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.

WU polyomavirus detected in respiratory tract specimens from young children in Japan.

Polyomaviruses (PyV) WU and KI are reportedly associated with respiratory tract disease (RTD) worldwide but their incidence is unclear in Japan. In a 2 year prospective study, WU/KIPyV were detected in 48 (13.9%) and in five (1.4%) of 345 children hospitalized with lower RTD, respectively. The seasonal distribution was observed in spring and early summer. Other respiratory viruses were co-detected in 51% of PyV-positive patients, but eight (2.3%) of the WUPyV-positive patients were negative for other known pathogens.

Early induction of interleukin-5 and peripheral eosinophilia in acute pneumonia in Japanese children infected by pandemic 2009 influenza A in the Tokyo area.

A novel influenza A (2009 H1N1) virus has led to a worldwide pandemic. A significant number of patients with pneumonia have been reported, although its pathogenesis remains to be elucidated. To determine its pathogenesis, we evaluated serum interleukin (IL)-5 and peripheral eosinophil counts in patients with acute pneumonia caused by the 2009 H1N1 virus. During the period from October to December 2009, 40 patients with laboratory-confirmed 2009 H1N1 pneumonia were under investigation. Their mean age at presentation was 6.8 years. The most characteristic finding was the early development of hypoxemic respiratory distress in the first 24 hr after the onset of fever. Bronchial mucous plugs included eosinophils in addition to neutrophils, even in patients without allergies. Serum IL-5 levels were elevated in 20 out of 24 patients (83%) whose samples were obtained in the first 24 hr after the onset of fever (26.5 ± 20.1 pg/mL), independent of the presence of underlying allergies. In contrast, induction of IL-5 was not documented in sera from eight patients with laboratory-confirmed 2009 H1N1 virus who developed neurological complications, but without lower respiratory infection (2.1 ± 0.7 pg/mL, P < 0.001 vs acute pneumonia). Peripheral eosinophilia was characteristic in acute pneumonia, but not in patients without a lower respiratory infection. There was a marked difference in the induction of IL-5 in 2009 H1N1 patients who developed acute pneumonia, compared with those without a lower respiratory infection. IL-5 may play a role in the early phase of acute pneumonia caused by the 2009 H1N1 virus in Japanese children.

[Three children with Rasmussen encephalitis showing marked improvement in daily life activity following the functional hemispherectomy].

We investigated seizure, intelligence quotient (IQ), and neurological outcomes including the process of motor function recovery after functional right hemispherectomy in 3 children with Rasmussen's encephalitis (RE). Before the procedure, they were unable to walk, nor sit without support due to progressive worsening of left hemiplegia and relentless epilepsia partialis continua (EPC) of the left extremities, which were refractory to antiepileptic drug and immunological treatment. After functional right hemispherectomy, EPC completely disappeared, although complete left hemiplegia was sustained. However, they recovered up to being able to walk independently with assistance devices, and to have an ordinary life with family support within 1.5 to 5 months through rehabilitation. At the same time, the interictal EEG improved on the unaffected side of hemisphere, exhibiting a posterior alpha rhythm. Their IQ also improved, and they were able to attend school. Early functional hemispherectomy should be considered before patients with RE are left in a serious condition due to progressive worsening of hemiplegia and seizures refractory to the available treatment.

Distinctive clinical features of human bocavirus in children younger than 2 years.

BACKGROUND AND OBJECTIVE: Clinical characteristics of human bocavirus (HBoV) infection have been studied worldwide, but their importance of those characteristics remains unknown. We investigated distinctive clinical features of HBoV-positive children with lower respiratory tract infection (LRTI). METHODS AND RESULTS: During April 2007-July 2009, for 402 hospitalized children younger than 2 years with LRTI, we prospectively examined virus genomes in nasopharyngeal swabs for HBoV, respiratory syncytial virus (RSV), rhinovirus, metapneumovirus, parainfluenzavirus, and adenovirus. The HBoV genomes were identified in 34 patients (8.5%). Clinical and laboratory data of HBoV-positive and other virus/bacteria-negative patients (n = 18) were analyzed and compared with data of RSV-single positive patients (n = 99). The seasonal distribution of HBoV exhibits a concentration of cases during March-September, with most RSV cases occurring during winter in Japan. The minimum age of HBoV-positive patients was 5 months, although 44 patients (44%) with RSV were younger than 6 months. The main clinical features were respiratory distress and hypoxia. Hypoxia advances within 3 days after onset. The mean oxygen saturation on arrival was 92.8%, which was significantly lower than that in patients with RSV (p < 0.001). White blood cell counts were similar among groups. However, the percentage of neutrophils in white blood cells were significantly higher in HBoV-positive patients (62 vs. 45%, p < 0.001). Their prognoses were good. Their hospital stays were 6.6 days. CONCLUSIONS: HBoV-single positive patients show several clinical characteristics, such as seasonality, age, hypoxia, and neutrophilia, which differ from those with RSV infection.

Laryngeal dystonia in xeroderma pigmentosum.

We report on three patients with xeroderma pigmentosum group A (XPA) who showed laryngeal stridor in their 20s. The stridor appeared on feeding and emotional excitation, was exaggerated during respiratory infection and was life-threatening on some occasions. Adduction of the vocal cords during inspiration, observed by laryngoscopy, confirmed laryngeal dystonia in all cases. This type of focal dystonia may be characteristic in XPA and requires special attention during the management of these patients to avoid serious complications.

[Clinical features and care of patients with congenital and childhood-onset myotonic dystrophy].

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder with variable expression. DM1 results from a trinucleotide expansion in the 3' untranslated region or the gene for myotonic dystrophy protein kinase (DMPK). Severity tends to increase and it shows a younger onset age with vertical transmission, a phenomenon known as anticipation. Congenital myotonic dystrophy (CDM) is classified as the most severe form of DM1, and its phenotype, with severe hypotonia, neonatal respiratory distress and feeding difficulties, is completely different from that of adult-onset type. Involvement of respiratory muscles may be the major cause of mortality in affected infants. Facial weakness with a tented upper lip is often recognized. If infants survive the neonatal period, muscle involvement symptoms gradually improve and most children do not require respiratory support or tube feeding. As CDM patients grow older, mental retardation or a developmental disorder becomes prominent. Furthermore, the main problems in childhood-onset DM, with an onset age under 10 years, are developmental disorders or learning disabilities, rather than muscle symptoms. Early meticulous support and cooperation with teachers are necessary. Medications such as methylphenidate may be helpful in DM1 children with attention deficit/hyperactivity disorder.

Transcatheter arterial chemoembolization (TACE) or embolization (TAE) for symptomatic bone metastases as a palliative treatment.

PURPOSE: This study was designed to evaluate the effect of transcatheter arterial chemoembolization (TACE)/embolization (TAE) for symptomatic bone metastases especially in palliation. METHODS: Between April 2006 and December 2009, 24 bone metastatic lesions of 18 patients (8 women and 10 men; mean age, 64 years) underwent palliative TACE or TAE. A total of 40 sessions were performed, with 1-4 sessions per lesion. The primary lesions included hepatocellular carcinoma, colorectal cancer, renal cell cancer, ovarian cancer, thyroid cancer, uterine cervical cancer, and esophageal cancer. Symptomatic lesions involved thoracic spine, lumbar spine, pelvis, rib, and femur. The procedures were performed with a coaxial catheter technique to catheterize selectively target arteries. If not possible due to small branches, blood flow alteration by coil was achieved. Gelatin sponge was the initial embolic materials. As anti-cancer agents, epirubicin, fluorouracil, and mitomycin were mainly used in consideration for primary lesion and past treatment. RESULTS: Sufficient devascularization of targeted lesions was obtained in 18 of 24 (75%) lesions without any serious complication. Pain relief was obtained in 20 lesions (83%), with significantly decrease in the visual analogue scale score (P < 0.001). A relationship was found between the devascularization grade and pain relief (r = 0.49, P < 0.05). Follow-up CT images at 1 month of nine lesions (50%) revealed necrotic change in the tumors. CONCLUSIONS: Palliative TACE/TAE for symptomatic bone metastases could be a suitable treatment method because it is minimally invasive, repeatable, effective, and rapid-acting.

Nationwide survey (incidence, clinical course, prognosis) of Rasmussen's encephalitis.

PURPOSE: Rasmussen's encephalitis (RE) is a progressive and catastrophic epileptic disorder caused by chronic localized encephalitis. We performed a nationwide survey of RE to assess the clinical picture, treatment effect, and prognosis of Japanese RE patients. SUBJECTS & METHODS: The subjects were 27 patients (male:12; female:15) from 13 medical facilities. All of them satisfied the clinical and neuroimaging criteria for RE, including 14 pathologically proven cases. RESULTS: They were divided into the childhood-onset rapidly progressive type (CORP, n=19), and late-onset slowly progressive type (LOSP, n=8). The mean age at epilepsy onset was 4 years and 4 months in CORP, and 16 years in LOSP. The mean period between the onset age of epilepsy and development of frequent seizures was 1 year and 4 months in the former, and 3 years and 4 months in the latter. The immunomodulatory treatment including high-dose steroid (n=14) and high-dose intravenous immunoglobulin therapies (IVIgG, n=12) achieved more than a 50% reduction in the seizure frequency in 5 (36%) and 4 (33%) patients, respectively. Eight and seven patients underwent focal cortical resection and functional hemispherectomy, leading to significant improvement in 5 of the 8 patients and excellent seizure control in all 7 patients, respectively. CONCLUSION: Although the high-dose steroid and IVIG therapies may have alleviated the exacerbation of seizures in those with RE, they could not halt the disease progression. Functional hemispherectomy is still the only curative therapy for RE, despite the fact that the early introduction of this procedure remains controversial.

Light to moderate alcohol consumption is associated with lower frequency of hypertransaminasemia.

