Favorable clinical course after discontinuation of omalizumab treatment in patients with allergic severe asthma: A real-world clinical practice.

The success rate of omalizumab discontinuation is 50-75.5%. However, such data are scarce in Japan. We retrospectively investigated the clinical progression following the cessation of long-term omalizumab treatment (>5 years) in severe allergic asthma patients who have achieved super-responder status, defined as being off any oral maintenance corticosteroids without experiencing exacerbations requiring systemic corticosteroids for >1 year. Six (28.6%) among 21 patients recommenced after a median period of 5.5 (4.3-12.5) months later due to exacerbated asthma control, resulting in improved asthma management for all patients. The rates of patients who successfully remained off omalizumab treatment for 1 and 2 years were 72.4% and 65.8%, respectively. Specific IgE levels after discontinuing omalizumab treatment significantly decreased compared to those at initiating this treatment in 10 patients who successfully remained off this treatment. Therefore, discontinuing omalizumab treatment may be considered for patients continuing treatment beyond 5 years and achieving super-responder status.

Super-responder and clinical remission in patients with asthma on treatment with single biologic therapy or cycling therapy using dupilumab in a real-world setting.

BACKGROUND: Regarding the therapeutic target in asthma, super-responder status (SR) is a status without systemic corticosteroids. Recently, clinical remission (CR), being a status of prolonged absence of asthma symptoms without systemic corticosteroids and/or normal pulmonary function, has gained attention as a new therapeutic target in asthma. Here, we examined the percentage and features of asthma patients on treatment with dupilumab showing SR and CR. MATERIALS AND METHODS: 49 asthma patients used subcutaneous dupilumab for > 1 year between April 2019 and November 2022. The status of SR and CR for 1 year was evaluated. Patients without any maintenance oral corticosteroids and exacerbations requiring systemic corticosteroids were classified as SR. CR was defined using three definitions based on changes in asthma symptoms and pulmonary function in addition to achieving SR for 1 year: CR without pulmonary function criteria (CR w/o F), fulfilment of asthma symptom improvement (asthma control questionnaire score < 0.75 or asthma control test score ≥ 23); and CR-70 or CR-80, pulmonary function improvement (%forced expiratory volume in 1 second ≥ 70% or ≥ 80%) in addition to achieving CR w/o F, respectively. RESULTS: 38 (77.6%), 22 (44.9%), 13 (26.5%), 12 (24.5%) of patients had SR, CR w/o F, CR-70, and CR-80, respectively. Severe eosinophilic chronic rhinosinusitis was significantly more found in patients with SR and CR based on all three definitions than in those without. CONCLUSION: This study identified the percentage and features of patients on treatment with dupilumab showing SR and CR in a real-world setting. The outcome beyond CR on biologic treatment should be clarified.

Evaluation of odor recognition threshold measurement methods in T&T olfactometry: A survey study.

OBJECTIVE: The odor recognition thresholds in T&T olfactometry are measured by either the examiner's judgment of the patients' odor expression for each standard odor or by the patient's choice of the correct response from an olfactory term table. This study aimed to clarify the correct odor expressions and use of the olfactory term table. METHODS: A questionnaire was administered to otolaryngologists or medical staff in charge of testing at facilities where T&T olfactometry is performed. The questionnaire consisted of the facility's background, environment and procedures of T&T olfactometry, choice of the correct answer with five different standard odors, and use of the olfactory term table. For the choices, the expressions used were those considered correct at Nippon Medical School Tama Nagayama Hospital and the Kyoto Nose and Allergy Clinic. RESULTS: A total of 81 valid responses were obtained. Most respondents belonged to medical and educational institutions (59.3%, 48/81). The laboratories in the respondents' institutions were completely ventilated using various methods. Clinical laboratory technicians inspected 51.7% (45/81) of the facilities. The order of standard odors in the odor recognition threshold test differs depending on the facility. When the examiner was unsure about the answer given by the patient in the odor recognition threshold test, 16.1% (9/56) of the respondents chose "present the olfactory term table," 33.9% (19/56) chose "increase the concentration," and 37.5% (21/56) chose "present the olfactory term table" or "increase the concentration," depending on the situation. A total of 96.4% (54/56) of the facilities treated odor expressions other than those in the olfactory term table as correct, and the odor expressions that were considered correct differed from facility to facility. Of the respondents, 80.2% (65/81) answered "I know the olfactory term table," and the mean value of satisfaction with the current olfactory term table was 4.4 ± 3.0. Of the respondents, 81.5% (53/65) answered that "the timing of presenting the olfactory term table should be standardized in all facilities." CONCLUSION: In the odor recognition threshold test by T&T olfactometry, this study revealed that the odor expressions considered as correct answers for the standard odors and the use of the olfactory term table differed among facilities.

