Impact of thirteen-valent pneumococcal conjugate vaccine on nasopharyngeal carriage in healthy children under 24 months in Okinawa, Japan.

In November 2013, a 13-valent pneumococcal conjugate vaccine (PCV13) for all infants aged younger than 5 years was incorporated into the Japan national immunization program. An annual survey of nasopharyngeal carriage rates was performed on healthy infants aged 2-24 months from Okinawa, Japan to evaluate the effect of PCV13 on pneumococcal colonization. Of 756 evaluable infants, 203 pneumococcal strains were detected in 193 infants. The overall nasopharyngeal carriage rate was 25.5%, which was not different from our previously reported isolation rate before the introduction of PCV13. The main serotypes of the Streptococcus pneumoniae strains are 15A (18.2%), non-typeable (14.8%), and 15B (11.8%). The carriage rates of pneumococcal strains with 7-valent pneumococcal conjugate vaccine serotypes and PCV13 serotypes were 3.0% and 9.9%, respectively. These values were significantly lower than we reported before the introduction of PCV13. However, the carriage rates of non-PCV13 serotypes have increased. Multivariate logistic regression analysis suggested that siblings and day care attendance are risk factors for pneumococcal carriage.

Proton Pump Inhibitor Ameliorates Taste Disturbance among Patients with Laryngopharyngeal Reflux: A Randomized Controlled Study.

Patients with laryngopharyngeal reflux (LPR) were reported to suffer from hypogeusia that affects quality of life. Proton pump inhibitor (PPI) is a useful drug in the treatment of LPR, but its effect on hypogeusia is not known. We therefore assessed the effects of PPI or a histamine H2 receptor antagonist (H2 blocker) on hypogeusia among patients with LPR. Both PPI and H2 blocker could inhibit acid reflux. LPR was diagnosed with reflux finding score and reflux symptom index. The visual analogue scale (VAS) of taste disturbance symptoms and the gustatory tests were assessed before and 8 weeks after treatment with esomeprazole, a PPI (20 patients, aged 50.0 ± 1.7 years) or famotidine, a H2 blocker (20 patients, aged 47.1 ± 1.8 years). There were no significant differences in VAS scores and recognition thresholds for four basic tastes between the two groups before treatment. Only PPI therapy significantly decreased the VAS scores, suggesting the improvement of taste perception. Moreover, PPI therapy significantly decreased recognition thresholds for bitter taste in the anterior tongue (chorda tympani nerve area) and the thresholds in the posterior tongue (glossopharyngeal nerve area) for salty, sour, and bitter tastes. By contrast, H2-blocker therapy caused no significant changes of thresholds in the anterior tongue, but improved the threshold only for bitter in the posterior tongue, the value of which was however significantly higher than that in PPI group. In conclusion, PPI could ameliorate hypogeusia by improving bitter, salty, and sour tastes among patients with LPR.

A novel allergen-specific therapy with regulatory T cells induced by CD40-silenced dendritic cells.

BACKGROUND: We previously reported that dendritic cells (DCs) transfected with CD40 siRNA and pulsed by ovalbumin (OVA) (CD40-silenced OVA DCs) inhibited allergic responses through facilitation of regulatory T cells (Tregs). However, to our knowledge, no prior study has examined allergen-specific therapy by administration of siRNA-induced Tregs for the control of allergy. OBJECTIVE: We aimed to investigate the effect of Tregs induced in vitro on allergic responses and symptoms in vivo. METHODS: Mice were treated with Tregs (OVA DCs-induced Tregs) induced by CD40-silenced OVA DCs or Tregs (nonantigen DCs-induced Tregs) induced by DCs transfected with CD40 siRNA and pulsed with no antigen, and the effects of these Tregs on allergic responses were estimated. RESULTS: Administration of nonantigen DCs-induced Tregs prevented not only OVA-induced allergy but also keyhole limpet hemocyanin-induced allergy. Administration of OVA DCs-induced Tregs significantly reduced the number of sneezes and nasal rubbing movements, eosinophilia in the nasal mucosa, and the level of OVA-specific IgE in mice with OVA-induced allergy, compared with CD40-silenced nonantigen DC-induced Tregs in numbers 20 times greater, even in mice with established allergic rhinitis. Furthermore, Tregs induced by CD40-silneced DCs pulsed with Cry j 1, a major allergen of Japanese cedar pollen, inhibited Japanese cedar-induced allergy. CONCLUSIONS: This study shows for the first time that both antigen-independent Tregs and antigen-specific Tregs can be induced by siRNA, and that therapy with siRNA-induced Tregs inhibits allergic responses and symptoms. It also shows that antigen-specific Tregs have more potent effects in inhibiting allergic responses than antigen-nonspecific Tregs.

