Atrial Flutter in Infants

ObjectivesWe sought to characterize the clinical nature of atrial flutter (AFL) in a large cohort of infants.BackgroundThere are no large studies describing the natural history of AFL in infants. Previous studies vary in the therapy used and expected prognosis.MethodsWe reviewed the records of all children younger than 1 year of age who were diagnosed with AFL at our hospital during the past 25 years, excluding those with previous cardiac surgery.ResultsWe identified 50 infants with AFL. Most, 36 (72%), presented within the first 48 h of life. Congestive heart failure was evident in 10 infants, with 6 presenting at 1 day of age, and 4 presenting beyond 1 month of age. The remainder were asymptomatic. A large atrial septal defect was the only structural heart disease. Spontaneous conversion to sinus rhythm occurred in 13 (26%) infants. Sinus rhythm was restored in 20 of 23 (87%) attempts at direct current cardioversion and 7 of 22 (32%) attempts at transesophegeal pacing; 7 required antiarrhythmic therapy. An additional arrhythmia, all supraventricular, appeared in 11 (22%) infants. The recurrence of AFL developed in 6 infants; 5 of 6 of these incidents occurred within 24 h of the first episode. All patients with recurrence had an additional arrhythmia.ConclusionsInfants with AFL usually present within the first 2 days of life. No association was found with structural heart disease. Direct current cardioversion appears to be most effective at establishing sinus rhythm. Chronic AFL has the potential to cause cardiovascular compromise. Atrial flutter in the absence of other arrhythmias has a low risk of recurrence. Once in sinus rhythm, infants with AFL have an excellent prognosis and may not require chronic antiarrhythmic therapy

Patterns of Fever in Children After Primary Treatment for Kawasaki Disease

OBJECTIVE: To determine if fever in the early post intravenous immunoglobulin (IVIG) time period (first 36 hours after IVIG completion) for Kawasaki disease (KD), with or without additional infliximab, can predict IVIG resistance and coronary artery abnormalities (CAA). METHODS: Acute KD subjects enrolled in a clinical trial of infliximab plus IVIG (n=96) versus placebo/IVIG (n=94) had temperatures recorded every 6 hours after completion of IVIG infusion. Fever was defined as temperature ≥38.0°C; patients with persistent or recrudescent fever ≥36 hours after completion of IVIG were classified as IVIG-resistant. Multivariable logistic regression by fever pattern was performed to predict outcomes (IVIG resistance and CAA). RESULTS: There was no difference in the time to defervescence between the infliximab/IVIG group (n=96) versus placebo/IVIG group (n= 94). There was no fever after completion of IVIG in the majority of subjects [66% of those with no CAA (n=139) and 76.5% of those with CAA, (n=51)]. Although subjects with at least one fever 24–36 hours post-IVIG had a higher probability of IVIG resistance (OR=30.6 [95%CI 6.7–139.8] p<0.0001), fever at 24–36 hours was not associated with higher likelihood of CAA. There were also 11% (n=19) of IVIG responders who had fever at 24–36 hours post-IVIG. The majority of subjects with CAA (43 of 51, 84.3%) were identified by the initial echocardiogram, so the effect of fever on development of CAA could not be assessed. CONCLUSION: Fever in the first 36 hours following IVIG completion is not predictive of CAA. Our data support refraining from re-treatment until 36 hours after completion of IVIG

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Creation of iPSC line NCHi004-A from a patient with down syndrome and congenital heart defects

Down syndrome is a congenital disorder resulting from an extra full or partial chromosome 21, which is characterized by a spectrum of systemic developmental abnormalities, including those affecting the cardiovascular system. Here, we generated an iPSC line from peripheral blood mononuclear cells of a male adolescent with Down syndrome-associated congenital heart defects through Sendai virus-mediated transfection of 4 Yamanaka factors. This line exhibited normal morphology, expressed pluripotency markers, trisomy 21 karyotype, and could be differentiated into three germ layers. This iPSC line can be used for studying cellular and developmental etiologies of congenital heart defects induced by aneuploidy of chromosome 21

The Utility of Screening Fetal Echocardiograms Following Normal Level II Ultrasounds in Fetuses with Maternal Congenital Heart Disease

Abstract Introduction Fetal echocardiograms (F-echo) are recommended in all pregnancies when maternal congenital heart disease (CHD) is present, even if there was a prior level II ultrasound (LII-US) that was normal. The goal of this study was to evaluate if any diagnosis of a critical CHD was missed in a fetus with maternal CHD who had a normal LII-US. Methods A retrospective chart review of all F-echoes where the indication was maternal CHD between 1/1/2015 to 12/31/2022 was performed. Fetuses were included if they had a LII-US that was read as normal and had an F-echo. Critical CHD was defined as CHD requiring catheterization or surgical intervention < 1 month of age. Results A total of 296 F-echoes on fetuses with maternal CHD were evaluated, of which 175 met inclusion criteria. LII-US was performed at 19.8 ± 2.9 weeks gestational age and F-echo was performed at 24.2 ± 2.8 weeks gestational age. No patient with a normal LII-US had a diagnosis of a critical CHD by F-echo (negative predictive value = 100%). Evaluating those patients that had a negative LII-US, ten patients were diagnosed with non-critical CHD postnatally (negative predictive value = 94.3%). F-echo correctly diagnosed two of the ten missed LII-US CHD. Conclusions Critical CHD was not missed with a normal LII-US in this at risk population. F-echo also missed the majority of CHD when a LII-US was read as normal. A cost–benefit analysis of screening F-echo in fetuses with maternal CHD should be conducted if a normal LII-US has been performed

Patterns of Fever in Children After Primary Treatment for Kawasaki Disease.

BackgroundWe sought to determine if fever in the early postintravenous immunoglobulin (IVIG) time period (first 36 hours after IVIG completion) for Kawasaki disease, with or without additional infliximab, can predict IVIG resistance and coronary artery abnormalities (CAA).MethodsAcute Kawasaki disease subjects enrolled in a clinical trial of infliximab plus IVIG (n = 96) versus placebo/IVIG (n = 94) had temperatures recorded every 6 hours after completion of IVIG infusion. Fever was defined as temperature &gt;38.0°C; patients with persistent or recrudescent fever &gt;36 hours after completion of IVIG were classified as IVIG resistant. Multivariable logistic regression by fever pattern was performed to predict outcomes (IVIG resistance and CAA).ResultsThere was no difference in the time to defervescence between the infliximab/IVIG group (n = 96) versus placebo/IVIG group (n = 94). There was no fever after completion of IVIG in the majority of subjects [66% of those with no CAA (n = 139) and 76.5% of those with CAA, (n = 51)]. Although subjects with at least 1 fever 24-36 hours post-IVIG had a higher probability of IVIG resistance [odds ratio = 30.6 (95% confidence interval: 6.7-139.8); P &lt; 0.0001], fever at 24-36 hours was not associated with higher likelihood of CAA. There were also 11% (n = 19) of IVIG responders who had fever at 24-36 hours post-IVIG. The majority of subjects with CAA (43 of 51, 84.3%) were identified by the initial echocardiogram, so the effect of fever on development of CAA could not be assessed.ConclusionsFever in the first 36 hours after IVIG completion is not predictive of CAA. Our data support refraining from retreatment until 36 hours after completion of IVIG

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease.

BACKGROUND:Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. METHODS:Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4-6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. RESULTS:We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. CONCLUSION:A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG