Helicobacter pylori protein that binds to and activates platelet specifically reacts with sera of H. pylori-associated chronic immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by antiplatelet antibodies and/or CD8 + T cells, resulting in the destruction of platelets and decreased platelet counts. Helicobacter pylori that persistently colonizes the stomach causes various disorders, including extragastric diseases such as chronic ITP (cITP). Several studies have reported increased platelet counts in H. pylori-infected cITP patients with eradication treatment and also the pathophysiological pathways involving cross-reaction of antibodies against H. pylori with platelets, the modulation of Fcrγ receptors balance and others. We previously reported an immunocomplex pathway comprising H. pylori low-molecular-weight (LMW) antigens, their antibodies, and platelets, involved in the development of H. pylori-associated cITP; however, the LMW antigens were not identified. In the present study, we demonstrated that the H. pylori LMW antigen of the immunocomplex was identified as Lpp20 of outer membrane proteins. Lpp20 could bind to platelets and specifically react with sera of H. pylori-associated cITP patients.

Common carotid arteritis and polymyalgia with Mycoplasma pneumoniae infection.

A few pediatric cases with brain vasculitis most frequently affecting the middle cerebral artery have been reported in association with Mycoplasma pneumoniae infection, but involvement of the common carotid artery (CCA) before the bifurcation has not been reported to date. We report herein a case of 10-year-old boy with common carotid arteritis and polymyalgia associated with Mycoplasma pneumoniae infection. His fever and cough began 2 weeks before, and his right upper and lower extremity pains began 2 days before admission. He had initially been treated with clarithromycin followed by tosufloxacin, but his symptoms persisted. His M. pneumonia-specific antibody titer was high on admission (1:10240 by particle agglutination method) and the gene of M. pneumoniae was detected in a throat swab specimen by the loop-mediated isothermal amplification method with initial high levels of serum interleukin-8, tumor necrosis factor-α, and interleukin-18 along with elevated blood levels of complements. On the 5th day of hospitalization, vascular echograms of the extremities and neck showed increasing intima-media thickness of bilateral CCAs without stenosis and/or thrombosis and T2-weighted with lipid suppression magnetic resonance imaging of the neck showed high signal intensity of bilateral CCA walls. Coagulation studies were unremarkable and no autoantibodies were detected as far as tested. He was successfully treated by intravenous administration of prednisolone and was stable without any neurological sequelae 17 months after the onset without medication. His particle agglutination titer decreased to 1:5120, and serum interleukin-8, tumor necrosis factor-α, interleukin-18, and complement levels returned to normal.

Monitoring of Epstein-Barr virus load and killer T cells in patients with juvenile idiopathic arthritis treated with methotrexate or tocilizumab.

OBJECTIVES: Methotrexate (MTX) is used for the treatment of polyarticular juvenile idiopathic arthritis (JIA), and an anti-interleukin-6 receptor monoclonal antibody (tocilizumab: TCZ) is also used and added for the treatment of intractable JIA. It has been reported that MTX might induce Epstein-Barr virus (EBV)-associated lymphoma, but the discussion about the effect of MTX and/or TCZ against reactivation of EBV in pediatric patients has been incomplete. METHODS: The EBV loads in four polyarticular JIA and three systemic arthritis JIA patients treated with MTX and/or TCZ, and the percentage of EBV-specific killer T cells (EBV-CTLs) in some patients were prospectively monitored. RESULTS: No patients had EBV-associated symptoms during the observation period. EBV loads in all patients were not significantly increased, and the levels of EBV loads were the same as EBV-seropositive healthy children following the administration of MTX and/or TCZ. EBV-CTLs were detectable during the observation period, but some patients had slightly low levels of EBV-CTLs. CONCLUSION: Treatment with MTX and/or TCZ did not severely affect EBV load and prevent induction of EBV-CTLs in JIA patients.

[A case of X-linked myotubular myopathy with chylothorax].

