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Background: Chronic rhinosinusitis with nasal polyps affects approximately 2–4% of the general population, and long-term use of systemic corticosteroids is associated with adverse effects. The aim of this study was to assess the efficacy and safety of mepolizumab in adults with recurrent, refractory severe bilateral chronic rhinosinusitis with nasal polyps. Methods: SYNAPSE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done at 93 centres, mainly hospitals, in 11 countries. Eligible patients were aged 18 years or older with recurrent, refractory, severe, bilateral nasal polyp symptoms (nasal obstruction symptom visual analogue scale [VAS] score of >5), were eligible for repeat nasal surgery (overall symptoms VAS score >7 and endoscopic nasal polyps score of ≥5, with a minimum score of 2 in each nasal cavity) despite standard of care treatment, and had to have at least one nasal surgery in the past 10 years. Patients were randomly assigned (1:1), using permuted block design, to receive either 100 mg mepolizumab subcutaneously or placebo once every 4 weeks, in addition to standard of care (mometasone furoate intranasal spray for at least 8 weeks before screening and during the study, saline nasal irrigations, systemic corticosteroids or antibiotics, or both), as required, for 52 weeks. Site staff, the central study team, and patients were masked to study treatment and absolute blood eosinophil counts. The coprimary endpoints were change from baseline in total endoscopic nasal polyp score at week 52 and in mean nasal obstruction VAS score during weeks 49–52, assessed in the intention-to-treat population (ITT). This study is registered with ClinicalTrials.gov, NCT03085797. Findings: From May 25, 2017, to Dec 12, 2018, 854 patients were screened for eligibility. 414 patients were randomly assigned with 407 included in the ITT population; 206 received mepolizumab and 201 received placebo. Total endoscopic nasal polyp score significantly improved at week 52 from baseline with mepolizumab versus placebo (adjusted difference in medians −0·73, 95% CI −1·11 to −0·34; p

Background Sinonasal fibro-osseous tumors involving the skull base sometimes result in the encasement of the optic canal and can cause the compressive optic neuropathy. This study aimed to elucidate the optimal timing of endoscopic optic nerve decompression (OND) in cases with optic neuropathy caused by fibro-osseous tumors. Methods Medical records were reviewed retrospectively from July 2008 through November 2016. Subjects who underwent surgery with endoscopic OND for optic neuropathy caused by fibro-osseous lesions were enrolled. Pre- and postoperative ophthalmologic evaluation were analyzed, including best-corrected visual acuity, visual field testing, and color vision. Results A total of 9 patients underwent OND. Seven patients had fibrous dysplasia and 2 patients had juvenile ossifying fibroma. Patients included 6 boys and 3 girls. The average age was 15 years with a range of 8–17 years. Symptom duration ranged from 2 months to 4 years. The mean follow-up period was 28 months (range, 0.8–76.4 months). There was no immediate deteriorated vision after OND. Eight eyes (88.9%) were improved and 1 eye (11.1%) had only visual field improvement. However, patients whose visual impairment was in the range of finger count and hand motion were not recovered beyond the quantitatively measurable level even after OND. Conclusions Endoscopic OND in patients with optic neuropathy caused by a fibro-osseous tumor in the sinonasal region is safe and worth trying to improve visual outcomes. Early therapeutic OND is recommended before the patient's visual function is decreased below quantitatively measurable vision.

Background and Objectives Chronic rhinosinusitis with nasal polyps (CRSwNP) recurs frequently after endoscopic sinus surgery (ESS). The aim of study was to evaluate the efficacy of triamcinolone-soaked absorbable gelatin foam (gelfoam) as a treatment for recurred polypoid changes after ESS. Subjects and Method A total of 35 patients and 57 nasal cavities was retrospectively reviewed. All patients underwent triamcinolone-infused gelfoam packing for 1 week under nasal endoscopic guidance. Endoscopic scores were evaluated at 1 week, 1 month, and 3 months. We analyzed clinical characteristics between success and failure groups. Results Endoscopic scores were significantly improved after triamcinolone-soaked gelfoam packing, and the effects were maintained at 3-month follow-up (1.85±0.61 vs. 0.82±0.77, p

Background Immunologic function in innate and adaptive immunity changes with the ageing process. Thus, age-related cytokine profiles in chronic rhinosinusitis (CRS) need to be investigated for precision medicine. Objective The objective of this study was to characterize age-related changes in immunologic profiles according to CRS subtypes. Methods Subjects in control (n = 29), CRS without nasal polyps (CRSsNP, n = 86), and CRS with nasal polyps (eosinophilic NP: ENP, n = 81; non-eosinophilic NP: NENP, n = 113) were enrolled in this study. Twenty markers for type 1/2/3 inflammation and other inflammatory processes were measured in homogenates of sinonasal tissues and statistically analysed. Results In control tissues, type 2/3 and proinflammatory mediators showed an inverse correlation with age. CRSsNP and NENP showed an age-related increase in type 2 cytokines and a decline in type 3 cytokines. Interestingly, the age-related decrease in type 3 mediators was associated with those of CT scores in NENP. ENP showed an age-related increase in type 3 cytokines with type 2 mediators sustained at high levels. Smokers with ENP demonstrated age-associated increases in type 1/2/3 mediators as well as CT scores. These age-related patterns in each CRS were confirmed by statistically adjusting atopy status, smoking history, and disease duration. Conclusion Age-associated cytokine changes differed among CRS subtypes and control tissues. CRSsNP and NENP demonstrated a decline in type 3 mediators and increase in type 2 mediators, whereas type 3 mediators increased with age in ENP.

