

Respiratory viral infection increases host susceptibility to secondary bacterial infections, yet the precise dynamics within airway epithelia remain elusive. Here, we elucidate the pivotal role of CD47 in the airway epithelium during bacterial super-infection. We demonstrated that upon influenza virus infection, CD47 expression was upregulated and localized on the apical surface of ciliated cells within primary human nasal or bronchial epithelial cells. This induced CD47 exposure provided attachment sites for Staphylococcus aureus, thereby compromising the epithelial barrier integrity. Through bacterial adhesion assays and in vitro pull-down assays, we identified fibronectin-binding proteins (FnBP) of S. aureus as a key component that binds to CD47. Furthermore, we found that ciliated cell-specific CD47 deficiency or neutralizing antibody-mediated CD47 inactivation enhanced in vivo survival rates. These findings suggest that interfering with the interaction between airway epithelial CD47 and pathogenic bacterial FnBP holds promise for alleviating the adverse effects of super-infection., (© 2024. The Author(s).)

The respiratory tract, the first-line defense, is constantly exposed to inhaled allergens, pollutants, and pathogens such as respiratory viruses. Emerging evidence has demonstrated that the coordination of innate and adaptive immune responses in the respiratory tract plays a crucial role in the protection against invading respiratory pathogens. Therefore, a better understanding of mucosal immunity in the airways is critical for the development of novel therapeutics and next-generation vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses. Since the coronavirus disease 2019 pandemic, our knowledge of mucosal immune responses in the airways has expanded. In this review, we describe the latest knowledge regarding the key components of the mucosal immune system in the respiratory tract. In addition, we summarize the host immune responses in the upper and lower airways following SARS-CoV-2 infection and vaccination, and discuss the impact of allergic airway inflammation on mucosal immune responses against SARS-CoV-2.

Many countries have implemented non-pharmaceutical interventions (NPIs) to prevent the spread of COVID-19. However, the impacts of NPIs on the epidemiology and treatment of chronic rhinosinusitis (CRS) remain unclear. We analyzed 671,216 patients to investigate changes in the incidence rate and treatment frequency of CRS using Korean nationwide health insurance data between 2017 and 2021. The incidence rate ( p < 0.001) and the number of outpatients ( p < 0.001), patients hospitalized ( p < 0.001), and patients prescribed antibiotics ( p < 0.001) or steroids ( p = 0.024) were significantly lower in the pandemic period than in the pre-pandemic period; however, the number of patients who underwent surgery was not different ( p = 0.205). Additionally, the frequency of surgeries per patient was significantly lower in patients during the pandemic period ( p < 0.001). In the interrupted time series analysis, the trends in the number of outpatients ( p < 0.001), patients hospitalized ( p < 0.001), patients who underwent surgery ( p < 0.001), and patients prescribed antibiotics ( p < 0.001) or steroids ( p < 0.001) significantly changed after the onset of the COVID-19 pandemic. In summary, NPI implementation during the COVID-19 pandemic was associated with a reduction in the incidence and treatment of CRS.

Background: Although interest in qualitative olfactory dysfunction (OD), including parosmia and phantosmia, has been increasing since the COVID-19 pandemic, little is known about the clinical characteristics and associated factors of qualitative OD., Methods: Adult patients with subjective smell disturbance who underwent both the olfactory questionnaire and psychophysical olfactory function test were retrospectively enrolled. Demographic and clinical characteristics were analysed according to the presence or absence of parosmia or phantosmia., Results: Among a total of 753 patients with self-reported OD, 60 (8%) and 167 (22.2%) patients reported parosmia and phantosmia, respectively. Younger age and female sex were related to both parosmia and phantosmia. The frequency of parosmia was significantly higher in patients with post-viral OD (17.9%) than in patients with the sinonasal disease (5.5%), whereas that of phantosmia was not different according to aetiologies of OD. Patients with COVID-19 had significantly younger ages and higher TDI scores than those with other viral infections. Remarkably, patients with parosmia or phantosmia had significantly higher TDI scores than those without but experienced more disruption in daily life. In the multivariate analysis, younger age and higher TDI score were identified as independent factors associated with both parosmia and phantosmia, while the viral infection was associated with parosmia but not with phantosmia., Conclusions: Patients with OD who have parosmia or phantosmia have higher odour sensitivity than those who do not, but experience more deterioration in the quality of life. Viral infection is a risk factor for parosmia but not for phantosmia.

