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Background Lipopolysaccharide ( LPS) has shown heterogeneous effects on eosinophilic inflammation in airways. However, little is known about how LPS regulates pathogenesis of chronic rhinosinusitis with nasal polyps, a major form of eosinophilic inflammation in the upper airway. Objective We sought to investigate the effect of LPS on cytokine production by dispersed nasal polyp cells ( DNPCs). Methods Either diclofenac-treated or untreated DNPCs were cultured with or without staphylococcal enterotoxin B ( SEB) in the presence or absence of LPS, after which the levels of IL-5, IL-13, IL-17A and IFN-γ within the supernatant were measured. The effects of PGE2 on LPS-induced responses by diclofenac-treated DNPCs were also examined. LPS-induced PGE2 production and mRNA expression of COX-1, COX-2 and microsomal PGE2 synthase-1 (m- PGES-1) were measured. Results Staphylococcal enterotoxin B induced IL-5, IL-13, IL-17A and IFN-γ production by DNPCs. Pre-treatment with LPS prior to SEB stimulation inhibited production of these cytokines. After stimulation with LPS, PGE2 production and expression of COX-2 and m- PGES-1 mRNA by DNPCs increased significantly. In the presence of diclofenac, the suppressive effects of LPS were eliminated. LPS pre-treatment enhanced SEB-induced IL-5, IL-13 and IL-17A production in diclofenac-treated DNPCs, while addition of PGE2 inhibited IL-5, IL-13 and IFN-γ production. LPS alone induced IL-5, IL-13 and IFN- γ production by diclofenac-treated DNPCs, while the addition of EP2 and EP4 receptor-selective agonists, as well as PGE2 itself, inhibited IL-5 and IL-13 production. Conclusions and Clinical Relevance These results suggest that the regulatory effects of LPS on eosinophilic airway inflammation are controlled via the COX-2/ PGE2 axis. For clinical implications, indiscreet use of non-steroidal anti-inflammatory drugs should be avoided in patients with chronic rhinosinusitis with nasal polyps. [ABSTRACT FROM AUTHOR]

Objective: There is no consensus on the optimal surgical technique for allergic rhinitis (AR). Furthermore, the appropriateness of surgical intervention in children and older individuals remains debatable. This study aimed to analyze trends and patterns in the surgical management of AR in Japan, focusing on parasympathetic neurectomy., Methods: Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), we conducted a comprehensive review of procedures performed between April 2014 and March 2022. In addition, a cross-sectional survey targeting otolaryngologists across Japan was conducted to gather insights into surgical preferences and practices., Results: The NDB data showed an increasing trend in neurectomies, with the most frequent age group being 25-29 years; the procedure was also performed in pediatric and older patients. The survey among otolaryngologists indicated that 58.2 % of surgeons preferred peripheral branch neurectomy of the posterior nasal nerve. The findings of this study also indicated a cautious approach toward conducting these procedures in children, with 51.2 % of surgeons considering patients less than 18 years of age unsuitable for the procedure., Conclusion: This study highlighted a shift toward simple and minimally invasive surgical methods, such as peripheral branch neurectomy, in Japan. However, further research is needed to understand the long-term outcomes and refine the surgical techniques. The findings of this study also emphasized the need for age-specific considerations when treating pediatric and older patients with AR., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