Objectives Endoscopic prelacrimal medial maxillectomy (EPMM) was previously reported to treat maxillary inverted papilloma. This study aimed to compare prelacrimal recess approach with the conventional Caldwell-Luc approach (CLA) to remove benign maxillary sinus tumors and to evaluate the usefulness of this approach based on our experience. Methods Ten patients who underwent EPMM at our hospital from January 2013 to December 2017 were reviewed. We also reviewed 30 patients who underwent benign maxillary sinus tumor resection via CLA during the same period. From medical records, postoperative pathological results complications due to surgery, and recurrence rate were evaluated. Results There were eight inverted papilloma, one ameloblastoma, and one ossifying fibroma in the EPMM group. In the CLA group, all 30 cases were inverted papilloma. There were no cases of failure at gross total removal during surgery, and no recurrences were observed during follow-up in either groups. Mean follow-up period was 13.0 months in CLA group and 10.8 months in EPMM group. Regarding postoperative complications, 11 patients of the CLA group (37%) and three patients of the EPMM group (30%) had numbness around the cheek and upper lip area after surgery (P=0.715). In the CLA group, there were eight patients who had numbness lasting more than 3 months after surgery, and two patients had numbness for more than 1 year. However, facial numbness disappeared within 3 months in all patients in the EPMM group, in which epiphora was not observed. Conclusion EPMM is the effective surgical approach for resecting benign maxillary sinus tumor compared with CLA. Although facial numbness was reported in EPMM, the duration of numbness was shorter than CLA.

Inflammatory pseudotumor (IPT) in the sinonasal cavity and skull base region is benign non-neoplastic inflammatory process. However, IPT can mimic malignant tumor or infectious disease and there are difficulties in confirmation of diagnosis. The aim of study is to evaluate the clinical significance of immunoglobulin G4 (IgG4) in IPT in terms of steroid response and differential diagnosis with other skull base infiltrative lesions. Medical records were reviewed retrospectively from 1998 to 2016. Subjects diagnosed with IPT by surgical biopsy were enrolled. IgG4 positivity was defined as IgG4/IgG ratio > 0.4. Additionally, IgG4/IgG ratio was calculated in eight skull base osteomyelitis (SBO) patients. Twenty-six IPT patients were included and the average age was 52.3 years, and 57.7% were male and 42.3% were female. Most lesions were involved in the sinuses (88.5%) and the incidence of extension beyond the sinuses itself was as follows: the cheek/hard palate/parapharynx (15.4%), orbit (61.5%), skull base (57.7%), and dura or brain (23.1%). All IPT cases revealed IgG4 + plasma cells and IgG4/IgG ratio over 0.4 was detected in 42.3% (11/26) of cases. In case of SBO, no patients had IgG4/IgG ratio exceed 0.4. Main treatment modality was systemic steroids (61.5%) and other modalities were used: surgery (3.8%), immunosuppressant (7.7%), radiotherapy (30.8%), or a combination of these modalities (15.4%). Steroid responses were not significantly different, but IgG4-positive group tended to have better response to steroid therapy. IgG4-positive and IgG4-negative IPT patients revealed no differences in involvement sites, clinical course, and steroid responses. However, IgG4/IgG ratio and IgG4 + plasma cell count can provide a diagnostic clue for infiltrative skull base lesions such as IPT and a differential diagnosis of SBO.

Background The endoscopic endonasal approach to the infratemporal fossa (ITF) has gained popularity. However, the inferior turbinate and/or lacrimal duct are often removed when performing endoscopic medial maxillectomy for ITF approach, and there is potential risk for empty nose syndrome or epiphora. Although the endoscopic prelacrimal recess approach was introduced to avoid these complications, there were some limitations associated with surgical freedom. We report a 2-port endoscopic technique using both prelacrimal recess and antral window as a means to preserve the inferior turbinate and lacrimal duct, while facilitating instrument availability during ITF tumor resection. Methods We retrospectively reviewed 3 patients between September 2016 and May 2018 who were treated with a modified 2-port technique for ITF tumors. Results There was 1 case of trigeminal schwannoma originating in the mandibular nerve, 1 recurrent meningioma, and 1 paraganglioma. The 2-port technique was not initially planned in these 3 cases, but it was decided to use the technique during surgery because tumors were extensively attached to surrounding muscles and had profuse bleeding. After tumor resection, sinonasal anatomy including inferior turbinate and lacrimal duct was well preserved. Conclusions We propose a hybrid endoscopic surgical procedure for ITF tumors using both endoscopic prelacrimal recess approach and transantral window. This technique provides surgeons an adequate working space via a bimanual technique through 2 different ports, while preserving normal sinonasal structures.