Preoperative transcatheter arterial embolization using a gelatin sponge for head and neck tumors.

Purpose: To evaluate the usefulness of preoperative transcatheter arterial embolization using a gelatin sponge for hypervascular head and neck tumors to reduce intraoperative blood loss (IBL).　　　　 Material and methods: Nineteen patients underwent preoperative transcatheter arterial embolization for hypervascular head and neck tumors using a gelatin sponge. The technical success rate, devascularization rate, IBL, and complications were evaluated. Angiography images obtained before and after preoperative embolization were compared in all patients, and the devascularization rate was assessed from the relative reduction rate of contrast agent volumes. Results: The technical success rate was 100%. The median devascularization rate was 95% (range, 75-100%). The median period between embolization and surgical resection was one day (range, 1-12 days). The median IBL was 122 ml (range, 0-3780 ml). Blood transfusions were required in three cases, and their IBL and devascularization rates were 850, 1959, and 3780 ml, and 75%, 90%, and 80%, respectively. There was a complication of cerebral embolism in one out of 19 cases (5%). Conclusions: Preoperative transcatheter arterial embolization using a gelatin sponge was feasible and may contribute to decreasing IBL.

Combined measurements of fractional exhaled nitric oxide and nasal nitric oxide levels for assessing upper airway diseases in asthmatic patients.

BACKGROUND: Despite the close linkage between rhinitis, chronic rhinosinusitis (CRS) and asthma, relevant biomarkers of both upper and lower airway inflammation are rare. METHODS: Patients with asthma (without upper airway disease [UAD; n = 24], with rhinitis [n = 25], CRS [n = 24], and nasal polyps [n = 2]), isolated rhinitis (n = 13), isolated CRS (n = 13), and 10 healthy controls were prospectively recruited. Fractional exhaled nitric oxide (NO) levels at 50 mL/s (FeNO50), nasal NO levels, Lund-Macay-scores of sinus computed tomography and an asthma control questionnaire (ACQ) were evaluated. RESULTS: Asthma was associated with higher FeNO50 levels irrespective of the UAD category. FeNO50 levels were higher in asthmatics with CRS (median: 54.0 ppb) than those with rhinitis (35.2 ppb, p = 0.02) and those without UAD (34.3 ppb, p = 0.002). Nasal NO levels were higher in rhinitis patients than other UAD categories, irrespective of the asthma concomitance. Nasal NO levels were higher in asthmatics with rhinitis (112.8 ppb) than those without UAD (67.2 ppb, p = 0.001) and those with CRS (57.6 ppb, p < 0.0001). A receiver-operating-characteristic curve analysis for detecting comorbid allergic rhinitis (AR) in asthmatics showed a high area under the curve (0.87). Nasal NO levels were positively correlated with FeNO50 levels (ρ = 0.56, p = 0.003) in asthmatics with rhinitis. In contrast, they were negatively correlated with the Lund-Macay (ρ = -0.46, p = 0.03) and ACQ scores (ρ = -0.52, p = 0.009) in asthmatics with CRS. CONCLUSIONS: Higher nasal NO levels reflect the presence of AR, irrespective of asthma concomitance. Higher FeNO50 levels reflect the presence of CRS and asthma. These NO measurements are useful for assessing comorbid UAD in asthmatics.

Sleep Disturbance and Hyperactivity Detected by Actigraphy in Rats with Allergic Rhinitis or Attention-Deficit Hyperactivity Disorder.