We report a challenging and uncommon case involving a 53-year-old Japanese man with cerebrospinal fluid (CSF) leakage caused by a meningocele in the lateral recess of the sphenoid sinus. Our innovative treatment approach involved a combination of transpterygoid and endoscopic modified medial maxillectomy techniques, with special emphasis on the preservation of the sphenopalatine artery. This strategic preservation was pivotal to the successful use of the ipsilateral nasoseptal flap for reconstruction, which played a crucial role in the prevention of postoperative CSF leakage. Otolaryngologists and neurosurgeons collaborated to perform the bath-plugging technique; effective collaboration was instrumental to the success of the procedure. This report highlights significant advancement from conventional frontal craniotomy to a more sophisticated endoscopic technique, shows the importance of meticulous surgical planning and execution, emphasizes careful preservation of critical anatomical structures during complex neurosurgical and otolaryngological procedures, and underscores the evolving landscape of surgical approaches for managing complex medical conditions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: In 2013, Japan established a standardized classification system for categorizing endoscopic sinus surgery (ESS) into types I-V, yet no evaluation has been conducted thereof., Objective: We assessed the ESS trends and status in Japan, focusing on outpatient and inpatient surgeries., Material and Methods: This descriptive retrospective cohort study used Japan's National Database of Health Insurance Claims and Specific Health Checkups between 2014 and 2021. The distribution of ESS types I-V and outpatient and inpatient surgeries was analysed, along with age groups and regional differences, focusing on ESS type III., Results: Overall, 427,813 ESS procedures were performed, with types III and IV being most common. Outpatient ESS type III increased substantially compared to inpatient surgeries. Younger individuals favoured outpatient ESS type III over inpatient surgeries, with substantial regional variations across prefectures., Conclusions and Significance: The adoption of a standardized ESS classification in Japan has facilitated a detailed understanding of surgical trends. The shift toward outpatient surgeries, especially for type III ESS, aligns with global trends toward minimally invasive procedures and reflects changing patient preferences and healthcare delivery practices. Consequently, continuous monitoring and research are crucial for adapting surgical practices to the evolving healthcare needs and patient expectations.

Here, we describe the unique case of a pneumocephalus originating from an inverted papilloma (IP) in the frontoethmoidal sinus. A 71-year-old man with diabetes presented with headaches and altered consciousness. Imaging revealed the pneumocephalus together with bone destruction in the left frontal sinus. He underwent simultaneous endoscopic endonasal and transcranial surgery using an ORBEYE exoscope. Pathological diagnosis of the tumor confirmed IP. Post-surgery, the pneumocephalus was significantly resolved and the squamous cell carcinoma antigen level, which had been elevated, decreased. This case underscores the importance of a multidisciplinary approach and innovative surgical methods in treating complex sinonasal pathologies., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Otitis media (OM) is a prevalent respiratory disease in children and poses significant public health challenges due to its impact on child health and economic burdens. However, there have no nationwide epidemiological studies conducted in Japan. This study investigates the epidemiological trends of OM in Japan, taking into account the impact of the 7-valent pneumococcal conjugate vaccine (PCV7) introduction., Method: This study was retrospective cohort study using secondary data on the nationwide longitudinal birth cohort. This survey followed two cohorts born in 2001 (pre-PCV era) and 2010 (post-PCV era) until the age of 9. Every year, parents were surveyed about their children's health status, including occurrences of OM. The annual period prevalence and cumulative incidence of OM were assessed in this study, and the two cohorts were compared using a modified Poisson regression model adjusted environmental factors with the 2001 cohort as reference., Result: The study included 47,015 children from the 2001 cohort and 38,554 from the 2010 cohort. Peak annual period prevalence of OM varied by era. Cumulative incidence was 13.8 % for the 2001 cohort and 18.5 % for the 2010 cohort by 1.5 years of age and 28.9 % and 33.3 %, respectively, by 3.5 years of age. In particular, from the fourth survey onward, covering ages 2.5-3.5 years, a shift was observed from an increased risk to a decreased risk of OM., Conclusion: This nationwide longitudinal study emphasizes variations in OM epidemiology across Japan over time, with changes potentially influenced by the introduction of PCV7. In this study, due to the absence of individual PCV7 vaccination data, the effect of PCV7 was estimated based on the vaccination rate at the population level. The results suggest a notable decrease in the incidence of OM in later years, aligning with the increased uptake of PCV7., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study investigated the association between housing type and clinical remission of infantile-onset allergic rhinitis (AR) in 53,575 children born in 2001 in Japan. Infantile-onset AR was defined as the presence of AR symptoms reported between ages 1.5 and 4.5 years, and remission was assessed between ages 10 and 12. The type of housing was categorized into detached houses and multi-unit residential buildings with 1-2, 3-5, or ≥6 floors. Among the 4,352 infantile-onset AR, 42.9% experienced remission. Notably, living in multi-unit residential buildings, particularly those with 1-2 and ≥6 floors, was positively associated with AR remission., (Copyright © 2023 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study is to investigate the lung function in Chronic Rhinosinusitis (CRS) patients with Chronic Cough (CC)., Methods: A total of 1413 CC patients were retrospectively screened and 109 CRS patients with CC were enrolled. Lung function, Lund-Mackay Computed Tomography (CT) score, smoking status, peripheral blood eosinophil count, and immunoglobulin E concentration in serum samples, and Sino-Nasal Outcome Test were examined. Normal control subjects are also recruited., Results: The Forced Expiratory Volume in 1 second (FEV 1.0 ), Percent Predicted FEV 1.0 , and FEV 1.0 /Forced Vital Capacity (FVC) ratio in the patients were significantly low as compared with the control subjects. The FEV 1.0 /FVC ratio was negatively correlated with the Lund-Mackay CT scores of the patients with a high CT score., Conclusions: The CRS patients with CC should be investigated with lung function. In addition, the multidisciplinary evaluation including a pulmonologist is needed to manage the CRS patients with CC., Level of Evidence: Level 4., (Copyright © 2024 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España S.L.U. All rights reserved.)