Many physicians recommend endoscopic sinus surgery (ESS) even when an asymptomatic paranasal sinus (PNS) fungal ball is detected incidentally. The aim of this study was to investigate the natural behavior of PNS fungal balls via sinus imaging techniques. A follow-up study of 74 pathologically confirmed fungus balls was conducted in 70 patients who underwent multiple head and neck computed tomography (CT) scans or magnetic resonance imaging (MRI). We investigated the changes in symptoms and lesion size, as well as any new occurrences. Of the 74 fungus balls detected in 70 patients, we observed the renewed formation of a fungal ball in 21 patients, which was not present on initial imaging conducted over a period of 2–162 months. The fungal ball was already present in 53 patients on the initial screening, and the longest follow-up was 197 months (range 1–197 months). Of these 53 lesions, 29 lesions showed an increase in size (29/53, 54.7%), whereas 12 lesions were not associated with any clinical symptoms (12/53, 22.6%). In the 21 newly formed fungal balls, further development was observed in 10 lesions, with 4 lesions showing an increase in size. Thus, size increment occurred in 33 of the 57 fungus balls. The fungal balls can exist without local tissue invasion for up to 17 years and new formation of the fungal balls was observed even within 2 months, especially when accompanied by initial clinical symptoms of sinusitis.

Objectives. Fibro-osseous lesions of the paranasal sinuses can present various clinical manifestations. This study aimed to report the long-term clinical course of benign fibro-osseous lesions (BFOLs) in the paranasal sinuses, including clinical and radiologic features.Methods. Radiologically confirmed BFOLs between 1994 and 2016, with the exclusion of osteoma cases, were retrospectively reviewed. We compared demographic characteristics between the surgery and observation groups. The reasons for the imaging study, radiographic features, histopathology, and clinical course based on serial image scans were analyzed.Results. In total, 183 subjects were selected from a thorough review of head and neck radiologic tests (n=606,068) at a tertiary referral hospital over 22 years. Patients’ mean age was 28.6±18.1 years, and 56.3% were males. A diagnostic imaging workup was performed in 55.7% of patients due to facial asymmetry, headache, skull mass, or other symptoms related to BFOLs. In other patients (37.7%), BFOLs were found incidentally on computed tomography or magnetic resonance imaging. The most common diagnosis was fibrous dysplasia, followed by ossifying fibroma, based on both radiologic exams and histopathologic results. In total, 42.6% of the patients underwent surgery because of subjective symptoms or esthetic concerns. The patients who underwent surgery were younger (P

Background Radionecrosis is a complication of nasopharyngeal carcinoma (NPC) that is difficult to treat. Endoscopic debridement is the first-line treatment for radionecrosis. After debridement, however, either bone or the internal carotid artery is exposed and requires mucosal coverage. Objectives This study sought to demonstrate the effectiveness of a nasoseptal flap (NSF) after endoscopic debridement of radionecrosis in the reconstruction ofnasopharyngeal or skull base defects. Methods Nine patients with NPC who underwent navigation-guided endoscopic debridement, followed by NSF reconstruction between April 2013 and July 2016, were included. The patients' clinical features and outcomes were evaluated. Results All nine patients had headaches, and eight had a foul odor associated with their radionecrosis. One patient underwent three radiotherapy treatments, four had two treatments, and the remaining four had just one treatment. The foul odor disappeared after treatment in all the patients who had been affected. The headache was significantly reduced after treatment in all patients. The NSF detached in two patients. In one patient, NSF failed, and the patient experienced postoperative rupture of the internal carotid artery. In the seven other patients, the NSF successfully covered the resultant defects, despite one intraoperative internal carotid artery rupture. Only two patients required further debridement, whereas the others experienced complete healing after just one surgical procedure. The nasopharyngeal surface was healthy-appearing in eight patients (median follow-up, median 11 months). Conclusion Reconstruction by using NSF after endoscopic debridement for radionecrosis of NPC allowed for faster healing and reduced the need for further debridement.