We report a case of X-linked myotubular myopathy with chylothorax. A male infant weighing 2,114 g was born to a mother whose pregnancy was complicated with polyhydramnios from gestational week 32. At gestational week 37, emergent caesarian section was performed due to membrane rupture followed by fetal bradycardia. Ventilatory support was necessary because the neonate showed severe birth asphyxia accompanied by hypotonia and dyspnea. He also showed a respiratory complication of chylothorax at 10 days old; therefore, thoracic drainage was performed. Congenital chylothorax associated with congenital myotonic dystrophy (CMD) has been described in a number of past reports. Specific findings of congenital myotubular myopathy and partial CMD, such as peripheral halo of muscle fibers, were demonstrated in biopsied muscle, and mutation of the myotubularin (MTM1) gene was identified. Tracheostomy was performed at 5 months old because of prolonged ventilatory support and severe dysphagia. The infant was able to be discharged at 17 months old. Congenital chylothorax might be associated with congenital myotubular myopathies such as CMD.

Suppressed pediatric asthma hospitalizations during the COVID-19 pandemic in Japan, from a national survey.

BACKGROUND: Acute asthma exacerbation in children is often caused by respiratory infections. In this study, a coordinated national surveillance system for acute asthma hospitalizations and causative respiratory infections was established. We herein report recent trends in pediatric acute asthma hospitalizations since the COVID-19 pandemic in Japan. METHODS: Thirty-three sentinel hospitals in Japan registered all of their hospitalized pediatric asthma patients and their causal pathogens. The changes in acute asthma hospitalization in children before and after the onset of the COVID-19 pandemic and whether or not COVID-19 caused acute asthma exacerbation were investigated. RESULTS: From fiscal years 2010-2019, the median number of acute asthma hospitalizations per year was 3524 (2462-4570), but in fiscal years 2020, 2021, and 2022, the numbers were 820, 1,001, and 1,026, respectively (the fiscal year in Japan is April to March). This decrease was observed in all age groups with the exception of the 3- to 6-year group. SARS-CoV-2 was evaluated in 2094 patients from fiscal years 2020-2022, but the first positive case was not detected until February 2022. Since then, only 36 of them have been identified with SARS-CoV-2, none of which required mechanical ventilation. Influenza, RS virus, and human metapneumovirus infections also decreased in FY 2020. In contrast, 24% of patients had not been receiving long-term control medications before admission despite the severity of bronchial asthma. CONCLUSION: SARS-CoV-2 was hardly detected in children with acute asthma hospitalization during the COVID-19 pandemic. This result indicated that SARS-CoV-2 did not induce acute asthma exacerbation in children. Rather, infection control measures implemented against the pandemic may have consequently reduced other respiratory virus infections and thus acute asthma hospitalizations during this period. However, the fact that many hospitalized patients have not been receiving appropriate long-term control medications is a major problem that should be addressed.

Development and Feasibility of a Mobile Asthma App for Children and Their Caregivers: Mixed Methods Study.

