Bisphenol A triggers activation of ocular immune system and aggravates allergic airway inflammation.

Bisphenol A (BPA) is widely used in manufacturing plastic products, and it has been reported that exposure through the airway or orally aggravates allergic airway inflammation. Because BPA is detected in the atmosphere and indoor environments, the eyes can also be exposed to BPA. After ocular exposure to BPA and antigen via eye drops, we observed enhanced antigen uptake of antigen-presenting cells (APCs) in tear duct-associated lymphoid tissue (TALT). Additionally, we observed the formation of germinal center (GC) B cells in TALT and induction of allergic airway inflammation in mice sensitized with BPA and antigen via eye drops. We also found that DNAX-activating protein of 12 kDa (DAP12)-deficient mice displayed impaired activation of APCs enhanced by ocular exposure to BPA. These results indicate that ocular sensitization to BPA and allergen triggers allergic inflammation via TALT activation, and that DAP12 might be a key molecule for modulating the ocular immune system.

Distribution of periodontopathic bacterial species between saliva and tonsils.

Periodontopathic bacteria cause an inflammatory disease localized in the periodontal tissue and are associated with various conditions in other body parts. The distribution of periodontopathic bacterial species in the tonsils is unknown, even though the tonsils are located close to the oral cavity, and inflammation of the tonsils causes various systemic diseases. We detected the major periodontopathic bacterial species residing in saliva and tonsil specimens from 25 subjects undergoing tonsillectomy. Nine of the ten major periodontopathic bacterial species were detected by polymerase chain reaction of tonsil specimens, among which Campylobacter rectus was the most common (80.0%), followed by Porphyromonas gingivalis (36.0%). The other seven types of periodontopathic bacterial species were distributed with 0% to 25.0% abundance in the tonsil specimens. C. rectus had a high detection rate in tonsil specimens (> 75.0%), regardless of whether it was detected in the corresponding saliva specimens. However, the detection rate for P. gingivalis in tonsil specimens was significantly higher in subjects with P. gingivalis-positive saliva (77.8%) than in those with P. gingivalis-negative saliva (6.3%; P < 0.001). Furthermore, 75.0% of P. gingivalis in tonsil specimens did not have the known fimA gene that encodes the 41-kDa filamentous appendage protein FimA, which is expressed on the cell surface of the bacteria. Our results suggest that certain periodontopathic bacterial species are detected in the tonsils either independently of or depending on their distribution in the oral cavity and may be involved in tonsil-related diseases.

Relationship between IgA Nephropathy and Porphyromonas gingivalis; Red Complex of Periodontopathic Bacterial Species.

IgA nephropathy (IgAN) has been considered to have a relationship with infection in the tonsil, because IgAN patients often manifest macro hematuria just after tonsillitis. In terms of oral-area infection, the red complex of periodontal bacteria (Porphyromonas gingivalis (P. gingivalis), Treponema denticol (T. denticola) and Tannerella forsythia (T. forsythia)) is important, but the relationship between these bacteria and IgAN remains unknown. In this study, the prevalence of the red complex of periodontal bacteria in tonsil was compared between IgAN and tonsillitis patients. The pathogenicity of IgAN induced by P. gingivalis was confirmed by the mice model treated with this bacterium. The prevalence of P. gingivalis and T. forsythia in IgAN patients was significantly higher than that in tonsillitis patients (p < 0.001 and p < 0.05, respectively). A total of 92% of tonsillitis patients were free from red complex bacteria, while only 48% of IgAN patients had any of these bacteria. Nasal administration of P. gingivalis in mice caused mesangial proliferation (p < 0.05 at days 28a nd 42; p < 0.01 at days 14 and 56) and IgA deposition (p < 0.001 at day 42 and 56 after administration). Scanning-electron-microscopic observation revealed that a high-density Electron-Dense Deposit was widely distributed in the mesangial region in the mice kidneys treated with P. gingivalis. These findings suggest that P. gingivalis is involved in the pathogenesis of IgAN.

IL-12 regulates the expansion, phenotype, and function of murine NK cells activated by IL-15 and IL-18.

