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The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains a serious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymerase consists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity. Fullerene (C60) is a unique carbon molecule that forms a sphere. To identify potential new anti-influenza compounds, we screened 12 fullerene derivatives using an in vitro PA endonuclease inhibition assay. We identified 8 fullerene derivatives that inhibited the endonuclease activity of the PA N-terminal domain or full-length PA protein in vitro. We also performed in silico docking simulation analysis of the C60 fullerene and PA endonuclease, which suggested that fullerenes can bind to the active pocket of PA endonuclease. In a cell culture system, we found that several fullerene derivatives inhibit influenza A viral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate that fullerene derivatives are possible candidates for the development of novel anti-influenza drugs. [ABSTRACT FROM AUTHOR]

Long-term efficacy of middle ear pressure therapy (MEPT) with the EFET01 device in patients in Japan with definitive Ménière's disease (MD) and delayed endolymphatic hydrops (DEH) was evaluated. To examine the effects of reducing vertigo attacks and improving hearing of MD and DEH patients by using MEPT with the EFET01 device for two years after treatment. A retrospective study was conducted of 32 MD patients and 2 DEH patients treated by MEPT with the EFET01 device from December 2018 to April 2021. According to Japan Society for Equilibrium Research (JSER) guidelines, patients were investigated for the frequency of vertigo attacks and change in hearing levels during a period of 6 months before to 18–24 months after start of treatment. The frequency of vertigo attacks significantly decreased in both MD and DEH patients, and hearing level has remained stable in the majority of our patients after treatment. Our study clarified that MEPT with the EFET01 device was effective in controlling vertigo symptoms of MD and DEH. It should be considered a safe option for patients failing medical treatment. The efficacy of MEPT with the EFET01 was shown over a 2-year follow-up period. [ABSTRACT FROM AUTHOR]

Objective: The prognosis of patients with relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) is poor. Although patients who fail first‐line salvage chemotherapy are candidates for second‐line salvage chemotherapy, the optimal treatment strategy for these patients has not yet been established. Methods: The present, single‐center, retrospective study included transplant‐eligible patients with R/R DLBCL who received second‐line salvage chemotherapy with curative intent. Results: Seventy‐six patients with R/R DLBCL received second‐line salvage chemotherapy. Eighteen (23.7%) patients were responders to the first‐line salvage chemotherapy. The overall response rate was 39.5%, and overall survival (OS) was significantly longer in patients who responded to second‐line salvage chemotherapy than those who did not. Forty‐one patients who proceeded to potentially curative treatment (autologous hematopoietic stem cell transplantation [ASCT], chimeric antigen receptor [CAR] T‐cell therapy, or allogeneic hematopoietic stem cell transplantation) had a better prognosis than those who did not. Among the 46 patients who failed to respond to the second‐line salvage regimen, only 18 (39.1%) could proceed to the curative treatments. However, among the 30 patients who responded to the second‐line salvage regimen, 23 (76.7%) received one of the potentially curative treatments. Among 34 patients who received CAR T‐cell therapy, OS was significantly longer in those who responded to salvage chemotherapy immediately prior to CAR T‐cell therapy than in those who did not respond. In contrast, the number of prior lines of chemotherapy was not identified as a statistically significant prognostic factor of survival. No significant difference was detected in OS between patients receiving ASCT and those receiving CAR T‐cell therapy after the response to second‐line salvage chemotherapy. Discussion: In this study, we demonstrated that chemosensitivity remained a crucial factor in predicting survival outcomes following CAR T‐cell therapy irrespective of the administration timing, and that both ASCT and CAR T‐cell therapy were acceptable after the response to second‐line salvage chemotherapy. [ABSTRACT FROM AUTHOR]

The optimal dose intensity of chemotherapy for elderly patients with diffuse large B cell lymphoma (DLBCL) remains controversial because of concerns about adverse events and comorbidities related to the patients' frailty. This single-center study retrospectively analyzed patients aged ≥ 70 years who were newly diagnosed with DLBCL and received chemotherapy between 2004 and 2022. Survival outcomes and treatment-related mortality (TRM) were stratified according to geriatric assessment variables, and the influence of chemotherapy dose intensity on outcomes was assessed using the frailty score with a Cox hazards model with restricted cubic spline (RCS) in patients aged 70–79 years. In total, 337 patients were included. The frailty score accurately predicted prognosis (5-year overall survival [OS]: 73.1%, 60.2%, and 29.7% in fit, unfit, and frail patients, respectively; P < 0.001) and TRM (5-year TRM: 0%, 5.4%, and 16.8 in fit, unfit, and frail patients, respectively; P < 0.001). Cox regression with RCS demonstrated a linear association between dose intensity and survival outcomes. Initial dose intensity (IDI) and relative dose intensity (RDI) had a significant impact on OS in fit patients. However, IDI and RDI had no significant effect on survival in non-fit (unfit and frail) patients. The frailty score identified non-fit patients with poorer survival and a higher risk of TRM. While fit patients were likely to benefit from full-dose R-CHOP, unfit and frail patients would likely benefit more from attenuated R-CHOP. This study suggested a potential role for the frailty score in individualizing treatment intensity in elderly patients with DLBCL. [ABSTRACT FROM AUTHOR]

Background: Synchronous multiple primary malignant tumors (sMPMTs) are sometimes diagnosed in patients with malignant lymphoma. We herein investigated the prognostic impact of sMPMT in lymphoma patients and the optimal treatment strategy.Methods: Seventy-five patients with sMPMTs (5.8%) among 1285 patients with lymphoma newly diagnosed between August 2004 and April 2020 were enrolled.Results: In patients with indolent lymphoma, those with sMPMTs had a worse prognosis than those without sMPMTs (5-year overall survival [OS]: 73.4% and 87.8%, respectively; P = 0.047). Among those with high and low tumor burden, the cumulative rate of death due to solid tumors was significantly higher in patients with sMPMTs than those without sMPMTs (high tumor burden: 26.7% vs. 1.6%, P < 0.001; low tumor burden: 12.7% vs. 1.0%, P = 0.003). The presence of sMPMTs did not have a significant impact on outcomes in patients with diffuse large B-cell lymphoma (DLBCL) (5-year OS: 65.4% and 66.9%, respectively; P = 0.74; 5-year progression-free survival [PFS]: 65.5% and 59.9%, respectively; P = 0.65). However, the cumulative rate of death from solid tumor in patients with sMPMTs was significantly higher than in patients without sMPMTs (5-year cumulative rate: 7.4% and 2.1%, respectively; P = 0.004). The treatment sequence did not have a significant effect on outcomes or the relative dose intensity of chemotherapy.Conclusions: In patients with indolent lymphoma, those with sMPMTs had a significantly worse prognosis than those without sMPMTs, mainly because of high mortality due to solid tumors. The presence of sMPMTs was not a significant prognostic factor in patients with DLBCL. It is important to assess the status and need for early treatment of each type of malignancy in patients with sMPMTs. [ABSTRACT FROM AUTHOR]

