[TWO CASES OF LARYNGEAL EDEMA CAUSED BY SUBLINGUAL ALLERGEN IMMUNOTHERAPY].

Sublingual immunotherapy is a widely used treatment, and serious adverse reactions such as anaphylaxis are rare. We report two cases of laryngeal edema as adverse reactions to sublingual immunotherapy, which could be continued due to a change in the administration method. Case 1 presents a 15-year-old male suspected to have had anaphylaxis due to the dust at the age of 6 years. He started treatment with Miticure® and developed laryngeal edema 30 minutes after taking the 10000JAU dose on the 10th day. laryngeal edema was treated with intravenous infusion. Case 2 presents a 48-year-old woman. She started treatment with Cidacure® and developed respiratory distress and laryngeal edema 1 hour after taking the 5000JAU dose on the 5th day. she had resolved mildly without therapeutic intervention. In both cases, the patients were switched to sublingual spitting, resumed with the initial dose cautiously, and were able to continue. Sublingual immunotherapy is a safe treatment, but sudden adverse reactions may occur. Laryngeal symptoms may be treated by changing to the sublingual spitting method, but laryngeal findings should be examined, and the dosage should be carefully increased.

Residual nasal polyp tissue following dupilumab therapy is associated with periostin-associated fibrosis.

PURPOSE: Dupilumab, an anti-interleukin-4 receptor alpha monoclonal antibody, is a new treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps. However, data on the effect of dupilumab on histological changes in nasal polyp tissue are lacking. We aimed to investigate the effect of dupilumab on real-life clinical conditions and nasal polyp tissues from patients with eosinophilic chronic rhinosinusitis (ECRS), which is a refractory subtype. METHODS: We conducted an open-label, prospective, observational, single-centre study on 63 patients with refractory ECRS on the basis of the criteria of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study. These patients had a history of surgery and received dupilumab for 24 weeks. Patient-reported sinonasal symptoms, T&T olfactometry and nasal polyp scores were prospectively evaluated. In 23 patients with residual nasal polyps following dupilumab treatment, changes in systemic and local periostin expression, and total collagen deposition in nasal polyp tissues were investigated before and after dupilumab administration. RESULTS: Dupilumab rapidly improved sinonasal symptoms and reduced the nasal polyp score 24 weeks after initiation. 40 (63.5%) patients had resolution of nasal polyps, but the reduction was limited in the remaining 23 (36.5%) patients. Periostin expression in serum and nasal lavage fluid was decreased, whereas periostin and the total collagen deposition area in subepithelial tissues in residual nasal polyps were enhanced after dupilumab administration. CONCLUSION: Dupilumab improves sinonasal symptoms and reduces the nasal polyp score in refractory ECRS. Periostin-associated tissue fibrosis may be involved in the differential effect of dupilumab on nasal polyp reduction.

Eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma: a case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA. CASE PRESENTATION: We report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy. CONCLUSION: To the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.

Role of the amygdala-medial orbitofrontal relationship in odor recognition in the elderly.

INTRODUCTION: In patients with mild cognitive impairment, pathological changes begin in the amygdala (AMG) and hippocampus (HI), especially in the parahippocampal gyrus and entorhinal cortex (ENT). These areas play an important role in olfactory detection and recognition. It is important to understand how subtle signs of olfactory disability relate to the functions of the above-mentioned regions, as well as the orbitofrontal cortex (OFC). In this study, we evaluated brain activation using functional magnetic resonance imaging (fMRI), performed during the presentation of olfactory stimuli (classified as "normal odors" not inducing memory retrieval), and investigated the relationships of the blood oxygen level-dependent (BOLD) signal with olfactory detection and recognition abilities in healthy elderly subjects. METHODS: Twenty-four healthy elderly subjects underwent fMRI during olfaction, and raw mean BOLD signals were extracted from regions of interest, including bilateral regions (AMG, HI, parahippocampus, and ENT) and orbitofrontal subregions (frontal inferior OFC, frontal medial OFC, frontal middle OFC, and frontal superior OFC). Multiple regression and path analyses were conducted to understand the roles of these areas in olfactory detection and recognition. RESULTS: Activation of the left AMG had the greatest impact on olfactory detection and recognition, while the ENT, parahippocampus, and HI acted as a support system for AMG activation. Less activation of the right frontal medial OFC was associated with good olfactory recognition. These findings improve our understanding of the roles of limbic and prefrontal regions in olfactory awareness and identification in elderly individuals. CONCLUSION: Functional decline of the ENT and parahippocampus crucially impacts olfactory recognition. However, AMG function may compensate for deficits through connections with frontal regions.

Mild-intensity running exercise recovered motor function by improvement of ankle mobility after unilateral brain injury of mice using three-dimensional kinematic analysis techniques.