NK cells, which are composed of phenotypically and functionally heterogeneous subpopulations, play critical roles in immunity against cancer. The mechanism of generation of distinct subsets such as the effector and regulatory subtypes is unclear. Here, we show that this process comprises several steps, including generation of proliferating, highly cytotoxic cells activated by IL-15/IL-18 and differentiation into distinct cell populations induced with IL-12. Freshly prepared murine splenic NK cells expressed IL-15Rs and IL-18Rs and rapidly began to proliferate following stimulation with IL-15/IL-18. The proliferating NK cells highly expressed various activation markers such as B220, CD49b (DX5), lysosome-associated membrane glycoprotein 1 (LAMP-1), DNAX accessory molecule 1, perforin, and granzyme B and showed reduced expression of natural killer cell p46-related protein (NKp46) and IL-18Rα. These cells exerted strong cytotoxicity against YAC-1 cells, but did not secrete cytokines. IL-12 rapidly activated STAT4 in these cells, induced IFN-γ production, and then upregulated p21 and p27, leading to withdrawal from the cell cycle. In parallel, IL-12-stimulated cells gradually reduced cytotoxicity, decreased expression of activation markers, and instead increased expression of Sca-1, CD25, CD49a, and NKp46. Some IL-15/IL-18-induced cells strongly expressed PD-1, whereas NK cells induced with IL-15/IL-18 and IL-12 expressed high levels of T cell immunoglobulin mucin-3, LAG-3, and natural killer group 2 A. Furthermore, these cells spontaneously secreted IL-10 and TGF-ß following prolonged incubation. Thus, IL-12 regulates expansion of NK cells activated with IL-15/IL-18, influences the population size of highly cytotoxic cells, and induces differentiation to unique cells sharing some phenotypes of ILCs.

Usefulness of our proposed olfactory scoring system during endoscopic sinus surgery in patients with chronic rhinosinusitis.

INTRODUCTION: The primary aim of the current study was to examine the usefulness of our proposed olfactory scoring system in chronic rhinosinusitis (CRS) patients with olfactory disorders (n = 213) receiving endoscopic sinus surgery (ESS). MATERIALS AND METHODS: Analyzed patients were divided into two groups: an eosinophilic CRS (ECRS) group (n = 153); and a non-ECRS group (n = 60). The T&T recognition threshold test was used to evaluate olfaction at baseline and at 3 and 12 months after ESS. Patients with mean recognition threshold < 2.0 at 3 or 12 months or with a decrease of ≥ 1.0 as compared with baseline were defined as showing clinical improvement. We scored mucosal conditions as normal (0 points), edema (1 point), and polyp (2 points) at the canopy of olfactory cleft (OC), middle and superior turbinates, superior nasal meatus, and sphenoethmoidal recess during ESS. The total score of OCs (SOCs) was calculated (range 0-20 points). We compared SOCs between ECRS and non-ECRS groups. Factors related to olfactory improvement were also investigated using uni- and multivariate analyses. RESULTS: SOCs in the ECRS and non-ECRS groups showed significant correlations with mean recognition thresholds at baseline and at 3 and 12 months. In the multivariate analysis for predicting improvement of mean recognition threshold, lower SOCs were significantly associated with olfactory improvement factors at 3 and 12 months postoperatively in the ECRS group. CONCLUSION: SOCs appears promising for estimating olfactory prognosis after ESS in CRS patients.

Nasal Symptom Questionnaire: Our Proposed Scoring System and Prognostic Factors in Chronic Rhinosinusitis.