Formalin-fixed paraffin-embedded (FFPE) blocks are used as biomaterials for next-generation sequencing of cancer panels. Cross-contamination is detected in approximately 5% of the DNA extracted from FFPE samples, which reduces the detection rate of genetic abnormalities. There are no effective methods available for processing FFPE blocks that prevent cells from mixing with other specimens. The present study evaluated 897 sheets that could potentially prevent cell transmission but allow for the movement of various solvents used in FFPE blocks. According to the International Organization for Standardization and Japanese Industrial Standards, six requirements were established for the screening of packing sheets: 1) filter opening ≤5 μm, 2) thickness ≤100 μm, 3) chemical resistance, 4) permeability ≥1.0 × 10−3 cm/s, 5) water retention rate <200%, and 6) cell transit test (≤2 cells/10 high-power fields). Polyamide, polyethylene terephthalate, and polypropylene/polyethylene composite sheets met all criteria. A pocket, which was designed to wrap the tissue uniformly, was made of these sheets and was found to effectively block the entry of all cell types during FFPE block processing. Using a sheet pocket, no single cell from the cell pellet could pass through the outer layer. The presence or absence of the sheet pocket did not affect hematoxylin and eosin staining. When processing FFPE blocks as a biomaterial for next-generation sequencing, the sheet pocket was effective in preventing cross-contamination. This technology will in part support the precise translation of histopathological data into genome sequencing data in general pathology laboratories. [ABSTRACT FROM AUTHOR]

Objective: To report an extremely rare case of transplanted cholesteatoma after traumatic tympanic membrane (TM) perforation. Materials and Methods: The patient was a one year and four month-old boy who accidentally bruised his left temporal region against the hard ground. Left TM perforation with fresh bleeding and swelling of the auricle were identified. Clinical observation with otomicroscopy and CT and then surgical treatment were performed. One month after the trauma, we confirmed that TM had spontaneously closed with thin membrane. Six months after the trauma, an isolated mass in the tympanic cavity was identified through closed area of TM. Intraoperative view showed that an isolated cholesteatoma existed without continuation with the TM. Results: We considered that the pathogenesis of present case could be explained as following, the TM was initially blown open medially due to pressure increase in the external auditory canal and epithelial tissue was transplanted to the tympanic cavity. Then, the TM perforation spontaneously closed and an isolated cholesteatoma occurred without continuation with the tympanic membrane. Conclusion: This case suggested that transplanted epithelium of TM has the potential to induce cholesteatoma in the tympanic cavity. [ABSTRACT FROM AUTHOR]

Tinnitus therapies have been combined with the use of varieties of sound/noise. For masking external sounds, location of the masker in space is important; however, effects of the spatial location of the masker on tinnitus are less understood. We aimed to test whether a masking sound location would affect the perception level of simulated tinnitus. The 4 kHz simulated tinnitus was induced in the right ear of healthy volunteers through an open-type earphone. White noise was presented to the right ear using a single-sided headphone or a speaker positioned on the right side at a distance of 1.8 m for masking the simulated tinnitus. In other sessions, monaurally recorded noise localized within the head (inside-head noise) or binaurally recorded noise localized outside the head (outside-head noise) was separately presented from a dual-sided headphone. The noise presented from a distant speaker and the outside-head noise masked the simulated tinnitus in 71.1% and 77.1% of measurements at a lower intensity compared to the noise beside the ear and the inside-head noise, respectively. In conclusion, spatial information regarding the masking noise may play a role in reducing the perception level of simulated tinnitus. Binaurally recorded sounds may be beneficial for an acoustic therapy of tinnitus. [ABSTRACT FROM AUTHOR]

Purpose: To determine patients with abnormal sensation in the throat (AST) who would respond to potassium-competitive acid blocker (P-CAB) or serotonin noradrenaline reuptake inhibitor (SNRI) treatment. Methods: AST patients were randomly divided into two groups. Thirty-one and 21 patients received P-CAB and SNRI treatment, respectively. GETS-J, the Japanese version of Glasgow Edinburgh Throat Scales (GETS), consisted of three subscales of throat symptoms (globus sensation, pain/swelling of the throat, and dysphagia) and somatic distress due to the disease, Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (FSSG), and Hospital Anxiety and Depression Scale (HADS) were used before and after treatments. Responders to treatments were defined as those who showed 50% or more decrease in symptom scores or somatic distress. Results: Pre-treatment GETS-J pain/swelling scores and FSSG acid reflux scores were higher in P-CAB responders and decreased after treatment. Receiver operating characteristic curve for pain/swelling subscale had an area under the curve (AUC) of 0.792 to predict P-CAB responders and a score of 11 provided the best combination of sensitivity (62.5%) and specificity (80%). Somatic distress and HADS anxiety scores, but no other GETS-J symptom scores, decreased after SNRI treatment. Pre-treatment globus scores were lower in SNRI responders. AUC value for globus subscale to predict SNRI responders was 0.741 and a score of 6.5 provided the best combination of sensitivity (70%) and specificity (73%). Conclusions: Pain/swelling is a characteristic symptom in AST patients who respond to P-CAB treatment. SNRI treatment would be effective for somatic distress in cases with mild symptoms. [ABSTRACT FROM AUTHOR]

Objective: Age-related cognitive decline involves a complex set of factors. Among these factors, hearing loss is considered to have a significant impact, but the effect of hearing aid use remains unresolved. The purpose of this study was to evaluate the effects of hearing aid use by simultaneously assessing various factors not only cognitive function but also frailty, anxiety, depression, and quality of life (QOL) in patients with hearing loss., Methods: The cross-sectional study at the Hearing Aid (HA) Center was conducted between 2020 and 2021. Initially, associations with cognitive function, QOL, frailty, and mental state among patients with hearing loss were examined, irrespective of whether they wore a hearing aid or not. Next, these patients were divided into HA users (using HA for more than 1 year) and non-users (no prior use of HA) with 42 patients in each group. The average age and 6-frequency pure tone audiometry (PTA) was 74.5 ± 6.5 years and 50.6 ± 12.1 dB, respectively. All participants filled out the questionnaire about their life style, medical condition. Mini-Mental State Examination (MMSE) for cognitive function, Hospital Anxiety and Depression Scale for mental state, Short Form 36 version 2 (SF-36v2) for QOL, and Kihon Checklist for frailty were compared between HA users and non-users and correlated with the auditory data (PTA and speech discrimination)., Results: Among 84 patients, 40 had an MMSE score ≦26. All eight scores and three components of SF-36v2 were lower than those of the control group. The patients with hypertension were significantly more in HA user than in non-HA user, whereas there was no difference in diabetes, heart attack, stroke and education. Although HA users were older and showed hypertension more their PTA was worse than that of non-users, MMSE scores were not different between the groups. MMSE scores correlated with both PTA and speech discrimination in non-users but not in HA users. However, a multivariate analysis of the effect of HA use on MMSE scores adjusting for age, hypertension, and hearing loss, could not be revealed. The vitality and mental component summary of the SF-36v2 was better in HA users than in non-users., Conclusion: Elderly patients with hearing loss were cognitively impaired and had low QOL. HA users showed better QOL score than non-HA user, especially about the mental condition. The absence of a correlation between MMSE scores and hearing loss in HA users suggests the potential use of HA in preventing cognitive decline., Competing Interests: Declaration of competing interest The authors declare no commercial or financial relationships that can be construed as potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To assess the location/number of otic capsule demineralization and hearing outcomes of stapes surgery (SS) for osteogenesis imperfecta (OI) compared with otosclerosis (OS)., Patients: This study included 11 and 181 consecutive ears from 6 and 152 patients with OI and OS, respectively., Interventions: Demineralization loci observed as hypodense area of the otic capsule were examined using high-resolution computed tomography. All patients underwent SS., Main Outcome Measures: Locations of the hypodense areas were classified into the anterior oval window, anterior internal auditory canal, and pericochlear area. The location/number of hypodense areas and preoperative/postoperative hearing parameters were correlated. Postoperative hearing outcome was evaluated 12 months after surgery., Results: Hypodense area was more frequently observed in OI (9 of 11 ears [81.8%]) than in OS (96 of 181 ears [53.0%]), with significant differences. Multiple sites were involved in 81.8% OI and 18.8% OS patients, showing significant differences. Preoperative air conduction (AC), bone conduction, and air-bone gap (ABG) were 48.9 ± 17.8, 28.0 ± 11.3, and 20.7 ± 8.4 dB, respectively, in OI and 56.2 ± 13.5, 30.5 ± 9.9, and 26.4 ± 9.7 dB, respectively, in OS, demonstrating greater AC and ABG in OS than in OI. Postoperative AC (31.3 ± 20.5 dB), ABG (10.6 ± 10.0 dB), and closure of ABG (12.1 ± 4.7 dB), that is, preoperative ABG minus postoperative ABG of OI, were comparable to those of OS (AC, 30.9 ± 13.3 dB; ABG, 7.0 ± 7.4 dB; closure of ABG, 20.1 ± 11.6 dB)., Conclusion: OI ears showed more severe demineralization of otic capsule than OS ears. However, favorable hearing outcomes could be obtained through SS for OI and OS ears., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Background: The aim of this study is to examine the outcomes of an accelerated fractionated irradiation for N0 glottic carcinoma., Methods: In this retrospective analysis, 29 patients with N0 glottic carcinoma treated by radiation therapy were enrolled. Thirteen patients had T1a disease, six had T1b disease, and ten had T2 disease. A fractional dose of 2.1 Gy was administered to seven patients. The total doses were 65.1 and 67.2 Gy in four and three patients, respectively. A fractional dose of 2.25 Gy was administered to 22 patients. The total doses were 63 and 67.5 Gy in 21 patients and 1 patient with T2 disease, respectively. Additionally, 13 patients underwent the use of TS-1 (80-100 mg per day)., Results: The median follow-up period was 33 months, and the 3-year local control rate was 95.6%. No patient had a lymph node or distant recurrence. As acute adverse events, grades 2 and 3 dermatitis were observed in 18 patients and 1 patient, and grades 2 and 3 mucositis were observed in 15 patients and 1 patient. As a late adverse event, one patient required tracheotomy because of laryngeal edema occurring., Conclusions: Accelerated fractionated irradiation may be an option in the radiation therapy of N0 glottic carcinoma because of its ability to shorten the treatment time.

Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.

Introduction: Persistent postural-perceptual dizziness (PPPD) is a functional chronic vestibular syndrome with symptom exacerbation by upright posture, motion, and complex visual stimuli. Among these exacerbating factors, visual exacerbation is the most specific characteristic of PPPD requiring further investigation. We hypothesized that stimulus-induced changes occur in the functional connectivity (FC) rather than simple neural activation that is involved in visual stimulation. The present study aimed to identify the neural basis of PPPD by investigating FC before and after visual stimulation., Methods: Eleven patients with PPPD and 11 age- and sex-matched healthy controls (HCs) underwent resting-state fMRI (rs-fMRI) before and after task-based fMRI with visual stimuli., Results: At pre-stimulus, FC between the vestibular cortex and visual areas was low, while that between the somatosensory and visual areas was high in PPPD compared with that in HCs. FC between the visuospatial (parahippocampal gyrus) and spatial cognitive areas (inferior parietal lobule) was elevated in PPPD even in the pre-stimulus condition, which no longer increased at post-stimulus as observed in HCs. In the post-stimulus condition, FC between the visual and spatial cognitive areas and that between the visual and prefrontal areas increased compared with that in the pre-stimulus condition in PPPD. Task-based fMRI demonstrated that no brain regions showed different activities between the HC and PPPD groups during visual stimulation., Discussion: In PPPD, vestibular inputs may not be fully utilized in the vestibulo-visuo-somatosensory network. Given that the FC between visuospatial and spatial cognitive areas increased even in HCs after visual stimuli, elevated status of this FC in combination with the high FC between the somatosensory and visual areas would be involved in the visual exacerbation in PPPD. An increase in FC from the visual areas to spatial cognitive and prefrontal areas after visual stimuli may account for the prolonged symptoms after visual exacerbation and anxious status in PPPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yagi, Morita, Yamagishi, Ohshima, Izumi, Takahashi, Watanabe, Itoh, Suzuki, Igarashi and Horii.)

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCL-unspecified (PIT) is used to predict the prognosis of PTCL. The hemoglobin-platelet index (HPI), based on anemia and thrombocytopenia status, is associated with the prognosis of diffuse large B-cell lymphoma. However, its significance in terms of predicting the prognosis of PTCL has not been fully investigated. We herein retrospectively analyzed 100 patients with newly diagnosed PTCL in our department. At a median follow-up of 3.2 years, the median progression-free survival (PFS) and overall survival (OS) was 0.72 (95% confidence interval [CI]: 0.56-1.2) years and 2.0 (95% CI: 1.5-4.7) years, respectively. Multivariate analysis revealed that elevated lactic dehydrogenase (LDH) and hypoalbuminemia were independent adverse variables for PFS. The HPI showed significant predictive value for both PFS and OS. As a new prognostic model comprising the HPI, LDH, and albumin, the LA-HPI allowed the stratification of patients into four distinct risk subgroups: low risk (zero risk factors), low-intermediate risk (one risk factors), high-intermediate risk (two or three risk factors), or high risk (four risk factors). The PFS and OS differed significantly among the patients by the LA-HPI score. The LA-HPI demonstrated better predictive performance compared to the IPI, PIT, and HPI. Our data demonstrated the prognostic utility of the HPI in patients with PTCL. The LA-HPI, incorporating four readily obtainable parameters, exhibited superior performance compared to traditional indices., Competing Interests: The authors declare they have no conflicts of interest., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Pola-BR (polatuzumab vedotin, bendamustine, and rituximab) therapy received approval for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in Japan in March 2021. There have been few reports on the efficacy and safety of Pola-BR therapy in Japanese clinical practice. A retrospective analysis was performed on twenty-nine patients with R/R DLBCL who received Pola-BR therapy at our institution (intent to cellular immunotherapy cohort: 20 patients, stand-alone treatment cohort: nine patients). The overall response rate was 69.0% (complete response 27.6%). The median progression-free survival was 5.1 months, with a 9.5-month median overall survival. In the intent to cellular immunotherapy cohort, 11 of 19 patients received chimeric antigen receptor T-cell (CAR-T) infusions, and one patient received allogeneic stem cell transplantation. Four patients received Pola-BR therapy, including bendamustine before leukapheresis, and all produced CAR-T products successfully. 3 of the 28 patients experienced grade3 or higher adverse events, and two required treatment discontinuation. Our single institution, a real-world cohort of R/R DLBCL patients showed high efficacy outcomes and a tolerable toxicity profile for Pola-BR therapy, which is comparable to previous studies. More cases are needed to determine its impact on CAR-T therapy and stem cell transplantation.