Motor dysfunction, such as gait impairment, is a major disability induced by traumatic brain injury or stroke. Treadmill running is often used as a physical exercise (Ex) clinically and experimentally for the recovery of patients. In animal experiments, although dynamic behavioral deficits can be evaluated using scoring systems, local and minor behaviors are difficult to determine. This study aims to evaluate motor dysfunction and recovery after brain damage (BD) with/without mild-intensity running Ex in mice using three-dimensional (3D) kinematic analysis. To determine exercise intensity, C57/BL6-strain male young adult mice were examined in an incremental running test while the pulmonary gas exchange of O2 and CO2 were measured. The animals were then subjected to left hemidecortication as BD, and some mice performed Ex (10 m/min for 30 min 5 times/wk) for 4 weeks. The BD with Ex and BD or sham-operated mice (sham) without (w/o) Ex had their gait recorded by four synchronized cameras, and gait was evaluated via 3D-kinematic analysis. The BD w/o Ex mice significantly differed in stride, step, and stride width for both limbs compared to the sham w/o Ex mice. The BD with Ex mice showed improvement. The BD w/o Ex mice had restricted ankle movements and impairment in dorsal/planter flexing using trajectory analysis. Consistent with these impairments, the nonaffected side also exhibited a different trajectory, suggesting compensatory movements. These results suggest that the appropriate Ex after BD recovered motor function. Furthermore, the present study suggested that 3D-kinematic analysis is a powerful tool for detecting minor behavioral alterations owing to the impairment of the affected side and the compensation of the unaffected side.

A 32-Year-Old Man with Persistent Olfactory Dysfunction Following COVID-19 Whose Recovery Was Evaluated by Retronasal Olfactory Testing.

BACKGROUND Anosmia, which is loss of smell, is a recognized complication of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may persist after recovery from infection. Retronasal olfactory testing includes both subjective questionnaires and physiological tests that can be used to evaluate recovery of smell. This report presents the case of a 32-year-old man with persistent loss of smell following COVID-19 whose recovery was evaluated by retronasal olfactory testing. CASE REPORT The patient was a 32-year-old man with confirmed SARS-CoV-2 infection. He was aware of his olfactory dysfunction. Using the orthonasal test, a T&T Olfactometer 2 months after disease onset showed an olfactory threshold score of 2.2 points (mild decrease) and olfactory identification result of 3.4 points (moderate decrease). However, the retronasal intravenous olfactory test showed no response, indicating severe olfactory dysfunction. After 3 months of olfactory training and therapy with steroidal nasal drops (Fluticasone Furoate, 27.5 µg/day) and oral vitamins (Mecobalamin, 1500 µg/day), the patient's orthonasal test olfactory threshold score improved to 0.6 points (normal), and his olfactory identification result improved to 1.2 points (mild decrease). Although the retronasal intravenous olfactory test showed a weak response, a reaction did occur. At this time, the patient did not report any improvement in his symptoms. CONCLUSIONS This report has shown that in cases of persistent anosmia following COVID-19, retronasal olfactory testing can be used to evaluate recovery of the sense of smell.

New granule cells in the olfactory bulb are associated with high respiratory input in an enriched odor environment.

New neurons are constantly generated in the olfactory bulb and the dentate gyrus of the hippocampus. The number of new cells depends on sensory experiences; an enriched odor environment increases neurogenesis and neural survival. The aim of this study was to investigate whether enriched olfactory stimuli affect neurogenesis of mitral and granule cells of the olfactory bulb and dentate gyrus, and whether respiratory activity accompanied by olfactory stimuli is associated with new cells in these regions. To this end, respiratory activity during enriched odor stimuli was continuously measured in mice and new cells were stained with 5-bromo-2'-deoxyuridine, which selectively labels proliferating cells. An enriched olfactory environment significantly increased neurogenesis of mitral and granule cells in the olfactory bulb, but not in the dentate gyrus. Additionally, an increase of new granule cells under the enriched odor condition was correlated to sniffing frequency power, which had a significantly different pattern from the no-odor condition. A high respiratory frequency with frequent odor stimuli may be associated with activation of granule cells to form inhibitory neurons and this active state might increase granule cell neurogenesis.

Reading on a smartphone affects sigh generation, brain activity, and comprehension.

Electronic devices have become an indispensable part of our daily lives, while their negative aspects have been reported. One disadvantage is that reading comprehension is reduced when reading from an electronic device; the cause of this deficit in performance is unclear. In this study, we investigated the cause for comprehension decline when reading on a smartphone by simultaneously measuring respiration and brain activity during reading in 34 healthy individuals. We found that, compared to reading on a paper medium, reading on a smartphone elicits fewer sighs, promotes brain overactivity in the prefrontal cortex, and results in reduced comprehension. Furthermore, reading on a smartphone affected sigh frequency but not normal breathing, suggesting that normal breathing and sigh generation are mediated by pathways differentially influenced by the visual environment. A path analysis suggests that the interactive relationship between sigh inhibition and overactivity in the prefrontal cortex causes comprehension decline. These findings provide new insight into the respiration-mediated mechanisms of cognitive function.

