Noriko Yodoya

Public access defibrillation improved the outcome after out-of-hospital cardiac arrest in school-age children: a nationwide, population-based, Utstein registry study in Japan.

Aims The purpose of this study was to determine whether implementation of public access defibrillation (PAD) improves the outcome after out-of-hospital cardiac arrest (OHCA) in school-age children at national level. Methods and results We conducted a prospective, nationwide, population-based Japanese Utstein registry study of consecutive OHCA cases in elementary and middle school children (7–15 years of age) who had a bystander-witnessed arrest of presumed cardiac origin during 2005–09 and received pre-hospital resuscitation by emergency responders. The primary endpoint was a favourable neurological outcome 1 month after an arrest. Among 230 eligible patients enrolled, 128 had ventricular fibrillation (VF) as an initial rhythm. Among these 128 patients, 29 (23%) children received a first shock by a bystander. Among these 29 patients, the proportion of the favourable neurological outcome after OHCA was 55%. During the study period, the proportion of patients initially shocked by a bystander among eligible patients increased from 2 to 21% (P = 0.002 for trend). The proportion of patients with a favourable neurological outcome after OHCA increased from 12 to 36% overall (P = 0.006). The collapse to defibrillation time was shorter in bystander-initiated defibrillation when compared with defibrillation by emergency responders (3.3 ± 3.7 vs. 12.9 ± 5.8 min, P < 0.001), and was independently associated with a favourable neurological outcome after OHCA [P = 0.03, odds ratio (OR) per 1 min increase, 0.90 (95% confidence interval 0.82–0.99)]. A non-family members witness was independently associated with VF as the initial rhythm [P < 0.001, OR 4.03 (2.08–7.80)]. Conclusion Implementation of PAD improved the outcome after OHCA in school-age children at national level in Japan.

Macitentan reverses early obstructive pulmonary vasculopathy in rats: early intervention in overcoming the survivin-mediated resistance to apoptosis

It remains unknown whether current disease-targeting therapy can histologically reverse obstructive pulmonary vasculopathy and how the timing of the therapy influences the antiremodeling effects of the compound. We test the hypothesis that a novel endothelin receptor antagonist macitentan reverses the early and/or late stages of occlusive pulmonary vascular disease (PVD) in rats. Rats with pulmonary arterial hypertension (PAH), which were produced by combined exposure to a vascular endothelial growth factor receptor inhibitor Sugen 5416 and hypobaric hypoxia for 3 wk, were assigned to receive macitentan or vehicle during 3-5 wk (early study) or during 5-8 wk (late study) after Sugen injection. Compared with vehicle-treated PAH rats and PAH rats evaluated before treatment initiation, the macitentan-treated rats showed decreases in the proportion of occlusive lesions in the early study, a finding consistent with the reversal of right ventricular systolic pressure and indexes of right ventricular hypertrophy and medial wall thickness. Macitentan ameliorated but did not reverse the proportion of occlusive lesions in the late study. Although macitentan decreased the proportion of Ki67+ lesions in both studies, macitentan increased the proportion of cleaved caspase 3+ lesions and suppressed an antiapoptotic molecule survivin expression in the early study but not in the late study. In conclusion, macitentan reversed early but not late obstructive PVD in rats. This reversal was associated with the suppression of survivin-related resistance to apoptosis and proliferation of cells in PVD.

Potential contribution of phenotypically modulated smooth muscle cells and related inflammation in the development of experimental obstructive pulmonary vasculopathy in rats.

We tested the hypothesis that phenotypically modulated smooth muscle cells (SMCs) and related inflammation are associated with the progression of experimental occlusive pulmonary vascular disease (PVD). Occlusive PVD was induced by combined exposure to a vascular endothelial growth factor receptor tyrosine kinase inhibitor Sugen 5416 and hypobaric hypoxia for 3 weeks in rats, which were then returned to ambient air. Hemodynamic, morphometric, and immunohistochemical studies, as well as gene expression analyses, were performed at 3, 5, 8, and 13 weeks after the initial treatment (n = 78). Experimental animals developed pulmonary hypertension and right ventricular hypertrophy, and exhibited a progressive increase in indices of PVD, including cellular intimal thickening and intimal fibrosis. Cellular intimal lesions comprised α smooth muscle actin (α SMA)+, SM1+, SM2+/-, vimentin+ immature SMCs that were covered by endothelial monolayers, while fibrous intimal lesions typically included α SMA+, SM1+, SM2+, vimentin+/- mature SMCs. Plexiform lesions comprised α SMA+, vimentin+, SM1-, SM2- myofibroblasts covered by endothelial monolayers. Immature SMC-rich intimal and plexiform lesions were proliferative and were infiltrated by macrophages, while fibrous intimal lesions were characterized by lower proliferative abilities and were infiltrated by few macrophages. Compared with controls, the number of perivascular macrophages was already higher at 3 weeks and progressively increased during the experimental period; gene expression of pulmonary hypertension-related inflammatory molecules, including IL6, MCP1, MMP9, cathepsin-S, and RANTES, was persistently or progressively up-regulated in lungs of experimental animals. We concluded that phenotypically modulated SMCs and related inflammation are potentially associated with the progression of experimental obstructive PVD.

Chronic intestinal pseudo-obstruction due to lymphocytic intestinal leiomyositis: Case report and literature review

Lymphocytic intestinal leiomyositis is a rare entity, which causes chronic intestinal pseudo-obstruction (CIPO) in children. We present the first case of a boy who had pure red cell anemia 1 year before onset. Prolonged ileus developed after gastroenteritis and the patient was diagnosed using a biopsy of the intestinal wall. Findings from the present case indicate that there are three important factors for accurate diagnosis: history of enteritis, positive serum smooth muscle antibody, and lymphocyte infiltration with muscle destruction in the muscularis propria in the intestinal wall. Earlier diagnosis and induction of immunosuppressive therapy may be essential for a better outcome.

Ewing Sarcoma of the Bone With EWS/FLI1 Translocation After Successful Treatment of Primary Osteosarcoma.

Although prognosis in patients with localized osteosarcoma has been dramatically improved by the introduction of multiple chemotherapy agents known as combination chemotherapy, there is growing concern about the development of secondary malignant neoplasms. We report the case of a 13-year-old girl in whom the diagnosis of Ewing sarcoma of bone localized on the shaft of left femur was made 2 years after successful treatment without radiotherapy for osteosarcoma of right proximal femur. EWS-FLI1 fusion gene was detected by reverse transcriptase-polymerase chain reaction. To our knowledge, this is the first case with Ewing sarcoma of the bone as a secondary malignant neoplasm developed in osteosarcoma survivor. We collected 15 cases, included this case, with secondary Ewing sarcoma family of tumor by utilizing the PubMed search and might consider the causes of this secondary cancer.