RESUMO
We treated a 27-year-old patient with Duchenne's muscular dystrophy (DMD) with recombinant adeno-associated virus (rAAV) serotype 9 containing dSaCas9 (i.e., "dead" Staphylococcus aureus Cas9, in which the Cas9 nuclease activity has been inactivated) fused to VP64; this transgene was designed to up-regulate cortical dystrophin as a custom CRISPR-transactivator therapy. The dose of rAAV used was 1×1014 vector genomes per kilogram of body weight. Mild cardiac dysfunction and pericardial effusion developed, followed by acute respiratory distress syndrome (ARDS) and cardiac arrest 6 days after transgene treatment; the patient died 2 days later. A postmortem examination showed severe diffuse alveolar damage. Expression of transgene in the liver was minimal, and there was no evidence of AAV serotype 9 antibodies or effector T-cell reactivity in the organs. These findings indicate that an innate immune reaction caused ARDS in a patient with advanced DMD treated with high-dose rAAV gene therapy. (Funded by Cure Rare Disease.).
Assuntos
Distrofina , Terapia Genética , Distrofia Muscular de Duchenne , Síndrome do Desconforto Respiratório , Transgenes , Adulto , Humanos , Anticorpos , Distrofina/genética , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/imunologia , Transgenes/genética , Transgenes/imunologia , Evolução Fatal , Imunidade Inata/genética , Imunidade Inata/imunologiaRESUMO
Objective To describe the clinical presentation and obstetrical outcomes of nonthyroid head and neck cancers (HNCs), and to review literature on this rare condition in pregnancy. Study Design Pregnant women with nonthyroid HNC were identified retrospectively from 1990 to 2017. Maternal, neonatal, pregnancy, and demographic data were collected. A review of the literature from January 1980 to May 2018 was performed. Results Over the 27-year time period, 16 women with history of nonthyroid HNC were identified (9 diagnosed during and 7 diagnosed before current pregnancy). The cases were analyzed in detail and the most updated review of management of each type of HNC was provided. Conclusions HNCs are rare with diagnosis and management challenges during pregnancy. In this series, the cases diagnosed and managed previously to pregnancy presented better perinatal outcomes than the cases presented during pregnancy. The maternal outcomes appeared similar for HNC diagnosed before or after pregnancy.
RESUMO
There are many established risk factors for babies who are small for gestational age (SGA) by population birth weight centiles (usually defined as <10th centile). The confirmed maternal risk factors include short stature, low weight, Indian or Asian ethnicity, nulliparity, mother born SGA, cigarette smoking and cocaine use. Maternal medical history of: chronic hypertension, renal disease, anti-phospholipid syndrome and malaria are associated with increased SGA. Risk factors developing in pregnancy include heavy bleeding in early pregnancy, placental abruption, pre-eclampsia and gestational hypertension. A short or very long inter-pregnancy interval, previous SGA infant or previous stillbirth are also risk factors. Paternal factors including changed paternity, short stature and father born SGA also contribute. Factors associated with reduced risk of SGA or increased birth weight include high maternal milk consumption and high intakes of green leafy vegetables and fruit. Future studies need to investigate risk factors for babies SGA by customised centiles as these babies have greater morbidity and mortality than babies defined as SGA by population centiles.