Differentiation between IgG4-related Mikulicz disease and Sjögren's syndrome: A review case report and literature review.

RATIONALE: IgG4-related diseases cause lesions in various organs throughout the body. In otorhinolaryngology, IgG4-related Mikulicz's disease is suspected and diagnosed based on the presence of lesions of the head and neck, salivary and lacrimal gland enlargement, and bilateral sinus opacity concentrated on the maxillary sinuses. However, in some cases, it is necessary to consider about differentiation between IgG4-related Mikulicz's disease and Sjögren syndrome. PATIENT CONCERNS AND DIAGNOSIS: A 75-years-old male patient visited our hospital with bilateral otitis media with effusion, which was resistant to conservative treatment. Other symptoms at presentation included enlarged bilateral submandibular and sublingual glands marked oral dryness, severe decrease in saliva secretion (1 mL/10 minutes), and dry eyes. We conducted a Schirmer's and fluorescent dye tests, both of which were positive. High serum IgG4 levels were observed, and although the Sjögren syndrome (SS)-A/SS-B antibodies were negative, marked hypolacrimation and tear secretion were observed. Therefore, a detailed examination considering both IgG4-related Mikulicz's disease and SS was conducted. Salivary gland scintigraphy performed prior to the salivary gland biopsy revealed a marked decrease in uptake, which satisfied the diagnostic criteria for SS; however, it was difficult to diagnose IgG4-related disease based on the diagnostic definition. INTERVENSIONS: Although a definitive diagnosis of SS was made, the persistent otitis media with effusion that was resistant to conservative treatment and bilateral mixed hearing loss were confirmed. As mixed hearing loss is considered an otological symptom of IgG4-related disease, oral steroid treatment was administered. OUTCOME: Thereafter, marked recovery of hearing and reduced swelling and induration of the bilateral parotid and submandibular glands were observed. Clinically, IgG4-related Mikulicz's disease was strongly suspected, but a definite diagnosis of SS was made. LESSONS: In the absence of an IgG4-related Mikulicz's disease diagnosis, careful differentiation between IgG4-related Mikulicz's disease and 2 diseases and their diagnostic criteria was essential.

Volume of the right supramarginal gyrus is associated with a maintenance of emotion recognition ability.

Emotion recognition is known to change with age, but associations between the change and brain atrophy are not well understood. In the current study atrophied brain regions associated with emotion recognition were investigated in elderly and younger participants. Group comparison showed no difference in emotion recognition score, while the score was associated with years of education, not age. We measured the gray matter volume of 18 regions of interest including the bilateral precuneus, supramarginal gyrus, orbital gyrus, straight gyrus, superior temporal sulcus, inferior frontal gyrus, insular cortex, amygdala, and hippocampus, which have been associated with social function and emotion recognition. Brain reductions were observed in elderly group except left inferior frontal gyrus, left straight gyrus, right orbital gyrus, right inferior frontal gyrus, and right supramarginal gyrus. Path analysis was performed using the following variables: age, years of education, emotion recognition score, and the 5 regions that were not different between the groups. The analysis revealed that years of education were associated with volumes of the right orbital gyrus, right inferior frontal gyrus, and right supramarginal gyrus. Furthermore, the right supramarginal gyrus volume was associated with the emotion recognition score. These results suggest that the amount of education received contributes to maintain the right supramarginal gyrus volume, and indirectly affects emotion recognition ability.

Entorhinal cortex and parahippocampus volume reductions impact olfactory decline in aged subjects.

INTRODUCTION: Pathological abnormalities first appear in the medial temporal regions including entorhinal cortex and parahippocampus in patients with Alzheimer's disease. Previous studies showed that olfactory decline in elderly subjects was associated with volume reductions in the left hippocampus and left parahippocampus without cognitive impairment. The aim of this study is to investigate the link between olfaction and volume reductions in the medial temporal regions including the parahippocampus, entorhinal cortex, and hippocampal subfields. METHOD: 27 elderly subjects and 27 young controls were measured olfaction acuity, cognitive function, and structural magnetic resonance imaging. Image processing and gray matter volumetric segmentation were performed with FreeSurfer. Volume data were analyzed with SPSS Statistics software. RESULTS: Interesting results of this study were that volume reduction in the entorhinal cortex was not directly linked with declining olfactory ability. Volume reduction in the left entorhinal cortex was correlated with volume reduction in the left parahippocampus and dentate gyrus. However, left parahippocampus volume reduction had the greatest impact on olfactory decline, and the entorhinal cortex and dentate gyrus might additionally contribute to olfactory decline. CONCLUSION: Our results indicate that olfactory decline may be directly reflected in the medial temporal regions as reduced parahippocampus volumes, rather than as morphological changes in the entorhinal cortex and hippocampus. The parahippocampus may play an important role in the association between memory retrieval and olfactory identification.