OBJECTIVES: The effect of light to moderate alcohol consumption on the liver is controversial. To determine the association between light to moderate alcohol consumption and frequency of hypertransaminasemia, a cross-sectional and a subsequent longitudinal cohort study were conducted using annual health checkup data at a Japanese workplace. METHODS: We analyzed 1,177 male subjects (age 20-59) without HCV or HBV infection or other chronic liver diseases. To determine the association between alcohol consumption (none or minimal <70 g/wk, light > or =70 g and <140 g/wk, moderate > or =140 g and <280 g/wk, excessive > or =280 g/wk) and hypertransaminasemia, we performed multiple logistic regressions. We then followed 326 subjects without a history of fatty liver or hypertransaminasemia up to 5 years for incidental hypertransaminasemia and performed Cox proportional hazard regressions. RESULTS: Excess alcohol consumption was associated with increased odds of hypertransaminasemia (adjusted odds ratio [AOR]versus none or minimal consumption 1.4[1.1-1.93], P= 0.023). There was significant interaction between age group and alcohol consumption (P < 0.01). In the younger group, moderate consumption was associated with decreased odds (AOR 0.5 [0.3-0.9], P= 0.032), while in the older group, light consumption was associated with decreased odds (AOR 0.6 [0.4-1.0], P= 0.036) and excess consumption was associated with increased odds (AOR 1.6 [1.1-2.3], P= 0.014) of hypertransaminasemia. During follow-up, moderate consumption was associated with decreased incidence of hypertransaminasemia versus none or minimal consumption (adjusted hazard ratio 0.4 [0.1-0.9], P= 0.02). CONCLUSION: Light to moderate alcohol consumption may protect against the development of hypertransaminasemia among male subjects without other liver conditions. Further studies are required before recommending light to moderate alcohol consumption.

Chronological development of elevated aminotransferases in a nonalcoholic population.

The incidence and risk factors of nonalcoholic fatty liver disease (NAFLD) have never been prospectively determined. To determine the frequency and risk factors of NAFLD and chronological ordering between NAFLD, weight gain, and features of insulin resistance, a historical cohort study was conducted in a Japanese workplace. A cohort free of previous liver injury, alcohol consumption of more than 140 g/wk, and hepatitis B or C infection (529 of 1537 subjects), and a subcohort of 287 subjects free of insulin resistance-related features were identified. Elevated aminotransferases in nonalcoholics were used as a surrogate for NAFLD. High aminotransferases together with weight gain of more than 2 kg and insulin resistance-related features in the subcohort were sought for up to 5 years. The incidence of high aminotransferases was 31 per 1000 person-years (71 events). A significant interaction occurred between age and sex in the development of high aminotransferases. In subjects younger than age 40 years, male sex (hazard ratio [HR]: 4.6), elevated body mass index (HR: 2.1), hypertension (HR: 2.6), and low high-density lipoprotein cholesterol (HR: 2.8) increased the risk of high aminotransferases, whereas age (HR: 0.6 for each 5 years) decreased the risk. In subjects older than age 40 years, glucose intolerance (HR: 5.3) was the only significant risk factor. In the subcohort, weight gain preceded high aminotransferases and other insulin resistance-related features, which appeared sequentially in order of low high-density lipoprotein cholesterol, hypertriglyceridemia/hypertransaminasemia/hypertension, and glucose intolerance. In conclusion, this cohort study clearly showed chronological ordering and an association between development of elevated aminotransferases and risk factors of NAFLD.

Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease.

BACKGROUND/AIMS: The effects of lifestyle modifications in nonalcoholic fatty liver disease (NAFLD) are incompletely defined. We aimed at determining the association of changes in body weight and lifestyle with changes in serum ALT levels. METHODS: We analyzed annual health checkup data from 1546 employees. Of 469 subjects with elevated ALT, we selected 348 male subjects by excluding those who had other causes of liver disease. They were followed for one year to assess the association of change in lifestyle with change in serum ALT. The 136 subjects who had ALT normalization were followed for two years to assess the association between lifestyle management and persistently normal ALT. RESULTS: In adjusted analysis, weight loss and regular exercise were significantly associated with improvement in serum ALT and increased the odds of ALT normalization, while starting smoking was significantly associated with deterioration in serum ALT. Subjects achieving > or = 5% weight reduction showed improvement in serum ALT. Reduction in alcohol consumption was not associated with changes in serum ALT. Maintaining reduced weight (<5% gain) was significantly associated with persistently normal ALT. CONCLUSIONS: Reducing weight by at least 5% with subsequent weight control and exercising regularly may be beneficial in treating NAFLD.

Precise localization of a recurrent tracheo-oesophageal fistula using retrograde guide wire placement.

A 4-month-old-infant was presented with a presumptive diagnosis of a recurrent tracheo-oesophageal fistula. Preoperative bronchoscopy failed to reveal any defects on the tracheal lumen; however, combined oesophagoscopy and bronchoscopy successfully identified the tracheal orifice of the fistula, which facilitated surgical identification of the recurrent fistula and proper placement of the tracheal tube.