Actigraphy is an easy and noninvasive method used to monitor human ultradian cycles. However, to our knowledge, it has been not applied to experiments with rodents. Therefore, using actigraphy, we assessed the ultradian cycles and behavior of rats. Rats with or without allergic rhinitis wore an actigraphy device, and triaxial acceleration was recorded. The counts that represent physical activity were lower from 8:00 to 20:00 than those from 20:00 to 8:00 in control rats, suggesting that their sleep phase was from 8:00 to 20:00 and their awake phase from 20:00 to 8:00. The counts from 8:00 to 10:00 were significantly higher in allergic rhinitis rats than in control rats (p < 0.01), suggesting the presence of difficulty with sleep induction in rats with allergic rhinitis. The counts from 18:00 to 20:00 were also significantly higher in allergic rhinitis rats than in control rats (p < 0.05), suggesting the presence of early awakening in rats with allergic rhinitis. Moreover, the counts were significantly higher in allergic rhinitis rats than in control rats from 20:00 to 8:00. These results suggest that rats with allergic rhinitis experienced hyperactivity disorder during the daytime. Additionally, hyperreactivity and difficulty with sleep induction were observed in 6-hydroxydopamine-lesioned rats, an animal model of attention-deficit hyperactivity disorder. This study shows for the first time that actigraphy can be successfully used for behavioral analysis in rodents. These rat models could be useful for analyzing the mechanisms involved in sleep disturbances and hyperactivity disorder.

Repair of Orbital Floor Fracture With Modified Transnasal Endoscopic Approach Through Anterior Space to Nasolacrimal Duct.

OBJECTIVES: Endoscopic approach provides excellent magnification and visualization, and a purely transnasal approach is minimally invasive method. However, it is very difficult to repair anterior and lateral fractures with the previous transnasal endoscopic approaches, since repair of orbital fractures is managed through the middle meatus and ostium from the posterior side of the nasolacrimal duct with side-viewing endoscope and curved instruments. Therefore, the authors used modified transnasal endoscopic approach as an alternative for repair of orbital floor fractures in order to effectively reach the lateral or anterior fracture of the orbital floor with straight endoscope and instruments endoscopically. METHODS: Modified transnasal endoscopic approach through anterior space to nasolacrimal duct was performed in patients with orbital floor fracture, when patients rejected extranasal approach and reconstruction could not be performed by the previous purely transnasal endoscopic approach. After removal of the medial maxillary bone, the lateral wall of nose was shifted in the medial direction to allow wider access to the maxillary sinus. The bone fragments entrapping the orbital content are removed carefully, and correction of periorbita is performed. After surgery, patients were asked whether they have symptoms and/or complications. RESULTS: This modified approach was performed in 15 patients (10 males and 5 females). Mean age at surgery was 37.6 years with a range between 17 and 67. Double vision disappeared in all patients. CONCLUSIONS: This novel approach appears to be a safe and effective technique for the repair of orbital floor fractures.

Intranasal administration of IL-35 inhibits allergic responses and symptoms in mice with allergic rhinitis.

BACKGROUND: IL-35 was recently identified as an anti-inflammatory cytokine. We previously reported that recombinant fusion protein of murine IL-35 and human IgG1 Fc fragment (rIL-35) reduced Th2 cytokines (IL-4 and IL-5) in vitro. However, it is unclear whether IL-35 can attenuate nasal allergic responses and symptoms of allergic rhinitis in vivo. METHODS: To investigate the in vivo effect of IL-35 on allergic rhinitis in mice, mice were sensitized with ovalbumin (OVA). Intranasal administration of rIL-35 and intranasal challenge of OVA were then performed. Nasal symptoms were estimated after the last nasal challenge. Nasal tissue and cervical lymph nodes (CLN) were collected. OVA-specific IgE in sera, OVA-specific T cell response, and the production of cytokines (IL-4, IL-5, and IL-10) stimulated by the OVA antigen were measured. The transcription level of Foxp3 and the frequency of CD4+CD25+ regulatory T cells were also measured. RESULTS: rIL-35 significantly inhibited the number of sneezes and nasal rubbing movements. It also reduced the number of eosinophils in the nasal mucosa and significantly decreased the level of OVA-specific IgE, the OVA-specific T cell proliferation, and the production of IL-4 and IL-5. Furthermore, rIL-35 significantly increased the production of IL-10, the transcription level of Foxp3, and the frequency of CD4+CD25+ regulatory T cells. CONCLUSIONS: This study showed for the first time that rIL-35 inhibits nasal allergic responses and symptoms in mice, and that rIL-35 increases IL-10, Foxp3, and CD4+CD25+ regulatory T cells in CLN. This study also suggests that intranasal administration of IL-35 can attenuate allergic rhinitis.