Objectives This study evaluated whether the symptoms of laryngopharyngeal reflux (LPR) change after multilevel surgery for obstructive sleep apnea (OSA). Methods Patients who underwent multilevel surgery for OSA between April 2009 and September 2014 were enrolled in this study. All patients underwent preoperative polysomnography prior to surgery and were asked to complete the reflux symptom index (RSI) questionnaire before and after surgery. Results Of 73 enrolled patients, 24 (33%) reported an RSI score >13 and were thus classified as having reflux. The mean RSI score before surgery was 11.48±7.95; this number decreased to 4.95±6.19 after surgery (P

The aim of this study is to determine the association among various sleep parameters for obstructive sleep apnea (OSA) and subclinical cardiovascular disease measured by coronary artery calcium (CAC) score. A cross-sectional study was conducted among 461 patients who underwent both polysomnography (PSG) and coronary artery computed tomography to evaluate CAC score. For each participant, coronary artery computed tomography was conducted within 12 months of PSG. We evaluated the possible association among various PSG parameters by evaluating overnight-attended PSG and CAC. A univariate analysis with lowest SaO 2 and stage 3 sleep % during sleep was significantly associated with CAC score (β = −5.528, 95% confidence interval [CI] −9.179 to −1.777, p = 0.004 and β = −8.658, 95% CI −16.461 to −0.855, p = 0.030, respectively). However, after adjustment for possible confounders, only the lowest SaO 2 was independently associated with CAC score (β = −5.234, 95% CI −9.215 to −1.253, p = 0.010). This association was stronger in participants aged ≥60 years (β = −26.966, 95% CI −41.874 to −12.058, p = 0.001). In a univariate analysis, apnea-hypopnea index, stage 3 sleep %, and moderate and severe OSA were significantly associated with CAC presence (odds ratio [OR] 1.010, p = 0.035; OR 0.949, p = 0.039; OR 2.186, p = 0.013; and OR 2.019, p = 0.020, respectively). However, after adjusting for possible confounders, there was no significant association. In conclusion, the patients with intermittent hypoxemia during sleep should be considered for evaluation of coronary artery calcification to detect cardiovascular disease in subclinical status.

Background Poloxamer 407 (P407) has been investigated for an intranasal drug delivery system. However, there is little known about the distribution and clearance of intranasally applied P407. The purpose of this study was to evaluate the distribution and clearance time of P407 in an animal model. Methods Five male pigs were administered the experimental solution (18% of P407 with 0.01% of fluorescein) and the control solution (normal saline with 0.01% of fluorescein) into their right and left nasal cavity, respectively. For quantitative analysis, endoscopic images of each nasal cavity were taken immediately and at 10, 20, 30, and 60 minutes after intranasal administration. Results The experimental group showed a significantly wider distribution of fluorescein than the control group at 10, 20, and 30 minutes. The experimental group also showed a significantly higher mean intensity of fluorescein than the control group at 10, 20, and 30 minutes. The mean intensity in the control group was significantly decreased during 30 minutes but the mean intensity in the experimental group was significantly decreased during 60 minutes. Conclusion A substantial amount of P407 remained in the nasal cavity for at least 30 minutes post-application.

Objectives Compliance with continuous positive airway pressure (CPAP) treatment remains a primary concern for improving treatment outcomes of obstructive sleep apnea. There are few studies that have considered the role of upper airway anatomy on the compliance with CPAP. We hypothesized that upper airway anatomy would influence the compliance with CPAP. Methods One hundred out of 161 consecutive patients were enrolled in this study. The following possible determinants were tested against CPAP use: demographic and anthropometric data, minimal cross-sectional area on acoustic rhinometry, cephalometric and polysomnographic data, questionnaires of Epworth sleepiness scale and Beck depression index, and histories of previous upper airway surgery, degree of nasal obstruction, daily cigarette consumption, and weekly frequency of alcohol intake. Results Univariate analysis showed that histories of previous upper airway surgery and less frequent alcohol consumption, and longer mandibular plane-hyoid length (MP-H) on cephalometry were associated with longer average daily CPAP use. After adjustment for the confounding factors with multiple linear regression analysis, alcohol consumption and MP-H were still associated with the compliance with CPAP significantly. Conclusion To improve compliance with CPAP, careful evaluations of upper airway problems and life style are important before initiating CPAP.

Background Acute invasive fungal rhinosinusitis (AIFR) is an aggressive opportunistic infection with a high mortality rate. Recently, non-invasive techniques have been introduced for diagnosis of invasive fungal disease. The purpose of this study is to evaluate the diagnostic significance of serum galactomannan measurement in patients with AIFR. Methodology We conducted a retrospective case-control study of 28 patients with AIFR and 36 fungus ball (FB) patients. We evaluated clinical, laboratory, and pathologic findings along with disease course. Results In 28 patients with AIFR, there were 21 cases of invasive aspergillosis (IA) and 7 cases of invasive mucormycosis (IM). The control group was comprised of 36 patients with FB. The three-group analysis showed a statistically significant difference among the groups. At the cut-off value of 0.48, the sensitivity and specificity were 71.4% and 93.0%, respectively. Comparison of mean serum galactomannan levels in 5 non-survivors and 9 survivors at initial measurement showed no significant difference, but that became significantly different 1 week later. Statistical analysis showed that the levels of serum galactomannan decreased significantly according to the measurement-point in within survivor-group analysis. The difference in between survivor-groups analysis was also significant. Conclusion Serum galactomannan measurement seems useful for early diagnosis and discrimination of fungal species in patients with AIFR. In addition, clinical outcomes may be related to the levels and patterns of serum galactomannan, especially in IA. The appropriate measurement of galactomannan might be helpful in treating the patients at high risk for AIFR.

