RESUMEN
OBJECTIVE: To determine the impact of damaging genetic variation in proangiogenic pathways on placental function, complications of pregnancy, fetal growth, and clinical outcomes in pregnancies with fetal congenital heart defect. STUDY DESIGN: Families delivering a baby with a congenital heart defect requiring surgical repair in infancy were recruited. The placenta and neonate were weighed and measured. Hemodynamic variables were recorded from a third trimester (36.4 ± 1.7 weeks) fetal echocardiogram. Exome sequencing was performed on the probands (N = 133) and consented parents (114 parent-child trios, and 15 parent-child duos) and the GeneVetter analysis tool used to identify damaging coding sequence variants in 163 genes associated with the positive regulation of angiogenesis (PRA) (GO:0045766). RESULTS: In total, 117 damaging variants were identified in PRA genes in 133 congenital heart defect probands with 73 subjects having at least 1 variant. Presence of a damaging PRA variant was associated with increased umbilical artery pulsatility index (mean 1.11 with variant vs 1.00 without; P = .01). The presence of a damaging PRA variant was also associated with lower neonatal length and head circumference for age z score at birth (mean -0.44 and -0.47 with variant vs 0.23 and -0.05 without; P = .01 and .04, respectively). During median 3.1 years (IQR 2.0-4.1 years) of follow-up, deaths occurred in 2 of 60 (3.3%) subjects with no PRA variant and in 9 of 73 (12.3%) subjects with 1 or more PRA variants (P = .06). CONCLUSIONS: Damaging variants in proangiogenic genes may impact placental function and are associated with impaired fetal growth in pregnancies involving a fetus with congenital heart defect.
Asunto(s)
Proteínas Angiogénicas/genética , Desarrollo Fetal/genética , Variación Genética/genética , Cardiopatías Congénitas/genética , Complicaciones del Embarazo/etiología , Estudios de Casos y Controles , Femenino , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/cirugía , Humanos , Recién Nacido , Masculino , EmbarazoRESUMEN
OBJECTIVES: To assess automated external defibrillator (AED) distribution and cardiac emergency preparedness in Michigan secondary schools and investigate for association with school sociodemographic characteristics. STUDY DESIGN: Surveys were sent via electronic mail to representatives from all public high schools in 30 randomly selected Michigan counties, stratified by population. Association of AED-related factors with school sociodemographic characteristics were evaluated using Wilcoxon rank sum test and χ(2) test, as appropriate. RESULTS: Of 188 schools, 133 (71%) responded to the survey and all had AEDs. Larger student population was associated with fewer AEDs per 100 students (P < .0001) and fewer staff with AED training per AED (P = .02), compared with smaller schools. Schools with >20% students from racial minority groups had significantly fewer AEDs available per 100 students than schools with less racial diversity (P = .03). Schools with more students eligible for free and reduced lunch were less likely to have a cardiac emergency response plan (P = .02) and demonstrated less frequent AED maintenance (P = .03). CONCLUSIONS: Although AEDs are available at public high schools across Michigan, the number of AEDs per student varies inversely with minority student population and school size. Unequal distribution of AEDs and lack of cardiac emergency preparedness may contribute to outcomes of sudden cardiac arrest among youth.