Effect of Japanese cedar-specific sublingual immunotherapy on allergen-specific TH2 cell counts in blood.

BACKGROUND: The contribution of antigen-specific TH cells in peripheral blood to immunologic mechanisms underlying sublingual immunotherapy (SLIT) remains unclear, partly because of the lack of a standardized method for the analysis of this rare lymphocyte subset. OBJECTIVE: To clarify the role of antigen-specific TH cells during SLIT using a sensitive method analyzing activation marker CD154-positive TH cells with multicolor flow cytometry. METHODS: We assessed antigen-specific TH cells using multicolor flow cytometry based on the expression of the activation marker CD154 and intracellular cytokines in patients with Japanese cedar pollinosis receiving SLIT at baseline and during the first pollen season after the initiation of SLIT. RESULTS: A total of 18 patients between 12 and 44 years of age were enrolled in the present study. Of these, 8 patients received SLIT (SLIT group) and 10 patients received symptomatic treatment only (control group). Although seasonal pollen exposure significantly increased the number of Japanese cedar-specific interleukin 5- and interleukin 4-producing TH cells in the control group (P < .01 for both), SLIT ameliorated this increase in the SLIT group (P = .64 and P = .84, respectively). CONCLUSION: The present study indicates that allergen-specific TH2 cells in peripheral blood are involved in mechanisms underlying SLIT. The analysis of antigen-specific TH cells using multicolor flow cytometry based on the expression of the activation marker CD154 represents a sensitive and relatively simple, standardized method for monitoring peripheral antigen-specific TH cells during allergen-specific immunotherapy.

Clinical impact of hyperbaric oxygen therapy combined with steroid treatment for sudden sensorineural hearing loss: A case-control study.

Objectives: The aim of present study was to evaluate the clinical efficacy of hyperbaric oxygen therapy (HBOT) as a primary therapy combined with standard systemic corticosteroid treatment for sudden sensorineural hearing loss (SSNHL) compared to treatment without the use of HBOT (non-HBOT) through clinical data and advanced analytical approaches. Study Design: Case-control study. Methods: Conducted across three Japanese medical centers involving 298 SSNHL patients diagnosed between 2020 and 2023. Inclusion criteria encompassed first onset and treatment, WHO grade 3 or 4 initial hearing impairment, receipt of systemic corticosteroid therapy within 14 days of symptom onset, and initiation of HBOT within the same timeframe for the case group. The primary outcome measure was the difference in hearing improvement (mean hearing level in decibels, dB) between the two groups, assessed by pure-tone audiometry at baseline and 3 months post-treatment, using the inverse probability of treatment weighting (IPTW) method adjusted for covariate differences. Results: The study included 67 patients in the HBOT group and 68 in the non-HBOT group. The HBOT group exhibited significantly greater hearing improvement (IPTW-adjusted difference: 7.6 dB, 95% CI 0.4-14.7; p = 0.038). Patients without vertigo in the HBOT group demonstrated substantial hearing improvement (11.5 dB, 95% CI 2.3-20.6; p = 0.014), whereas those with vertigo showed no significant improvement (-1.8 dB, 95% CI -11.8-8.3; p = 0.729). The HBOT group also had a significantly higher association with complete recovery (IPTW-adjusted odds ratio: 2.57, 95% CI 1.13-5.85; p = 0.025). Conclusion: In SSHNL, HBOT combination therapy yielded slightly but significantly improved hearing outcomes compared to non-HBOT treatment. Level of Evidence: 4.

Math1, retinoic acid, and TNF-α synergistically promote the differentiation of mucous cells in mouse middle ear epithelial cells in vitro.