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.

Barrier Factors of Adherence to Dupilumab Self-Injection for Severe Allergic Disease: A Non-Interventional Open-Label Study.

Purpose: The status of dupilumab self-injection at home is not well understood. We therefore aimed to identify the barriers to adherence to dupilumab self-injection. Patients and Methods: This non-interventional open-label study was conducted between March 2021 and July 2021. Patients with atopic dermatitis, bronchial asthma, and chronic rhinosinusitis with nasal polyps receiving dupilumab, from 15 sites, were requested to complete a self-administered questionnaire regarding the frequency and effectiveness of dosing as well as their use and satisfaction with dupilumab. Barriers to adherence were assessed using the Adherence Starts with Knowledge-12. Results: We included 331 patients who used dupilumab for atopic dermatitis (n = 164), chronic rhinosinusitis with nasal polyps (n = 102), and bronchial asthma (n = 65). The median efficacy of dupilumab scored 9.3 on the visual analog scale. Overall, 85.5% of the patients self-injected dupilumab, and 70.7% perfectly complied with the established injection dates. The pre-filled pen was significantly superior to the conventional syringe in terms of usability, operability, ease of pushing the plunger, and patient satisfaction. However, the pre-filled pen caused more pain during self-injection than did the syringe. Multivariate logistic regression analysis showed that adherence decreased with longer dupilumab treatment duration (p = 0.017) and was not associated with age, sex, underlying disease, or device type. There was a difference in responses related to "inconvenience/forgetfulness" between the good and poor adherence groups. Conclusion: The pre-filled dupilumab pen was superior to the syringe in terms of usability, operability, ease of pushing the plunger, and satisfaction. Repetitive instructions are recommended for preventing poor adherence to dupilumab self-injection.

One-third of vertiginous episodes during the follow-up period are caused by benign paroxysmal positional vertigo in patients with Meniere's disease.

CONCLUSION: In the present study, about one-third of patients with Meniere's disease developed benign paroxysmal positional vertigo (BPPV)-like attacks. Additionally, more than one-third of all vertigo attacks were BPPV-like attacks. Thus, vertigo attacks in patients with Meniere's disease must be carefully treated because the therapy for such vertigo attacks is totally different from the therapy for BPPV. OBJECTIVE: Physicians sometimes encounter patients with previously diagnosed Meniere's disease who develop BPPV attacks during the course of clinical follow-up. In this study, we explored the frequency with which BPPV was involved in all vertiginous episodes among patients with Meniere's disease. METHODS: This retrospective study involved 296 patients with Meniere's disease who visited Kyoto University Hospital. The diagnosis of Meniere's disease was based on the guidelines for the diagnosis of Meniere's disease proposed by the Committee on Hearing and Equilibrium. We judged the cause of vertigo as one of the following five types: (1) definite Meniere's disease attack, (2) suspicious Meniere's disease attack, (3) definite BPPV attack, (4) suspicious BPPV attack, or (5) unknown. RESULTS: In all, 96 patients (32.8%) developed BPPV-like attacks, and 187 vertiginous episodes (37.9%) were caused by BPPV. The lateral semicircular canal was the most frequently involved canal.

Identification of tympanic border cells as slow-cycling cells in the cochlea.