Background: Calprotectin is an antimicrobial peptide primarily secreted by neutrophils. Furthermore, calprotectin secretion increases in patients with chronic rhinosinusitis (CRS) with polyps (CRSwNP) and positively correlates with neutrophil markers. However, CRSwNP is known to be associated with type 2 inflammation related to tissue eosinophilia. Therefore, the authors investigated calprotectin expression in eosinophils and eosinophil extracellular traps (EETs) and explored the associations between tissue calprotectin and the clinical findings of patients with CRS., Methods: A total of 63 patients participated, and patients diagnosed with CRS were classified based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score. The authors performed hematoxylin and eosin staining, immunohistochemistry, immunofluorescence with calprotectin, myeloperoxidase (MPO), major basic protein (MBP), and citrullinated histone H3 with the participant's tissues. Finally, correlations between calprotectin and the clinical data were examined., Results: Calprotectin-positive cells are co-localized not only in MPO-positive cells but also in MBP-positive cells in human tissues. Calprotectin was also involved in EETs and neutrophil extracellular traps. The number of calprotectin-positive cells in the tissue was positively correlated with the number of tissue and blood eosinophils. In addition, calprotectin in the tissue is associated with the olfactory function, Lund-Mackay computed tomography score, and JESREC score., Conclusions: Calprotectin, known to be secreted by neutrophils, in CRS was also expressed in eosinophils. In addition, calprotectin, which functions as an antimicrobial peptide, may play an important role in the innate immune response based on its EET involvement. Therefore, calprotectin expression could reflect as a disease severity biomarker for CRS., (© 2023 ARS-AAOA, LLC.)

Interpreting the relationship between different taste function tests of different stimuli, such as chemical and electrical stimulation, is still poorly understood. This study aims to analyze visually as well as quantitatively how to interpret the relationship of results between taste function tests using different stimuli. Patients who underwent the whole mouth test and Electrogustometry (EGM) at a tertiary medical center between August 2018 and December 2018 were reviewed retrospectively with electronic medical records. Of the 110 patients, a total of 86 adults who self-reported that their taste function was normal through a questionnaire were enrolled. EGM measured the thresholds of the chorda tympani (CT) and glossopharyngeal nerve (GL) area of the tongue. The whole mouth test measured detection and recognition thresholds for sweet, salty, bitter, sour, and umami taste. Statistical analyses of Pearson's, Spearman's rank and polyserial correlation and multidimensional scaling (MDS) was performed. The EGM threshold for the average value of both CT regions and the recognition threshold of the whole mouth test were significantly correlated in sweet, salty, bitter, and sour taste (r = 0.244-0.398, P < 0.05), and the detection threshold was correlated only significant in sweet (r = 0.360, P = 0.007). In the MDS analysis results, the three-dimensional (D) solution was chosen over the 2-D solution because of the lower stress. Detection-, recognition threshold of whole mouth test and EGM thresholds of CT and GL area, those were standardized by Z-score, formed well-distinguished sections in the MDS analyses. The EGM threshold of the CT area was closer to the detection and recognition thresholds than the EGM threshold of the GL area. In general, the EGM threshold was closer to the recognition threshold than the detection threshold for each taste. Overall, visualization of the relationship of whole mouth test and EGM by MDS was in good agreement with quantitative analysis. EGM and whole mouth test seem to reflect different aspects of taste. However, when interpreting the EGM results, the EGM threshold of the CT area will show more similarity to the recognition threshold than the detection threshold for the whole mouth test., (© 2023. The Author(s).)

Introduction: The olfactory epithelium (OE) and olfactory bulb (OB) are the major components of the olfactory system and play critical roles in olfactory perception. However, the embryonic development of OE and OB by using the olfactory specific genes has not been comprehensively investigated yet. Most previous studies were limited to a specific embryonic stage, and very little is known, till date, about the development of OE., Methods: The current study aimed to explore the development of mouse olfactory system by spatiotemporal analysis of the histological features by using the olfactory specific genes of olfactory system from the prenatal to postnatal period., Results: We found that OE is divided into endo-turbinate, ecto-turbinate, and vomeronasal organs, and that putative OB with putative main and accessory OB is formed in the early developmental stage. The OE and OB became multilayered in the later developmental stages, accompanied by the differentiation of olfactory neurons. Remarkably, we found the development of layers of olfactory cilia and differentiation of OE to progress dramatically after birth, suggesting that the exposure to air may facilitate the final development of OE., Discussion: Overall, the present study laid the groundwork for a better understanding of the spatial and temporal developmental events of the olfactory system., 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 © 2023 Kim, Rha, Cho, Yoon and Kim.)