OBJECTIVES: We aimed to verify the usefulness of our proposed nasal symptom questionnaire (NSQ) scoring system and to determine predictors linked to the improvement in nasal symptoms in chronic rhinosinusitis (CRS) patients undergoing endoscopic sinus surgery (ESS). PATIENTS AND METHODS: Ninety-one CRS patients undergoing ESS and 144 volunteers with results of NSQ available were enrolled. The NSQ consists of 10 items. Receiver-operating-characteristic (ROC) curve, area under the ROC curve (AUC), internal consistency, and test-retest reproducibility of the NSQ were analyzed. The relationship of the NSQ score with the visual analogue scale (VAS) was examined. After classifying into two groups, i.e., (i) "improvement group" and (ii) "no-improvement group," factors linked to the improvement in NSQ after ESS were investigated. RESULTS: ROC-AUC (0.9318), the Cronbach α coefficient (0.8696), and the test-retest coefficient (0.8131) showed high reliability. NSQ score significantly correlated with VAS in both pre- (p < 0.0001, rs = 0.6007) and postoperative stages (p < 0.0001, rs = 0.5975). The postoperative NSQ scores significantly decreased compared with baseline levels (p < 0.0001). In multivariate analysis, the computed tomography (CT) score by the Lund-Mackay scoring system revealed to be significant (p = 0.0481). CONCLUSION: Our proposed NSQ scoring system was well verified. The CT score can be helpful for predicting the improvement in nasal symptoms after ESS in CRS patients.

Clinical Study of 1,515 Patients Presenting with Epistaxis Over the Last 6 Years.

AIM: This study reviews our clinical experience of patients with epistaxis and discusses proper management. PATIENTS AND METHODS: We retrospectively investigated 1,515 patients with epistaxis treated in our department between 2005 and 2010. RESULTS: Men over 50 years old predominated. More than half of the patients (n = 828) first visited after consultation hours, and 40% (n = 606) were brought by ambulance. The most common underlying diseases were circulatory diseases (69%, n = 1,047). Antithrombotics were being administered to 23% (n = 345). Kiesselbach's plexus was the most commonly observed bleeding site (51%, n = 769). In 20% (n = 297), no bleeding point was confirmed because hemostasis had been achieved on arrival. Anterior packing was the most common primary treatment, followed by electrocauterization. Hospitalization was required in 2% (n = 30). Re-bleeding occurred within 14 days after primary treatment in 14% (n = 206). Surgical treatment was performed for 5% (n = 11). CONCLUSIONS: Patients showing repeated pulsatile arterial bleeding require hospitalization for surgical therapy, although outpatient therapy is sufficient in most cases. A risk of re-bleeding should be considered if patients show unclarified bleeding points and circulatory diseases.

Clinical Features of Patients Treated with Endoscopic Sinus Surgery for Posttraumatic Paranasal Sinus Mucocele.

AIM: The purpose of this study was to analyze the clinical features of patients with posttraumatic paranasal sinus mucocele (PSM). SUBJECTS AND METHODS: Between 2009 and 2013, we performed endoscopic sinus surgery (ESS) on 68 patients with PSM at the Department of Otolaryngology - Head and Neck Surgery at Hyogo College of Medicine. Five male patients (age range, 45-76 years) with posttraumatic PSM were analyzed retrospectively. Diagnosis was based on the history of injury and radiological findings. RESULTS: Posttraumatic PSM was found in 7% (5/68) of patients. The mean interval from injury to diagnosis was 28.4 years. All patients had frontal sinus mucocele. Four patients had symptoms of headache, diplopia, visual field defect, and forehead swelling, and 1 patient was asymptomatic. ESS was performed under general anesthesia in all cases, and the symptoms improved postoperatively. Reoperation was required in 1 patient (20%) because headache developed with obstruction of the frontal drainage route 7 months after ESS. CONCLUSIONS: Posttraumatic PSM was the least frequent form of PSM and was located predominantly in the frontal sinus, causing symptoms long after the forehead injury. The important lessons to be learned for treating posttraumatic PSM are to obtain a detailed history and to enlarge the route to the cyst to avoid its recurrence.

Diagnosis and treatment of taste disorders in Japan.