Introduction Cerebrospinal fluid (CSF) leaks usually happen in the early postoperative period. However, delayed CSF leak can happen several years after treatment. The purpose of this study was to review the characteristics and clinical course of delayed CSF leak after treating skull base tumors. Methods We treated 9 patients with delayed CSF leak (occurring at least 3 months after treatment) between December 2015 and February 2018. Clinical data including initial treatment modality for skull base tumor, time between treatment and CSF rhinorrhea, and the result of endoscopic CSF repair were evaluated by retrospective chart review. Results Nine patients with delayed CSF leak were evaluated. The mean age was 42.3 ± 5.2 (mean ± SD) years. Six patients with pituitary adenomas, 1 with a Rathke cleft cyst, 1 with a meningioma, and 1 with an osteosarcoma were enrolled. Seven patients (78%) received radiation, and the mean radiation dose was 55.7 ± 2.6 Gy. The median time between the end of treatment for the skull base tumor and CSF rhinorrhea was 137.0 (interquartile range 24–145) months. Seven patients (78%) had meningitis at the time of operation. CSF rhinorrhea was treated with endoscopic reconstruction using a multilayer technique. Meningitis was improved without neurologic sequelae after reconstruction and antibiotic therapy. One patient had recurrence of CSF leak. Conclusion Patients with delayed CSF leak are more likely to have a history of radiation and to present with meningitis at diagnosis. Therefore, CSF rhinorrhea should always be suspected, even several years after treatment, if early symptoms of CSF leak develop in patients with a history of skull base tumor.

Background Asthma and allergic rhinitis (AR) are chronic inflammatory diseases of airway and affect the disease severity each other. Objective We performed this study to examine whether nasal saline irrigation (NSI) improves bronchial hyperresponsiveness and clinical parameters in children with asthma and allergic rhinitis (AR). Methods We enrolled 20 children with AR and asthma aged between 6-18 years. Patients were randomized into two groups: irrigation group (8 boys and 2 girls) and control group (8 boys and 2 girls). The irrigation group performed daily NSI. All patients received 12-week treatment with montelukast, levocetirizine, and inhaled glucocorticoids. Provocative concentrations of methacholine causing a 20% decrease in FEV1 (PC20), Asthma Control Test (ACT), the Questionnaire for Quality-of-Life Specific to Allergic Rhinitis in Korean Children (QQOL-ARK) and exhaled nitric oxide (FENO) were compared before and after the study. Results The PC20 at week 12 was higher than baseline measurements in the irrigation group (P = 0.017), while there was no difference in PC20 before and after treatment in the control group (P = 0.333). ACT score increased after 12 weeks of NSI (P = 0.007), while QQOL-ARK score decreased compared to baseline scores (P = 0.028) in the irrigation group. No differences in ACT and QQOL-ARK were found between weeks 0 and 12 in the control group. No differences were found in the median value of changes in PC20, ACT, QQOL-ARK and FENO between the irrigation and control groups. Conclusions Our results suggest that NSI is beneficial for treatment of asthma and AR in children.

Purpose Despite medical and surgical treatments, some cases of nasal polyps (NP) exhibit recidivism. However, the endotype of refractory chronic rhinosinusitis with NP (CRSwNP) remains unclear. Therefore, the objective of this study was to characterize the immunological profile of refractory CRSwNP. Methods The control (n =23), primary NP group (pNP, n =70) and refractory NP group (rNP, n =86) were enrolled in this study. Patients who underwent revision surgeries due to failed maximal medical treatment after primary surgery were defined as the rNP group. A total of 18 inflammatory markers were investigated in nasal tissues using multiplex cytokine assay or enzyme-linked immunosorbent assay. Results The clinical characteristics of rNP included more extensive disease and worse clinical course after surgery. Additionally, rNP subjects showed higher infection rate (mucopurulence and culture-positive rate), more frequent use of antibiotics and suffered from symptomatic bacterial infection, increased asthma morbidity compared to pNP. Cytokine profile analysis showed that levels of Th17-associated mediators (myeloperoxidase, interleukin (IL)-8, IL-17A and IL-23), B-cell activating factor (BAFF) and Th1 cytokine (interferon-γ) were up-regulated in rNP compared to controls and pNP. Human neutrophil elastase-positive cells were also enhanced in rNP compared with pNP. Upregulation of Th17/Th1mediators and BAFF were observed in rNP, regardless of tissue eosinophilia or asthmatic comorbidity. Interestingly, eosinophilic markers, such as eosinophil cationic protein and C-C motif chemokine ligand 24, were up-regulated in asthmatic rNP compared to pNP and controls. Levels of anti-dsDNA immunoglobulin (Ig) G and IgA were up-regulated in rNP and highest in asthmatic eosinophilic rNP among subtypes of rNP. Conclusions Our results suggest that Th17/Th1-associated mediators and BAFF may play a role and be a potential therapeutic target in refractory CRSwNP. Additionally, eosinophilic markers and autoantibodies may contribute to refractoriness in asthmatic rNP.

