Reimplantation approach for an anomalous aortic origin of the right coronary artery with an aberrant right subclavian artery.

Anomalous aortic origin of the right coronary artery is a rare disease. Although there are various reports on its treatment, the method of the surgical approach is still controversial. Here, we present a rare case of a 17 year-old man who had an anomalous aortic origin of the right coronary artery with an aberrant right subclavian artery. As a treatment, he underwent reimplantation of the right coronary artery. The surgical approach for the anomalous aortic origin of the right coronary artery should be selected by considering the age of the patient and size of the right coronary artery.

Risk Factors of Coronary Artery Abnormalities and Resistance to Intravenous Immunoglobulin Plus Corticosteroid Therapy in Severe Kawasaki Disease: An Analysis of Post RAISE.

BACKGROUND: Coronary artery abnormalities (CAAs) still occur in patients with Kawasaki disease receiving intensified treatment with corticosteroids. We aimed to determine the risk factors of CAA development and resistance to intensified treatment in Post RAISE (Prospective Observational Study on Stratified Treatment With Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease)-the largest prospective cohort of Kawasaki disease patients to date. METHODS: In Post RAISE, 2648 consecutive patients with Kawasaki disease were enrolled. The present study analyzed 724 patients predicted to be intravenous immunoglobulin (IVIG) nonresponders (Kobayashi score ≥5) who received intensified treatment consisting of IVIG plus prednisolone. The association between the baseline characteristics and CAA at 1 month after disease onset was examined. The association between the baseline characteristics and treatment resistance was also investigated. RESULTS: Maximum Z score at baseline ≥2.5 (odds ratio, 3.4 [95% CI, 1.5-7.8]), age at fever onset <1 year (odds ratio, 3.4 [95% CI, 1.6-7.4]), and nonresponsiveness to IVIG plus prednisolone treatment (odds ratio, 6.8 [95% CI, 3.3-14.0]) were independent predictors of CAA development. Nonresponsiveness to IVIG plus prednisolone was significantly associated with 8 baseline variables. Baseline total bilirubin (odds ratio, 1.4 [95% CI, 1.2-1.7]) was the only significant independent predictor other than the variables included in the Kobayashi score, enabling treatment resistance to be identified at diagnosis. The area under the ROC curve was 0.74 (95% CI, 0.69-0.79). At a cutoff point of 1.0, the sensitivity and specificity for predicting treatment resistance were 71% and 65%, respectively. CONCLUSIONS: In Post RAISE, younger age at fever onset, a larger maximum Z score at baseline, and nonresponsiveness to IVIG plus prednisolone were risk factors significantly associated with CAA development. Nonresponders were able to be identified at diagnosis based on the total bilirubin value. To prevent CAA, more intensified or adjunctive therapies using other agents, such as pulsed methylprednisolone, ciclosporin, infliximab, and Anakinra, should be considered for patients with these risk factors. Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000007133.

A neonatal case of HDR syndrome and a vascular ring with a novel GATA3 mutation.

HDR syndrome (OMIM #146255) is caused by haploinsufficiency of the GATA3 gene. A vascular ring has not been reported in patients with GATA3-associated HDR syndrome. We report a neonatal case of HDR syndrome and a vascular ring that were possibly due to a novel frameshift mutation in the GATA3 gene.

Combination therapy of propranolol, levothyroxine, and liothyronine was effective in a case of severe consumptive hypothyroidism associated with infantile hepatic hemangioma.

Infantile hepatic hemangioma (IHH) can be accompanied by consumptive hypothyroidism. We report the case of a 4-mo-old boy who showed massive hepatomegaly, peripheral coldness, lethargy, and failure to thrive. An enhanced computed tomography scans demonstrated multiple hemangiomas in both lobes of the liver, and a thyroid function tests showed severe hypothyroidism: TSH 561.5 µIU/mL, free triiodothyronine (fT3) 1.0 pg/mL, and free thyroxine (fT4) < 0.7 ng/dL. IHH gradually regressed following propranolol treatment and fT4 increased to a low normal level (1.0 ng/dL) by high dose replacement of levothyroxine, while fT3 remained very low (< 1.0 pg/mL), even following high doses of levothyroxine; fT3 eventually normalized following the administration of liothyronine. We suggest that treatment strategies should be individualized based on thyroid function, and that the combination therapy of propranolol for anti-tumor treatment and levothyroxine and liothyronine for respective thyroid hormone replacement is effective, particularly in cases of severe consumptive hypothyroidism due to multiple IHHs.