Mammalian cochlear sensory epithelial cells are believed to possess minimal regenerative potential because they halt proliferation during late stage of embryogenesis and never regenerate after birth. This means that sensorineural hearing loss caused by the death of cochlear sensory epithelial cells is a permanent condition. However, stem cells were recently identified in neonatal mice following dissociation of their inner ear organs. This suggests that regenerative therapy for sensorineural hearing loss may be possible. Unfortunately, dissociation distorts the microanatomy of the inner ear, making it difficult to determine the precise location of stem cells in unaltered specimens. To develop new therapeutic approaches based on sensory epithelial cell regeneration, the location of these stem cells must be elucidated. Stem cells normally proliferate at a slow rate in adult organs. In fact, so-called label-retaining cells, or slow-cycling cells, of the brain and skin are recognized as stem cells. In this study, using the exogenous proliferation marker, 5'-bromo-2'-deoxyuridine (BrdU) in combination with the endogenous proliferation marker Ki-67, we identified tympanic border cells. These cells, which are located beneath the basilar membrane in vivo, represent slow-cycling cells of the murine cochlea. Immunohistochemically, these cells stained positive for the immature cell marker Nestin. But it will be difficult to achieve regeneration of the cochlear function because these slow-cycling cells disappear in the mature murine cochlea.

Outcome of ossiculoplasty in Kyoto University Hospital.

CONCLUSION: We performed ossiculoplasty under conditions preventing inflammation by adopting a planned staged operation, which is suitable for ossiculoplasty using an artificial prosthesis. We identified the presence of chorda tympani nerve as a candidate predictive factor for successful ossiculoplasty. OBJECTIVES: We aimed to summarize the outcome of ossiculoplasty and to find factors to improve the success rate. METHODS: This was a retrospective chart review of 96 patients who underwent ossiculoplasty in Kyoto University Hospital from 2001 to 2008. Patients' backgrounds, hearing outcomes, and surgical procedures were analyzed. To find predictive factors for successful ossiculoplasty, we performed logistic regression analysis. RESULTS: The improvement in the mean air conduction level was 12.9 dB. The mean postoperative air-bone gap (ABG) was 25.0 dB. The ABG decreased to within 20 dB in 40.7% of the cases. As a result of univariate logistic regression analysis, primary or planned second stage surgery, closed mastoid cavity, and presence of the chorda tympani nerve were identified as favorable factors for successful ossiculoplasty.

Management of labyrinthine fistulae in Kyoto University Hospital.

CONCLUSION: In cases of labyrinthine fistulae, we performed complete removal of the cholesteatoma matrix in a one-stage procedure, resulting in a satisfactory bone conduction (BC) hearing preservation rate. Preoperative evaluation of labyrinthine fistulae using high resolution computed tomography (HRCT) detected 86% of cases, and this contributed to favorable results achieved with the surgical treatment of labyrinthine fistulae. We aimed to review cases of labyrinthine fistulae to summarize their outcomes and establish standards of management. METHODS: This was a retrospective chart review of 22 patients with labyrinthine fistulae at Kyoto University Hospital from 2001 to 2009. Patient background (age and sex), location and stage of the fistulae, facial nerve status, preoperative and postoperative BC hearing levels, preoperative CT diagnosis, and surgical procedures were analyzed. RESULTS: The incidence rate of the labyrinthine fistulae was 11.2%. All but one patient had labyrinthine fistula due to cholesteatoma. The fistulae were found in the lateral semicircular canal in 17 cases (77%) and in multiple organs in 4 cases (18%). The BC hearing level was preoperatively scaled out in seven cases. Preoperative HRCT scan revealed the presence of fistulae in 19 cases (86%). For all cases of cholesteatoma, the matrix was completely removed in a one-stage procedure and the fistulae were sealed using bone pate, temporal fascia, and temporal bones. Of the 15 cases with residual BC hearing ability, BC hearing was preserved in up to 12 cases. Two cases with postoperative deterioration of BC hearing had stage 4 fistulae in the cochleae.

New interdisciplinary approach for removing large clivus and upper cervical spine tumors.

We have developed a new interdisciplinary approach for removing large clivus and upper cervical spine tumors. This approach is a combination of the Le Fort I osteotomy, midfacial degloving, and median labiomandibular glossotomy. Our approach gives an excellent, wide surgical field from the nasopharynx, including the base of the skull, to the base of the tongue and permits sufficiently safe extirpation of clivus and upper cervical spine tumors that may not be removed by transoral or transcervical approaches. Our approach not only incorporates the merits of each approach but also creates a larger surgical field that may be modified or expanded to accommodate the removal of more bulky tumors in this region. This novel approach will facilitate more successful resection of tumors arising between the nasopharynx, including the skull base, and the retropharyngeal area.