BACKGROUND: A key issue in otitis media (OM) is mucous cell metaplasia in the middle ear mucosa, a condition for hyperproduction of mucus in the middle ear mucosa and development of chronic OM. However, little is known about the driving force for the differentiation of mucous cells in OM. METHODS: Mouse middle ear epithelial cells (mMEECs) were used in this study to test whether Math1, a critical transcription factor for the development of mucous cells in the intestine, synergizes with inflammatory cytokines (tumor necrosis factor-α (TNF-α)) and other epithelial differentiation factors (retinoid acid (RA)) to induce the differentiation of mMEECs into mucus-like cells in vitro. Simultaneously, Math1 was transduced into the middle ear mucosa in order to observe whether it induces mucous cell hyperplasia in vivo. RESULTS: Math1 significantly increased the mucus cell numbers in the middle ear mucosa of mice. Math1, in the presence of TNF-α and epithelial differentiation factor RA, synergistically promoted the differentiation of mMEECs into mucus-like cells through upregulation of mucins and their chaperones: trefoil factors in vitro. RA treatment for 12 h activated Math1, although RA alone had very limited effects on mucus-like cell differentiation. CONCLUSION: Math1 plays a critical role in the pathogenesis of OM by induction of mucous cell differentiation in the presence of TNF-α and RA.

Pneumococcal peptidoglycan-polysaccharides regulate Toll-like receptor 2 in the mouse middle ear epithelial cells.

Toll-like receptor 2 (TLR2) plays a key role in the host defense against Gram staining positive (Gram) bacteria and their cell wall envelope components. However, little is known about the expression of TLR2 in the middle ear under otitis media (OM) conditions, and its role in the persistent otitis media with effusion (OME). In this study, we demonstrated that the pneumococcal cell wall component, peptidoglycan-polysaccharides (PGPS), activated the expression of TLR2 in the middle ear epithelial cells through the nuclear factor kappa B (NF-κB)-cytokine signaling pathway while I kappa B alpha mutant (IκBαM), a dominant negative inhibitor of NF-κB, abrogated the expression of TLR2 induced by PGPS. This study suggests that the existence of residual PGPS may maintain a low profile of cytokine production in the middle ear mucosa and thus contribute to the pathogenesis of OME.

A novel allergen-specific therapy for allergy using CD40-silenced dendritic cells.

BACKGROUND: Induction of RNA interference with small interfering RNA (siRNA) has demonstrated therapeutic potential through the knockdown of target genes. We have previously reported that systemic administration of CD40 siRNA is capable of attenuating allergic symptoms but in an allergen-nonspecific fashion. However, siRNA-based allergen-specific therapy for allergy has not been developed. OBJECTIVE: We attempted to develop a new allergen-specific therapy for allergy using CD40-silenced and allergen-pulsed dendritic cells (DCs). METHODS: Bone marrow-derived DCs were silenced with CD40 siRNA and pulsed with ovalbumin (OVA). Mice had allergy after intraperitoneal sensitization with OVA and keyhole limpet hemocyanin, followed by intranasal challenge with the same allergens. The mice were treated with CD40-silenced and OVA-pulsed DCs (CD40-silenced OVA DCs) either before allergic sensitization or after establishing allergic rhinitis. RESULTS: Mice receiving CD40-silenced OVA DCs either before or after the establishment of allergic rhinitis showed remarkable reductions in allergic symptoms caused by OVA challenge, as well as anti-OVA IgE levels in sera. Additionally, CD40-silenced OVA DCs suppressed eosinophil infiltration at the nasal septum, OVA-specific T-cell responses, T-cell production of IL-4 and IL-5 after stimulation with OVA, and CD4(+)CD25(-) effector T-cell responses. Furthermore, CD40-silenced OVA DCs facilitated the generation of CD4(+)CD25(+) forkhead box protein 3-positive OVA-specific regulatory T cells, which inhibit allergic responses in vivo. However, CD40-silenced OVA DCs suppressed only OVA-specific allergy but did not inhibit keyhole limpet hemocyanin-induced allergy, suggesting that CD40-silenced OVA DCs induce allergen-specific tolerance. CONCLUSIONS: This study is the first to demonstrate a novel allergen-specific therapy for allergy through DC-mediated immune modulation after gene silencing of CD40.

Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis.