Introduction: Persistent postural-perceptual dizziness (PPPD) is a chronic vestibular syndrome lasting more than 3 months. The core vestibular symptoms are dizziness, unsteadiness, and non-spinning vertigo, which are exacerbated by upright posture or walking, active or passive motion, and exposure to moving or complex visual stimuli. Among these, visual exacerbation is a key feature of PPPD for which the neural mechanisms are unknown. We hypothesized that vestibular symptoms may be exacerbated by visual stimuli through gaze behavioral change after exposure to moving or complex visual stimuli. The study aimed to examine gaze stability after exposure to moving visual stimuli in patients with PPPD., Methods: Fourteen healthy controls (HCs), 27 patients with PPPD, and 12 patients with unilateral vestibular hypofunction (UVH), showing chronic vestibular symptoms for >3 months, were enrolled in the study. The participants were instructed to fixate on the gazing point at the center of a screen for 30 s before and after 90 s of exposure to moving visual stimuli. Gaze stability, best represented by the bivariate contour ellipse area (BCEA), was compared among three groups, both before and after exposure to the moving visual stimuli. Comparisons between pre- and post-moving visual stimuli in BCEA were also conducted. Correlation between the post/pre ratio of BCEA and vestibular tests, several clinical symptom scales including the Dizziness Handicap Inventory, Niigata PPPD Questionnaire, and Hospital Anxiety and Depression Scale, and the exacerbation of dizziness by exposure to moving visual stimuli was examined in the PPPD group., Results: BCEA, both before and after exposure to moving visual stimuli in the PPPD group, was not different from that in HC and UVH groups. In the PPPD group, BCEA increased significantly after exposure to moving visual stimuli. The post/pre ratio of BCEA correlated with the occurrence of exacerbation of the dizziness sensation by exposure to moving visual stimuli; however, it did not correlate with vestibular tests or clinical symptom scales., Conclusion: Patients with PPPD were more likely to exhibit gaze instability after exposure to moving visual stimuli, which potentially exacerbated vestibular symptoms. This phenomenon may help elucidate the neural mechanisms of visual exacerbation in patients with PPPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yagi, Morita, Yamagishi, Ohshima, Izumi, Takahashi, Itoh, Suzuki, Igarashi and Horii.)

Objective: To determine the locations and predictive factors of hypertrophic pachymeningitis (HP), a serious central complication of otitis media with antineutrophil cytoplasmic antigen-associated vasculitis (OMAAV)., Study Design: Retrospective study., Setting: University hospital., Patients: Thirty-six patients with OMAAV underwent contrast-enhanced magnetic resonance imaging (CE-MRI) of the brain, of whom 18 and 18 had or did not have HP, respectively., Main Outcome Measures: The location of HP lesions, which were detected as dural thickening on CE-MRI, was reviewed. Clinical characteristics, laboratory data, and audiometric data before treatment were correlated with the occurrence of HP., Results: HP lesions were most frequently observed in the middle cranial fossa, followed by the internal auditory meatus, tentorium cerebelli, and posterior cranial fossa, which were adjacent to the middle ear primary lesion. Headache was more frequently observed in patients with HP than without HP. The neutrophil-to-lymphocyte ratio (NLR) of the HP (+) group (median, 3.91; interquartile range, 2.50-6.06) was higher than that of the HP (-) group (median, 2.40; interquartile range, 2.01-3.03). The area under the receiver operating characteristic curve for the NLR was 0.741. An NLR of 3.46 had the highest sensitivity (61.1%) and specificity (94.4%) for predicting HP. Other markers of systemic inflammation and comorbidities of systemic diseases were not different between the groups., Conclusions: HP may not be a systemic manifestation of OMAAV but may be related to local lesions in the adjacent brain. A high NLR may be a predictive factor for comorbid HP. Therefore, CE-MRI should be considered for patients with a high NLR., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Abstract: Maintaining relative dose intensity (RDI) of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). Pegfilgrastim was approved in Japan in November 2014 to prevent febrile neutropenia (FN) and maintain RDI.In this retrospective study, we reviewed 334 patients with DLBCL who received 6 or more courses of R-CHOP and analyzed the differences in the RDI, overall survival (OS), and progression-free survival between patients whose treatment started after November 2014 (postapproval group) and those whose treatment started before October 2014 (pre-approval group).The incidence of FN was lower (20% vs 38.3%, P < .001) and the RDI of R-CHOP was higher (86.8% vs 67.8%, P < .001) in the postapproval group. Pegfilgrastim was administered to many of these patients (76.8%) and was thought to have contributed to the high RDI maintenance in the postapproval group. Interrupted time-series analysis showed a significant rise of the RDI at the timing of pegfilgrastim approval in patients aged <70 years (estimated change: 18.1%, P < .001). The 5-year OS (85.7% vs 69.9%, P = .009) and progression-free survival (81.4% vs 64.4%, P = .011) were superior in the postapproval group. However, the differences were not significant in matched-pair analysis matching National Comprehensive Cancer Network-International Prognostic Index scores. Improved survival outcomes in this group were observed only among patients with Ann Arbor stage 3/4 (5-year OS: 83.7% vs 61.3%, P = .019) and high-risk on the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 80.7% vs 32.4%, P = .014). Multivariate analysis showed that a high RDI and low lactate dehydrogenase were associated with superior OS (RDI ≥ 85%, hazard ratio: 0.48, P = .016; lactate dehydrogenase > institutional upper limit of normal, hazard ratio: 2.38, P = .005).The RDI of R-CHOP was able to be maintained at higher levels, the incidence of FN was lower, and significantly better clinical outcomes were achieved in clinically high-risk groups after pegfilgrastim approval. Maintaining a high RDI in R-CHOP by administering pegfilgrastim to those who are likely to have low RDI without it is important for achieving favorable outcomes in patients with DLBCL., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.

An analytical method based on LC-MS/MS was developed for the determination of chlorothalonil metabolite I in livestock products. Chlorothalonil metabolite I in livestock products was extracted with acetone. The crude extracts were defatted by acetonitrile and n-hexane partitioning. Cleanup was carried out using a combination of ethylene diamine-N-propyl silylation silica gel (PSA) and silica gel (SI) mini columns with acidic condition. The sample solution was subjected to LC-MS/MS using an external solvent calibration curve. The average recovery (n=5) of chlorothalonil metabolite I from five types of livestock products (cattle muscle, cattle fat, cattle liver, milk and egg) spike at the maximum residue limits (MRLs) or at a uniform limit of 0.01 mg/kg was 97.1-102.9%, with a relative standard deviation of 1.4-6.8%. The limit of quantitation of the developed method was calculated to be 0.01 mg/kg.

