Background & Aims Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed ≤5 y of age, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Methods Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (ages 3 weeks to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by post-processing and variant calling. Following functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency <0.1%, and scaled combined annotation dependent depletion scores ≤10. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n=45) or adult-onset Crohn's disease (n=20) and healthy individuals (controls, n=145) were obtained from the University of Kiel, Germany and used as control groups. Results Four-hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling > 1 Mbp of coding sequence, were selected from the whole exome data. Our analysis revealed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. Conclusions In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the identification of previously unidentified IBD-associated variants.

Abstract-Because hypertensive pregnancies have been associated with increased cardiovascular disease, we aimed to identify whether angiographically characterized coronary artery disease differed in women with previous normotensive pregnancies or hypertensive pregnancies (HPs Key Words: hypertension in pregnancy Ⅲ preeclampsia Ⅲ coronary artery disease Ⅲ cardiovascular risks Ⅲ coronary angiography I ndirect evidence has linked preeclampsia, other forms of hypertension in pregnancy, and placentation-related defects to cardiovascular (CV) disease later in life. [1][2][3][4][5][6][7][8][9][10][11][12] Although most studies have used registry bases, one includes clinical follow-up, 10 one compares women with angiographically characterized coronary lesions with patients who only underwent clinical screening for coronary disease, 8 and another evaluates coronary calcification, a predictor of coronary artery disease. 11 A prospective study performed in a cohort of women with a precise classification of obstetric outcomes would be necessary to evaluate the tentative association between reproductive and CV complications, but because this is a relatively new finding, any ongoing or new study will need at least a couple of decades to be completed. Furthermore, included subjects would have to be left to the natural evolution of CV disease, and it is ethically inadmissible to abstain from CV preventive management.We decided to take an intermediate stance, by testing whether those subjects who had hypertensive pregnancies (HPs) developed earlier or more extensive coronary lesions than controls who had normotensive pregnancies (NPs). For this purpose, we evaluated the remote obstetric histories in women who underwent coronary angiography, the gold standard for defining coronary disease. MethodsThis investigation was a case-control observational retrospective study, with the results of coronary angiography as the dependent variable. Women undergoing coronary angiographies because of suspected coronary disease at Hospital Sótero del Río, in the southeast zone of Santiago, Chile, from January 1, 2006, to December 31, 2007, completed a questionnaire (please see the online data supplement at http://hyper.ahajournals.org) to determine their CV risk factors, including the following: family history; age of onset and end of menstrual cycles; hormonal replacement therapy; number of

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The efficacy of thrombolysis in clinical stroke subtypes is unclear. We compared the benefit of intravenous rt-PA in 11 patients with lacunar syndrome with that in 33 patients with a non-lacunar syndrome. Patients were matched by NIHSS score and time to treatment. Although no statistically significant differences were detected in outcome, the benefit was greater in the non- lacunar syndrome group.

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Reportar nuestra experiencia en el tratamiento endovascular de la Coartación Aórtica (CoAo). Métodos: Se revisaron los registros clínicos de los pacientes mayores de 4 años intervenidos por una CoAo nativa o recoartación en el Hospital Clínico de la Universidad Católica entre los años 2007 y 2012. Se realizaron estadísticas descriptivas y se utilizó el test de Wilcoxon signed rank, con una p <0,05. Resultados: En ese período se realizaron 27 intervenciones en pacientes con CoAo. El promedio de edad fue 20.6 años (5-64); 8 (30%) eran mujeres y 8 (30%) menores de 14 años. Quince pacientes (55%) tenían una cardiopatía congénita asociada, de los cuales 9 (33%) tenían válvula aórtica bicúspide, 3 (11%) una comunicación interventricular (CIV) y 3 co-existencia de ambas entidades (11%). Nueve (33%) pacientes eran hipertensos. En 20 (74%) pacientes la intervención fue sobre una coartación aórtica nativa y en 7 (26%) sobre una recoartación (2 con cirugía previa y 5 con angioplastia anterior). Se implantó un stent en 23 (85%) pacientes y se utilizó sólo balón en 4 (15%). En 26 pacientes (96%) se logró una reducción del gradiente a menos de 20 mmHg (gradiente pre 32 vs gradiente post 6 mmHg, p<0,01). Hubo complicaciones del sitio de punción en 3 pacientes (2 hematomas y 1 disección focal en el origen de la arteria ilíaca externa) y complicaciones mayores en 2 pacientes (disección aórtica tipo B) que requirieron tratamiento intervencional (uno percutáneo y uno quirúrgico). No hubo mortalidad en nuestra serie. Conclusiones: La intervención endovascular es una opción de tratamiento efectiva para la CoAo.

Recibido 23 de diciembre 2012 / Aceptado 12 de marzo 2013Objetivos: Analizar comparativamente las características clínicas y angiográficas, y el tratamiento utilizado, en pacientes jóvenes cursando un infarto agudo del miocardio (IAM) con supradesnivel del segmento ST (SDST).Métodos: Análisis retrospectivo de los pacientes que se presentaron con un IAM con SDST y fueron sometidos a angiografía coronaria durante el período entre enero de 2009 y diciembre de 2011. Se identificó a los pacientes menores de 40 años y se registraron sus características clínicas y angiográficas, las terapias utilizadas y sus resultados a mediano plazo. Estos datos fueron comparados con los pacientes de 40 o más años atendidos durante el mismo período.Resultados: De 613 IAM con SDST, 40 (6,5%) casos correspondieron a menores de 40 años (edad promedio 36,6 años). De éstos, 7 (17,5%) fueron mujeres, 32 (80%) fumadores y 17 (42,5%) referían uso de cocaína. La mayoría presentó alta carga trombótica (TIMI Thrombus Grade 4/5 en 87,5%), pero con enfermedad de baja severidad anatómica (Syntax Score promedio 13,1 (DE 5,8)). Treinta (75%) pacientes recibieron angioplastía con stent y 21 (52,5%) aspiración de trombos. El seguimiento tardío reveló 5 (12,5%) eventos mayores. Comparado con los pacientes mayores de 40 años, la mortalidad al año fue marcadamente inferior: 2,5% versus 12%, p<0,01.Conclusiones: En menores de 40 años con IAM con SDST, el tabaquismo, uso de cocaína, fueron los principales factores asociados. Aunque la enfermedad coronaria anatómica no fue severa, hubo una gran carga trombótica en la mayoría de los pacientes. Esto se asoció a escasos eventos cardiovasculares y una mortalidad menor a la de los pacientes mayores. Palabras claves:Infarto al miocardio, grupos poblacionales, abuso de cocaína.