Though 270,000 patients with complaints of taste abnormalities visited medical institutions annually in 2019 survey, there are no drugs for the treatment of taste disorders that are covered by health insurance in Japan. In the survey, the number of patients with taste disorders was correlated with age, and the need for medical treatment for taste disorders is expected to increase in the future because of the super-aging society. The pathophysiology of taste disorders varies widely. There is an obvious need to decide the site and the causes of the disorder and understand the mechanism, by performing various examinations. It needs to first adjust the causative systemic diseases and medications in the treatment for taste disorder. Damage of taste cells due to zinc deficiency is the main pathophysiological mechanism of taste disorders, and zinc supplementation is a standard treatment in Japan. Oral zinc therapy is the treatment for taste disorders due to zinc deficiency or idiopathic taste disorder; though a double-blind study was conducted, it was considered low-level evidence in a clinical review. In Japan, the off-label use of polaprezinc for taste disorders was approved in 2011, and zinc acetate hydrate was approved for hypozincemia in March 2017, making it easier to use oral zinc therapy in general. In some cases, psychotherapy or herbal medicine therapy has been used with remarkable success, although its effectiveness has not been clearly tested. It might be expected to offer some help to patients. In the treatment of elderly patients with taste disorders, physicians need to consider the difference between "age-related changes in taste in healthy people" and "taste disorders in elderly persons", and they should separate them. Aggressive treatment is desirable regardless of age, because no significant difference in the efficacy of various treatments was found between patients older and younger than 65 years.

Usefulness of post-operative endoscopic score for optimal treatment selection in recurrent eosinophilic chronic rhinosinusitis.

OBJECTIVE: This study retrospectively analysed post-operative endoscopic scores to determine the optimal post-operative treatment in patients with eosinophilic chronic rhinosinusitis undergoing functional endoscopic sinus surgery. METHODS: In total, 339 adults who underwent initial bilateral functional endoscopic sinus surgery for eosinophilic chronic rhinosinusitis were enrolled. Patients were divided into group A, which required no additional post-operative treatment; group B, which required local/systemic steroids post-operatively; and group C, which further required dupilumab and/or revision surgery. RESULTS: Sixty-five per cent of patients could be treated with initial functional endoscopic sinus surgery (group A). Post-operative steroids were required in 35 per cent of patients with a post-operative endoscopic score of 30 per cent (group B). Further advanced treatments with dupilumab and/or revision functional endoscopic sinus surgery were required in 10 per cent of patients with a post-operative endoscopic score of 65 per cent (group C). CONCLUSION: The post functional endoscopic sinus surgery endoscopic score can be used as an index to determine treatment at the time of eosinophilic chronic rhinosinusitis recurrence.

Impact of the Coronavirus Disease 2019 Pandemic on Medical Practices in Awaji Island.

Introduction: Since the first confirmed case of coronavirus disease 2019 (COVID-19) in China, COVID-19 continues to be a global threat and exerts a significant impact on medical practices. This study aims to investigate the impact of the COVID-19 pandemic on medical practices in Awaji Island, a remote island in Japan. Methods: First, we conducted a survey on the epidemiological characteristics of COVID-19 on Awaji Island before and during the pandemic. Next, using a questionnaire, we conducted a survey with doctors working full time at Hyogo Prefectural Awaji Medical Center, which is the only designated infectious disease hospital on Awaji Island. Results: The COVID-19 infection rate of Awaji Island was lower than that of Hyogo Prefecture and of Japan as a whole, although the peaks occurred simultaneously. Outpatient visits as well as hospitalized patients, i.e., inpatients, decreased during the pandemic as a result of restrictions on surgeries and hospitalizations, with no changes in the disease composition ratio. The results of the questionnaire show that during the pandemic, doctors working full time at our hospital worked less and slept more. Furthermore, data obtained from the Medical Affairs Department showed a decrease in overtime hours worked and an increase in the number of days of paid holidays taken. Conclusions: Epidemiologically, the impact of the COVID-19 pandemic on Awaji Island showed a similar trend to that in Japan, but the results of the survey questionnaire indicated that doctors working full time at our hospital were not necessarily adversely affected.

Efficacy of tokishakuyakusan and mecobalamin on post-infectious olfactory dysfunction: A prospective multicenter study.