Objective: To examine the validity of head roll-tilt subjective visual vertical (HT-SVV) in diagnosing persistent postural-perceptual dizziness (PPPD)., Study Design: Retrospective review., Setting: Tertiary referral center., Patients: Sixty-one patients with PPPD, 10 with unilateral vestibular hypofunction (UVH), and 11 with psychogenic dizziness (PD), showing chronic vestibular symptoms for >3 months., Interventions: Head-tilt perception gain (HTPG, i.e., mean perceptual gain [perceived/actual tilt angle]) during right or left head tilt of approximately 30° (HT-SVV) and conventional head-upright SVV (UP-SVV) were measured. Bithermal caloric testing, cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP), and posturography were conducted., Main Outcome Measures: Multiple comparisons were performed for the HT-SVV and other vestibular tests among the disease groups. A receiver operating characteristic curve was created to predict PPPD using HTPG., Results: HTPG was significantly greater in the PPPD group than in the UVH and PD groups. There were no significant differences in UP-SVV, cVEMP, oVEMP, and posturography (foam ratio and Romberg ratio on foam) among the disease groups, while the UVH group had the highest canal paresis compared to the other two groups. The area under the curve of the receiver operating characteristic curve for predicting PPPD was 0.764, and the HTPG value of 1.202 had a specificity of 95.2% for diagnosing PPPD., Conclusions: While conventional vestibular tests including UP-SVV, VEMPs, and posturography did not show abnormalities in PPPD, high HTPG in the HT-SVV test, an excessive perception of head tilt, can be a specific marker for discriminating PPPD from other chronic vestibular diseases., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Objective: To develop a diagnostic algorithm for chronic vestibular syndromes by determining significant items that differ among diagnoses. Methods: Two hundred thirty-one patients with chronic vestibular syndromes lasting for >3 months were included. Full vestibular tests and questionnaire surveys were performed: bithermal caloric test, cervical and ocular vestibular-evoked myogenic potential assessment, video head impulse test (vHIT), posturography, rotatory chair test, dizziness handicap inventory, hospital anxiety and depression scale (HADS), and Niigata persistent postural-perceptual dizziness (PPPD) questionnaire (NPQ). Differences in each item of the vestibular tests/questionnaires/demographic data were tested among the diagnoses. A receiver operating characteristic (ROC) curve was created for the significant items. The value that provided the best combination of sensitivity/specificity on the ROC curve was adopted as a threshold for diagnosing the targeted disease. Multiple diagnostic algorithms were proposed, and their diagnostic accuracy was calculated. Results: There were 92 patients with PPPD, 44 with chronic dizziness due to anxiety (CDA), 31 with unilateral vestibular hypofunction (UVH), 37 with undifferentiated dizziness (UD), and 27 with other conditions. The top four diagnoses accounted for 88% of all chronic vestibular syndromes. Five significant items that differed among the four diseases were identified. The visual stimulation and total NPQ scores were significantly higher in the patients with PPPD than in those with UVH and UD. The percentage of canal paresis (CP %) was significantly higher in the patients with UVH than in those with PPPD, CDA, and UD. The patients with CDA were significantly younger and had higher anxiety scores on the HADS (HADS-A) than those with UVH and UD. Moreover, catch-up saccades (CUSs) in the vHIT were more frequently seen in the patients with UVH than in those with PPPD. The most useful algorithm that tested the total and visual stimulation NPQ scores for PPPD followed by the CP%/CUSs for UVH and HADS-A score/age for CDA showed an overall diagnostic accuracy of 72.8%. Conclusions: Among the full vestibular tests and questionnaires, the items useful for differentiating chronic vestibular syndromes were identified. We proposed a diagnostic algorithm for chronic vestibular syndromes composed of these items, which could be useful in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kitazawa, Morita, Yagi, Takahashi, Ohshima, Yamagishi, Izumi, Koizuka and Horii.)

Rationale: Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed and refractory B-cell non-Hodgkin lymphoma. However, because of the mortality risk associated with immune effector cell-associated neurotoxicity syndrome and pseudoprogression, patients with central nervous system (CNS) involvement are less likely to receive CAR T-cell therapy., Patients Concerns: We report a case of a 61-year-old, male patient with intravascular large B-cell lymphoma who suffered a CNS relapse after standard chemotherapy., Diagnosis: A diagnosis of intravascular large B-cell lymphoma with CNS involvement was made., Interventions: We treated the patient using CAR T-cell therapy following a conditioning regimen consisting of thiotepa and busulfan and autologous stem cell transplantation. Although he experienced grade 1 cytokine release syndrome, no other serious adverse events, such as immune effector cell-associated neurotoxicity syndrome or pseudoprogression, were observed., Outcomes: The patient achieved complete remission after the CAR T-cell infusion., Lessons: CAR T-cell therapy following autologous stem cell transplantation is a viable option for relapsed/refractory lymphoma with CNS infiltration. Further clinical studies are warranted to verify its safety and efficacy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Lemierre's syndrome is characterized by internal jugular vein thrombosis and systemic septic embolism; it is a fatal complication of upper respiratory tract infections. To date, it has not been demonstrated how the upper respiratory tract inflammation spreads from the primary infection site to internal jugular vein and systemic thrombosis. We report a very rare case of Lemierre's syndrome derived from malignant otitis externa in which the spread of infection and thrombosis process were identified by imaging. A 61-year-old man with severe diabetes mellitus visited our hospital with consciousness disturbance and right posterior neck pain. He complained of right ear pain and otorrhea several days prior to the neck pain. Contrast-enhanced computed tomography demonstrated thrombosis in internal jugular vein and multiple lung abscesses. Temporal bone images revealed continuous lesions from skull base osteomyelitis to suboccipital abscess and sigmoid sinus thrombosis. We diagnosed the patient as having Lemierre's syndrome secondary to skull base osteomyelitis following malignant otitis externa. The patient clinically recovered with a combination of drainage of suboccipital abscess and long-term administration of antibiotics, which is the standard treatment of malignant otitis externa. Considering the details of imaging and bacterial examination is very useful for understanding the pathophysiology and determining appropriate treatment in Lemierre's syndrome pathophysiology and determining appropriate treatment in Lemierre's syndrome.

We examined the role of lateral temporal bone resection (LTBR) in the treatment of external ear canal (EAC) carcinoma between 2007 and 2018. The estimated 3-year disease-free survival (DFS) and disease-specific survival (DSS) according to the tumor stage and treatments were investigated in 36 patients with EAC squamous cell carcinoma. T stage classification according to the University of Pittsburgh staging system was as follows: 14 patients in T1, four patients in T2, nine patients in T3, and nine patients in T4. The 3-year DFS rate was 77.4% for T1 tumors, 100% for T2, 44.4% for T3 tumors, and 11.1% for T4 tumors ( p < 001). The 3-year DSS rate was 100% for T1/T2 tumors, 87.5% for T3 tumors, and 11.1% for T4 tumors ( p < 0.01). T1/T2 patients received mostly LTBR. Among nine T3 tumors, five patients (56%) received LTBR combined with preoperative chemotherapy and/or postoperative radiation (RT). Four of them had negative surgical margin and survived with no evidence of disease. The DFS of T3 patients who underwent concurrent chemoradiotherapy and LTBR was 0 and 80%, respectively ( p = 0.048). For T1/T2 tumors, surgery achieved an excellent outcome. For T3 tumors, LTBR achieved negative surgical margin and showed good survival when combined with preoperative chemotherapy and/or postoperative RT. In contrast, the prognosis of T3 patients who could not undergo surgery was as poor as that of T4 patients. Therefore, in addition to subtotal temporal bone resection, LTBR-based treatment strategy may be a treatment option for limited cases of T3 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saijo, Ueki, Tanaka, Yokoyama, Omata, Takahashi, Ota, Shodo, Yamazaki, Togashi, Okabe, Matsuyama, Honda, Sato, Morita, Takahashi and Horii.)