BACKGROUND: Intranasally administered dendritic cells (DCs) migrate into blood and thymus to induce immune responses. Regulatory dendritic cells (DCs) are also useful agents for allergy control. However, to the best of our knowledge, the effects of intranasal administration of regulatory DCs on allergy have not been reported until now. Therefore, we examined the effects of intranasal route of administration of CD40-silenced DCs on allergic responses and compared these with the effects of other administration routes, based on our previous findings on the inhibitory effects of CD40-silenced DCs on allergic responses. METHODS: Mice with allergic rhinitis were treated intranasally, subcutaneously, intraperitoneally, or intravenously with CD40-silenced ovalbumin (OVA)-pulsed DCs that were transfected with CD40 siRNAs and pulsed with OVA antigen. The effects of these DCs on allergic reactions and symptoms were estimated. RESULTS: Intranasal, subcutaneous, intraperitoneal, or intravenous administration of OVA-pulsed CD40-silenced DCs inhibited allergic responses and symptoms in mice. Furthermore, intranasal administration of OVA-pulsed CD40-silenced DCs significantly reduced allergic symptoms and the number of eosinophils in the nasal mucosa compared with subcutaneous, intraperitoneal, or intravenous administration of these DCs. Intranasal administration of OVA-pulsed CD40-silenced DCs resulted in significantly up-regulated IL-10, IL-35, and Foxp3 expression, and enhanced the percentage of CD11c+CD40- and CD4+CD25+ cells within the cervical lymph nodes compared to subcutaneous, intraperitoneal, or intravenous routes of administration. CONCLUSIONS: We believe that this is the first report to demonstrate that regulatory DCs infiltrate into the cervical lymph nodes after intranasal administration of these cells and that intranasal administration of regulatory DCs is more effective for the induction of tolerance in the nasal mucosa than subcutaneous, intraperitoneal, or intravenous administration.

A novel pathophysiologic link between upper and lower airways in patients with chronic rhinosinusitis: Association of sputum periostin levels with upper airway inflammation and olfactory function.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma are collectively called unified airway diseases. Periostin has been implicated in the pathophysiologic link of these conditions but only by serum measurements. We sought to investigate sputum levels of periostin and their association with upper airway inflammation and olfactory function in CRS patients. METHODS: We prospectively recruited 56 CRS patients who underwent endoscopic sinus surgery (20 with and 36 without comorbid asthma), and 28 healthy controls between October 2015 and December 2017. Lower and upper airway indices such as sputum periostin levels and eosinophil and neutrophil counts, exhaled fractional nitric oxide (FeNO) levels, and olfactory function were evaluated in the three groups. Radiological severity of CT images and tissue eosinophilia of surgical specimens were also assessed in the CRS patients. RESULTS: Sputum periostin levels were highest, and olfactory function was most impaired, in the CRS patients with comorbid asthma, followed by those without asthma and controls in this order. CRS with asthma group showed higher sputum eosinophils and FeNO levels than the other two groups, while CRS patients without asthma showed significantly higher neutrophils in sputum than the other two groups. When confined to CRS patients, olfactory dysfunction was correlated with sputum eosinophil counts. Eosinophil counts of nasal polyps showed a significant positive correlation with sputum periostin and FeNO levels. Radiological severity of CRS was correlated with sputum eosinophil counts and FeNO levels. CONCLUSIONS: Periostin levels and inflammatory cells such as eosinophils and neutrophils in the lower airways are increased in patients with CRS, suggesting the presence of mutual interactions between upper and lower airways even if asthma does not coexist. Olfactory dysfunction and eosinophilic nasal polyps may be potential indicators of Th2-driven inflammation in the lower airways. TRIAL REGISTRATION: This study was registered on the UMIN Clinical Trials Registry (Registry ID UMIN000018672).

Japanese Cedar Pollen-Specific IgA in Nasal Secretions and Nasal Allergy Symptoms.