OBJECTIVE: To determine if tokishakuyakusan (TSS) is effective for treating post-infectious olfactory dysfunction (PIOD) compared with vitamin B12 (mecobalamin). METHODS: We conducted a randomized, nonblinded clinical trial. Patients with PIOD enrolled in 17 hospitals and clinics from 2016 to 2020 were randomly divided into two groups, and we administered TSS or mecobalamin for 24 weeks. Their olfactory function was examined using interviews and T&T olfactometry. The improvement of olfactory dysfunction was assessed following the criteria of the Japanese Rhinologic Society. RESULTS: Overall, 82 patients with PIOD were enrolled in this study. In the TSS and mecobalamin groups, 39 patients completed the medication regimen. In the TSS and mecobalamin groups, olfactory dysfunction was significantly improved based on self-reports and olfactory test results. The improvement rate of olfactory dysfunction was 56% in the TSS group and 59% in the mecobalamin group. Early intervention within 3 months produced a better prognosis than the treatment initiated after 4 months. Furthermore, age and sex differences were not observed. Both medications produced no severe adverse events. CONCLUSION: The present study showed that TSS and mecobalamin might be useful for treating PIOD.

Decreased expression of VE-cadherin and claudin-5 and increased phosphorylation of VE-cadherin in vascular endothelium in nasal polyps.

VE-cadherin and claudin-5 are major components of adherens and tight junctions of vascular endothelial cells and a decrease in their expression and an increase in the tyrosine-phosphorylation of VE-cadherin are associated with an increase in endothelial paracellular permeability. To clarify the mechanism underlying the development of edema in nasal polyps, we studied these molecules in polyp microvessels. Normal inferior turbinate mucosal tissues and nasal polyps from patients treated with or without glucocorticoid were stained for VE-cadherin or claudin-5 and CD31 by a double-immunofluorescence method and the immunofluorescence intensities were graded 1-3 with increasing intensity. To correct for differences in fluorescence intensity attributable to a different endothelial area being exposed in a section or to the thickness of a section, the relative immunofluorescence intensity was estimated by dividing the grade of VE-cadherin or claudin-5 by that of CD31 in each microvessel. Tyrosine-phosphorylation of VE-cadherin was examined by Western blot analysis. The relative intensities of VE-cadherin and claudin-5 in the CD31-positive microvessels significantly decreased in the following order; inferior turbinate mucosa, treated polyps and untreated polyps. The ratio of tyrosine-phosphorylated VE-cadherin to VE-cadherin was significantly higher in untreated polyps than in the inferior turbinate mucosa and treated polyps, between which no significant difference in the ratio was seen. Thus, in nasal polyps, the barrier function of endothelial adherens and tight junctions is weakened, although glucocorticoid treatment improves this weakened barrier function.

Therapeutic evaluation of outpatient submucosal inferior turbinate surgery for patients with severe allergic rhinitis.

BACKGROUND: Surgical treatment for inferior turbinate (IT) is selected to treat severe allergic rhinitis (AR) that is unresponsive to conservative treatment. This study aimed to determine the clinical effects of outpatient submucosal IT surgery (OSITS) on patients with severe AR. METHODS: Between January 2008 and August 2012, 95 patients with severe AR who underwent OSITS at the Department of Otolaryngology, Hyogo College of Medicine, were retrospectively analyzed. There were 53 men and 42 women. Their mean age was 27 years (11-75 years). OSITS was bilaterally performed using a bipolar radiofrequency electrocautery under local anesthesia. Symptoms, QOL, and physical findings were evaluated using scores from both pre- and postoperative periods (average: 12.4 months), according to Practical Guideline for the Management of AR in Japan 2009. RESULTS: In perennial AR, all mean scores of nasal symptoms, QOL, and physical findings significantly improved after OSITS (p < 0.05, n = 83). Nasal obstruction, sleep problems, and IT congestion were the most strongly affected. Eye symptoms were not influenced by OSITS. OSITS also showed significant effects on nasal obstruction and IT congestion in seasonal AR (p < 0.05, n = 12), but not sneezing, nasal discharge, and QOL. In terms of the efficacy, OSITS was beneficial in 90% of perennial AR cases and 75% of seasonal AR cases. Epistaxis (1%), vestibulitis (1%), and IT atrophy (4%) were observed after OSITS. CONCLUSIONS: These data indicate that OSITS using radiofrequency electrocautery could be a beneficial therapeutic option in patients with severe AR.