Asunto(s)
Defensa Civil/estadística & datos numéricos , Desfibriladores/provisión & distribución , Servicios Médicos de Urgencia/estadística & datos numéricos , Servicios de Salud Escolar/estadística & datos numéricos , Estudios Transversales , Muerte Súbita Cardíaca/epidemiología , Humanos , Michigan , Instituciones Académicas , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To comprehensively characterize the immunologic characteristics of patients with protein-losing enteropathy (PLE) post-Fontan and compare them with patients without PLE post-Fontan. STUDY DESIGN: Patients with PLE post-Fontan and age-matched controls post-Fontan were prospectively studied with laboratory markers of immune function. Infectious history was obtained by interview and chart review. The groups' demographics, cardiac history, immune characteristics, and infection history were compared using appropriate 2-group statistics. RESULTS: A total of 16 patients enrolled (8 patients with PLE and 8 controls). All patients with PLE had lymphopenia compared with 25% of controls (P = .01). All patients with PLE had markedly depressed CD4 T cell counts (median 58 cells/µL) compared with controls (median 450 cells/µL, P = .0002); CD4% was also low in the PLE group (12.3%) and normal in control (36.9%, P = .004). Both groups had mildly depressed CD8 T cells and normal to slightly elevated natural killer and B-cell subsets. A majority of patients with PLE (62.5%) had negative titers to measles, mumps, and rubella vaccination, compared with no control Fontan with a negative titer (P = .03). Despite profoundly low CD4 counts, the frequency of infection was not different between groups with no reported opportunistic infections. CONCLUSIONS: Patients with Fontan-associated PLE have extensive quantitative immune abnormalities, particularly CD4 deficiency. These immune abnormalities are similar to those found in non-Fontan patients with PLE caused by intestinal lymphangiectasia.
Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Procedimiento de Fontan/efectos adversos , Cardiopatías Congénitas/cirugía , Linfopenia/epidemiología , Enteropatías Perdedoras de Proteínas/inmunología , Recuento de Linfocito CD4 , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/inmunología , Humanos , Isotipos de Inmunoglobulinas/sangre , Lactante , Masculino , Estudios Prospectivos , Enteropatías Perdedoras de Proteínas/sangreRESUMEN
OBJECTIVE: To characterize the medical history, disease progression, and treatment of current-era patients with the rare diseases Fontan-associated protein-losing enteropathy (PLE) and plastic bronchitis. STUDY DESIGN: A novel survey that queried demographics, medical details, and treatment information was piloted and placed online via a Facebook portal, allowing social media to power the study. Participation regardless of PLE or plastic bronchitis diagnosis was allowed. Case control analyses compared patients with PLE and plastic bronchitis with uncomplicated control patients receiving the Fontan procedure. RESULTS: The survey was completed by 671 subjects, including 76 with PLE, 46 with plastic bronchitis, and 7 with both. Median PLE diagnosis was 2.5 years post-Fontan. Hospitalization for PLE occurred in 71% with 41% hospitalized ≥ 3 times. Therapy varied significantly. Patients with PLE more commonly had hypoplastic left ventricle (62% vs 44% control; OR 2.81, 95% CI 1.43-5.53), chylothorax (66% vs 41%; OR 2.96, CI 1.65-5.31), and cardiothoracic surgery in addition to staged palliation (17% vs 5%; OR 4.27, CI 1.63-11.20). Median plastic bronchitis diagnosis was 2 years post-Fontan. Hospitalization for plastic bronchitis occurred in 91% with 61% hospitalized ≥ 3 times. Therapy was very diverse. Patients with plastic bronchitis more commonly had chylothorax at any surgery (72% vs 51%; OR 2.47, CI 1.20-5.08) and seasonal allergies (52% vs 36%; OR 1.98, CI 1.01-3.89). CONCLUSIONS: Patient-specific factors are associated with diagnoses of PLE or plastic bronchitis. Treatment strategies are diverse without clear patterns. These results provide a foundation upon which to design future therapeutic studies and identify a clear need for forming consensus approaches to treatment.
Asunto(s)
Bronquitis/etiología , Procedimiento de Fontan/efectos adversos , Cardiopatías Congénitas/cirugía , Enteropatías Perdedoras de Proteínas/etiología , Adolescente , Bronquitis/epidemiología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Michigan/epidemiología , Proyectos Piloto , Complicaciones Posoperatorias , Enteropatías Perdedoras de Proteínas/epidemiología , Factores de RiesgoRESUMEN
An adolescent girl with a history of anxiety associated seizure-like episodes was ultimately diagnosed with catecholaminergic polymorphic ventricular tachycardia. She tested positive for a novel mutation of the ryanodine receptor. The report underscores how genetic arrhythmia syndromes may be mistaken for neurologic disorders.