Impacts of surgical interventions on the long-term outcomes in individuals with trisomy 18.

OBJECTIVE: We aim to clarify whether surgical interventions can contribute to improve the long-term outcomes among individuals with trisomy 18. METHODS: We retrospectively studied 69 individuals with trisomy 18 admitted to 4 tertiary neonatal centers between 2003 and 2017. A cohort was divided into two groups: subjects with surgical interventions and conservative treatments. We compared the rates of survival and achieving homecare between the groups. RESULTS: Gestational age and birth weight were 37 (27-43) weeks and 1,700 (822-2,546) g, respectively. There were 68 patients with congenital heart disease and 20 patients with digestive disease. Surgical interventions including cardiac and digestive surgery were provided in 41% of individuals. There was no difference in gestational age (p=0.30), birth weight (p=0.07), gender (p=0.30), and fetal diagnosis (p=0.87) between the groups. During the median follow up duration of 51 (2-178) months, overall survival rates in 6, 12 and 60 months were 57%, 43% and 12%, respectively. Survival to hospital discharge occurred in 23 patients, and the rates of achieving homecare in 1, 6, and 12 months are 1%, 18% and 30%, respectively. There was no significant difference in survival rate (p=0.26) but in the rate of achieving home care (p=0.02) between the groups. Cox hazard analysis revealed that prenatal diagnosis (hazard ratio 0.30, 95%CI: 0.13-0.75), cardiac surgery (hazard ratio 2.40, 95%CI:,1.03-5.55), and digestive surgery (hazard ratio 1.20, 95%CI: 1.25-3.90) were related to the rate of achieving homecare. CONCLUSION: Aggressive surgical interventions contribute not to the long-term survival but to achieve homecare among individuals with trisomy 18. EVIDENCE LEVEL: Level 3 (Prognostic study, Case-Control study).

JNK-mediated Slit-Robo signaling facilitates epithelial wound repair by extruding dying cells.

Multicellular organisms repair injured epithelium by evolutionarily conserved biological processes including activation of c-Jun N-terminal kinase (JNK) signaling. Here, we show in Drosophila imaginal epithelium that physical injury leads to the emergence of dying cells, which are extruded from the wounded tissue by JNK-induced Slit-Roundabout2 (Robo2) repulsive signaling. Reducing Slit-Robo2 signaling in the wounded tissue suppresses extrusion of dying cells and generates aberrant cells with highly upregulated growth factors Wingless (Wg) and Decapentaplegic (Dpp). The inappropriately elevated Wg and Dpp impairs wound repair, as halving one of these growth factor genes cancelled wound healing defects caused by Slit-Robo2 downregulation. Our data suggest that JNK-mediated Slit-Robo2 signaling contributes to epithelial wound repair by promoting extrusion of dying cells from the wounded tissue, which facilitates transient and appropriate induction of growth factors for proper wound healing.

Pulmonary arterial compliance is a useful predictor of pulmonary vascular disease in congenital heart disease.

Histopathological assessment of the pulmonary arteries is crucial to determine the surgical indications in patients with congenital heart disease (CHD) and intractable pulmonary vascular disease (PVD). We aimed to clarify whether pulmonary hemodynamic parameters can predict PVD in patients with CHD and pulmonary arterial hypertension (PAH) We performed histopathological evaluations of lung specimens and cardiac catheterizations in 27 patients with CHD-PAH. We divided these patients into the patients with and without PVD, and compared pulmonary hemodynamic parameters including pulmonary arterial compliance (Cp) between two groups. Age at lung biopsy was 4 (2-7) months. There were 16 patients with trisomy 21. Cardiac diagnosis included ventricular septal defect in 16, atrial septal defect in 5, atrioventricular septal defect in 4, and others in 2. There were 11 patients with histopathologically proven PVD (Heath-Edwards classification grade ≥ 3 in 5; the index of PVD ≥ 1.1 in 3; extremely thickened media in 6; hypoplasia of the pulmonary arteries in 3). Cp in the patients with PVD was significantly lower than that in patients without PVD (0.99 [0.74-1.42] vs 1.56 [1.45-1.88], p = 0.0047), although there was no significant difference in the ratio of systemic to pulmonary blood flow, pulmonary arterial pressure, and resistance between two groups. A Cp cutoff value of < 1.22 ml/mmHg m2 as a predictor of PVD yielded a sensitivity and a specificity of 93% and 64%, respectively. Pulmonary arterial compliance can be a predictor of PVD among patients with CHD-PAH.

Takotsubo cardiomyopathy associated with Paragonimiasis westermani.

An 11-year-old boy collapsed during morning assembly at his junior high school. The automated external defibrillator detected ventricular fibrillation and provided shock delivery. He was successfully resuscitated and reverted to sinus rhythm. Electrocardiography showed ST-T elevation in the precordial leads. Echocardiography and angiography demonstrated akinesia of the apex and mid-wall of the left ventricle with preserved contraction of the basal segments, which suggested Takotsubo cardiomyopathy. The patient and his family had often eaten uncooked crab, and his father had a past history of infection with Paragonimiasis westermani. The patient had had a persistent cough and chest pain for several weeks. Chest radiograph showed cystic cavities in the left upper lung. Microbiological examination of the sputum demonstrated an egg of P. westermani and immunological assay showed a raised antibody titre to P. westermani. On the12th day of admission, he developed seizures, and magnetic resonance imaging demonstrated cerebral involvement. After the administration of praziquantel for 3 days, the clinical manifestations improved immediately, and echocardiography normalised within 3 weeks. The patient was discharged on the 32nd day + and follow-up was normal. Takotsubo cardiomyopathy following a potentially fatal arrhythmia is a rare cardiac complication associated with pulmonary and central nervous system infection by P. westermani.

Intravascular Ultrasound-Guided Cardiac Intervention in a Fontan Patient with Allergy to Contrast Media.

Allergy to contrast media is hazardous in patients who need multiple cardiac catheterizations. We describe the case of a 16-year-old boy who presented with fatigue and cyanosis. He had undergone a Fontan operation 14 years previously, after which he developed an allergy to iodinated contrast media. Contrast echocardiograms by manual injection of microbubbles suggested the presence of a venovenous collateral vessel from the brachiocephalic vein draining into the pulmonary vein. We used intravascular ultrasound as the sole imaging method to identify the target vessel and to guide deployment of an Amplatzer Vascular Plug II. The patient experienced immediate improvement in his systemic saturation. Our experience shows that intravascular ultrasound may be a feasible alternative to standard imaging methods in patients with congenital heart disease who need cardiac interventional procedures and are allergic to contrast media.

Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma with Cardiac Metastasis and Arterial Tumor Embolisms during First-Course Chemotherapy.

We described an 11-year-old boy suffering from pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with heart metastasis at diagnosis and arterial tumor embolisms during chemotherapy. Both the heart metastasis and pericardial effusion showed improvement with prednisolone, but numbness and pallor sequentially developed in his lower extremities during the first course of chemotherapy. Contrast-enhanced imaging revealed occlusion of the right anterior tibial artery and left popliteal artery. These symptoms were spontaneously remitted due to the compensation of other arteries. Arterial tumor embolism is a rare but possible complication when a lymphoma shows intracardiac infiltration.