Clinical features of olfactory dysfunction in elderly patients.

OBJECTIVE: This study aimed to investigate the causes of olfactory dysfunction (OD) and to discuss the benefits of understanding the characteristics of OD in elderly patients. METHODS: A total of 4300 patients with OD who were treated at our hospital between January 1996 and December 2020 were retrospectively analyzed. There were 1833 men and 2467 women, with ages ranging from 4 to 95 years. The patients were divided into two groups: younger (less than 65 years old, n = 2947) and elderly (65 years old or more, n = 1353) groups. Causative diseases were chronic rhinosinusitis (CRS), post-viral (PV), post-traumatic (PT), central nervous system dysfunction (CNS), peripheral nervous system dysfunction (PNS), congenital, psychogenic, and unknown. Visual analogue scale (VAS) and olfactory detection and recognition thresholds using the T&T olfaction test were used to evaluate olfaction. The mean detection and recognition thresholds, as well as the deviation difference (the difference between the mean detection and recognition thresholds) were compared by causative disease. RESULTS: The causative diseases in elderly group were CRS (32%), PV (28%), PT (3%), CNS (2%), and PNS (4%). OD of unknown cause was significantly more in elderly (30%) than in younger patients (12%). Olfactory detection and recognition thresholds in elderly group were significantly worse than in younger group (p < 0.05). The olfactory detection and recognition thresholds were not any significant differences between patients with OD of unknown cause and those with CNS. CONCLUSION: OD of unknown cause was predominantly observed in elderly group. The olfactory acuity of OD of unknown cause was similar to CNS OD. These findings suggest the importance of continuous follow-up due to the potential of neurodegenerative diseases in elderly OD patients.

Analysis of risk factors for post-tonsillectomy hemorrhage in adults.

OBJECTIVES: To identify the risk factors for post-tonsillectomy hemorrhage (PTH) in adult patients (>19 years). METHODS: 275 adult patients who underwent tonsillectomy between 2009 and 2019 were retrospectively analyzed. Possible risk factors associated with PTH were investigated by univariate and multivariate logistic regression analyses. RESULTS: PTH occurred in 39 of 275 patients (14.2%). Regarding underlying diseases, PTH occurred more frequently in focal infection of IgA nephropathy. Furthermore, bipolar electrocautery was the other risk factor for PTH on multivariate analysis. CONCLUSION: Focal infection of IgA nephropathy and bipolar electrocautery were identified as the risk factors for PTH.

Microglia Negatively Regulate the Proliferation and Neuronal Differentiation of Neural Stem/Progenitor Cells Isolated from Poststroke Mouse Brains.

We previously demonstrated that neural stem/progenitor cells (NSPCs) were induced within and around the ischemic areas in a mouse model of ischemic stroke. These injury/ischemia-induced NSPCs (iNSPCs) differentiated to electrophysiologically functional neurons in vitro, indicating the presence of a self-repair system following injury. However, during the healing process after stroke, ischemic areas were gradually occupied by inflammatory cells, mainly microglial cells/macrophages (MGs/MΦs), and neurogenesis rarely occurred within and around the ischemic areas. Therefore, to achieve neural regeneration by utilizing endogenous iNSPCs, regulation of MGs/MΦs after an ischemic stroke might be necessary. To test this hypothesis, we used iNSPCs isolated from the ischemic areas after a stroke in our mouse model to investigate the role of MGs/MΦs in iNSPC regulation. In coculture experiments, we show that the presence of MGs/MΦs significantly reduces not only the proliferation but also the differentiation of iNSPCs toward neuronal cells, thereby preventing neurogenesis. These effects, however, are mitigated by MG/MΦ depletion using clodronate encapsulated in liposomes. Additionally, gene ontology analysis reveals that proliferation and neuronal differentiation are negatively regulated in iNSPCs cocultured with MGs/MΦs. These results indicate that MGs/MΦs negatively impact neurogenesis via iNSPCs, suggesting that the regulation of MGs/MΦs is essential to achieve iNSPC-based neural regeneration following an ischemic stroke.