The aim of this study was to evaluate the effect of topical administration of onion (Allium cepa) extract on nasal cavity for treatment of allergic rhinitis (AR). BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and challenged with intranasal instillation of OVA with or without onion extracts for five times a week on 3 consecutive weeks. Allergic symptom score according to frequencies of sneezing, serum total and OVA specific immunoglobulin E (IgE) level, cytokine levels of nasal mucosa and eosinophilic infiltration were analyzed. Allergic symptom score, serum total and OVA specific IgE, cytokine levels of nasal mucosa (interleukin (IL)-4, IL-5, IL-10, IL-13, IFN-γ, TNF-α and COX-2) and eosinophilic infiltration were higher in allergic mouse group than negative control group. Topical application of onion extracts significantly reduced allergic symptoms and OVA specific IgE levels. Cytokine levels of IL-4, IL-5, IL-10, IL-13 and IFN-γ were significantly decreased in groups treated with onion extract. In addition, eosinophil infiltration of nasal turbinate mucosa was also significantly decreased after treatment with onion extract. Topical administration of onion extract significantly reduces allergic rhinitis symptom and allergic inflammatory reaction in a murine allergic model. It can be assumed that the topical application of onion extract regulates allergic symptoms by suppressing the type-1 helper (Th1) and type-2 helper (Th2) responses and reducing the allergic inflammatory reaction.

Summary Background In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. Methods We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. Findings 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% [23/117] vs 5% [3/58] in group B vs 1% [4/500] in group C; p vs 11 days [6–12]; p Interpretation Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. Funding None.

Invasive fungal sinusitis (IFS) has rarely been reported to develop from non-IFS. The purpose of this study was to disclose the nature of the extrasinonasal infiltrative process in the presence of a sinonasal fungus ball (FB).We retrospectively reviewed the medical records, computed tomography, magnetic resonance images of 13 patients with sinonasal FB and the extrasinonasal infiltrative process. Based on histology and clinical course, we divided the extrasinonasal infiltrative process into IFS and the nonfungal inflammatory/infectious process (NFIP). The images were analyzed with particular attention to the presence of cervicofacial tissue infarction (CFTI).Of the 13 patients, IFS was confirmed in only one, while the remaining 12 were diagnosed to have presumed NFIP. One patient with IFS died shortly after diagnosis. In contrast, all 12 patients with presumed NFIP, except one, survived during a mean follow-up of 17 months. FB was located in the maxillary sinus (n=4), sphenoid sinus (n=8), and both sinuses (n=1). Bone defect was found in five patients, of whom four had a defect in the sphenoid sinus. Various sites were involved in the extrasinonasal infiltrative process, including the orbit (n=10), intracranial cavity (n=9), and soft tissues of the face and neck (n=7). CFTI was recognized only in one patient with IFS.In most cases, the extrasinonasal infiltrative process in the presence of sinonasal FB did not seem to be caused by IFS but probably by NFIP. In our study, there were more cases of invasive changes with the sphenoid than with the maxillary FB.

Objective Patients experience significant postoperative sinonasal symptoms for the first few months after endoscopic transnasal transsphenoidal approach (ETN-TSA) surgery. We modified this technique by bypassing the nasal mucosa and approaching through the septum bilaterally. In this study, we analyze whether these technical modifications, which we have termed the endoscopic modified transseptal transsphenoidal approach (EMTS-TSA), decrease postoperative sinonasal morbidity after endoscopic TSA. Methods We retrospectively reviewed a prospectively collected database. Patients who underwent endoscopic TSA from December 2012 to June 2014 were included. Thirty patients underwent ETN-TSA, and 51 underwent EMTS-TSA. Sino-Nasal Outcome Test-20, anterior skull base nasal inventory, and visual analog scale (VAS) for subjective olfaction were evaluated before and 1 and 3 months after surgery. Cross Cultural Smell Identification Test also was measured before and 3 months after surgery. Results There was a significant difference between the preoperative and 3-month VAS for olfaction in the ETN-TSA group (from 92.5 to 81.3; P = 0.002) but not the EMTS-TSA group (from 90.6 to 88.8; P = 0.403). There was no statistical difference in Sino-Nasal Outcome Test-20 or Cross-Cultural Smell Identification Test scores between 2 groups during follow-up. The EMTS-TSA group scored better than the ETN-TSA group in the anterior skull base nasal inventory subdomain ("nasal discharge," "urge to blow," and "trouble breading") 1 month postoperatively. Conclusions EMTS-TSA could preserve almost all nasal mucosa, including the septum and turbinates. EMTS-TSA may be useful for preserving early postoperative olfactory function and some sinonasal quality of life. We believe that EMTS-TSA is a good endoscopic pituitary surgery option.

Background The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. Conclusion As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.