Background: The pharyngeal flap (PF) is useful for reconstruction of soft palate defects, but effective arrangements of PF for various types of soft palate defects are controversial. Here, we classify three types of soft palate defects and discuss the arrangements of PF and their functional prognosis., Methods: Reconstruction was performed based on the classification of the defects. Clinical details were collected, and postoperative function was analyzed., Results: Eight patients were included in the study. The defect sizes ranged from 25 (width) × 40 (depth) to 40 × 60 mm. Six patients underwent pharyngeal flap reconstruction with free-flap reconstruction, and two underwent pharyngeal flap reconstruction. The pharyngeal flap was harvested at the maximum width of the posterior pharyngeal wall, ranging from 25 to 40 mm in length. Eating and speaking functions were maintained in all patients., Conclusions: Good postoperative function can be maintained by narrowing the velopharyngeal space with a pharyngeal flap., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy., Methods: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure., Results: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits., Conclusion: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objectives This retrospective study aimed to investigate the relationships between the Keros classification, the Gera classification, the vertical height of the posterior ethmoid roof (ER), and anterior ethmoidal artery (AEA) types in Japanese patients. Methods We investigated the computed tomography (CT) slices of paranasal sinuses (120 sides) of 60 patients; measured the cribriform plate (CP) depth, lateral lamella CP angle (LLCPA), and vertical height of the lateral ER from the hard palate (LERHP) at the coronal plane of the posterior ethmoidal artery (PEA); and reviewed the AEA types, whether floating or non-floating. Results CP depth was positively correlated with LLCPA (r=0.63; p<0.01) and the height of LERHP (r=0.19;   p<0.05). The height of the LERHP in females was significantly lower than that in males. With increased CP depth, floating AEAs became prevalent (p<0.001). Conclusion In females, low height of the posterior ethmoid sinus roof, where cerebrospinal fluid (CSF) leaks occurred while penetrating the basal lamella, often existed; the heights positively correlated with the Keros classification in Japanese patients. The Keros and Gera classifications, AEA type, and posterior ER height do not individually constitute a complete risk assessment but may correlate, preventing major complications, such as CSF leak and orbital hemorrhage., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Makihara et al.)

