The clinical characteristics of pediatric coronavirus disease 2019 in 2020 in Japan.

BACKGROUND: The COVID-19 pandemic has affected the lives of people of all ages. Most reports on pediatric cases suggest that children experience fewer and milder symptoms than do adults. This is the first nationwide study in Japan focusing on pediatric cases reported by pediatricians, including cases with no or mild symptoms. METHODS: We analyzed the epidemiological and clinical characteristics and transmission patterns of 840 pediatric (<16 years old) COVID-19 cases reported between February and December 2020 in Japan, using a dedicated database which was maintained voluntarily by members of the Japan Pediatric Society. RESULTS: Almost half of the patients (47.7%) were asymptomatic, while most of the others presented mild symptoms. At the time of admission or first outpatient clinic visit, 84.0% of the cases were afebrile (<37.5°C). In total, 609 cases (72.5%) were exposed to COVID-19-positive household members. We analyzed the influence of nationwide school closures that were introduced in March 2020 on COVID-19 transmission routes among children in Japan. Transmission within households occurred most frequently, with no significant difference between the periods before and after declaring nationwide school closures (70.9% and 74.5%, respectively). CONCLUSIONS: COVID-19 symptoms in children are less severe than those in adults. School closure appeared to have a limited effect on transmission. Controlling household transmission from adult family members is the most important measure for prevention of COVID-19 among children.

Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus.

OBJECTIVE: High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs). METHODS: Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively. RESULTS: Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs. CONCLUSION: Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS.

Therapeutic potential of ciclesonide inahalation for COVID-19 pneumonia: Report of three cases.

No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.

Combined effect of anti-high-mobility group box-1 monoclonal antibody and peramivir against influenza A virus-induced pneumonia in mice.

Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post-infection (dpi). The anti-HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti-HMGB1 mAb significantly improved survival rate whereas the anti-HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti-HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti-HMGB1 with conventional anti-influenza therapy might be useful against severe influenza virus infection.

Anti-high mobility group box-1 monoclonal antibody treatment of brain edema induced by influenza infection and lipopolysaccharide.

Encephalopathy is a major cause of influenza-associated child death and severe neurological sequelae in Japan, highlighting the urgent need for new therapeutic strategies. In this study, we evaluated the effects of anti-high mobility group box-1 monoclonal antibody (α-HMGB1) treatment on brain edema induced by influenza A virus (IAV) and lipopolysaccharide in 4-week-old BALB/c female mice. The results showed that administration of 7.5 mg/kg α-HMGB1 1 h after IAV (A/Puerto Rico/8/34) inoculation significantly alleviated brain edema at 48 h after IAV inoculation, as confirmed by the suppression of Evans Blue dye leakage and matrix metallopeptidase-9 mRNA expression in the brain. Moreover, we also observed suppression of oxidative stress and different cytokines in IAV-inoculated mice. The expression of plasminogen activator inhibitor-1 was also attenuated following treatment with α-HMGB1. Notably, α-HMGB1 treatment had no effect on virus propagation in the lung. In summary, anti-HMGB1 treatment may improve the prognosis in cases with influenza-associated encephalopathy by attenuating brain edema and reducing the inflammatory responses induced by HMGB1.

Epidemiology of Pediatric Acute Encephalitis/Encephalopathy in Japan.

We studied the etiology of pediatric acute encephalitis/encephalopathy (pAEE) using epidemiological data obtained from a nationwide survey in Japan. Two-step questionnaires were sent to the pediatric departments of hospitals throughout the country in 2007, querying the number of the cases during 2005-2006 as the first step, and asking for the details of clinical information as the second step. In all, 636 children with pAEE (age ≤ 15 years) were enrolled. For the known etiology of pAEE (63.5% of the total cases), 26 microbes and 2 clinical entities were listed, but the etiology of 36.5% remained unknown. Influenza virus (26.7%), exanthem subitum (12.3%), and rotavirus (4.1%) were the most common, and the incidence of pAEE peaked at the age of 1 year. This trend was common among all etiologies. Among the neurological symptoms observed at the onset of pAEE, seizures were observed more often in patients aged ≤ 3 years, although abnormal speech and behavior were also common in older children. Undesirable outcomes (death and neurological sequelae) occurred at high rates in patients with any known etiology other than mycoplasma. In conclusion, these findings provide comprehensive insight into pAEE in Japan.

