Inflammatory molecular endotypes of nasal polyps derived from White and Japanese populations.

BACKGROUND: Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Currently, little is known about possible underlying distinguishing factors between these inflammatory differences. OBJECTIVE: Our aim was to interrogate differences in CRSwNP disease between White/non-Asian patients and Japanese patients by using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs). METHODS: We performed whole transcriptome RNA sequencing with endotype stratification of NPs from 8 White patients (residing in the United States) and 9 Japanese patients (residing in Japan). Reproducibility was confirmed by quantitative PCR in an independent validation set of 46 White and 31 Japanese patients. Single-cell RNA sequencing (scRNAseq) was used to stratify key cell types for contributory transcriptional signatures. RESULTS: Unsupervised clustering analysis identified 2 major endotypes that were present within both cohorts of patients with NPs and had previously been reported at the cytokine level: (1) type 2 endotype and (2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct subgroups with NPs (P = .03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells. CONCLUSION: NPs from both racial groups harbor the same 2 major endotypes, which we have determined to be present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed.

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.

Predictors of Visual Acuity and Usefulness of a Treatment Algorithm in Rhinogenous Optic Neuritis.

Rhinogenous optic neuritis, which causes neuropathy associated with visual dysfunction, greatly reduces patient quality of life and requires suitable early treatment. This study aimed to analyze visual outcome predictors in patients with rhinogenous optic neuritis and to develop and investigate the usefulness of an algorithm to facilitate early treatment. Prospective and retrospective investigations were conducted at the Department of Otorhinolaryngology. The visual outcomes after sinus surgery of 24 of 53 patients suspected of having rhinogenous optic neuritis were analyzed. Furthermore, the usefulness of the treatment algorithm was evaluated in 27 of these 53 patients. Data from 24 patients who underwent surgery were included in a multiple regression analysis to investigate the associations between visual outcomes and concomitant symptoms and the time from symptom onset to surgery. The mean time from the initial examination to a request for otorhinolaryngological examination to assess the usefulness of the treatment algorithm was compared in 27 patients who did not undergo an initial otorhinolaryngological examination. Visual acuity improved in 23 participants who underwent surgery. Multivariate analysis identified the time from onset to surgery and headache as significant predictors of postoperative visual acuity. The mean time from the initial examination to a request for otorhinolaryngological examination was significantly shorter after the algorithm was introduced (1.13 days, 8 patients; P = .008). Early surgical treatment is essential to avoid further postoperative visual acuity decreases in patients with rhinogenous optic neuritis. Patients who experience headache may have poorer postoperative outcomes.

Comparison of Current Staging Systems for Sinonasal Inverted Papilloma.

BACKGROUND: A staging system is essential for determining the optimal surgical approach and predicting postoperative outcomes for inverted papilloma (IP). Although staging systems based on the extent to which the location is occupied by an IP have been widely used, an origin site-based classification of IP using unsupervised machine learning algorithms has recently been reported. OBJECTIVE: To determine the most appropriate of five staging systems for sinonasal IP by comparing recurrence rates for each stage according to each of those systems. METHODS: Eighty-seven patients with sinonasal IP were enrolled in the study. Their tumors were retrospectively categorized according to the Krouse, Oikawa, Cannady, and Han staging systems, which are based on the extent of IP, and the Meng system, which is based on the site of origin. The rates of recurrence for each stage of the five systems were compared. RESULTS: Seven of the 87 patients (8.0%) had recurrences during an average 45.5 months (12-138 months) of follow-up. There were significant differences in disease-free survival between the stages specified by Han and Meng (p = 0.027 and p < 0.001, respectively), but not between the stages specified by Krouse, Oikawa, and Cannady (p = 0.236, 0.062, and 0.130, respectively). Cox proportional hazard models revealed that Meng system (adjusted hazard ratio [aHR] 4.32, 95% confidence interval [CI] 1.10-17.04) and presence of dysplasia (aHR 7.42, 95% CI 1.15-47.85) were significantly associated with recurrence. CONCLUSION: The staging systems proposed by Han and Meng were found to be accurate in terms of tumor recurrence. We recommend use of the Han staging system before surgery and the Meng system after intraoperative identification of the origin of the tumor.

