Activation of Human Peripheral Basophils in Response to High IgE Antibody Concentrations without Antigens.

Basophils and mast cells have high affinity IgE receptors (FcεRI) on their plasma membrane and play important roles in FcεRI-associated allergic diseases, such as pollen allergy, food allergy, chronic spontaneous urticarial (CSU), and atopic dermatitis (AD). To date, several reports have revealed that high IgE antibody concentrations activate mast cells-which reside in tissue-in the absence of any antigens (allergens). However, IgE antibody-induced activation of basophils-which circulate in blood-has not been reported. Here, we investigated whether IgE antibodies may regulate functions of human peripheral basophils without antigens in vitro. We successfully removed IgE antibodies bound to FcεRI on the surface of human peripheral basophils by treating with 0.1% lactic acid. We also demonstrated that high IgE antibody concentrations (>1 µM) induced histamine release, polarization, and CD203c upregulation of IgE antibody-stripped basophils. Thus, high IgE antibody concentrations directly activate basophils, which express IgE-free FcεRI on the cell surface. This mechanism may contribute to the pathogenesis of patients with AD and CSU who have higher serum IgE concentrations compared to healthy donors.

Effect of expiratory resistive loading in expiratory muscle strength training on orbicularis oris muscle activity.

[Purpose] The purpose of this study was to elucidate the effect of expiratory resistive loading on orbicularis oris muscle activity. [Subjects] Subjects were 23 healthy individuals (11 males, mean age 25.5±4.3 years; 12 females, mean age 25.0±3.0 years). [Methods] Surface electromyography was performed to measure the activity of the orbicularis oris muscle during maximum lip closure and resistive loading at different expiratory pressures. Measurement was performed at 10%, 30%, 50%, and 100% of maximum expiratory pressure (MEP) for all subjects. The t-test was used to compare muscle activity between maximum lip closure and 100% MEP, and analysis of variance followed by multiple comparisons was used to compare the muscle activities observed at different expiratory pressures. [Results] No significant difference in muscle activity was observed between maximum lip closure and 100% MEP. Analysis of variance with multiple comparisons revealed significant differences among the different expiratory pressures. [Conclusion] Orbicularis oris muscle activity increased with increasing expiratory resistive loading.

Early achievement of walkability after cardiac surgery and the risk of cardiovascular disease after hospital discharge.

AIMS: This study aimed to investigate the association between the time to achieve walkability after cardiac surgery and the risk of cardiovascular disease after hospital discharge. METHODS: We conducted a prospective cohort study involving 553 ambulatory patients aged 71.5 (range, 64.0-77.0) years who underwent cardiac surgery. All patients were divided into five groups based on the time to achieve walkability ≥100 m within 1, 2, 3, 4 or 5 days after cardiac surgery. We examined the risk of post-cardiovascular disease outcomes, including readmission due to heart failure, ischaemic heart disease and other cardiovascular disease, according to the time to achieve walkability with reference to 5 days using the Fine and Gray regression model, considering competing risks. RESULTS: In the survival curve analysis, we examined the time to experience post-cardiovascular disease incidence after hospital discharge. During a median of 3.3 years of follow-up, 118 patients developed cardiovascular disease. We observed a positive association between the time to achieve walkability and cardiovascular disease risk, particularly heart failure. The multivariate hazard ratios (95% confidence intervals) for heart failure readmission were N/A (not assessed due to the sample size being too small) for 1 day, 0.31 (0.10-0.99) for 2 days, 0.60 (0.21-1.79) for 3 days and 0.76 (0.22-2.72) for 4 days (P for trend = 0.032). CONCLUSIONS: The shorter walkability achievement time was associated with a lower risk of cardiovascular diseases, more specifically heart failure readmission, among patients who underwent cardiac surgery. The time required to achieve walkability is a useful predictor for cardiovascular diseases after hospital discharge.

Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation.

Importance: Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation. Objective: To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population. Design, Setting, and Participants: This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab. Main Outcomes and Measures: Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation. Results: In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness. Conclusion and Relevance: This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.