Subsets of the human CD8 + T cell population express inhibitory NK cell receptors, such as killer immunoglobulin-like receptors (KIRs) and NKG2A. In the present study, we examine the phenotypic and functional characteristics of KIR + CD8 + T cells and NKG2A + CD8 + T cells. KIRs and NKG2A tend to be expressed by human CD8 + T cells in a mutually exclusive manner. In addition, TCR clonotypes of KIR + CD8 + T cells barely overlap with those of NKG2A + CD8 + T cells, and KIR + CD8 + T cells are more terminally differentiated and replicative senescent than NKG2A + CD8 + T cells. Among cytokine receptors, IL12Rβ1, IL12Rβ2, and IL18Rβ are highly expressed by NKG2A + CD8 + T cells, whereas IL2Rβ is expressed by KIR + CD8 + T cells. IL-12/IL-18-induced production of IFN-γ is prominent in NKG2A + CD8 + T cells, whereas IL-15-induced NK-like cytotoxicity is prominent in KIR + CD8 + T cells. These findings suggest that KIR + CD8 + and NKG2A + CD8 + T cells are distinct innate-like populations with different cytokine responsiveness., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study was aimed to investigate clinical implications of mixed apnea (MA) in patients with obstructive sleep apnea (OSA), particularly whether surgical outcomes differ between OSA patients with and without MA events., Study Design: Retrospective cohort study., Setting: Single tertiary medical center., Methods: Eighty-eight patients with OSA who underwent multilevel upper airway surgery were included. Patients were divided into 2 groups according to the presence of MA events: "pure group" (n = 30) and "mixed group" (n = 58). The clinical characteristics and surgical outcomes were compared between the 2 groups., Results: The mixed group included more males (P = .020) and hypertensive patients (P = .009) and had a higher apnea-hypopnea index (AHI; P < .001) than the pure group. The surgical success rate was lower in the mixed group (29.3%) than in the pure group (73.3%; P < .001). Furthermore, the postoperative improvements in total AHI (P < .001), supine AHI (P < .001), and oxygen desaturation index (P = .006) were lower in the mixed group than in the pure group. Logistic regression analysis confirmed that the presence of MA (P = .002) was an independent predictor of poor surgical outcomes in patients with OSA., Conclusion: OSA patients with MA showed different clinical features and poor surgical outcomes compared to those without MA. These results imply that OSA with MA components may have a distinct pathophysiology, and the presence of MA should be considered in the surgical treatment of OSA., (© 2022 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objectives: This study is aimed to investigate the differences in the clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea (OSA)., Design: Cohort study., Setting: Single tertiary care centre., Participants: This study included 190 patients with OSA who underwent multilevel upper airway surgery between September 2012 and September 2021. The patients were divided into two groups according to the proportion of each respiratory event: hypopnea-predominant (n = 102) and apnea-predominant (n = 88)., Main Outcome Measures: The primary outcome measure was the percentage improvement in the apnea-hypopnea index (AHI) from baseline AHI after surgery., Results: The apnea-predominant group included more male patients and had higher AHI, respiratory disturbance index (RDI) and oxygen desaturation index (ODI) than the hypopnea-predominant group. Both groups showed significant improvements in AHI, apnea index, RDI, supine AHI, REM AHI, non-REM AHI, ODI, lowest O 2 saturation and Epworth Sleepiness Scale scores following the surgery. Notably, hypopnea index increased after surgery in the apnea-predominant OSA group. Although the improvement in the absolute value of AHI by surgery was significantly greater in the apnea-predominant group than in the hypopnea-predominant group, the two groups showed no significant difference in the percentage improvement in AHI from baseline AHI., Conclusion: Patients with apnea-predominant OSA had more severe disease than those with hypopnea-predominant OSA; however, surgical outcomes, as evaluated by percentage AHI improvement, were comparable between the two groups. In addition, multilevel upper airway surgery may induce the transition from apnea to hypopnea in patients with apnea-predominant OSA., (© 2022 John Wiley & Sons Ltd.)

Background & Aims: The liver provides a unique niche of lymphocytes enriched with a large proportion of innate-like T cells. However, the heterogeneity and functional characteristics of the hepatic T-cell population remain to be fully elucidated., Methods: We obtained liver sinusoidal mononuclear cells from the liver perfusate of healthy donors and recipients with HBV-associated chronic liver disease (CLD) during liver transplantation. We performed a CITE-seq analysis of liver sinusoidal CD45 + cells in combination with T cell receptor (TCR)-seq and flow cytometry to examine the phenotypes and functions of liver sinusoidal CD8 + T cells., Results: We identified a distinct CD56 hi CD161 - CD8 + T-cell population characterized by natural killer (NK)-related gene expression and a uniquely restricted TCR repertoire. The frequency of these cells among the liver sinusoidal CD8 + T-cell population was significantly increased in patients with HBV-associated CLD. Although CD56 hi CD161 - CD8 + T cells exhibit weak responsiveness to TCR stimulation, CD56 hi CD161 - CD8 + T cells highly expressed various NK receptors, including CD94, killer immunoglobulin-like receptors, and NKG2C, and exerted NKG2C-mediated NK-like effector functions even in the absence of TCR stimulation. In addition, CD56 hi CD161 - CD8 + T cells highly respond to innate cytokines, such as IL-12/18 and IL-15, in the absence of TCR stimulation. We validated the results from liver sinusoidal CD8 + T cells using intrahepatic CD8 + T cells obtained from liver tissues., Conclusions: In summary, the current study found a distinct CD56 hi CD161 - CD8 + T-cell population characterized by NK-like activation via TCR-independent NKG2C ligation. Further studies are required to elucidate the roles of liver sinusoidal CD56 hi CD161 - CD8 + T cells in immune responses to microbial pathogens or liver immunopathology., Lay Summary: The role of different immune cell populations in the liver is becoming an area of increasing interest. Herein, we identified a distinct T-cell population that had features similar to those of natural killer (NK) cells - a type of innate immune cell. This distinct population was expanded in the livers of patients with chronic liver disease and could thus have pathogenic relevance., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Little is known about the occurrence of gustatory dysfunction (GD) in relation to different aetiologies of olfactory dysfunction (OD) as assessed by psychophysical chemosensory tests. The aim of this study was to analyse gustatory function in patients with OD and to investigate clinical factors associated with GD., Methods: A total of 742 individuals who underwent both olfactory and gustatory function tests at a tertiary medical centre from November 2019 to March 2021 were retrospectively enrolled. Olfactory and gustatory function were assessed by the YSK olfactory and gustatory function tests, respectively. Patients with OD were classified into four groups according to the aetiology: sinonasal disease, post-infection OD (PIOD), post-traumatic OD (PTOD), and others. Secondary outcomes included age, sex, smoking history, and alcohol history., Results: Among the 488 patients with OD, 93 (19.1%) showed GD and 395 (80.9%) had normal gustatory function. Only 25 (9.8%) among 254 individuals with normosmia showed GD. Analyses of these frequencies revealed a significant association between OD and GD. In addition, the taste score was significantly lower in patients with OD than individuals with normosmia. The frequency of GD was significantly higher in patients with PTOD (53.6%) than in those with OD of other aetiologies (sinonasal disease, 6.7%; PIOD, 13.0%; others, 24.4%). In the multivariate analysis, age >=5 years and PTOD were associated with a high frequency of GD among patients with OD., Conclusions: The current study show that GD is significantly associated with OD. In particular, GD is more common in patients with PTOD than in those with OD of other aetiologies.