Objective: This study was aimed to determine the characteristics of middle ear cholesteatoma and to investigate short-term outcomes regarding the rates of residual and recurrent cholesteatoma and the postoperative hearing results in Japan, via a nationwide survey using staging and classification criteria for middle ear cholesteatoma, as proposed by the Japan Otological Society (JOS)., Methods: The first-round survey was conducted in 2016. The target was patients with middle ear cholesteatoma who were surgically treated in Japan between January and December 2015. Medical information on the patients was anonymized. The questionnaire entries were age, sex, cholesteatoma classification and stage, preoperative hearing level, mastoid development, status of the stapes, and surgical method. There were a total of 1,787 registered patients from 74 facilities from all over Japan. The second survey was conducted in January 2018 and received 1,456 responses from 49 facilities in Japan. Of the 1,456 cases, 1,060 were conducted in the postoperative hearing survey and 1,084 in the residual recurrence survey., Results: The most common cholesteatoma type was pars flaccida cholesteatoma (63.3%), followed by pars tensa cholesteatoma (13.0%), congenital cholesteatoma (12.9%), and cholesteatoma secondary to chronic tensa perforation (5.6%). Cholesteatoma of uncertain origin accounted for 5.0% (90 cases). Stage II was predominant in pars flaccida and pars tensa cholesteatoma, which frequently involves the mastoid, whereas about half of cases of cholesteatoma secondary to chronic tensa perforation and congenital cholesteatoma were classified as stage I. One hundred fifty-two of 1,084 cases (14.0%) had recurrent cholesteatoma, residual cholesteatoma, or both following first surgeries. The postoperative rates of hearing success rate was 63.3%., Conclusion: We were able to clarify not only the current epidemiological status of middle ear cholesteatoma but also the current trends of cholesteatoma surgery in Japan. The development of a staging system by the JOS Committee serving an epidemiological database for international or time-dependent comparison. It is possible to use this staging system with reasonable reliability., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: To assess the general health-related quality of life (QOL) in children with intermittent exotropia (IXT) before and 3 months after surgery, by interviewing individual patients and their parents., Study Design: Prospective, interventional case series., Methods: Twenty-one patients undergoing IXT surgery and their parents were included. Using the Pediatric Quality of Life Inventory (PedsQL), children and parents were separately questioned about QOL of patients., Results: The mean patients' age was 8.6 ± 3.2 years (SD), with range of 5-16 years. The children responded that all PedsQL scores were significantly improved by surgery, and the highest improvement was observed in the school subscale score. When the parents rated the children's QOL, significant improvements were limited to 3 out of 7 subscales, including the emotional, psychosocial health summary, and total scores. The improvements in the PedsQL score were not correlated with age, size of deviation changes following surgery, nor the improvement in binocular vision., Conclusions: The general health-related QOL significantly improved by surgery in pediatric patients with IXT, while the improvement was considerably underestimated by the parents. The children reported the greatest improvement in the school functioning subscale, whereas parents failed to discern this improvement. The discrepancy in children' and parents' views can be an important factor when considering indication of corrective surgery and evaluating surgical outcomes.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes(MELAS)is the most dominant form of mitochondrial diseases, presenting with headaches, seizures, and stroke-like episodes. Stroke-like episodes is a distinguishing feature of MELAS. Symptoms appear before the age of 20 years in 65-76% of patients. For the clinical diagnosis of MELAS, evidence of lactate accumulation in the central nervous system is important. The radiographic features of MELAS are stroke-like lesions in the affected brain areas, primarily the occipito-parietal or posterior temporal lobe. MRI shows high signal intensities on T2-weighted or FLAIR images. The cerebral blood flow in lesions can be increased in the acute phase. MR spectroscopy(MRS)shows a lactate peak in the brain lesions, which is important evidence of lactate accumulation. In pediatric or young adult patients with occipito-parietal stroke-like lesions, a prominent lactate peak in MRS is the key radiographic sign that supports the diagnosis of MELAS.

An analytical method based on LC-MS/MS was developed for the determination of asulam in livestock products. Asulam in livestock products was extracted with acetone. The crude extracts were defatted by acetonitrile and n-hexane partitioning. Cleanup was carried out using a combination of ethylene diamine-N-propyl silylation silica gel (PSA) and octadecyl silylated silica gel (C 18 ) mini columns with acidic condition. The sample solution was subjected to LC-MS/MS using an external solvent calibration curve. The average recovery (n=5) of Asulam from four types of livestock products (bovine muscle, bovine fat, bovine liver and milk) spike at the maximum residue limits (MRLs) or at a uniform limit of 0.01 mg/kg was 92.7-98.7%, with a relative standard deviation of 3.1-11.6%. The limit of quantitation of the developed method was calculated to be 0.01 mg/kg.

Purpose: The aim of this study was to evaluate the advantages of ultra-high-resolution computed tomography (U-HRCT) for automatic bronchial segmentation., Materials and Methods: This retrospective study was approved by the Institutional Review Board, and written informed consent was waived. Thirty-three consecutive patients who underwent chest CT by a U-HRCT scanner were enrolled. In each patient, CT data were reconstructed by two different protocols: 512 × 512 matrix with 0.5-mm slice thickness (conventional HRCT mode) and 1024 × 1024 matrix with 0.25-mm slice thickness (U-HRCT mode). We used a research workstation to compare the two CT modes with regard to the numbers and total lengths of the automatically segmented bronchi., Results: Significantly greater numbers and longer lengths of peripheral bronchi were segmented in the U-HRCT mode than in the conventional HRCT mode (P < 0.001, for fifth- to eighth-generation bronchi). For example, the mean numbers and total lengths of the sixth-generation bronchi were 81 and 1048 mm in the U-HRCT mode and 59 and 538 mm in the conventional HRCT mode., Conclusions: The U-HRCT mode greatly improves automatic airway segmentation for the more peripheral bronchi, compared with the conventional HRCT mode. This advantage can be applied to routine clinical care, such as virtual bronchoscopy and automatic lung segmentation.

Objective: To present a case of pediatric cholesteatoma that invaded the petrous apex (PA) and discuss the usefulness of preoperative three-dimensional (3D) surgical simulation on a personal computer (PC) and patient-specific 3D printed model-assisted surgery., Patient: A 5-year-old boy with congenital cholesteatoma underwent a planned two-stage canal wall up mastoidectomy. The cholesteatoma had invaded the PA from a small space anterior to the superior semicircular canal (SSCC). During the removal of this lesion in the first surgery, the tip of a 1-mm round knife broke off and fell into the PA. The surgeon could not remove it, as it was thought that opening the space might damage the SSCC and the facial nerve (FN)., Intervention: Before the second surgery, a preoperative 3D surgical simulation on a PC was performed, and an approach to the PA via the triangle surrounded by the SSCC, FN, and middle cranial fossa, namely, the supracochlear approach, was discovered. A patient-specific 3D-printed model, which had been drilled to make each surface of the triangle including the SSCC, FN, and middle cranial fossa visible in the PC simulation surgery, was then created and a 3D-printed model-assisted surgery was planned., Results: By placing the sterilized patient-specific 3D model close to the surgical field, the cholesteatoma and iatrogenic foreign body could be successfully removed from the PA without damaging the important surrounding structures., Conclusions: Preoperative 3D surgical simulations and intraoperative patient-specific 3D-printed model-assisted surgeries are new, powerful tools that aid in performing challenging surgeries on temporal bones.

Objective: To test whether the threshold of nerve integrity monitor (NIM) responses during facial nerve decompression surgery can predict the postoperative outcome., Study Design: Retrospective study., Setting: University hospital., Patients: Twenty peripheral facial palsy patients who underwent transmastoid decompression surgery., Intervention: During decompression surgery, thresholds of NIM responses were measured via direct facial nerve stimulation at three sites: the geniculate ganglion (GG), the second genu (2 G), and the stylomastoid foramen., Main Outcome Measures: Facial nerve function was evaluated before and 6 months after surgery using the Yanagihara grading score (maximum score = 40 points). Complete recovery was defined as an improvement of the grading score to ≥ 36 points without synkinesis. Variables including age, sex, disease (Bell's palsy or Ramsay Hunt syndrome), time after onset, Yanagihara grading score, and electroneurography before surgery, and the thresholds of NIM responses during surgery were compared in the complete and incomplete recovery groups. NIM responders were defined as those exhibiting a NIM response of < 1.5 mA at any site. Postoperative Yanagihara grading scores in NIM responders and NIM nonresponders were compared., Results: No variables differed significantly in the complete and incomplete recovery groups before surgery. NIM response thresholds in the complete recovery group at the GG and the 2nd G were significantly lower than the corresponding thresholds in the incomplete recovery group. The postoperative Yanagihara grading scores of NIM responders were significantly better than those of NIM nonresponders., Conclusion: NIM responses to intraoperative direct facial nerve stimulation were useful for predicting outcomes after decompression surgery.

