A systematic review of clinical trials for gene therapies for ß-hemoglobinopathy around the world.

BACKGROUND AIMS: Amidst the success of cell therapy for the treatment of onco-hematological diseases, the first recently Food and Drug Administration-approved gene therapy product for patients with transfusion-dependent ß-thalassemia (TDT) indicates the feasibility of gene therapy as curative for genetic hematologic disorders. This work analyzed the current-world scenario of clinical trials involving gene therapy for ß-hemoglobinopathies. METHODS: Eighteen trials for patients with sickle cell disease (SCD) and 24 for patients with TDT were analyzed. RESULTS: Most are phase 1 and 2 trials, funded by the industry and are currently recruiting volunteers. Treatment strategies for both diseases are fetal hemoglobin induction (52.4%); addition of wild-type or therapeutic ß-globin gene (38.1%) and correction of mutations (9,5%). Gene editing (52.4%) and gene addition (40.5%) are the two most used techniques. The United States and France are the countries with the greatest number of clinical trials centers for SCD, with 83.1% and 4.2%, respectively. The United States (41.1%), China (26%) and Italy (6.8%) lead TDT trials centers. CONCLUSIONS: Geographic trial concentration indicates the high costs of this technology, logistical issues and social challenges that need to be overcome for gene therapy to reach low- and middle-income countries where SCD and TDT are prevalent and where they most impact the patient's health.

Congenital hydrocephalus: gestational and neonatal outcomes.

PURPOSE: To evaluate gestational and neonatal outcomes in pregnancies complicated by fetal hydrocephalus. METHODS: Retrospective analysis of 287 cases of fetal hydrocephalus followed at the Fetal Medicine Unit of the University of Campinas in the period of 1996 to 2006. RESULTS: Mean maternal age was 25 years, mean gestational age at diagnosis was 27 weeks. There were 50 cases of isolated ventriculomegaly, 95 cases of Chiari II malformation and 142 cases of ventriculomegaly associated with other malformations. Preterm delivery and vaginal delivery were more frequent in the group of ventriculomegaly associated with other malformations. Cardiac, skeletal and renal malformations were the most common associated malformations. Cesarean section was common (95%) in the Chiari II group. Fetal and neonatal death occurred more frequently (29 and 68%, respectively) in the group of ventriculomegaly associated with other malformations. Chromosomal anomalies were present in 15% of 165 investigated cases. CONCLUSIONS: Fetal and neonatal prognosis and outcome are associated with the presence of associated anomalies and aneuploidy.

Sustained Ventricular Tachycardia and Cardiogenic Shock due to Scorpion Envenomation.

We describe a case of severe scorpion envenomation in an adult patient, with the presence of very rapid sustained ventricular tachycardia followed by cardiogenic shock, which was reversed by scorpion antivenom administration. Scorpion venom causes cardiac changes that can lead to an environment favoring arrhythmogenesis.