Objective: The liver acts as a frontline barrier against diverse gut-derived pathogens, and the sinusoid is the primary site of liver immune surveillance. However, little is known about liver sinusoidal immune cells in the context of chronic liver disease (CLD). Here, we investigated the antibacterial capacity of liver sinusoidal γδ T cells in patients with various CLDs., Design: We analysed the frequency, phenotype and functions of human liver sinusoidal γδ T cells from healthy donors and recipients with CLD, including HBV-related CLD (liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC)), alcoholic LC and LC or HCC of other aetiologies, by flow cytometry and RNA-sequencing using liver perfusates obtained during living donor liver transplantation. We also measured the plasma levels of D-lactate and bacterial endotoxin to evaluate bacterial translocation., Results: The frequency of liver sinusoidal Vγ9 + Vδ2 + T cells was reduced in patients with CLD. Immunophenotypic and transcriptomic analyses revealed that liver sinusoidal Vγ9 + Vδ2 + T cells from patients with CLD were persistently activated and pro-apoptotic. In addition, liver sinusoidal Vγ9 + Vδ2 + T cells from patients with CLD showed significantly decreased interferon (IFN)-γ production following stimulation with bacterial metabolites and Escherichia coli . The antibacterial IFN-γ response of liver sinusoidal Vγ9 + Vδ2 + T cells significantly correlated with liver function, and inversely correlated with the plasma level of D-lactate in patients with CLD. Repetitive in vitro stimulation with E. coli induced activation, apoptosis and functional impairment of liver sinusoidal Vγ9 + Vδ2 + T cells., Conclusion: Liver sinusoidal Vγ9 + Vδ2 + T cells are functionally impaired in patients with CLD. Bacterial translocation and decreasing liver functions are associated with functional impairment of liver sinusoidal Vγ9 + Vδ2 + T cells., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this systematic review and meta-analysis was to investigate the association between obstructive sleep apnea (OSA) and erythrocytosis., Methods: The PubMed, Web of Science, and Cochrane Library databases were searched for articles examining hematocrit values in patients with OSA and control individuals published till September 1, 2021. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated, and subgroup analyses were performed., Results: Eleven eligible studies with a total of 4608 patients with OSA were included in this meta-analysis. Pooled outcomes revealed that hematocrit values were significantly higher in patients with OSA than in controls (SMD, 0.19; 95% CI, 0.08-0.29; p  < .01). When studies were stratified by disease severity, the significant differences in hematocrit values between patients and controls were only observed in the severe OSA group (SMD, 0.34; 95% CI, 0.08-0.59; p  < .01), but not in the mild and moderate OSA groups. In subgroup analyses according to sex and publication year, significant differences in hematocrit values between patients and controls remained stable in studies with only female patients (SMD, 0.25; 95% CI, 0.12-0.38; p  < .01) and in studies published after 2012 (SMD, 0.17; 95% CI, 0.06-0.28, p  < .01)., Conclusion: Our meta-analysis revealed that the hematocrit value was significantly increased in patients with OSA, particularly in severe patients, compared with that in controls. However, the elevation was modest, and the hematocrit value is expected to be within the normal range in patients with OSA. These data suggest that OSA leads to slight increases in hematocrit but does not cause clinically significant erythrocytosis., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Whether the use of electronic cigarettes (ECs) is associated with upper airway diseases, including chronic rhinosinusitis (CRS) and allergic rhinitis (AR), remains unclear., Methods: We analyzed data from the nationwide cross-sectional surveys: the Korea National Health and Nutrition Examination Survey VI (2013-2015), VII (2016-2018), and VIII (2019). Logistic regression analysis was performed to assess the association between EC use and CRS or AR., Results: Among a total of 38,413 participants, 6.4% were former EC users and 2.5% were current EC users. Former EC users and current EC showed a significantly increased OR for CRS or AR compared with never EC users. In the subgroup analysis, the "current CC (conventional cigarette)-current EC" and the "current CC-formal EC" group had a significantly higher OR for CRS or AR than the "current CC-never EC" group. In addition, former CC smokers who currently use ECs showed a significantly higher OR for AR than former CC smokers without EC use., Conclusions: EC use is significantly associated with a high prevalence of CRS and AR in the adult population. These results indicate that the use of ECs may increase the risk of upper airway disease.