Purpose: A longitudinal study was conducted to examine the effects of handwashing and gargling education for children on the prevention of respiratory tract infections (RTIs) in children in Japan., Methods: The study included 38,554 children born in 2010 who were enrolled in a longitudinal study. Information on children's hygiene education regarding handwashing and gargling was collected in a survey at the age of 3.5 years. Based on parents' reports of doctors' diagnoses, airway infections and influenza events in the 12-month duration before the survey were evaluated for RTIs at the ages of 4.5 and 9 years. Poisson regression with robust variance was performed to examine the effects of hygiene education on RTIs prevention. The supplementary analysis was stratified by household income., Results: Children were categorized into different groups: 38% in the handwashing and gargling group, 29% in the handwashing group, 0.1% in the gargling group, and 9.7% in the no-education group. Exclusions were made for non-respondent children (23%) and those in the gargling group. Hygiene education was associated with decreased influenza at the age of 4.5 years in the handwashing (adjusted RR [aRR] = 0.8; 95% CI, 0.8-0.9) and handwashing and gargling groups (aRR = 0.8; 95% CI, 0.8-0.9) compared with no education. However, no preventive effects on airway infections at the age of 4.5 and 9, influenza at the age of 9, or hospitalization between the ages of 3.5 and 9 years were detected. Handwashing and gargling could significantly prevent influenza in low-income households (aRR = 0.7; 95% CI, 0.6-0.8).     Conclusions: Gargling education was widespread and mostly combined with handwashing education in Japan. Hygiene education significantly affected prevention of influenza infections at the age of 4.5 years, especially in low-income households., What Is Known: • Previous intervention studies showed handwashing and gargling are effective in preventing respiratory tract infections., What Is New: • We conducted a longitudinal study on handwashing and gargling education in Japanese children and found that handwashing and gargling were widely practiced together. • Handwashing and gargling education were related to a reduction in influenza, particularly in low-income households., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic rhinosinusitis (CRS) can be divided into endotypes by functional or pathophysiologic findings., Objective: The aim of this study was to analyze the expression of cytokines, prostaglandin (PG) synthases, and their receptors related to the pathogenesis of CRS, especially those contributing to nasal polyp (NP) formation., Methods: NPs and uncinate tissue (UT) samples were collected from 90 patients who underwent endoscopic sinus surgery. They included 75 patients with CRS (including 45 with eosinophilic CRS [eCRS] and 30 with non-eCRS) and 15 patients without CRS. A total of 30 genes were selected for our original DNA array plate to analyze the levels of expression of 10 cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-13, IL-17A, IL-22, IL-25, IL-33, and TSLP), 4 prostaglandin synthases (prostaglandin D 2 [PGD 2 ] synthase, prostaglandin E 2 synthase, COX-1, and COX-2), and their 16 receptors. Clustering analysis was performed according to the expression results, and clinical findings of patients from each cluster were investigated., Results: The samples could be divided into 3 clusters. Cluster 1 showed elevated levels of expression of IL4, IL5, IL13, TSLP, IL1RL1 (ST2 [an IL-33 receptor]), HPGDS , and GPR44 (CRTH2, a PGD 2 receptor); cluster 2 showed elevated levels of expression of IL17A and PTGES ; and cluster 3 showed an elevated level of expression of IL25 . Regarding clinical features, the main characteristics of each cluster were as follows: NPs from patients with eCRS for cluster 1, NPs and/or UT samples from patients with non-eCRS for cluster 2, and UTs from patients with non-CRS for cluster 3., Conclusion: The results suggest that there are associations between type 2 inflammation/PGD 2 and eCRS and also between type 3 inflammation/prostaglandin E 2 and non-eCRS., (© 2023 The Author(s).)

Mirror movements (MM) disorder is characterized by involuntary movements on one side of the body that mirror intentional movements on the opposite side. We performed genetic characterization of a family with autosomal dominant MM and identified ARHGEF7 , a RhoGEF, as a candidate MM gene. We found that Arhgef7 and its partner Git1 bind directly to Dcc. Dcc is the receptor for Netrin-1, an axon guidance cue that attracts commissural axons to the midline, promoting the midline crossing of axon tracts. We show that Arhgef7 and Git1 are required for Netrin-1-mediated axon guidance and act as a multifunctional effector complex. Arhgef7/Git1 activates Rac1 and Cdc42 and inhibits Arf1 downstream of Netrin-1. Furthermore, Arhgef7/Git1, via Arf1, mediates the Netrin-1-induced increase in cell surface Dcc. Mice heterozygous for Arhgef7 have defects in commissural axon trajectories and increased symmetrical paw placements during skilled walking, a MM-like phenotype. Thus, we have delineated how ARHGEF7 mutation causes MM.

Competing Interests: No potential conflict of interest relevant to this article was reported.