Anxiety and its risk factors among non-Japanese residents living in Japan undergoing COVID-19 situation: A cross-sectional survey.

INTRODUCTION: In the context of collective efforts taken in Japan to control the spread of COVID-19, the state of emergency and social distancing have caused a negative impact on the mental health of all residents, including foreign communities in Japan. This study aimed to evaluate the level of anxiety and its associated factors among non-Japanese residents residing in Japan during the COVID-19 pandemic. METHODS: A web-based survey in 13 languages was conducted among non-Japanese residents living in Japan during the COVID-19 situation. The State-Trait Anxiety Inventory assessed the level of anxiety-State (STAI-S) scores prorated from its six-item version. The multivariable logistic regression using the Akaike Information Criterion (AIC) method was performed to identify the associated factors of anxiety among participants. RESULTS: From January to March 2021, we collected 392 responses. A total of 357 valid responses were analyzed. 54.6% of participants suffered from clinically significant anxiety (CSA). In multivariable logistic model analysis, the CSA status or the high level of anxiety was associated with three factors, including having troubles/difficulties in learning or working, decreased sleep duration, and decreased overall physical health (p<0.05). CONCLUSION: Our study suggests several possible risk factors of anxiety among non-Japanese residents living in Japan undergoing the COVID-19 pandemic, including the troubles or difficulties in learning or working, the decrease in sleep duration, and the decrease in overall physical health.

Change in tongue morphology in response to expiratory resistance loading investigated by magnetic resonance imaging.

[Purpose] The purpose of this study was to investigate the effect of expiratory resistance load on the tongue area encompassing the suprahyoid and genioglossus muscles. [Subjects] The subjects were 30 healthy individuals (15 males, 15 females, mean age: 28.9 years). [Methods] Magnetic resonance imaging was used to investigate morphological changes in response to resistive expiratory pressure loading in the area encompassing the suprahyoid and genioglossus muscles. Images were taken when water pressure was sustained at 0%, 10%, 30%, and 50% of maximum resistive expiratory pressure. We then measured tongue area using image analysis software, and the morphological changes were analyzed using repeated measures analysis of variance followed by post hoc comparisons. [Results] A significant change in the tongue area was detected in both sexes upon loading. Multiple comparison analysis revealed further significant differences in tongue area as well as changes in tongue area in response to the different expiratory pressures. [Conclusion] The findings demonstrate that higher expiratory pressure facilitates greater reduction in tongue area.

Capsule endoscopy findings reflect the gastrointestinal conditions of patients with systemic sclerosis.

Systemic sclerosis (SSc) is characterized by fibrosis of the skin and various internal organs. However, there is limited knowledge concerning small-bowel lesions. We evaluated the clinical state of patients with SSc according to the capsule endoscopy (CE) findings. Sixty-five consecutive patients with SSc (61 females; mean age, 64.3 years) underwent CE at Hiroshima University Hospital between April 2012 and December 2019. SSc was subclassified into diffuse and limited cutaneous SSc. Among the 65 patients, 55 (51 females; mean age, 64.5 years; diffuse cutaneous SSc, 27 patients) were evaluated for the presence of fibrosis in the gastrointestinal tract by biopsy. Small-bowel lesions were detected in 27 (42%) patients with SSc. Type 1b angioectasia (Yano-Yamamoto classification) was more frequent in limited cutaneous SSc patients (p = 0.0071). The average capsule transit time of the esophagus was significantly longer in diffuse cutaneous SSc patients (p = 0.0418). There were more cases of Type 1a angioectasia in SSc patients without fibrosis. The average capsule transit time of the esophagus was significantly longer in SSc patients with fibrosis. Thus, this study revealed that the frequency of small-bowel angioectasia and gastrointestinal motility in patients with SSc differed depending on SSc subclassification and the presence of fibrosis.

The clinical characteristics and predictors of severe digital ischemia in patients with anti-aminoacyl transfer RNA synthetase antibodies.