The aim of this study was to compare sinonasal-related quality of life (QOL) in patients treated by extended or transsellar endoscopic skull base surgery.Prospective data analysis.Prospectively collected data from patients who underwent endoscopic skull base surgery between 2012 and 2017 were analyzed. Primary outcomes were preoperative Sino-Nasal Outcome Test-20 (SNOT-20) scores and then 1-month, 3-month, and 6-month follow-up. Comparative analysis was performed between the endoscopic transsellar approach (ETA) group (n = 647) and an extended endoscopic endonasal approach (EEEA) group (n = 120). In ETA group, the SNOT-20 score was compared between patients with a nasoseptal flap (NSF) (ETA-NSF) and without an NSF (ETA-no NSF).The mean total SNOT-20 score was significantly worse in the EEEA than ETA group at 1, 3, and 6 months postoperatively (P .05). Although there was no significant difference in total SNOT-20 score between the ETA-NSF and ETA-no NSF group at 3 and 6 months after surgery, the percentage of patients with significant change (≥0.8) in the SNOT-20 score was higher in the NSF used group at 1, 3, and 6 months postoperatively (22.92% vs. 13.51%, P = .029; 20.59% vs. 5.59%, P = .039; and 24.00% vs. 4.03%, P = .003, respectively). According to multivariate analysis conducted regarding factors that deteriorate sinonasal QOL at 6 months following surgery, only NSF usage is significantly associated with poor outcome (odds ratio: 4.371, P = .011) CONCLUSIONS: Sinonasal-related QOL was significantly worse in patients treated by the EEEA versus ETA. Use of an NSF is the only poor prognostic factor in sinonasal QOL after endoscopic skull base surgery.2b Laryngoscope, 129:1318-1324, 2019.

Endoscopic endonasal approach to infratemporal fossa (ITF) had gained popularity. However, the inferior turbinate and/or lacrimal duct are often removed when performing endoscopic medial maxillectomy for ITF approach and there were potential risk of empty nose syndrome or epiphora. Although endoscopic prelacrimal recess approach (EPRA) had been introduced to avoid these complications, there were some limitations associated with surgical freedom. The objective was to report the two-port endoscopic technique using both prelacrimal recess and antral window as a means to preserve inferior turbinate and lacrimal duct while facilitating instrument availability during ITF tumor resection.We retrospectively reviewed three patients between September 2016 and May 2018 who were treated with this modified two port technique for ITF tumors.There was one case of trigeminal schwannoma originating in the mandibular nerve, one recurrent meningioma, and one paraganglioma. This two-port technique was not initially scheduled in these three cases but decided during surgery because tumors were extensively attached to surrounding muscles and have profuse bleeding. After tumor resection, sinonasal anatomy such as inferior turbinate or lacrimal duct was well preserved.We propose a hybrid endoscopic surgical procedure for ITF tumors using both EPRA and transantral window. It allows the surgeons to have an advantage of utilizing an adequate working space by bimanual technique through different two ports while preserving normal sinonasal structures.

Background The most common tests for allergen sensitization in patients with allergic rhinitis are the skin-prick test (SPT) and an in vitro test to detect serum specific immunoglobulin E (sIgE). However, in vitro allergen test results were interpreted dichotomically as positive or negative at a threshold of 0.35 kU/L of sIgE, regardless of the patient characteristics or antigen types. Objective The purpose of this study was to determine the cutoff value for sIgE in house-dust mites and animal dander, and to analyze differences in cutoff value according to age and gender. Methods A total of 16,209 patients with more than one allergic rhinitis symptom who underwent both SPT and serum sIgE testing were retrospectively evaluated between March 2008 and May 2012. There were 9374 male (57.8%) and 6835 female (42.2%) patients. The mean age was 31.8 years (range, 2–89 years). The criterion standard for allergen sensitization was defined as a wheal of >3 mm or an allergen-to-histamine ratio of ≥1 in SPT results. The Youden index was used to calculate the cutoff value of sIgE. Results Cutoff values of sIgE for Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, and dog were 0.69, 1.16, 0.13, and 0.45 kU/L, respectively. The cutoff value of sIgE changed according to age for D. pteronyssinus and D. farinae but not for cat and dog allergens. When categorizing according to age group, the cutoffvalues ofsIgE for D. pteronyssinus and D. farinae had a tendency to decrease with age. There was no significant difference in cutoffvalue according to gender. Conclusion The cutoffvalue for sIgE differed for each antigen and changed with age. Physicians should select the proper cutoffvalue for sIgE for appropriate criteria according to antigen and patient age rather than using a uniform cutoffvalue.