Sinonasal inverted papilloma (SNIP) can recur; however, the factors related to tumor recurrence remain unclear. This study aimed to analyze risk factors, including human papillomavirus (HPV) infection, as well as other factors associated with SNIP recurrence. Thirty-two patients who were diagnosed with SNIP and underwent surgery between 2010 and 2019 were enrolled: 24 men and 8 women, with a mean age of 59.2 years. The mean follow-up was 57.3 months. Demographics and information about history of smoking, diabetes mellitus (DM), hypertension, allergic rhinitis, alcohol consumption, tumor stage, surgical approach, and recurrence were reviewed retrospectively. Specimens were investigated using polymerase chain reaction to detect HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11). Seven patients (21.9%) experienced recurrence. HPV DNA was detected in five (15.6%) patients (high-risk subtypes, n = 2; low-risk subtypes, n = 3). Patients with recurrence of SNIP had a higher proportion of young adults and displayed higher rates of HPV infection, DM, and advanced tumor stage than those without recurrence. HPV infection, young adulthood, DM, and advanced tumor stage could be associated with a high recurrence rate, which suggests that patients with these risk factors could require close follow-up after surgery.

Background: Several surgical procedures for posterior nasal neurectomy have been reported, but no conclusion has been reached about which procedure is best., Objectives: The aim is to evaluate the improvement in symptom medication scores for resection of the posterior nasal nerve trunk in an underwater environment, with submucous inferior turbinectomy, without injuring the sphenopalatine artery (SPA) in severe allergic rhinitis., Material and Methods: Improvements in symptom medication scores were retrospectively compared between 27 consecutive cases who underwent resection of the posterior nasal nerve trunk with turbinoplasty in an underwater environment without injuring the SPA (Underwater group) and, as a historical control, 16 consecutive cases who underwent resection of peripheral branches of the posterior nasal nerve with turbinoplasty (Control group)., Results: The improvements in symptom medication scores in the Underwater group were significantly better than in the Control group (3.07 vs. 1.96, p  = 0.02)., Conclusions and Significance: By using underwater posterior nasal neurectomy, we can easily and safely resect the posterior nasal nerve trunk under a clear surgical view without injuring the SPA. This technique with submucous inferior turbinectomy may, more than resection of peripheral branches of the posterior nasal nerve, be able to reduce the medication score and symptom medication score.

Objective: Infected mucocele of the paranasal sinuses can induce orbital infection, including orbital subperiosteal abscess, which may lead to life-threatening intracranial complications. Effective diagnosis is important, and treatment should be aggressive. This paper presents our experiences in endoscopic surgical management of orbital complications secondary to infected paranasal sinus mucoceles., Methods: From our retrospective review of the medical charts for 82 patients with 92 sides diagnosed with paranasal sinus mucoceles, we present 7 sides in 7 adult patients with orbital complications secondary to infected mucoceles. The collected data include the suggested etiology, side of sinus involvement, localization of abscess in the orbit, orbital wall bone defects caused by mucocele compression, ophthalmic symptoms, duration between symptom onset and initial visit, operation date, type of surgery performed, and follow-up., Results: The mucocele was located in the ethmoid-frontal region in 9.8% of the sides (9/92), in the frontal sinus in 7.6% (7/92), in the ethmoidal sinus in 9.8% (9/92), in the maxillary sinus in 67.4% (62/92), in the maxillary-ethmoidal sinus in 3.3% (3/92), and in the sphenoid sinus in 2.2% (2/92). The patients with ethmoid-frontal mucoceles had a significantly higher incidence of orbital complications (6/9) as compared with the other sub-types of mucoceles (frontal, 0/7; ethmoidal, 0/9; maxillary, 1/62; maxillary-ethmoidal, 0/3; sphenoid, 0/2). Chandler's classification showed Type I in one, Type II in three, and Type III in three. Sinus involvement was observed at the ethmoid-frontal sinuses in six cases and the maxillary sinus in one case. All seven cases had a partial defect of the orbital wall bone (lamina papyracea, or inferior orbital wall bone) by mucocele compression, and the patients underwent endoscopic marsupialization. For the cases with subperiosteal abscess, the lamina papyracea was also removed partially for draining the abscess. In all cases, symptoms were resolved without any recurrence of the mucocele., Conclusions: Infected ethmoid-frontal mucoceles with a defect of the lamina papyracea tend to induce orbital infection, so prompt surgery for the infected mucoceles should be considered early even with Types I and II, before visual acuity is impaired, because surgery is the only curative treatment for the mucoceles., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Hypothesis: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1β and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in lipopolysaccharide-induced otitis media., Background: NLRP3 inflammasome and macrophage migration inhibitory factor are critical molecules mediating inflammation. However, the interaction between the NLRP3 inflammasome and macrophage migration inhibitory factor has not been fully examined., Methods: Wild-type mice and macrophage migration inhibitory factor gene-deficient (MIF) mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 hours after the injection. Concentrations of IL-1β, NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry., Results: In the immunohistochemical study using the wild-type mice, positive staining of macrophage migration inhibitory factor, NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear. The number of inflammatory cells caused by lipopolysaccharide administration decreased remarkably in the MIF mice as compared with the wild-type mice. The concentrations of IL-1β, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF mice with lipopolysaccharide had decreased levels of IL-1β, NLRP3, ASC, and caspase-1 as compared with the wild-type mice., Conclusion: Macrophage migration inhibitory factor has an important role in the production of IL-1β and the NLRP3 inflammasome. Controlling the inflammation by modulating macrophage migration inhibitory factor and the NLRP3 inflammasome may be a novel therapeutic strategy for otitis media.