Background: Although the role of human papillomavirus (HPV) in sinonasal inverted papilloma (SNIP) has been investigated, the link between HPV infection and SNIP recurrence remains controversial. This meta-analysis aimed to investigate the association between HPV infection and recurrence of SNIP., Methods: The PubMed, Web of Science, Google Scholar, and Cochrane Library databases were searched (until 16 June 2021) to collect all relevant articles. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed effects model. In addition, subgroup analysis, assessment of publication bias, and sensitivity analyses were performed., Results: Fourteen eligible articles, including 592 patients with SNIP, were included in this study. Pooled analysis revealed that HPV-positive cases exhibited a significantly higher OR of tumour recurrence than HPV-negative counterparts). A significant association between HPV infection and tumour recurrence remained stable in subgroup analyses according to the publication year of the studies., Conclusions: Our meta-analysis demonstrates that HPV infection is significantly associated with the recurrence of SNIP, suggesting the pathological role of HPV in SNIP. These results suggest that HPV infection should be considered in the management of SNIP.

Background: Diverse immune cells contribute to the pathogenesis of chronic rhinosinusitis (CRS), an inflammatory disease of the nasal cavity and paranasal sinuses. However, whether mucosal-associated invariant T (MAIT) cells are present in human sinonasal tissues remains unclear. Furthermore, the characteristics of sinonasal MAIT cells have not been studied in patients with CRS., Objective: We investigated the phenotype, function, and clinical implications of MAIT cells in patients with CRS., Methods: Peripheral blood and sinonasal tissue were obtained from patients with CRS with (CRSwNP) or without nasal polyps (CRSsNP) and healthy controls. MAIT cells were analyzed by flow cytometry., Results: We found that MAIT cells are present in human sinonasal tissues from healthy controls and patients with CRS. The sinonasal MAIT cell population, but not peripheral blood MAIT cells, from patients with CRSsNP, noneosinophilic CRSwNP (NE-NP), or eosinophilic CRSwNP (E-NP) had a significantly higher frequency of activated cells marked by CD38 expression. In functional analysis, the sinonasal MAIT cell population from NE-NP and E-NP had a significantly higher frequency of IL-17A + cells but lower frequency of IFN-γ + or TNF + cells than control sinonasal tissues. Furthermore, CD38 expression and IL-17A production by sinonasal MAIT cells significantly correlated with disease extent evaluated by the Lund-Mackay computed tomography score in patients with E-NP., Conclusions: Sinonasal MAIT cells exhibit an activated phenotype and produce higher levels of IL-17A in patients with CRSwNP. These alterations are associated with the extent of disease in patients with E-NP., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

IL-15 exhibits pleiotropic effects on NK and CD8 + T cells and contributes to host protection or immunopathology during infection. Although both type I IFNs and IFN-γ upregulate IL-15 expression, their effects on IL-15 upregulation and underlying mechanisms have not been compared comprehensively. In addition, little is known about trans -presentation of IL-15 by epithelial cells to lymphocytes. In this study, we analyzed the expression of IL-15 and IL-15Rα in the human hepatocyte-derived Huh-7 cell line after stimulation with IFN-α, IFN-β, or IFN-γ using RT-PCR, flow cytometry, and confocal microscopy. We also performed knockdown experiments to investigate the signaling pathway involved in IL-15 upregulation. IFN-γ more potently upregulated IL-15 expression in Huh-7 cells than IFN-α and IFN-β. Knockdown experiments revealed that IFN-γ- and IFN-β-induced IL-15 expression relied on IFN regulatory factor 1 (IRF1), which is upregulated by STAT1 and IFN-stimulated gene factor 3, respectively. Inhibitor of κB kinase α/β was also involved in IFN-γ-induced upregulation of IL-15. Furthermore, human NK cells were activated by coculture with IFN-γ-treated Huh-7 cells, which was abrogated by knocking down IL-15Rα in IFN-γ-treated Huh-7 cells, indicating that IFN-γ-induced IL-15 on Huh-7 cells activates NK cells via trans -presentation. In summary, our data demonstrate that IFN-γ potently elicits IL-15 trans -presentation by epithelial cells via IRF1. These data also suggest that the IFN-γ-IRF1-IL-15 axis may be a regulatory target for the treatment of diseases with IL-15 dysregulation., (Copyright © 2022 by The American Association of Immunologists, Inc.)