Rhinosinusitis in patients who undergo kidney transplantation (KT) might have specific clinical characteristics due to immune status of recipients. The aim of this study was to identify the clinical course of rhinosinusitis after KT and to evaluate the efficacy of routine sinonasal evaluation before KT. The study included 1589 kidney transplant adult patients who underwent preoperative sinonasal evaluation including sinonasal symptoms, nasal endoscopy, and plain X-ray between November 1994 and December 2013 (19 years). Demographic data and clinical course of rhinosinusitis were evaluated retrospectively. The study population consisted of 897 men (56.5%) and 692 women (43.5%) with a mean age of 42.5 years (range 18–75 years). The prevalence of pre-KT rhinosinusitis was 4.2% (66/1589), and that of post-KT rhinosinusitis was 0.9% (13/1503). The prevalence of acute rhinosinusitis and chronic rhinosinusitis (CRS) was 0.13 and 2.33% in pre-KT patients and 0.2 and 0.6% in post-KT patients, respectively. The recurrence rate of CRS in pre-KT patients was 37.8%. Of the 27 asymptomatic patients, the recurrence rate was 11.1%. Symptomatic patients had more severe endoscopic findings and higher Lund-Mackay CT scores than asymptomatic patients. The prevalence of fungal ball (0.8% in pre-KT and 0.3% in post-KT patients) was similar to that in the general population, and only one patient experienced invasive fungal rhinosinusitis after KT. No patient with pre-KT rhinosinusitis experienced severe complications. The prevalence and recurrence rate of rhinosinusitis in KT patients was not increased after KT. Symptomatic patients needed surgical or medical treatment before KT, but asymptomatic patients showed no deterioration of clinical course after KT. Routine sinonasal evaluation for asymptomatic patients is not recommended before KT.

Background Endoscopic findings of extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, are heterogeneous, but not fully understood. The objective of this study was to evaluate the role of nasal endoscopic examination and its implications for treatment of stage I/II ENKTL. Methods This retrospective study included 60 consecutive patients diagnosed with stage I/II ENKTL, nasal type, from 2000 to 2011. Results The endoscopic findings were classified into early (45%) and advanced (55%) lesions. Furthermore, the primary tumor extent assessed by endoscopy was significantly correlated with the radiologic imaging (p < 0.001). The results of univariate analysis showed that the patients with advanced lesions had worse overall survival (p = 0.004) and disease-free survival (p = 0.001) than those with early lesions. In multivariate analysis, advanced lesions on nasal endoscopy was an independent prognostic factor (p = 0.024; hazard ratio 5.29; 95% confidence interval, 1.25–22.39). Conclusion We found that nasal endoscopic findings were important prognostic factors in stage I/II ENKTL, nasal type, suggesting that comprehensive endoscopic evaluation of primary tumor should be performed in this setting.

Background The aim of this work was to evaluate factors that influence local recurrence and survival after surgical resection of sinonasal malignant melanoma, using a large population-based multicenter study in Korea. Methods Retrospective analysis was performed for 155 newly diagnosed sinonasal malignant melanoma patients gathered from 15 university hospitals throughout Korea. Demographic data, tumor characteristics, surgical approach, adjuvant treatment, recurrence, and outcomes were analyzed. Results Three-year and 5-year overall survival rates were 48.8% and 40.1%, respectively. Local recurrence rate was 46.6%, with a mean recurrence time of 15.5 months. On multivariate analysis, patients who underwent surgery that included an endoscopic approach showed decreased local recurrence rate (p = 0.042) and increased survival rate (hazard ratio [HR], 1.702; 95% confidence interval [CI], 1.007 to 2.875; p = 0.047) compared to those who underwent an external approach. Patients with postoperative radiotherapy showed a decreased local recurrence rate (p = 0.001), but without impact on survival rate. Male gender, tumor beyond the nasal cavity, and presence of distant metastasis were associated with poor survival. Conclusion An endoscopic-including surgical approach was associated with improved local control and survival in sinonasal malignant melanoma patients. Postoperative radiotherapy helped increase the local control rate.

Background There have been few comparative studies on olfactory function and sinonasal-specific quality of life (QOL) after endoscopic or microscopic surgery using a transsphenoidal approach (TSA). Methods A retrospective review of a prospectively collected database was performed. Thirty-five patients who underwent a transnasal endoscopic approach and 20 patients who underwent a transnasal transseptal microscopic approach for treatment of pituitary adenoma were evaluated. An anterior skull base (ASK) nasal inventory and a subjective visual analog scale (VAS) (0-100) for olfaction were evaluated before and at one and three months after surgery. A cross-cultural smell identification test (CC-SIT) and a butanol threshold test (BTT) were also measured before and three months after surgery. Results There was no significant difference in subjective olfaction or CC-SIT or BTT score between the endoscopic and microscopic groups. The microscopic group (11.35 ± 3.67 and 9.72 ± 2.54, respectively) showed better ASK nasal inventory outcomes at one and three months after surgery compared with the endoscopic group (14.00 ± 4.85 and 11.70 ± 3.28, respectively; p = 0.029 and 0.036, respectively) especially in the subdomains of “nasal crusting” and “urge to blow nose.” Conclusion Transnasal transseptal microscopic pituitary surgery confers a better early postoperative sinonasal QOL with a comparable olfactory outcome compared with the endoscopic approach. Although many believe that an endoscopic approach is less invasive, preservation of the sinonasal mucosa proves to be more important in terms of sinonasal QOL than use of an endoscope or microscope.