Purpose: Chronic cough is a common complaint. Because the pathophysiology of chronic cough is complicated, the management of chronic cough is challenging. To the best of our knowledge, no previous study has examined the effect of macrolide antibiotics in chronic cough patients with chronic rhinosinusitis. The purpose of this study is to determine the changes in lung function for chronic cough patients with chronic rhinosinusitis who are treated by clarithromycin and carbocisteine., Materials and Methods: Thirty-two chronic cough patients with chronic rhinosinusitis were recruited. Patients using inhaled corticosteroids and/or a bronchodilator, asthmatic patients, and patients with abnormal findings on auscultation and/or chest X-ray examination were excluded from this study. The patients received low-dose clarithromycin treatment for 3 months. Both before and after the treatment, a computed tomography (CT) scan of the paranasal sinuses, lung function test, peripheral blood test, and sino-nasal outcome test (SNOT-20) were applied., Results: Both the lung function and Lund-MacKay CT scores were improved by the long-duration therapy with macrolide antibiotics. The change in obstructive pulmonary function and the improvement of the CT score in each subject were significantly correlated. SNOT scores also improved after the treatment., Conclusions: The macrolide antibiotics treatment has beneficial effects on lung function in non-asthmatic chronic cough patients with normal chest X-ray findings. The improvement of chronic rhinosinusitis may have some role in the lung condition. Upper respiratory tract examination and treatment may be useful for the management of chronic cough., (Copyright © 2019 Elsevier Inc. All rights reserved.)