In addition to CD4 + T cells and neutralizing antibodies, CD8 + T cells contribute to protective immune responses against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In patients with COVID-19, CD8 + T cells exhibiting activated phenotypes are commonly observed, although the absolute number of CD8 + T cells is decreased. In addition, several studies have reported an upregulation of inhibitory immune checkpoint receptors, such as PD-1, and the expression of exhaustion-associated gene signatures in CD8 + T cells from patients with COVID-19. However, whether CD8 + T cells are truly exhausted during COVID-19 has been a controversial issue. In the present review, we summarize the current understanding of CD8 + T-cell exhaustion and describe the available knowledge on the phenotypes and functions of CD8 + T cells in the context of activation and exhaustion. We also summarize recent reports regarding phenotypical and functional analyses of SARS-CoV-2-specific CD8 + T cells and discuss long-term SARS-CoV-2-specific CD8 + T-cell memory., (© 2021. The Author(s).)

Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. Here we conduct ex vivo assays to evaluate SARS-CoV-2-specific CD4 + and CD8 + T cell responses in COVID-19 convalescent patients up to 317 days post-symptom onset (DPSO), and find that memory T cell responses are maintained during the study period regardless of the severity of COVID-19. In particular, we observe sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4 + and CD8 + T cells detected by activation-induced markers, the proportion of stem cell-like memory T (T SCM ) cells is increased, peaking at approximately 120 DPSO. Development of T SCM cells is confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of T SCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19, thus support the feasibility of effective vaccination programs as a measure for COVID-19 control.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In the current review, we describe SARS-CoV-2-specific CD4 + and CD8 + T-cell responses in acute and convalescent COVID-19 patients. We also discuss the relationships between COVID-19 severity and SARS-CoV-2-specific T-cell responses and summarize recent reports regarding SARS-CoV-2-reactive T cells in SARS-CoV-2-unexposed individuals. These T cells may be cross-reactive cells primed by previous infection with human common-cold coronaviruses. Finally, we outline SARS-CoV-2-specific T-cell responses in the context of vaccination. A better understanding of SARS-CoV-2-specific T-cell responses is needed to develop effective vaccines and therapeutics., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2021. The Korean Association of Immunologists.)

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8 + T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer + cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer + cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8 + T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1 + cells than PD-1 - cells among multimer + cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8 + T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8 + T cells elicited by infection or vaccination., Competing Interests: Declaration of Interests The authors have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background & Aims: Mucosal-associated invariant T (MAIT) cells, the most abundant innate-like T cells in the human liver, can be activated by cytokines during viral infection without TCR stimulation. Here, we examined the mechanisms underlying TCR/MR1-independent innate-like cytotoxicity of cytokine-activated liver MAIT cells. We also examined the phenotype and function of MAIT cells from patients with acute viral hepatitis., Methods: We obtained liver sinusoidal mononuclear cells from donor liver perfusate during liver transplantation and examined the effect of various cytokines on liver MAIT cells using flow cytometry and in vitro cytotoxicity assays. We also obtained peripheral blood and liver-infiltrating T cells from patients with acute hepatitis A (AHA) and examined the phenotype and function of MAIT cells using flow cytometry., Results: IL-15-stimulated MAIT cells exerted granzyme B-dependent innate-like cytotoxicity in the absence of TCR/MR1 interaction. PI3K-mTOR signaling, NKG2D ligation, and CD2-mediated conjugate formation were critically required for this IL-15-induced innate-like cytotoxicity. MAIT cells from patients with AHA exhibited activated and cytotoxic phenotypes with higher NKG2D expression. The innate-like cytotoxicity of MAIT cells was significantly increased in patients with AHA and correlated with serum alanine aminotransferase levels., Conclusions: Taken together, the results demonstrate that liver MAIT cells activated by IL-15 exert NKG2D-dependent innate-like cytotoxicity in the absence of TCR/MR1 engagement. Furthermore, the innate-like cytotoxicity of MAIT cells is associated with liver injury in patients with AHA, suggesting that MAIT cells contribute to immune-mediated liver injury., Lay Summary: Immune-mediated liver injury commonly occurs during viral infections of the liver. Mucosal-associated invariant T (MAIT) cells are the most abundant innate-like T cells in the human liver. Herein, we have identified a mechanism by which MAIT cells circumvent conventional T cell receptor interactions to exert cytotoxicity. We show that this innate-like cytotoxicity is increased during acute hepatitis A virus infection and correlates with the degree of hepatocyte injury., Competing Interests: Conflict of interest The authors have no conflicting financial interests. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells are innate T cells that acquire memory phenotype in the thymus and share similar biological characteristics. However, how their effector differentiation is developmentally regulated is still unclear. Here, we identify analogous effector subsets of these three innate T cell types in the thymus that share transcriptional profiles. Using single-cell RNA sequencing, we show that iNKT, MAIT and γδ T cells mature via shared, branched differentiation rather than linear maturation or TCR-mediated instruction. Simultaneous TCR clonotyping analysis reveals that thymic maturation of all three types is accompanied by clonal selection and expansion. Analyses of mice deficient of TBET, GATA3 or RORγt and additional in vivo experiments corroborate the predicted differentiation paths, while human innate T cells from liver samples display similar features. Collectively, our data indicate that innate T cells share effector differentiation processes in the thymus.