Metabolic pathway catalyzed by Vanin-1 pantetheinase plays a suppressive role in influenza virus replication in human alveolar epithelial A549 cells.

Our previous analysis of gene expression profiles in the peripheral blood from patients with influenza A (H1N1) pdm09 pneumonia revealed elevated transcription levels of the vanin-1 (vascular non-inflammatory molecule 1, VNN1) gene, which encodes an epithelial ectoenzyme with pantetheinase activity involved in recycling coenzyme A. Here, to elucidate the role of VNN1 in influenza A virus (IAV) H1N1 infection, we investigated the change of VNN1 expression in the context of IAV infection and the effects of its related substances, i.e., its direct substrate pantetheine and its two metabolites pantothenic acid and cysteamine on the replication of IAV in the human alveolar epithelial carcinoma cell line A549. The messenger RNA expression of VNN1 in A549 cells was significantly increased (by 4.9-fold) after IAV infection under an elevated concentration of pantetheine. Moreover, VNN1 mRNA levels were elevated by > 100-fold in response to pro-inflammatory cytokines, especially TNF-α and IL-1ß. Pantetheine significantly reduced the IAV replication and IAV Matrix 1 (M1) mRNA levels when it was administered prior to and during infection. In addition, cysteamine treatment during IAV infection significantly reduced the viral replication and IAV M1 mRNA levels, whereas pantothenic acid did not. These findings suggest that the metabolic pathway catalyzed by VNN1 pantetheinase plays a suppressive role in IAV infection in the respiratory tract, especially in severe conditions under hypercytokinemia.

Monitoring of human herpesviruses-6 and -7 DNA in saliva samples during the acute and convalescent phases of exanthem subitum.

The amounts of the DNAs of human herpesviruses-6 (HHV-6) and -7 (HHV-7) in saliva samples were monitored during the acute and convalescent phases of exanthem subitum (ES) to elucidate the kinetics of virus shedding after ES. A total of 247 saliva samples were collected from 17 children (5 males and 12 females: 8-31 months old at onset). The monitoring period ranged from 152 to 721 days after onset, and in 15 children it was longer than 1 year. Among the 17 cases, 16 were attributed to HHV-6B, while a single case was attributed to HHV-7. Detection rates and average amounts of HHV-6 DNA in saliva samples after ES attributed to HHV-6B were low in the acute phase, increased to the maximum in the convalescent phase at 3-7 months, and then decreased. In addition, to investigate the source of infection, saliva samples from the older siblings (age 3-9 years) and parents of ES patients and children with a history of ES were also examined. The detection rate of HHV-6 DNA in saliva samples from 3- to 9-year-old children was significantly higher than the rate in adult saliva samples. Taken together, these findings suggest that the saliva of children in the convalescent phase of ES might be a more likely source of HHV-6 infection than that of adults. J. Med. Virol. 89:696-702, 2017. © 2016 Wiley Periodicals, Inc.

Analysis of the synthetic house-tree-person drawing test for developmental disorder.

BACKGROUND: Some patients cannot draw three subjects on the same page during the synthetic house-tree-person drawing test (S-HTP). We call this phenomenon "no synthetic sign". The aim of this study was to clarify the pathological meaning of no synthetic sign and investigate its use for the early detection of developmental disorders at a pediatric primary care center. METHODS: We administered the S-HTP to 283 people who consulted the child psychosomatic medical clinic of Okayama University Hospital in 2007-2012. We diagnosed developmental disability based on DSM-IV-TR criteria and compared findings between the different diagnostic groups. RESULTS: A total of 241 patients completed the S-HTP (S-HTP group) and 22 patients were not able to complete the S-HTP, but did complete the HTP (an original version of the S-HTP) or tree test (HTP group). Significantly more people in the HTP group had autism spectrum disorder (ASD) compared with the S-HTP group. Full-scale intelligence quotient was significantly lower in the HTP group compared with the S-HTP group. CONCLUSIONS: There were two types of patients with no synthetic sign. The first involved patients with a suspected mental age younger than 5 years 11 months. The second type consisted of patients with ASD. Although drawing ability reflects multiple domains, it may help in early identification of children with developmental problems and facilitate earlier initiation of interventions.

Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice.

INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.

Brain magnetic resonance imaging in acute phase of pandemic influenza A (H1N1) 2009--associated encephalopathy in children.

Pandemic influenza A (H1N1) 2009 has been shown to be associated more with neurological complications than the seasonal influenza virus. In this study, we focused on the clinical usefulness of magnetic resonance imaging (MRI) in the acute phase of influenza A (H1N1) 2009-associated encephalopathy. A questionnaire was distributed to pediatric and general hospitals in Japan that treat children with encephalopathy. We conducted a questionnaire-based study involving the collection of information regarding 207 patients with encephalopathy. Brain MRI was performed in 97 of these 207 patients in the age group of 9 months to 15 years (mean, 7.5 years) within 48 hours after the development of encephalopathy symptoms. Sixty-six patients (68%) showed normal imaging. Diffuse brain edema was visible in five patients and an abnormal signal in the deep gray matter in two patients which is consistent with acute necrotizing encephalopathy. Abnormal signals of the splenial lesion, subcortical white matter (bright tree appearance), and cortical area were observed in 15, 1, and 8 patients, respectively. From our findings based on the questionnaire results, we suggest that MRI is useful for determining fatal cases of pandemic influenza A (H1N1) 2009 infection when performed in the acute phase. However, MRI is not useful in predicting the development of sequelae.

Inhibitory Effects of Edaravone, a Free Radical Scavenger, on Cytokine-induced Hyperpermeability of Human Pulmonary Microvascular Endothelial Cells:A Comparison with Dexamethasone and Nitric Oxide Synthase Inhibitor.

Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Fluorescein-labeled dextran was added. Then the trans-human PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α＋IL-1ß markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS.

Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

Cytokine profile of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during seasonal H1N1 infection.

BACKGROUND: Several studies support the role of viral infections in the pathogenesis of asthma exacerbation. However, several pediatricians believe that influenza virus infection does not exacerbate bronchial asthma, except for influenza A H1N1 2009 pandemic [A(H1N1)pdm09] virus infection. We previously reported that A(H1N1)pdm09 infection possibly induces severe pulmonary inflammation or severe asthmatic attack in a mouse model of bronchial asthma and in asthmatic children. However, the ability of seasonal H1N1 influenza (H1N1) infection to exacerbate asthmatic attacks in bronchial asthma patients has not been previously reported, and the differences in the pathogenicity profiles, such as cytokine profiles, remains unclear in bronchial asthma patients after A(H1N1)pdm09 and H1N1 infections. METHODS: The cytokine levels and viral titers in the bronchoalveolar lavage (BAL) fluid from mice with and without asthma after H1N1 infection (A/Yamagata and A/Puerto Rico strains) were compared. RESULTS: The interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, IL-5, interferon (IFN)-α, IFN-ß, and IFN-γ levels were significantly higher in the BAL fluids from the control/H1N1 mice than from the asthmatic/H1N1 mice. The viral titers in the BAL fluid were also significantly higher in the control/H1N1mice than in the asthmatic/H1N1 mice infected with either A/Yamagata or A/Puerto Rico. CONCLUSIONS: A(H1N1)pdm09 infection, but not H1N1 infection, can induce severe pulmonary inflammation through elevated cytokine levels in a mouse model of asthma.

Detection of RBM15-MKL1 fusion was useful for diagnosis and monitoring of minimal residual disease in infant acute megakaryoblastic leukemia.

Acute megakaryocytic leukemia (AMKL) with t(1;22)(p13;q13) is a distinct category of myeloid leukemia by WHO classification and mainly reported in infants and young children. Accurate diagnosis of this type of AMKL can be difficult, because a subset of patients have a bone marrow (BM) blast percentage of less than 20% due to BM fibrosis. Therefore, it is possible that past studies have underestimated this type of AMKL. We present here the case of a 4-month-old female AMKL patient who was diagnosed by presence of the RBM15-MKL1 (OTT-MAL) fusion transcript by RT-PCR. In addition, we monitored RBM15-MKL1 fusion at several time points as a marker of minimal residual disease (MRD), and found that it was continuously negative after the first induction chemotherapy even by nested RT-PCR. Detection of the RBM15-MKL1 fusion transcript thus seems to be useful for accurate diagnosis of AMKL with t(1;22)(p13;q13). We recommend that the RBM15-MKL1 fusion transcript be analyzed for all suspected AMKL in infants and young children. Furthermore, monitoring of MRD using this fusion transcript would be useful in treatment of AMKL with t(1;22)(p13;q13).