OBJECTIVE:: IgA-dependent degranulation of eosinophils and positive correlation between IgA and eosinophil cytotoxic protein levels in nasal secretions have been reported. However, the association between IgA and allergic reactions remains unclear. Therefore, we evaluated the changes in Japanese cedar-specific IgA levels and allergy symptoms after Japanese cedar pollen scattering in symptomatic and asymptomatic individuals sensitized to Japanese cedar pollen. METHODS:: Nasal secretion and serum samples were collected from 31 participants (21 symptomatic and 10 asymptomatic participants) in January (preseason) and March (peak season). Japanese cedar-specific IgA or IgE levels were measured using ELISA with diamond-like carbon-coated chips. RESULTS:: The ratio of Japanese cedar pollen-specific IgA to total IgA (rIgA) in the nasal secretions of symptomatic participants increased significantly in March compared with that in January ( P < .01); however, the ratio of specific IgE to total IgE (rIgE) in nasal secretions did not. rIgA in nasal secretions among asymptomatic participants also did not increase during pollen season. rIgA in nasal secretions was significantly correlated with nasal allergic symptoms (r = 0.82; P < .0001) with no significant correlation between rIgE and symptoms. CONCLUSIONS:: To our knowledge, this is the first study to show an association between nasal symptoms and rIgA in nasal secretions, suggesting that rIgA is useful as an antigen-specific biomarker for allergic rhinitis or pollinosis. Furthermore, rIgA values in nasal secretions do not increase in asymptomatic participants sensitized to Japanese cedar during the pollen season.

Transplantation of Olfactory Stem Cells with Biodegradable Hydrogel Accelerates Facial Nerve Regeneration After Crush Injury.

Olfactory mucosa contains neural stem cells, called olfactory stem cells (OSCs), which produce trophic support required for promoting axonal regeneration after nerve injury. However, the local tissue environment can reduce the viability/function of transplanted cells when placed directly on the injury. Although gelatin hydrogels have been shown to aid cell survival during transplantation, such OSC-hydrogel combinations have not been extensively tested, particularly during recovery from facial nerve palsy. In this study, OSCs were isolated from the olfactory mucosae of newborn mice and were shown to express neural stem cell markers before differentiation, as well as cell-type specific markers after differentiation, confirming their multipotency. The OSCs also secrete growth factors and various cytokines that promote nerve regeneration. To test the effects of OSC transplantation in vivo, Medgel, a biodegradable hydrogel sponge, was applied to retain OSCs around the injury site and to lessen the detrimental effects of the local environment in an established facial nerve palsy mouse model. When OSCs were transplanted into the injury site, accelerated recovery was observed for 1 week. When OSCs were transplanted with Medgel, a higher level and duration of accelerated recovery was observed. OSCs in Medgel also increased peripheral nerve function and increased the number of regenerated nerve fibers. These results suggest that OSCs implanted with Medgel accelerate and enhance recovery from facial palsy in mice. Because human OSCs can be easily obtained from olfactory mucosa biopsies with limited risk, this OSC-Medgel combination is a candidate treatment option for accelerating recovery after facial nerve injury. Stem Cells Translational Medicine 2019;8:169&10.

Sinonasal inverted papilloma associated with small cell neuroendocrine carcinoma: A case report and literature review of rare malignancies associated with inverted papilloma.

We report a rare case of sinonasal inverted papilloma (IP) associated with small cell neuroendocrine carcinoma (SNEC). To our knowledge, this is the first report to describe SNEC found during the treatment of sinonasal IP. Surgery and five cycles of cisplatin plus etoposide with concurrent intensity modulated radiation therapy were performed. Neither local recurrence nor distant metastasis was noted during 6 years of post-diagnostic follow-up. The prognosis of SNEC is very poor. Treatment planning for sinonasal IP should consider a possible association with this rare but aggressive malignancy, whose treatment is completely different from that of squamous cell carcinoma, a malignancy which is commonly associated with IP. We also performed a PubMed review of the literature to identify the incidence and pathological diagnosis of associated malignancy. Among a total of 5286 cases of sinonasal IP (61 studies), the incidence of associated malignancy was 8.02% in squamous cell carcinoma, 0.19% in transitional cell carcinoma, 0.04% in mucoepidermoid carcinoma, 0.02% in verrucous cell carcinoma and 0.02% in adenocarcinoma. The incidence of associated malignancy was significantly higher in East and Southeast Asia (11.0%) and North America (10.4%) than in Europe (3.9%) (p=0.04 and p=0.03, respectively; T-test).