Accessory mitral valve tissue causing severe left ventricular outflow tract obstruction in a post-Senning patient with transposition of the great arteries

Accessory mitral valve tissue is a rare congenital anomaly associated with congenital cardiac defects and is usually detected in the first decade of life. We describe the case of an 18-year old post-Senning asymptomatic patient who was found to have accessory mitral valve tissue on transthoracic echocardiography producing severe left ventricular outflow tract obstruction

Agreement of Clinician-Administered and Modified Parent-Administered House-Brackmann Scales in Children with Bell's Palsy

Objective. Currently there is no parent administered scale for facial nerve function in children. We set out to assess the agreement between a newly developed parent-administered modified version of the House-Brackmann (HB) scale and the standard clinician-administered HB scale in children with Bell's palsy. Study Design. Secondary analysis of a triple-blind, randomized, placebo-controlled trial of corticosteroids to treat idiopathic facial paralysis (Bell's palsy) in children (6 months to <18 years). Setting. Multicenter study at pediatric hospitals with recruitment in emergency departments. Methods. Children were recruited within 72 hours of symptom onset and assessed using the clinicianadministered and the parent-administered modified HB scales at baseline, and at 1, 3, and 6 months until recovered. Agreement between the 2 scales was assessed using intraclass coefficient (ICC) and a Bland-Altman plot. Results. Data were available for 174 of the 187 children randomized from at least 1 study time point. The mean ICC between clinician and parent HB scores across all time points was 0.88 (95% confidence interval, CI: 0.86, 0.90). The ICC for the data collected at baseline was 0.53 (95% CI: 0.43, 0.64), at 1 month was 0.88 (95% CI: 0.84, 0.91), at 3 months was 0.80 (95% CI: 0.71, 0.87) and at 6 months was 0.73 (95% CI: 0.47, 0.89). A Bland-Altman plot indicated a mean difference between the 2 scores (clinician-reported minus parent-reported) of only −0.07 (95% limits of agreement −1.37 to 1.23). Conclusion. There was good agreement between the modified parent-administered and the clinician-administered HB scales.Franz E. Babl, Nitaa Eapen, David Herd, Meredith L. Borland, Amit Kochar, Michael Zhang, Ed Oakley, Sandy M. Hopper, Robert G. Berkowitz, Catherine L. Wilson, Amanda Williams, Mark T. Mackay, Katherine J. Lee, Stephen Hearps, and the PREDICT (Paediatric Research in Emergency Departments International Collaborative) research networ

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Reduced-intensity conditioning regimens for allogeneic transplantation in children with acute lymphoblastic leukemia

10.1016/j.bbmt.2010.03.009Biology of Blood and Marrow Transplantation1691237-1244BBMT