BACKGROUND: Mobile health apps can support the self-management of pediatric asthma. Previous studies on mobile apps for children aged >7 years with asthma are limited, and most reports on asthma apps do not consider interactions between the children and their caregivers. Therefore, we developed an asthma app for children aged 0-12 years and their caregivers based on the results of our previous study regarding user needs. OBJECTIVE: The aim of this study was to evaluate the feasibility of a developed mobile app for children with asthma and their caregivers and to modify and complete the app according to the feasibility results. METHODS: We recruited children diagnosed with persistent asthma by an allergy specialist at 2 children's hospitals, 1 university hospital, 2 general hospitals, and 1 pediatric clinic. Thereafter, the app usage was assessed, and questionnaires were administered. This study used convergent mixed methods, including providing user feedback about the pediatric asthma app, completing questionnaire surveys regarding preferences, and obtaining quantitative data about app usage. Quantitative data were analyzed based on the ratings provided for the app features used by the participants, and the usage of the app features was analyzed using descriptive statistics. Qualitative data were analyzed via a descriptive qualitative research analysis and were used to identify codes from the content-characteristic words. RESULTS: In total, 30 pairs of children aged 2-12 years and their caregivers responded to the 3-month survey, and 20 pairs of children aged 4-12 years and their caregivers responded to the 6-month survey. In the 3- and 6-month surveys, "record" was the most commonly used feature by both caregivers and children. The average access logs per month among the 20 pairs ranged from 50 to 79 in the 6-month survey. The number of access logs decreased over time. In the qualitative results, app utilization difficulties were identified for 6 categories: record, preparing, alert settings, change settings, mobile phone owner, and display and motivation. Regarding app feasibility, 60% (12/20) of the caregivers strongly agreed or agreed for all evaluation items, while 63% (7/11) of the children strongly agreed or agreed for 6 items, excluding satisfaction. In the qualitative results, feasibility evaluation of the app was classified into 3 categories: high feasibility of the app, improvement points for the app, and personal factors preventing app utilization. Based on the results of the feasibility analysis, the final version of the app was modified and completed. CONCLUSIONS: The app feasibility among children with asthma and their caregivers was generally good. Children aged 7-12 years used elements such as record, quiz, and manga. This app can support the continuous self-management of pediatric asthma. However, efforts must be taken to maintain and improve the app quality. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000039058; https://tinyurl.com/3na9zyf8.

Respiratory syncytial virus infection exacerbates pneumococcal pneumonia via Gas6/Axl-mediated macrophage polarization.

Patients with respiratory syncytial virus (RSV) infection exhibit enhanced susceptibility to subsequent pneumococcal infections. However, the underlying mechanisms involved in this increased susceptibility remain unclear. Here, we identified potentially novel cellular and molecular cascades triggered by RSV infection to exacerbate secondary pneumococcal pneumonia. RSV infection stimulated the local production of growth arrest-specific 6 (Gas6). The Gas6 receptor Axl was crucial for attenuating pneumococcal immunity in that the Gas6/Axl blockade fully restored antibacterial immunity. Mechanistically, Gas6/Axl interaction regulated the conversion of alveolar macrophages from an antibacterial phenotype to an M2-like phenotype that did not exhibit antibacterial activity, and the attenuation of caspase-1 activation and IL-18 production in response to pneumococcal infection. The attenuated IL-18 production failed to drive both NK cell-mediated IFN-γ production and local NO and TNF-α production, which impair the control of bacterial infection. Hence, the RSV-mediated Gas6/Axl activity attenuates the macrophage-mediated protection against pneumococcal infection. The Gas6/Axl axis could be a potentially novel therapeutic target for RSV-associated secondary bacterial infection.

[Mother and two siblings with cockroach asthma].

We report 2 siblings, an 11 year-old girl and a 10 year-old boy, with cockroach asthma who developed the symptoms in May and October, 1999, respectively. Both children were considered as psychogenic asthma because of poor familial environment and late onset. Their mother also had asthmatic attacks since September, 2001. It became clear in the detailed clinical history that their rooms had not been cleaned up at all for a long period, and a lot of cockroaches had lived in the house. A significantly high titer of cockroach specific IgE-antibody (CAP-RAST) was detected in all three patients, and cockroach was considered as the main allergen of asthma in these patients. Although many cases with cockroach allergy including asthma have been reported in United States, it has not been recognized well in Japan yet. We would like to emphasize that cockroach should be kept in one' s mind as an important allergen of asthma.

Infliximab treatment for refractory Kawasaki disease with coronary artery aneurysm.

Tumor necrosis factor-alpha (TNF-alpha) is considered to be 1 of the factors that induce vasculitis, including coronary artery aneurysm (CA), in Kawasaki disease (KD), because the blood concentration of TNF-alpha is higher in patients with CA compared with those without. Therefore, an anti-TNF-alphaagent (infliximab) was administered to a 1-month-old girl with refractory KD complicated by CA and subsequently, the CA improved and KD was controlled without complications 20 months after the onset.