Objective: To examine the association between hearing impairment and cognitive decline and to identify possible risk factors for presbycusis., Study Design: Cross-sectional survey in prospective cohort study., Setting: University hospital., Patients: A total of 322 participants aged >60 years, for whom all the below data were available, were enrolled in the study. There were 168 females and 154 males with a median age of 71 years (range: 60-89 yrs)., Interventions: PROST (Project in Sado for Total Health), a medical database in Sado island Japan, was analyzed., Main Outcome Measures: Data on pure-tone audiometry, mini-mental state examination (MMSE), polymorphism of apolipoprotein E4 (ApoE4), diabetes mellitus, hypertension, smoking, and alcohol consumption were extracted. Hearing impairment was defined as an average frequency between 0.25 and 8 kHz that exceeded 30 dB. Multivariate analysis was used to identify which of the above factors could predict the hearing impairment. Hearing threshold of each Hz was compared between the ApoE4 (+/+), (+/-), and (-/-) groups., Results: Among various factors, only low MMSE scores (<24) showed significant association with hearing impairment. There were no differences in the hearing threshold of all frequencies between ApoE status groups., Conclusions: Hearing impairment was associated with low MMSE sores, regardless of the ApoE4 status. If ApoE4 status would be a common upstream predictor for both the hearing and cognitive impairment, hearing threshold would be related to ApoE4 status. However, these results may suggest that hearing impairment may be causally related to the cognitive dysfunction, perhaps via the cognitive load mechanisms.

Objective: To establish a questionnaire to diagnose and assess the severity of persistent postural-perceptual dizziness (PPPD)., Study Design: Retrospective chart review., Setting: Tertiary referral center., Patients: Fifty PPPD patients and 50 consecutive control patients with other vestibular disorders., Interventions: Patients answered questions on three exacerbating factors of PPPD (upright posture/walking, movement, and visual stimulation), and each factor was evaluated using four questions scoring the severity from 0 (none) to 6 (unbearable). Somatic and psychological distress was evaluated by the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS), respectively., Main Outcome Measures: The questionnaire's reliability was tested by Cronbach's alpha, and it was validated by examining the differences in the questionnaire's scores between PPPD patients and controls. The area under the curve (AUC) of the receiver operating characteristic curve for each factor was calculated., Results: Cronbach's alpha coefficient was >0.8 for all factors, except the movement factor. There were no significant differences in the VAS and HADS scores between the two groups. However, the combined and individual questionnaire scores for each factor were higher in PPPD patients than in controls, indicating the questionnaire's high validity. The AUC was widest for the visual stimulation factor (0.830), and a score of 9 (full score 24) had the best sensitivity (82%) and specificity (74%) for discriminating PPPD patients from controls., Conclusions: We developed a questionnaire that exhibited high reliability and validity in evaluating PPPD severity. The visual stimulation factor may be the most characteristic among the three exacerbating factors.

A new linear tetraphosphine containing a PNP phosphazane bridge, rac-bis[(diphenylphosphinomethyl)phenylphosphino]phenylamine (rac-dpmppan), was synthesized and utilized to support a series of Pd/Pt mixed metal tetranuclear chains, [Pd 4-n Pt n (μ-rac-dpmppan) 2 (XylNC) 2 ](PF 6 ) 2 (XylNC=xylyl isocyanide; n=0: Pd 4 (1), 1: PtPd 3 (2), 2: PtPd 2 Pt (3), 2: Pt 2 Pd 2 (4), 3: Pt 2 PdPt (5)), in which the number and positions of additional Pt atoms were successfully controlled depending on the respective synthetic procedures using transformations from 1 to 3 through 2 and from 4 to 5 by redox-coupled exchange reactions. The 31 P{ 1 H} NMR and ESI mass spectra and X-ray diffraction analyses revealed almost identical tetranuclear structures, with slight contraction of metal-metal bonds according to incorporation of Pt atoms. The electronic absorption spectra of 1-5 exhibited characteristic bands at 635-510 nm with an energy propensity depending on the number and positions of Pt centres, which were assigned to HOMO (dσ*σσ*) to LUMO (dσ*σ*σ*) transition by theoretical calculations. The present results demonstrated that the electronic structures of Pd/Pt mixed-metal tetranuclear complexes are finely tuned as orbital-overlapping alloyed metal chains by atomically precise Pt incorporation in the Pd 4 chain., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Assessment of validity of the Japanese Otological Society and the European Academy of Otology and Neurotology (EAONO-JOS) cholesteatoma staging system (EJS) through international collaboration to investigate: (a) feasibility of retrospectively staging previously acquired data, (b) strengths and weaknesses of the staging system., Method: Nine centers with prospective cholesteatoma databases were recruited. Cases were allocated to EJS Stage at each center using details from time of initial surgery. An independent rater also staged the cases and noted any discrepancies. At one center results from database staging were compared with staging based on contemporaneous operative records. Inter and intrarater reliabilities were calculated, and recidivism rates calculated according to Stage., Results: Of 1482 cases of cholesteatoma, 320 (22%) were Stage 1, 977 (67%) Stage 2, 153 (11%) Stage 3 and 4 (0.3%) Stage 4. No database contained details of all parameters required for accurate staging. Staging discrepancies occurred in >10% cases but inter and intrarater reliability of staging were high (Kappa 0.8; 95% confidence interval between 0.7-0.9). At 5 years, 11% had residual and 8% had recurrent cholesteatoma: rates increased with Stage but generally not significantly (Kaplan-Meier Log Rank analysis)., Conclusion: The EJS Staging system provides an internationally agreed standard for collecting data to classify cholesteatoma severity. Although data can be applied retrospectively with reasonable reliability, prospective data collection would prevent inaccuracies that arise from missing data fields. To enhance validity of the EJS system, we propose clearer definitions of some categories. Refinements to definitions of stage may improve prognostic utility of the EJS but should be made using evidence powered by large-scale collaboration.

Purpose: To clarify the anatomical distribution of otosclerotic loci in otosclerosis., Methods: Ninety-five patients with surgically confirmed uni- or bilateral otosclerosis were enrolled into the study. Hypodense areas observed in the otic capsule by high-resolution computed tomography (HRCT) were defined as otosclerotic loci. The location and number of lesions were examined, and the probability of lesion overlap and correlation with age/hearing parameters (air and bone conduction threshold, air-bone gaps) were tested., Results: Otosclerotic loci were confirmed by HRCT in 77 out of 115 operated ears. The three commonly affected sites were the anterior part of the oval window (ant-OW), anterior part of the internal auditory canal (ant-IAC), and pericochlear area (PCochA), with lesions detected in 96.1%, 46.8%, and 26.0% of ears, respectively. Only the ant-OW area was affected in 48.1% of the ears; the ant-IAC in 3.9%; and PCochA in none with significant differences (p < 0.01). The ant-OW lesions preferentially overlapped with ant-IAC (44.6%) than PCochA lesions (27.0%) (p < 0.05). Among double sites diseases, triple sites diseases occurred more commonly in the ant-OW + PCochA group (80%) than ant-OW + ant-IAC group (48.5%) (p < 0.05). There was no correlation between a number of lesions and age/hearing parameters., Conclusions: Based on the probability of lesion overlap, otosclerotic lesions may initiate at ant-OW followed by ant-IAC and later PCochA. Although the number of lesions showed no immediate correlation with hearing level or age, anatomical stage of the disease estimated by the location and the number of otosclerotic loci could be useful in predicting the future hearing status.

Objective: To examine the risk factors of recurrence in pediatric congenital cholesteatoma., Study Design: Retrospective chart review., Setting: University hospital., Patients: Sixty-seven patients having tympanic type of congenital cholesteatoma under 15-years old at surgery., Interventions: Canal wall-up tympanomastoidectomy (n = 30) or transcanal atticotomy/tympanoplasty (n = 37) was performed depending on cholesteatoma extension, 16 of which were followed by second-look surgery. Preoperative computed tomography (CT) before second-look surgery or follow-up CT was performed to detect residual recurrence 1 year after the surgery. Cholesteatoma found at the second surgery was also included in the recurrence. All patients had no recurrent cholesteatoma at the last follow-up (median, 61 mo after surgery)., Main Outcome Measures: Possible predictive factors were compared between the groups., Results: Residual cholesteatoma and retraction cholesteatoma occurred in 21 and 6%, respectively. There was no significant difference in age, sex, and type of cholesteatoma (open or closed) between the groups; however, Potsic stage and status of stapes involvement were more advanced in the residual cholesteatoma group. All residual lesions could be detected by follow-up CT or by second-look surgery. All of four retraction cholesteatoma patients were male, young at the surgery and in stage IV., Conclusion: Recurrence mostly occurred as residual cholesteatoma, suggesting that CT is recommended as a follow-up tool for congenital cholesteatoma. Advanced lesions had the risk of residual cholesteatoma, suggesting that complete removal of epithelium is important. Although rare, young advanced-stage patients had risk of retraction cholesteatoma and therefore normal mucosa should be preserved as much as possible for these patients.

Hypothesis: The temporal bone shows regional differences in bone development., Background: The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis., Methods: Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions., Results: The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively., Conclusion: To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages.

Objective: We aimed to analyze clinical features and treatment outcomes of otitis media caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), i.e. otitis media with AAV (OMAAV)., Methods: This survey was performed between December 2013 and February 2014. The study began with a preliminary survey to 123 otolaryngology institutions in Japan to inquire about their experiences with OMAAV patients during the past 10 years, and was followed by a questionnaire survey to investigate clinical and laboratory findings. OMAAV was defined using the criteria described in the text., Results: Two hundred and thirty-five patients classified as OMAAV were enrolled in this study. They were characterized as follows: (1) disease onset with initial signs/symptoms due to intractable otitis media with effusion or granulation, which did not respond to ordinary treatments such as antibiotics and insertion of tympanic ventilation tubes, followed by progressive hearing loss; (2) predominantly female (73%) and older (median age: 68 years); (3) predominantly myeloperoxidase (MPO)-ANCA-positive (60%), followed by proteinase 3 (PR3)-ANCA-positive (19%) and both ANCAs-negative (16%); (4) frequently observed accompanying facial palsy (36%) and hypertrophic pachymeningitis (28%); and (5) disease often involving lung (35%) and kidney (26%) lesions. Four factors associated with OMAAV were found to be related to an unfavorable clinical course threatening the patient's hearing and/or lives, namely facial palsy, hypertrophic pachymeningitis, both ANCAs-negative phenotype, and disease relapse. The occurrence of hypertrophic pachymeningitis was associated with facial palsy (p < 0.05), both ANCAs-negative phenotype (p < 0.001), and headache (p < 0.001). The administration of corticosteroid together with an immunosuppressant was an independent predicting factor for lack of disease relapse (odds ratio [OR] = 1.90, p = 0.03) and an improvement in hearing loss (OR =2.58, p = 0.0002)., Conclusion: Since OMAAV has novel clinical features, the disease may be categorized as a subentity for the classification of AAV.

Objective: Otitis media (OM) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is a novel concept of ear disease that is characterized by progressive mixed or sensorineural hearing loss with occasional systemic involvement. Considering the accumulating knowledge about the characteristics of and treatment for auditory dysfunction in OMAAV, the objective of this study was to investigate the vestibular function and symptoms of patients with OMAAV., Study Design: Retrospective chart review., Setting: University hospital., Patients: Thirty-one OMAAV patients met criteria proposed by the OMAAV study group in Japan., Main Outcome Measures: Clinical characteristics and vestibular tests., Results: Eleven of 31 OMAAV patients had vestibular symptoms; 3 patients had acute vertigo attack with sudden hearing loss and 8 patients had chronic dizziness. Episodic vertigo was not seen in any of the patients. Three patients who received a less intensive therapy without immunosuppressive agents developed intractable persistent dizziness. All symptomatic patients and six of the nine OMAAV patients without vestibular symptoms showed unilateral or bilateral caloric weakness; therefore, vestibular involvement was present in 84% of OMAAV patients. Gain of vestibulo-ocular reflex was reduced in symptomatic patients. The eye-tracking test and optokinetic nystagmus revealed no evidence of central dysfunction., Conclusion: Vestibular dysfunction was seen in 84% of OMAAV patients. One-third of OMAAV patients showed vestibular symptoms such as acute vertigo attack or chronic dizziness, which are of peripheral origin. One-third of the symptomatic patients developed intractable dizziness. Initial intensive treatment by combination therapy with steroid and immunosuppressive agents may be essential for preventing the development of intractable dizziness.

This study examined the differences between congenital cholesteatoma (CC) and acquired cholesteatomas (AC) in children by comparing clinical features and treatment courses. This was a retrospective study which retrospectively evaluated 127 children with middle ear cholesteatomas using medical records from January 1999 to December 2012 in the Department of Otolaryngology, Niigata University Hospital. The study comprised 69 and 58 cases of CC and AC, respectively. The main outcome measures include patient backgrounds, the opportunities for consultations, mastoid cell development, intraoperative finding of stapes, surgical procedure and number of surgeries. The average age at operation was 6.4 and 9.8 years in CC and AC, respectively. AC was more prevalent in boys. Mastoid development was better in CC than in AC. We adopted a two-stage operation in 17 cases (25 %) of CC and in 22 cases (38 %) of AC. The repeat surgery rate was 11.6 % in CC and 27.6 % in AC. Three times as many operations were required for three cases (4.3 %) of CC and 10 cases (17.2 %) of AC. The lesions in AC were more difficult to control. In the treatment of pediatric middle ear cholesteatoma, we had to keep the outcome in mind.

We report a case of a 31-year-old healthy man with marathon-induced pulmonary edema. Chest radiograph revealed pulmonary edema without cardiomegaly. Contrast-enhanced chest computed tomography (CT) revealed transient pulmonary edema without filling-defect in pulmonary arteries. As marathon running increases in popularity, radiologists and emergency physicians should be familiar with diagnosis of this entity on chest radiograph, avoiding unnecessary CT examination without additional clinical information.

Duodenal stenosis due to periduodenal hematoma is a rare condition. Although clinical presentations should vary among causes, symptoms of duodenal stenosis due to periduodenal hematoma commonly include abdominal pain, nausea, or vomiting. We describe three cases of duodenal stenosis due to periduodenal hematoma with similar clinical courses. All patients had mass-like hardness in the upper abdomen on physical examination and showed prolonged symptoms of duodenal stenosis given the usual time of hematoma resolution. On the basis of anatomic and embryologic background, hemorrhage presumably occurs in the duodenal compartment, which includes the distal part of the duodenum and its potential embryonic mesentery. Hematoma itself and the increased intracompartmental pressure result in distinctive clinical features, which suggest a concept of duodenal compartment syndrome.