Further evidence of a causal association between AGO1, a critical regulator of microRNA formation, and intellectual disability/autism spectrum disorder.

Among the many regulators of microRNA formation, Argonaute 1 (AGO1) plays critical roles in RNA interference, which controls a wide range of biological activities. Recent large-scale genomic studies have identified at least five patients with intellectual disability/autism spectrum disorder who had de novo mutations in AGO1, but detailed clinical information was not available. The recognizable clinical features that are associated with AGO1 mutations remain to be determined. The proposita was a 15-year-old girl with diffuse hypotonia, infrequent seizures, and intellectual disability with an intelligence quotient of 41. She had characteristic facial features consisting of telecanthus, wide nasal bridge with bulbous nasal tip, and a round face with downslanted palpebral fissures. Serial computed tomography scans showed progressive calcification in the globus pallidus that became evident during childhood. A whole exome analysis in trio revealed a de novo heterozygous mutation in AGO1, i.e., c.595G > A p.(Gly199Ser). The distinctive facial features, i.e., telecanthus, wide nasal bridge with bulbous nasal tip, and a round face with downslanted palpebral fissures, closely resembled previously reported patients who had a chromosomal microdeletion encompassing AGO1 locus. The combinatory phenotype of such characteristic facial features and radiographic features, i.e. progressive calcification in the globus pallidus, in the presently reported patient suggest that AGO1 mutations lead to a syndromic form of intellectual disability/autism spectrum disorder. Distinctive facial features with early and progressive calcification in the globus pallidus may be suggestive of the presence of AGO1 mutations.

Efficacy and safety of intravenous immunoglobulin plus prednisolone therapy in patients with Kawasaki disease (Post RAISE): a multicentre, prospective cohort study.

BACKGROUND: The RAISE study showed that additional prednisolone improved coronary artery outcomes in patients with Kawasaki disease at high risk of intravenous immunoglobulin (IVIG) resistance. However, no studies have been done to test the steroid regimen used in the RAISE study. We therefore aimed to verify the efficacy and safety of primary IVIG plus prednisolone. METHODS: We did a multicentre, prospective cohort study at 34 hospitals in Japan. We included patients diagnosed with Kawasaki disease according to the Japanese diagnostic criteria, and excluded those who were treated at other hospitals before being transferred to a participating hospital. Patients who were febrile at diagnosis received primary IVIG (2 g/kg per 24 h) and oral aspirin (30 mg/kg per day) until the fever resolved, followed by oral aspirin (5 mg/kg per day) for 2 months after Kawasaki disease onset. We stratified patients using the Kobayashi score into predicted IVIG non-responders (Kobayashi score ≥5) or predicted IVIG responders (Kobayashi score <5). For predicted non-responders, each hospital independently decided whether to add prednisolone (intravenous injection of 2 mg/kg per day for 5 days) to the primary IVIG treatment, according to their respective treatment policy, and we further divided these patients based on the primary treatment received. The primary endpoint was the incidence of coronary artery abnormalities determined by two-dimensional echocardiography at 1 month after the primary treatment in predicted non-responders treated with primary IVIG plus prednisolone. Coronary artery abnormalities were defined according to the criteria of the Japanese Ministry of Health and Welfare and of the American Heart Association (AHA). This study is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000007133. FINDINGS: From July 1, 2012, to June 30, 2015, we enrolled 2628 patients with Kawasaki disease, of whom 724 (27·6%) were predicted IVIG non-responders who received IVIG plus prednisolone as primary treatment. 132 (18·2%) of 724 patients did not respond to primary treatment. Among patients with complete data, coronary artery abnormalities were present in 40 (incidence rate 5·9%, 95% CI 4·3-8·0) of 676 patients according to the AHA criteria or in 26 (3·8%, 2·5-5·6) of 677 patients according to the Japanese criteria. Serious adverse events were reported in 12 (1·7%) of 724 patients treated with primary IVIG plus prednisolone; two of these patients had hypertension and bacteraemia that was probably related to prednisolone. One patient died possibly due to severe inflammation from the Kawasaki disease itself. INTERPRETATION: Primary IVIG plus prednisolone therapy in this study had an effect similar to that seen in the RAISE study in reducing the non-response rate and decreasing the incidence of coronary artery abnormalities. A primary IVIG and prednisolone combination therapy might prevent coronary artery abnormalities and contribute to lowering medical costs. FUNDING: Tokyo Metropolitan Government Hospitals and the Japan Kawasaki Disease Research Center.