Redox-active protein thioredoxin-1 administration ameliorates influenza A virus (H1N1)-induced acute lung injury in mice.

OBJECTIVES: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice. DESIGN: Prospective animal trial. SETTING: Research laboratory. SUBJECTS: Nine-week-old male C57BL/6 mice inoculated with H1N1. INTERVENTION: The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day -1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days -1, 1, and 3. MEASUREMENTS AND MAIN RESULTS: Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice. CONCLUSIONS: Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans.

Analysis of bronchoalveolar lavage fluid in a mouse model of bronchial asthma and H1N1 2009 infection.

BACKGROUND: Bronchial asthma is known as a risk factor of admission to the intensive care unit. However, the mechanism by which pandemic 2009 H1N1 (A(H1N1)pdm09) infection increases the severity of symptoms in patients with bronchial asthma is unknown; therefore, we aimed at determining this mechanism. METHODS: Inflammatory cell levels in the bronchoalveolar lavage (BAL) fluid from the non-asthma/mock, non-asthma/A(H1N1)pdm09, asthma/mock, and asthma/A(H1N1)pdm09 groups were determined using BALB/c mice. Cell infiltration levels, cytokine levels, and viral titers were compared among the groups. RESULTS: Neutrophil, monocyte, interleukin (IL)-5, IL-6, IL-10, IL-13, and tumor necrosis factor (TNF)-α levels were significantly higher in the BAL fluid from the non-asthma/A(H1N1)pdm09 and asthma/A(H1N1)pdm09 groups than in the mock groups (p<0.05 for neutrophils and monocytes; p<0.01 for the rest). The number of eosinophils and CD8(+) lymphocytes and the level of transforming growth factor beta 1 (TGF-ß1) in BAL fluid in the asthma/A(H1N1)pdm09 group were significantly higher among all groups (p<0.05 for eosinophils and CD8(+) lymphocytes; p<0.01 for TGF-ß1). The levels of IL-6, IL-10, IL-13, and TNF-α were significantly higher in the asthma/A(H1N1)pdm09 group than in the non-asthma/A(H1N1)pdm09 group (p<0.05 for IL-6 and IL-10; p<0.01 for IL-13 and TNF-α). The level of IFN-γ in the asthma/A(H1N1)pdm09 group was significantly lower than that in the non-asthma/A(H1N1)pdm09 group (p<0.05). The viral titers in the BAL fluids were higher in the asthma/A(H1N1)pdm09 group than in the non-asthma/A(H1N1)pdm09 group (p<0.05). Histopathological examination showed more severe infiltration of inflammatory cells and destruction of lung tissue in the asthma/A(H1N1)pdm09 group than in the non-asthma/A(H1N1)pdm09 group. CONCLUSIONS: Severe pulmonary inflammation induced by elevated levels of cytokines, combined with increased viral replication due to decreased IFN-γ levels, may contribute to worsening respiratory symptoms in patients with bronchial asthma and A(H1N1)pdm09 infection.

Usefulness of balloon angioplasty for the right ventricle-pulmonary artery shunt with the modified Norwood procedure.