Change in chorda tympani nerve function after two-stage tympanoplasty for cholesteatoma.

Objectives: Chorda tympani nerve (CTN) function may be damaged more by two-stage than by one-stage surgery for middle ear cholesteatoma. However, few studies have reported the relationship between two-stage cholesteatoma surgery and CTN function. This study aimed to investigate CTN function after two-stage surgery for cholesteatoma. Methods: In this prospective study, 35 patients underwent two-stage canal wall up tympanoplasty (CWUT). Perioperative CTN function was assessed using questionnaires and electrogustometry (EGM). Participants were categorized into minor, major, and section groups, based on the degree of CTN manipulation during surgery. Results: In the first-stage surgery, posterior tympanotomy with an intact canal wall reduced the degree of CTN manipulation. The incidence of taste disorder after the first-stage surgery was 71.4%. Postoperative taste disorder and the EGM threshold improved early in the minor manipulation group. In the second-stage surgery, no new CTN damage occurred, even if this surgery involved removal of residual cholesteatoma. The incidence of taste disorder after second-stage surgery was less than that after first-stage surgery, independent of CTN preservation. However, the recovery rate of the EGM threshold after second-stage surgery was significantly lower in the section group than in those with CTN preservation. Conclusion: CTN function, including symptoms and EGM threshold, can be preserved during two-stage cholesteatoma surgery if care is taken to preserve the CTN in both the first- and second-stage surgeries. A two-stage CWUT, ensuring an intact bony annulus, may be effective to facilitate CTN preservation. Level of Evidence: 2b.

A Phase II, Multicenter, Randomized, Placebo-Controlled Study of Benralizumab, a Humanized Anti-IL-5R Alpha Monoclonal Antibody, in Patients With Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: To assess the efficacy and safety of benralizumab in patients with ECRS. METHODS: This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12. RESULTS: Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, -0.5 ± 0.8; benralizumab single, -0.3 ± 0.8; benralizumab q4w, -0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted. CONCLUSION: Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

[Clinical features of patients with paranasal sinus cysts].

This study retrospectively analyzed the clinical features of patients with paranasal sinus cysts. Between April 1995 and March 2008 at Hyogo College of Medicine, we performed sinus surgery on 218 patients with paranasal sinus cysts. There were 125 men and 93 women with the mean age of 57.5 years (17-85 years old). Diagnosis was based on the preoperative endonasal and radiological findings as well as surgical findings. The patients were followed for 6 months or more after surgery. Of 218 patients, postoperative cysts were observed in 173 patients (79.4%), and idiopathic cysts were found in 45 patients (20.6%). In postoperative cysts, the maxillary sinus was the most common lesion (124/173 patients, 71.7%). Most patients (53.8%) presented with cheek swelling and pain. The mean interval between the first and most recent surgery was 31.2 years (4-55 years). Among idiopathic cysts, anterior ethmoid sinus (19/45 patients, 42.2%) and frontal sinus (15/45 patients, 33.3%) were common lesion sites. More than a half of them (53.3%) presented with ophthalmologic symptoms. For treatment, endoscopic sinus surgery (ESS) was performed on 206 patients. The navigation system for ESS was utilized in 6 patients (2.8%). External approaches were required in 23 patients (10.6%). The Caldwell-Luc procedure for maxillary sinus cysts and Killian's procedure for frontal sinus cysts were performed on 18 and 5 patients, respectively. Dacryocystorhinostomy (DCR) with the endonasal approach was additionally performed on 4 patients with epiphora due to postoperative maxillary sinus cysts. Recurrence of cysts was observed in 5 patients (2.3%) at the mean interval of 25 months after surgery, comprising three patients with maxillary sinus cysts, one patient with a frontal sinus cyst, and one patient with a sphenoid sinus cyst. In conclusion, most paranasal sinus cysts (approximately 80%) occurred postoperatively. Symptoms were predominantly ophthalmologic. Selecting an endoscopic and/or an external approach is critical, considering minimally invasive surgery and risk of recurrence.