Regulatory T (Treg) cells are important in preventing acute rejection (AR) in solid organ transplantation, but the clinical relevance of the different kinetics early after liver transplantation (LT) in acute rejectors and non-rejectors is unclear. We analyzed peripheral blood samples of 128 LT recipients receiving basiliximab induction plus tacrolimus immunosuppression. Samples were obtained at pretransplant, D7, and D30 after LT. Frequency and phenotype of Tregs were analyzed by flow cytometry. The predictive value of Treg frequency at D7 was assessed for suspected acute rejection (SAR) and was validated for biopsy-proven AR (BPAR). We found that the frequencies of total and activated Tregs at D7 were significantly lower in recipients with SAR and BPAR. Treg was more reduced in BPARs by in vitro tacrolimus treatment in the presence of basiliximab. Moreover, an early reduction of Treg frequency in rejectors was associated with a greater increase in Treg apoptosis and further attenuated IL-2 signaling. D7 Treg frequency was an independent risk factor for SAR, which was also validated for BPAR. In conclusion, first-week peripheral blood Treg frequency correlates with AR after LT under tacrolimus-based immunosuppression, which needs to be proven in larger, geographically and clinically diverse populations., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

This meta-analysis is aimed to investigate the association between the neutrophil-to-lymphocyte ratio (NLR) and obstructive sleep apnea (OSA). The PubMed, Web of Science, Google Scholar, and Cochrane Library databases were searched to collect all relevant articles. The pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated using the random effects model. In addition, subgroup analysis and meta-regression analysis were performed. Eleven eligible articles containing 2,259 patients with OSA were included in this study. Pooled outcomes revealed that the NLR was significantly higher in patients with OSA than in controls (SMD 0.62, 95% CI 0.29-0.94, P = 0.002). In subgroup analyses, differences in the NLR between patients and controls increased with worsening OSA grades. Furthermore, meta-regression analysis showed that differences in mean BMI exerted a significant effect on differences in the NLR (P = 0.0003). In summary, our meta-analysis demonstrated that the NLR in OSA patients was significantly higher than that in controls, and the difference was larger in patients with severe OSA. These results indicate that the NLR may be a reliable marker for detecting systemic inflammation and predicting disease severity in patients with OSA.

