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ATP11A translocates phosphatidylserine (PtdSer), but not phosphatidylcholine (PtdCho), from the outer to inner leaflet of plasma membranes, thereby maintaining the asymmetric distribution of PtdSer. We herein detected a de novo heterozygous point mutation in ATP11A in a patient with developmental delays and neurological deterioration. Mice carrying the corresponding mutation died perinatally or soon after birth with signs of neurological disorders. This mutation caused an amino acid substitution (Q84E) in the first transmembrane segment of ATP11A, and mutant ATP11A flipped PtdCho. Molecular dynamic simulations revealed that the mutation allowed PtdCho binding at the substrate entry site. Aberrant PtdCho flipping markedly decreased the concentration of PtdCho in the outer leaflet of plasma membranes, whereas sphingomyelin (SM) concentrations in the outer leaflet increased. This change in the distribution of phospholipids altered cell characteristics, including cell growth, cholesterol homeostasis, and sensitivity to sphingomyelinase. MALDI-imaging mass-spectrometry showed a marked increase of SM levels in the brains of Q84E knock-in mouse embryos. These results provide insights into the physiological importance of the substrate specificity of plasma membrane flippases for the proper distribution of PtdCho and SM.

Amiodarone (AMD) is a class III anti-arrhythmic drug that is highly effective for tachyarrhythmia treatment. AMD is widely used in adults with congenital heart disease (CHD); however, higher doses of AMD (> 200 mg/day) can cause various non-cardiac side effects. The purpose of this study was to assess the efficacy, safety, and adverse events of low-dose AMD (≤ 200 mg/day) for tachyarrhythmia in patients with CHD. We retrospectively studied 80 patients with CHD and tachyarrhythmia who received oral low-dose AMD (≤ 200 mg/day) from January 2004 to March 2016. Low-dose AMD therapy was used to treat supraventricular tachycardia (SVT) in 51 patients and ventricular tachycardia (VT) in 29 patients. After a mean follow-up of 2.9 years for SVT and 3.2 years for VT, 36% and 65% of the patients with SVT and VT, respectively, were free from a first tachyarrhythmia recurrence for 3 years. The incidence of AMD-induced side effects was 23%, and all these cases consisted of thyroid dysfunction. Low-dose AMD was effective for the treatment of tachyarrhythmia in patients with CHD and had a relatively low incidence of side effects. These findings suggest that low-dose AMD is useful and effective for decreasing the frequency of tachyarrhythmia in patients with CHD and has a low incidence of side effects.

Background Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that occurs in premature infants and the prognosis is variable depending on the comorbidities including fibrosis, emphysema, or pulmonary hypertension (PH). We present a case of a 9‐year‐old girl who developed PH associated with severe BPD (BPD‐PH) and underwent bilateral lung transplantation (BLTx). Case description A 9‐year‐old girl was admitted to our department to undergo BLTx. She was born at 23 weeks and 4 days gestation with a weight of 507 g. She received ventilation for the first 2 months and required further respiratory care due to repetitive, severe respiratory infections. She was diagnosed with BPD‐PH at 6 months of age and oral administration of pulmonary vasodilators were initiated. She was registered as a lung transplant candidate at 4 years of age after the life‐threatening exacerbation. Chest computed tomography (CT) revealed severe lung conditions with ground‐glass opacities and emphysematous low‐density areas in the upper and lower lobes. BLTx from a brain‐dead male donor was performed. The pathological findings of her resected lung revealed saccular, hypoplastic lung with alveolar repair/regeneration, and medial hypertrophy and muscularization of peripheral arteries. The postoperative course was mostly uneventful. She was free from oxygen administration and showed no signs of PH after 6 months of the surgery. Conclusion This is the first case report of BLTx in a pediatric, irreversible BPD‐PH patient with detailed pathohistological findings and clinical examination. Lung transplantation is one of the treatment options for severe BPD‐PH.

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Thoracic empyema usually occurs as a complication of bacterial pneumonia, but in rare cases, it is caused by hematogenous dissemination secondary to nonpulmonary diseases. Congenital chylothorax or chylothorax in children is associated with maldevelopment of the lymphatic system, nonimmune hydrops fetalis, several syndromes including Down syndrome, Noonan syndrome, or Turner syndrome, a complication of thoracic surgery, right heart failure with high central venous pressure, or tumors. There are very few reports of empyema associated with preexisting chylothorax. In the present study, we describe a rare case of thoracic empyema associated with congenital chylothorax and supravalvular pulmonary stenosis associated with clinically diagnosed Noonan syndrome. It is necessary to closely monitor patients with chylothorax because they are at risk of developing severe lung infections, such as pleural empyema or lung abscesses.