Successful treatment of a 12-year-old boy with Guillain-Barré syndrome requiring tracheostomy due to respiratory muscle paralysis: A case report.

Childhood Guillain-Barré syndrome (GBS) occasionally leads to respiratory failure early after onset, requiring long-term ventilation management after tracheal intubation. However, patients requiring tracheostomy management are rare. In the present study, a case of a 12-year-old boy with GBS who required artificial respiration management due to rapid progression of respiratory muscle paralysis is reported. Intravenous immunoglobulin (IVIg) and pulse steroid therapy were provided; however, both were ineffective and tracheostomy was necessary 26 days after onset. A second course of IVIg and pulse steroid therapy was administered on day 34. With continued rehabilitation, the patient was able to walk long distances on day 74 and was subsequently discharged on day 89. In cases of severe GBS, when IVIg and pulse steroid therapy do not improve the respiratory muscle strength of the patient, early tracheostomy may improve the patient's quality of life during artificial respiration management.

Long-term postoperative control of eosinophilic chronic rhinosinusitis recurrence by inserting a steroid-eluting, sinus-bioabsorbable device reduces the dosage of oral steroid.

OBJECTIVE: We employed a steroid-eluting, sinus-bioabsorbable device for local treatment after surgery for eosinophilic chronic rhinosinusitis (ECRS). One year later, we investigated its efficacy in suppressing recurrence and reducing the use of oral steroids. METHODS: At one year after ECRS surgery, both 18 cases treated with a postoperative steroid-eluting, sinus-bioabsorbable device (Post-ST group) and 25 cases receiving conventional postoperative therapy (Post-Con group) showed significant improvement in the nasal symptoms (nasal obstruction, nasal discharge and olfactory dysfunction), CT score and threshold test (discrimination test). RESULTS: The olfactory dysfunction, CT score and threshold test were significantly improved in the Post-ST group compared with the Post-Con group, but the polyp score was not. The mean total number of oral steroid tablets ingested during one year after surgery was 24.3±2.8 tablets in the Post-ST group, which was significant lower than the 36.3±3.7 tablets used in the Post-Con group. CONCLUSION: The above results indicate that insertion of a steroid-eluting, sinus-bioabsorbable device after ECRS surgery can reduce the oral steroid intake while maintaining long-term suppression of disease recurrence.

Postoperative evaluation of olfactory dysfunction in eosinophilic chronic rhinosinusitis - comparison of histopathological and clinical findings.

Background: Olfactory dysfunction in eosinophilic chronic rhinosinusitis (ECRS) is poorly understood. Objective: To compare olfactory mucosal injury due to eosinophil infiltration in ECRS with postoperative olfactory function. Methods: Seventeen ECRS patients (ECRS group) and 18 bilateral rhinosinusitis (non-ECRS group) patients were compared. At 3 and 12 months post-endoscopic sinus surgery (ESS), all patients were evaluated for subjective symptoms (nasal obstruction, nasal discharge and olfactory dysfunction), endoscopic nasal findings, CT score and T&T olfactometer recognition threshold test. The eosinophil count, OMP-positive cells and epithelial erosion in olfactory mucosa collected during ESS were compared with the postoperative olfactory function. Results: The non-ECRS group showed significant improvement in all clinical findings at 3 and 12 months, but the ECRS group showed worsening of the olfactory dysfunction symptoms and T&T olfactometer recognition threshold at 12 months because of recurrence of sinusitis. The groups differed significantly in the ΔT&T value (i.e. pre-ESS T&T recognition threshold - post-ESS T&T recognition threshold) at both 3 and 12 months, and the degree of olfactory improvement differed. Histologically, the ECRS group showed significantly more eosinophils, fewer OMP-positive cells and greater epithelial erosion than the non-ECRS group. Conclusions: Eosinophilic inflammation was thought to cause olfactory mucosal injury/dysfunction.

Prognostic value of C-reactive protein/albumin ratio for patients with hypopharyngeal and laryngeal cancer undergoing invasive surgery involving laryngectomy.

BACKGROUND: The C-reactive protein/albumin (CRP/Alb) ratio has been recently established as a prognostic indicator in various cancer types. However, few reports regarding the prognostic value of the CRP/Alb ratio in head and neck cancer exist. This study aimed to investigate the significance of the CRP/Alb ratio in clinical outcomes after invasive surgery involving laryngectomy for hypopharyngeal and laryngeal cancer. METHODS: We evaluated 56 patients who underwent total laryngectomy or total pharyngolaryngectomy between 2003 and 2012. Univariate and multivariate analyses were retrospectively performed to examine the prognostic value of the CRP/Alb ratio in these patients. RESULTS: The optimal cutoff value of the CRP/Alb ratio was 0.32. Multivariate analysis showed that the CRP/Alb ratio was a significant and independent predictor of poor overall and disease-free survival. CONCLUSION: The CRP/Alb ratio may be a novel and useful indicator for predicting postoperative outcomes in patients with hypopharyngeal and laryngeal cancer.

Adenoid cystic carcinoma of the larynx presenting with unusual subglottic mass: Case report.

A 33-year-old woman presented with an unusual subglottic bulging mass accompanied by prolonged cough and wheeze. Laryngeal endoscopy revealed a bilateral, symmetrical mass immediately below the vocal cords with marked airway obstruction. Chronic subglottic laryngitis with inflammation or another condition such as amyloidosis was initially suspected. Cervicothoracic computed tomography revealed an obvious reduction of laryngeal caliber caused by an engulfing mass extending from just under the vocal cords to the cricoid ring, which was associated with thyroid, arytenoid, and cricoid cartilage destruction. Histopathological diagnosis of a biopsy specimen collected via a tracheotomy revealed that the lesion was a cT4aN0M0 adenoid cystic carcinoma (ACC) originating from the laryngeal minor salivary glands. The patient was treated by total laryngectomy with elective bilateral neck dissection under general anesthesia. Gross inspection of resected tissue confirmed yellowish-white, solid tumor mainly circumferentially encompassing the lumina of the cricoid ring. The histopathological findings confirmed typical ACC accompanied by a predominant cribriform appearance with no evidence of lymph node metastasis. The patient remains well and free of recurrence or metastasis. We herein describe laryngeal ACC and discuss radiological images and the surgical pathology.

A simple method to improve the clarity and rheological properties of polymer/clay nanocomposites by using fractionated clay particles.

We present a simple method to improve the transparency and rheological properties of polystyrene/organoclay nanocomposites. Such composites are typically prepared using organophilic derivatives of commercial montmorillonite (MMT) clays that contain a wide range of particle sizes. Our approach is to fractionate the native MMT clay to exclude large aggregates and then modify the fractionated clay (FMT) by a surfactant treatment (the resulting organoclay is termed o-FMT). Polystyrene nanocomposites made from the o-FMT are then compared with those made from a commercial organoclay having the same surfactant treatment. The o-FMT-based composites exhibit much better rheological properties (e.g., their elastic moduli at low frequencies are approximately 10 times higher) at equivalent mass loadings. Moreover, the o-FMT-based materials also have better transparency: e.g., a 10% o-FMT sample transmits as much light as a sample with 5% commercial clay. Transmission electron microscopy confirms that these differences in properties are related to microstructural differences; i.e., large aggregates are generally absent in the o-FMT samples. Clay fractionation may thus be a general strategy to enhance the properties of polymer/clay nanocomposites.

Nanoparticle networks reduce the flammability of polymer nanocomposites.

Synthetic polymeric materials are rapidly replacing more traditional inorganic materials, such as metals, and natural polymeric materials, such as wood. As these synthetic materials are flammable, they require modifications to decrease their flammability through the addition of flame-retardant compounds. Environmental regulation has restricted the use of some halogenated flame-retardant additives, initiating a search for alternative flame-retardant additives. Nanoparticle fillers are highly attractive for this purpose, because they can simultaneously improve both the physical and flammability properties of the polymer nanocomposite. We show that carbon nanotubes can surpass nanoclays as effective flame-retardant additives if they form a jammed network structure in the polymer matrix, such that the material as a whole behaves rheologically like a gel. We find this kind of network formation for a variety of highly extended carbon-based nanoparticles: single- and multiwalled nanotubes, as well as carbon nanofibres.