OBJECTIVE: We sought to evaluate the efficacy of balloon angioplasty (BA) for severely desaturated patients due to a stenotic right ventricle (RV) to pulmonary artery (PA) shunt following modified Norwood procedure. METHODS: Of 87 patients who underwent a Norwood procedure with the RV-PA shunt between February 1998 through March 2010, 22 (25%) patients underwent BA. The efficacy of BA was assessed by angiographic measurement of the changes in the internal diameters of the stenotic portions of the shunt, changes in arterial saturation and clinical outcomes. RESULTS: BA was performed for stenotic RV-PA shunts following stage I palliation (n = 17, 77%), or those placed as an additional blood source (n = 5, 23%, 3 patients awaiting biventricular repair, 2 patients following stage II palliation). The location of the BA was at the distal anastomosis in 12 (54.5%), proximal anastomosis in 21 (95.4%) and in the mid-portion of the shunt in 11 (50%) cases. The diameters of these three shunt portions were measured from the anterior-posterior and lateral angiographic images, increasing significantly after BA (p < 0.0001) in all. Arterial saturation significantly improved after BA in all cases (66.5 ± 4.3% to 79.4 ± 3.4%, p < 0.0001). Freedom from reintervention was 100%. All patients underwent subsequent elective planned surgery at an appropriate age with no mortality. CONCLUSIONS: A BA-alone strategy for a stenotic RV-PA shunt was effective for all three shunt portions, minimizing shunt-related premature surgical intervention.

Regional variation in survival following pediatric out-of-hospital cardiac arrest.

BACKGROUND: Although regional variation in outcome after adult out-of-hospital cardiac arrest (OHCA) is known, no clinical studies have assessed this in pediatric OHCA. METHODS AND RESULTS: This nationwide, prospective, population-based observation of the whole of Japan included consecutive OHCA patients with resuscitation attempt from January 2005 through December 2009. Primary outcome was 1-month survival with neurologically favorable outcome. Japan was divided into the following 7 regions as the largest administrative units: Hokkaido-Tohoku, Kanto, Tokai-Hokuriku, Kinki, Chugoku, Shikoku, and Kyushu-Okinawa. The outcome of pediatric OHCA was then compared between the regions. Multiple logistic regression analysis was used to adjust for other factors that were considered to influence the relationship between region and outcome. A total of 8,240 pediatric OHCA patients were registered during the study period. One-month survival with neurologically favorable outcome significantly differed by region: 2.5% (24/967) in Hokkaido-Tohoku (adjusted odds ratio [AOR], 1.65; 95% confidence interval [CI]: 0.94-2.90), 2.9% (47/1614) in Tokai-Hokuriku (AOR, 2.06; 95% CI: 1.28-3.31), 2.1% (26/1239) in Kinki (AOR, 1.45; 95% CI: 0.84-2.51), 3.4% (16/465) in Chugoku (AOR, 3.11; 95% CI: 1.62-6.00), 1.5% (4/259) in Shikoku (AOR, 0.79; 95% CI: 0.26-2.43), and 2.8% (27/974) in Kyushu-Okinawa (AOR, 2.15; 95% CI: 1.24-3.74) referred to Kanto (1.4%, 37/2722). CONCLUSIONS: According to Japanese nationwide OHCA registry data there are significant regional variations in the outcome of pediatric OHCA.

Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated on gene expression profiling.

BACKGROUND: The pathogenic mechanisms underlying influenza A(H1N1)pdm09-associated central nervous system (CNS) manifestations and pneumonia remain unclear. This study examined A(H1N1)pdm09 host responses using gene expression profiles of patients' peripheral blood. METHODS: Sixteen A(H1N1)pdm09-infected children in three groups were examined: a CNS group, with convulsion and altered consciousness (n = 6); a pneumonia (Pneu) group (n = 5); and a group of infected control patients (n = 5). The signal ratios of the acute to recovery phases in CNS or Pneu were analyzed versus those of the control. RESULTS: The CNS (619 transcripts) and Pneu (656 transcripts) groups had significantly increased signal ratios compared to the control group. Regarding the increased ratios of transcripts shown by multiple probes, contactin-associated protein-like 3 transcripts, oleoyl-ACP hydrolase transcripts, and interleukin 1 type 1 receptor were observed in CNS and Pneu. Increased ratios of prostaglandin-endoperoxide synthase 2 and α-synuclein were characteristic of CNS. Alkaline phosphatase and the Fc fragment of IgA receptor were characteristic of Pneu. Regarding enriched gene ontology terms, 'response to lipopolysaccharide', 'innate immune response', and 'intrinsic to membrane' were observed commonly in CNS and Pneu. Enriched gene ontology terms related to 'hemoglobin' and 'hemostasis' were, respectively, characteristic of CNS and Pneu. CONCLUSION: These symptom-associated transcripts might be some clues to the pathogenesis of the A(H1N1)pdm09 infection.