Severe digital ischemia (SDI), which presents with digital ulcers, necrosis, or gangrene, has been reported to be a rare manifestation of anti-aminoacyl transfer RNA synthetase (ARS) antibody-positive polymyositis/dermatomyositis or anti-synthetase syndrome. A retrospective study was conducted between 2009 and 2020 at our department to investigate the clinical features of anti-ARS antibody-positive patients with SDI and identify their predictors. A total of 46 patients who were positive for anti-ARS antibody were included, four of whom (8.7%) presented with SDI. The characteristics of the patients with SDI were as follows: the median age was 74 years, with 75% being female; anti-Jo-1 antibody, Raynaud's phenomenon, interstitial lung disease, and myositis were observed in two (50%), four (100%), four (100%), and three patients (75%), respectively. Next, we reviewed the literature of anti-ARS antibody-positive patients with SDI and investigated the predictors of SDI by analyzing a total of 51 patients, including the previously reported five patients with SDI. Multivariable analyses revealed that Raynaud's phenomenon and myositis independently predicted the development of SDI in patients with anti-ARS antibody. In conclusion, digital ulcers, necrosis, or gangrene seem to be more common presentations in our study, and Raynaud's phenomenon and myositis can predict the complications of SDI in anti-ARS antibody-positive patients.

Balloon Cell Malignant Melanoma in a Young Female: A Case Report and Review of the Literature.

Balloon cell malignant melanoma (BCMM) is a very rare malignant melanoma subtype. The clinical appearance of BCMM varies; it may be nodular, ulcerated, polypoid, papillomatous and often non-pigmented. The tumor cells histologically appear large, polygonal or round and contain abundant granular or vacuolated cytoplasm. We herein report the case of a 32-year-old female who presented with a focal eccentric pigmented mass in the left lumbar region of 15 mm in diameter that had been present for several years. She underwent tumor excision. The histopathological analysis showed epithelioid melanocytes with clear cytoplasm. An immunohistochemical analysis revealed that the cells were positive for HMB-45 and S-100 protein and negative for cytokeratin. The balloon cell component stained negative for Fontana-Masson. A month later, the patient underwent excision of the bilateral inguinal lymph nodes and metastatic BCMM was revealed. The lymph node metastases showed the complete replacement of lymph nodes by balloon cells. A diagnosis of BCMM (Breslow depth 10 mm, Clark level V) without ulcer was rendered. Staining with Ki-67 was positive in almost 44% of the balloon cells.

Effect of a postoperative outpatient pulmonary rehabilitation program on physical activity in patients who underwent pulmonary resection for lung cancer.

AIM: Physical activity (PA) has been associated with an improvement in survival for individuals with cancer. However, little is known about the effect of postoperative pulmonary rehabilitation on PA after lobectomy in patients with lung cancer. The present study investigated the effect of outpatient rehabilitation on PA in patients with cancer after lung resection. METHODS: A total of 19 patients with lung cancer were recruited for this study and completed a preoperative rehabilitation program. One group of nine patients completed a postoperative outpatient pulmonary rehabilitation program (rehabilitation) and another group of 10 patients did not (control), but were similarly followed up. Preoperative lung function, assessed by forced expiratory volume in 1 s (FEV1 ), body mass index (BMI) and St. George's Respiratory Questionnaire (SGRQ) score were not different between groups. PA was measured before and 2 months after surgery using a three-axis accelerometer for 5-6 days. PA level (PAL) was defined as total energy expenditure divided by basal metabolic rate. RESULTS: Preoperative PAL was not different between groups. However, postoperative versus preoperative PAL was significantly lower in the control versus the rehabilitation group (P < 0.01), and PAL decline was less for the rehabilitation versus the control group (P < 0.001). A subgroup analysis showed improvement in postoperative PAL in rehabilitation patients aged <75 years and older. CONCLUSIONS: Two months after lung resection surgery, patients had not recovered to the preoperative PAL. However, compared with the control group, there was an improvement in the postoperative PAL in patients, including older patients, who underwent outpatient pulmonary rehabilitation. Geriatr Gerontol Int 2016; 16: 550-555.

[Rehabilitation for gait and activity of daily livings at home: an informed form for Parkinson's disease patients].

Rehabilitation aims to provide patients and their supporters with the knowledge, skills and support necessary to maintain their autonomy, minimize disability and maximize the level of participation of individual. This may be the case in Parkinson's disease (PD) patients. However, to our knowledge, previous papers concerning rehabilitation for PD patients have been not easily to understand and not suit for usage in clinical activities. In this review, we provide comprehensive explanations for daily rehabilitation in their habitation for PD patients and doctors.

Intralimb incoordination in patients with ataxia.

Intralimb incoordination needs to be distinguished from interlimb incoordination, which is observed in Parkinson's disease (PD). With this aim, intra and inter-limb coordination impairment in the lower limbs were measured in 13 patients with cerebellar ataxia during pedaling of an ergometer with left and right pedals that can be rotated independently. Intralimb incoordination in patients with cerebellar ataxia was compared with interlimb incoordiation in patients with PD. We concluded that impairment of intralimb coordination in ataxia patients leads to inability to maintain pedaling amplitude and speed, but unlike in PD, right and left coordination was roughly preserved. Our method may be useful for assessing the severity of ataxia and detecting hidden parkinsonism in ataxic patients.

Classifying lower limb dynamics in Parkinson's disease.

To classify lower limb dynamics in patients with Parkinson's disease (PD), we conducted a clinical study by using pedaling exercise.Twenty-seven patients with idiopathic PD were included in this study. We measured rotational velocities of pedals during pedaling movements with a newly developed ergometer. The velocity waveforms exhibited different characteristics among patients, which could be categorized into four different clusters. In cluster 1, the amplitude on each side was constant and the relative phase was locked at 180 degrees. The pattern was the same as seen in normal subjects. In cluster 2, the amplitude on each side was constant, but the relative phase was locked at 90 degrees. In cluster 3, the amplitude on each side was modulated, and the relative phase drifted monotonously from 0 to 360 degrees during pedaling cycles. In cluster 4, the amplitude on each side was synchronously and irregularly modulated, and the relative phase fluctuated with intermittent spike-like decrement. In order to evaluate, the correlation between pattern and severity of PD, we divided 13 patients, who underwent measurement of pedaling patterns more than three times, into three groups, and found that the abnormal coordination pattern correlated with the presence of freezing phenomenon in patients with PD. Our clinical analysis may contribute in analyzing and classifying the dynamics of PD.

Classification of dynamics of a model of motor coordination and comparison with Parkinson's disease data.

In our recent reports motor coordination of human lower limbs has been investigated during pedaling a special kind of ergometer which allows its left and right pedals to rotate independently. In particular, relative phase between left and right rotational-velocity waveforms of the pedals and their amplitude modulation have been analyzed for patients with Parkinson's disease (PD). Several patients showed peculiar interlimb coordination different from the regular anti-phase pattern of normal subjects. We have reported that these disordered patterns could be classified into four groups. Moreover, it has been demonstrated that a mathematical model could reproduce most of the disordered patterns. Such a model includes a schematization of the central pattern generator with two identical half-centers mutually coupled and two tonic control signals from higher motor centers, each of which inputs to one of the half-centers. Depending on the intensities of the tonic signals and on the differences between them, the model could generate a range of dynamics comparable to the clinically observed disordered patterns. In this paper, we explore the dynamics of the model by varying the intensities of the tonic signals in the model. Using the same method used for classifying the clinical data, the dynamics of the model are classified into several groups. The classified groups for the simulated data are compared with those for the clinical data to look at qualitative correspondence. Our systematic exploration of the model's dynamics in a wide range of the parameter space has revealed global organization of the bifurcations including Hopf bifurcations and cascades of period-doubling bifurcations among others, suggesting that the bifurcations, induced by instability of stable dynamics of the human motor control system, are responsible for the emergence of the disordered coordination in PD patients.