Respiratory arrest at the onset of idiopathic childhood occipital epilepsy of Gastaut.

Occipital lobe epilepsy of childhood includes two entities: Panayiotopoulos syndrome in pre-school children, and idiopathic childhood occipital epilepsy of Gastaut (ICOEG) in school-age children. The typical initial manifestation of the former is vomiting, and that of the latter is visual hallucinations. Ictal cardiopulmonary arrest at initial presentation has been reported for Panayiotopoulos syndrome, but not for ICOEG. We document a 7-year-old previously healthy girl who experienced an acute elemental visual hallucination of seeing insects, followed by a new-onset generalized seizure. Upon arrival at the local hospital, she was unconscious and soon thereafter, developed respiratory arrest. She was resuscitated and initiated on mechanical ventilation. An electroencephalogram taken three days after seizure cessation showed frequent occipital spikes, consistent with the diagnosis of ICOEG. The sequence of acute elementary visual hallucination followed by a motor seizure, and then witnessed respiratory arrest illustrated occurrence of life-threatening autonomic involvement at initial onset in ICOEG. We speculate that the epileptic propagation from the occipital lobes eventually compromised the respiratory center in the brainstem. The possibility of occipital lobe epilepsy should be considered in school-age children presenting with acute visual hallucination followed by respiratory arrest. Such a presentation should prompt an urgent electroencephalogram and initiation of antiepileptic treatment if indicated.

Predicting outcomes of neonates born to GBS-positive women who received inadequate intrapartum antimicrobial prophylaxis.

We determined the predicting factors of early-onset group B streptococcal (EOGBS) infection in neonates who were born to GBS carrier mothers with inadequate intrapartum antibiotic prophylaxis (IAP). Medical records of all neonates born from January 1, 2008 to April 1, 2010 were reviewed. Inadequate IAP was defined as delivery less than 4 hours (h) after the first administration of antimicrobial. Of 1910 neonates, 273 were born from mothers colonized with GBS, including 69 who received inadequate IAP. Of 69 neonates, nine showed symptoms, including respiratory distress, fever, tachycardia, vomiting, and irritability. Abnormalities in complete blood count (CBC) and C-reactive protein (CRP) were noted in three and four neonates, respectively. Three infants were diagnosed with EOGBS infection confirmed by positive rectal and throat cultures, and all three presented with respiratory distress and CRP abnormalities. Respiratory distress (p=0.0004) and CRP (p=0.0001) offered reliable indicators for detecting EOGBS infections.

Pediatric mumps with laryngeal edema.

Mumps virus infection primarily affects the salivary glands and may incur various complications. Laryngeal edema is such a rare complication that few adult cases have been reported. We report the first known pediatric patient with mumps with laryngeal edema. An 8-year-old boy developed dyspnea after a rapidly progressive swelling of his face and neck. Laryngoscopy revealed edematous changes in the supraglottic and subglottic regions, and computed tomography confirmed significant laryngeal edema in addition to swelling of the cervical soft tissue and the salivary glands. Laboratory findings revealed a high serum amylase level and confirmed the diagnosis of mumps. Intravenous steroid administration alleviated the dyspnea, although the patient required temporary tracheal intubation to maintain airway patency. He did not need tracheotomy and did not experience any other complications. Laryngeal edema must be regarded as a rare, potentially life-threatening complication of mumps. When mumps is diagnosed with significant swelling of the neck, an emergency airway should be established to prevent airway obstruction.

Young athlete with sudden cardiac arrest treated with therapeutic hypothermia.