Background & Aims: Human liver CD69 + CD8 + T cells are ~95% CD103 - and ~5% CD103 + . Although CD69 + CD103 + CD8 + T cells show tissue residency and robustly respond to antigens, CD69 + CD103 - CD8 + T cells are not yet well understood., Methods: Liver perfusate and paired peripheral blood were collected from healthy living donors and recipients with cirrhosis during liver transplantation. Liver tissues were obtained from patients with acute hepatitis A. Phenotypic and functional analyses were performed by flow cytometry. Gene expression profiles were determined by microarray and quantitative reverse transcription PCR. PT-2385 was used to inhibit hypoxia-inducible factor (HIF)-2α., Results: Human liver CD69 + CD103 - CD8 + T cells exhibited HIF-2α upregulation with a phenotype of tissue residency and terminal differentiation. CD103 - cells comprised non-hepatotropic virus-specific T cells as well as hepatotropic virus-specific T cells, but CD103 + cells exhibited only hepatotropic virus specificity. Although CD103 - cells were weaker effectors on a per cell basis than CD103 + cells, following T cell receptor or interleukin-15 stimulation, they remained the major CD69 + CD8 + effector population in the liver, surviving with less cell death. An HIF-2α inhibitor suppressed the effector functions and survival of CD69 + CD103 - CD8 + T cells. In addition, HIF-2α expression in liver CD69 + CD103 - CD8 + T cells was significantly increased in patients with acute hepatitis A or cirrhosis., Conclusions: Liver CD69 + CD103 - CD8 + T cells are tissue resident and terminally differentiated, and their effector functions depend on HIF-2α. Furthermore, activation of liver CD69 + CD103 - CD8 + T cells with HIF-2α upregulation is observed during liver pathology., Lay Summary: The immunologic characteristics and the role of CD69 + CD103 - CD8 + T cells, which are a major population of human liver CD8 + T cells, remain unknown. Our study shows that these T cells have a terminally differentiated tissue-resident phenotype, and their effector functions depend on a transcription factor, HIF-2α. Furthermore, these T cells were activated and expressed higher levels of HIF-2α in liver pathologies, suggesting that they play an important role in immune responses in liver tissues and the pathogenesis of human liver disease., Competing Interests: Conflict of interest The authors have no conflicting financial interests. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Staphylococcus aureus enterotoxin (SAE) superantigens are detected in nasal polyps (NPs), and SAE-specific IgE predicts asthma comorbidity in patients with NPs. However, roles of SAE superantigens and superantigen-related T-cell responses remain to be elucidated in nonasthmatic patients., Objective: We investigated the presence of SAEs and SAE-related T-cell receptor (TCR) Vβ (TCRVβ) in nonasthmatic NPs, the phenotypes and functions of SAE-related T cells, and the clinical implication of SAE-related T-cell expansion., Methods: Sinonasal tissue samples were obtained from patients with nonasthmatic chronic rhinosinusitis (CRS) with NPs (CRSwNP), patients with CRS without NPs (CRSsNP), and control subjects. SAE genes were detected by PCR, and the TCRVβ distribution and T-cell phenotypes were examined by flow cytometry., Results: Various SAE genes were detected not only in NPs but also in sinonasal mucosa from patients with CRSsNP and from controls. The S aureus enterotoxin I (SEI) gene was detected in all NPs. The fraction of SEI-responsive TCRVβ + (TCRVβ1 + and Vβ5.1 + ) CD4 + T cells was significantly increased only in NPs and the ethmoidal mucosa of patients with CRSwNP, indicating superantigen-induced expansion. The expanded TCRVβ5.1 + CD4 + T cells expressed proliferation marker Ki-67 and the T H 2 transcription factor GATA3. Furthermore, TCRVβ5.1 + CD4 + T cells in NPs highly expressed T H 2 markers, including IL-17RB, thymic stromal lymphoprotein receptor, and chemoattractant receptor-homologous molecule expressed on T H 2 cells, with a potent T H 2 cytokine-producing ability. Moreover, the expansion of TCRVβ1 + or Vβ5.1 + CD4 + T cells was associated with the Lund-Mackay computed tomography score, indicating disease extent., Conclusion: In nonasthmatic patients with CRSwNP, superantigen-related expansion of CD4 + T cells with T H 2 differentiation was associated with the disease extent., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to reveal diagnosis, management, and treatment outcome characteristics of sinonasal pleomorphic adenoma and to identify predictors for disease recurrence., Methods: This study comprised a retrospective review of data from seven patients with sinonasal pleomorphic adenoma who were treated by the authors at a tertiary medical center between January 2005 and May 2017. In addition, the MEDLINE database was searched for literature published in English. A systematic review of the published articles was performed., Results: A total of 42 articles were eligible for review. Data from the seven treated patients and 101 patients described in the literature were included in the analysis. An endoscopic approach was employed in all cases treated at our institution, and recurrence was found in one patient with a large, 5.5-cm tumor. In reviewing prior publications, the mean age at surgery was 45.4 years, and the primary sign at diagnosis was nasal obstruction. The most common primary tumor site was the nasal septum (57.4%), and the mean tumor size was 3.6cm (range, 0.5-10cm) in 76 cases for which detailed information was available. Endoscopic endonasal resection achieved successful oncologic control in applied cases (25/25, 100%). Recurrence was found in eight of 101 patients. Multivariate analysis identified tumor origin of the paranasal sinus (adjusted OR 31.000, p=0.016) as being significantly associated with a high prevalence of recurrence., Conclusion: Pleomorphic adenoma is a rare benign tumor of the sinonasal tract. Surgery that achieves clear margins is the treatment of choice. The tumor may be accessible via an endoscopic endonasal approach in most cases, although incomplete resection of the tumor stem may allow for tumor recurrence. In addition, our findings suggest that a tumor originating from the paranasal sinus is significantly associated with a high prevalence of recurrence., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A 68-year-old man presented with periorbital pain with progressive decrease in visual acuity of the right eye. The patient began to experience these symptoms 6 months ago, but they had become significantly worse in the last month. On examination, the patient had ptosis, proptosis, and impaired movement of the right eye. His medical history was notable for peripheral T-cell lymphoma. During chemotherapy, he had developed pulmonary aspergillosis, which resolved with antifungal medication. The magnetic resonance imaging scan, which was taken because of orbital symptoms, was suggestive of optic neuritis. For 6 months, his visual symptoms deteriorated and improved with intermittent steroid treatment. However, the patient began to experience worsening pain and visual disturbance for the month leading up to the referral visit and could not recognize light in the involved eye. A repeat magnetic resonance imaging study revealed a diffuse involvement of right orbital apex. Subsequent to this finding, an endoscopic biopsy was performed. The pathologic examination confirmed the diagnosis of invasive aspergillosis. Orbital pain, ptosis, and limitation of eye movements improved with antifungal medication, and the patient was able to recognize hand movements.

Background: The immune-modulating effects of alcohol and smoking are well known through a great body of research. Furthermore, many studies have been performed on the influence of alcohol and smoking on the development of allergic disease. However, previous studies have reported conflicting results with associations between alcohol intake or smoking and risk of allergy. The purpose of this study was to evaluate the effects of alcohol consumption and smoking on total serum immunoglobulin E (TIgE) and prevalence of sensitization to Dermatophagoides farinae in a representative sample of Korean adults., Methods: TIgE levels and IgE levels specific to D. farinae were measured. Alcohol, smoking habit, and other influencing variables were obtained from the 2010 Korean National Health and Nutrition Examination., Results: Smoking (smoked five packs or more in lifetime) was independently associated with increased risk of sensitization to D. farinae (odds ratio [OR], 1.439; 95% CI, 1.075-1.927). Frequent alcohol drinking (more than four times a week) also showed similar association when compared with subjects who drank less than once per month (OR, 2.052; 95% CI, 1.257-3.350). TIgE levels were also increased along with increased frequency of alcohol drinking. However, smoking habit was not related to TIgE levels., Conclusion: These findings suggest that history of smoking and frequent alcohol consumption are significantly associated with increased prevalence of sensitization to D. farinae. In addition, frequency of alcohol drinking was also related to a moderate increase in TIgE levels in Korean adults.