As has been well recognized, methotrexate (MTX) leads to a state of immunosuppression and can provide a basis for the development of lymphoproliferative disorders (LPDs). MTX-associated LPDs can affect nodal sites as well as extranodal sites, though the manifestation of an LPD in the form of multiple pulmonary nodules is rare. Here, we report two cases of MTX-associated LPD with multiple bilateral pulmonary nodules, which was a finding suggestive of lung cancer, and bilateral cervical lymphadenopathy. After withdrawal of MTX, the multiple bilateral pulmonary nodules and bilateral cervical lymphadenopathy disappeared without chemotherapy in both cases. From these results, patients with pulmonary nodules and cervical lymphadenopathy should be examined for head and neck malignant tumors. Also, physicians should carefully check the administration of MTX. In patients with an MTX-associated LPD, we need to make an early diagnosis and consider discontinuing the administration of MTX as soon as possible., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: The agger nasi cell (ANC) is an easily identifiable landmark when approaching the frontal sinus. The success of endoscopic frontal sinus surgery may be influenced by the width of the frontal recess (FR). The aim of this study is to examine the relationship between the FR width and the ANC size in Japanese patients. In addition, the effect of various frontal recess cells (FRCs) on the development of frontal sinusitis has been examined., Materials and Methods: Multiplanar computed tomography (CT) scans of the nasal cavities and paranasal sinuses in 95 patients (190 sides) before endoscopic sinus surgery were reviewed. The presence of FRCs, the thickness of the frontal beak (FB), the ANC size, and the anterior-to-posterior (A-P) length of the frontal isthmus (FI) and FR were evaluated in patients with and without frontal sinusitis., Results: The prevalence of the ANC, frontal cell types 1, 2, 3, and 4, frontal bullar cell (FBC), suprabullar cell, supraorbital ethmoid cell, and interfrontal sinus septal cell was 85.3%, 11.6%, 0%, 7.9%, 0%, 25.3%, 45.8%, 16.8%, and 15.3%, respectively. The ANC volume showed a significant positive correlation with the A-P length of the FI and FR. The incidence of frontal sinusitis in the patients with FBCs was significantly higher than that without FBCs., Conclusion: A large ANC offers a greater potential to facilitating the approach to the frontal sinus because of the extensiveness of the FR in Japanese patients. The presence of FBCs may be related to a higher incidence of frontal sinusitis., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Objective: The treatment of all forms of sinonasal inverted papilloma (IP) is a complete, wide, local resection. The main surgical purpose is to remove all diseased mucosa and mucoperiosteum, together with a cuff of normal-looking mucosa at the attachment site, followed by drilling and/or coagulation. Our aim is to present our experiences in endoscopic surgical management of IP by using attachment-oriented excision., Methods: We present 20 cases of sinonasal IP. The data collected includes the histopathological diagnosis, staging, extension of the tumor, tumor attachment site, approach to surgery, serum squamous cell carcinoma antigen (SCCA) level, and recurrences., Results: All patients underwent endoscopic surgery. A Caldwell-Luc operation was required in addition to the endoscopic surgery in one case. There was one case of recurrence (5%). After the additional operation, there was no recurrence. The tumor attachment sites vary, and the case of recurrence had a wide attachment site at the primary surgery. No major intra- or post-operative complications were observed., Conclusion: The present study shows that attachment-oriented excision for IP is useful for complete resection of IP. Surgeons should choose the surgical approach according to the location of the tumor attachment site rather than the Krouse staging system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Allergic fungal rhinosinusitis (AFRS) is a noninvasive fungal disease of the sinuses with a very high recurrence rate. A very small number of Japanese cases have been reported., Material and Methods: The subjects were 6 patients with AFRS out of 429 patients who underwent endoscopic sinus surgery at Kagawa Rosai Hospital between December 2011 and November 2017. We retrospectively examined the clinical features and outcomes of these 6 patients., Results: The incidence of AFRS was 1.4% (6/429). Allergic fungal rhinosinusitis was unilateral in 5 cases and bilateral in 1. Computed tomography revealed hyperdense areas representing allergic mucin, but no patient exhibited bone erosion. Magnetic resonance imaging showed hypointense or no signal regions at the locations of allergic mucin. Postoperatively, 1 patient developed recurrence. Because the recurrent patient had no significant symptoms, he refused further surgery and received drug therapy. Preoperative eosinophil counts and total IgE levels were elevated in all patients; postoperatively, both remained high in the patient who developed recurrence. Postoperative treatments included steroid therapy and nasal irrigation., Conclusions: Allergic fungal rhinosinusitis is less prevalent in Japan than in Western nations. Peripheral blood eosinophil and serum IgE values may be used as the biomarkers., Significance: Allergic fungal rhinosinusitis is prone to recurrence. Postoperative treatment including steroid therapy is important in the management of AFRS., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

During development, Shh attracts commissural axons toward the floor plate through a non-canonical, transcription-independent signaling pathway that requires the receptor Boc. Here, we find that Shh induces Boc internalization into early endosomes and that endocytosis is required for Shh-mediated growth-cone turning. Numb, an endocytic adaptor, binds to Boc and is required for Boc internalization, Shh-mediated growth-cone turning in vitro, and commissural axon guidance in vivo. Similar to Boc, Ptch1 is also internalized by Shh in a Numb-dependent manner; however, the binding of Shh to Ptch1 alone is not sufficient to induce Ptch1 internalization nor growth-cone turning. Therefore, the binding of Shh to Boc is required for Ptch1 internalization and growth-cone turning. Our data support a model where Boc endocytosis via Numb is required for Ptch1 internalization and Shh signaling in axon guidance. Thus, Boc acts as a Shh-dependent endocytic platform gating Ptch1 internalization and Shh signaling., (Copyright © 2019 Elsevier Inc. All rights reserved.)