Reported herein is a coronary anomaly that occurred in a young adolescent athlete who presented with cardiopulmonary arrest. The patient was resuscitated and treated with therapeutic hypothermia. The patient had no associated neurological complications at follow up. Enhanced computed tomography of the heart indicated an anomalous left main coronary artery originating from the right coronary sinus and coursing between the aorta and the pulmonary artery. The patient underwent surgical intervention with coronary artery bypass grafting to prevent symptom recurrence.

Neocentromere marker chromosome of distal 3q mimicking dup(3q) syndrome phenotype.

Supernumerary marker chromosomes (SMCs) lacking alpha-satellite sequences and possessing a newly derived functional centromere are referred to as neocentromere marker chromosomes (NMCs). Although the delineation of the chromosome content of these NMCs would be helpful for genetic counseling, such fine mapping has been difficult because of the limited sizes of the involved segments. We report on a female patient with mosaic NMC involving 3q26.3-3qter, the content of which was determined using an array CGH analysis. Our results support the validity of an array CGH-based approach to investigating the origins of SMCs. Further FISH analyses revealed that the NMC is characterized by an asymmetric inv-dup structure separated by a single-copy region. The present case had many manifestations of dup(3q) syndrome, the critical interval of which is considered to be 3q26.3-q27. Common features included mental and growth retardation, hirsutism, synophrys, a broad nasal root, anteverted nares, downturned corners of the mouth, and malformed ears. The observation gives further credence to the concept that the critical region responsible for the dup(3q) phenotype to 3q26.3-q27.

Thresholds of color attribute differences in detecting camouflaged textures.

We examined the threshold at which a camouflaged color texture pattern (target) embedded in a surrounding colored texture pattern (background) was discriminated by making the difference between their color distributions serve as a cue. The texture consisted of 900 colored disks. The color applied to the disk was chosen from a normal distribution with the mean and the standard deviation set beforehand. The mean of the background's distribution was a standard achromatic color set at L*=40, u*=0, and v*=0 of CIELUV. In experiment 1, the mean of the target's color distribution was shifted from the background's one. The threshold for the mean of the target's color distribution depended on the standard deviation and increased as the standard deviation became bigger. In experiment 2, the standard deviation of the target's color distribution was shifted. There was the slight dependence of threshold of the standard deviation of the target's distribution on that of the background's distribution. In experiment 3, both of the mean and the standard deviation of the target's color distribution were shifted at the same time. The threshold was not determined by each of the mean and the standard deviation independently. There seemed to be some compensating contribution between them to each other. The threshold could be characterized by Doyle metric or modified Doyle metric.

Determination of plasma concentrations of endothelin-1(1-31) and endothelin-1 in healthy subjects and patients with atherosclerosis.

We previously found that human chymase cleaves big endothelins at the Tyr31-Gly32 bond and produces 31-amino-acid endothelins, endothelins(1-31). Endothelin-1(1-31) has been isolated from a number of human organs, including the heart and lungs. As endothelin-1 has been shown to play a significant role in the paracrine regulation of cardiovascular functions in humans, it is possible that endothelin-1(1-31) may also exhibit biological activity on human tissues. We previously reported that synthetic endothelin-1(1-31) exhibits a number of physiological actions on cultured cells in vitro. In the present study, we investigated the plasma concentrations of endothelin-1(1-31) and endothelin-1 in healthy subjects and compared them with those in patients with cardiovascular diseases. Endothelin-1(1-31) and endothelin-1 in human plasma was measured using a sandwich-enzyme-immunoassay system, which was recently described for measurement of endothelin-1(1-31). The plasma concentrations of endothelin-1(1-31) and endothelin-1 in healthy volunteers were 19.24 +/- 5.70 and 15.54 +/- 4.45 pg/ml (n = 5), respectively. We also measured plasma concentrations of endothelin-1(1-31) and endothelin-1 before and after surgery in patients with abdominal aortic aneurysms. Before surgery, plasma concentrations of endothelin-1(1-31) and endothelin-1 in these patients were higher than those in healthy individuals. After surgery, both endothelin-1(1-31) and endothelin-1 in plasma decreased to levels similar to those of healthy subjects. This suggests that endothelin-1(1-31) may have similar physiological significance to endothelin-1 in patients with atherosclerosis.