Browsing by Subject "Clinical Trials and Observations"

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    Metabolic syndrome increases risk of venous thromboembolism recurrence after acute deep vein thrombosis
    (American Society of Hematology, 2020-01-09) Stewart, Lauren K.; Kline, Jeffrey A.; Pediatrics, School of Medicine
    An improved understanding of which patients are at higher risk of recurrent venous thromboembolism (VTE) is important to designing interventions to reduce degraded quality of life after VTE. Although metabolic syndrome (MetS), the clustering of hypertension, hyperlipidemia, diabetes mellitus, and obesity has been associated with a hypofibrinolytic state, data linking VTE recurrence with MetS remain limited. The purpose of this study was to measure the prevalence of MetS in patients with deep vein thrombosis (DVT) across a large population and determine its effect on VTE recurrence. This was a retrospective analysis of a large statewide database from 2004 to 2017. We measured the frequency with which patients with DVT carried a comorbid International Coding of Diseases diagnosis of MetS components. Association of MetS with VTE recurrence was tested with a multiple logistic regression model and VTE recurrence as the dependent variable. Risk of VTE recurrence conferred by each MetS component was assessed by Kaplan-Meier curves with the log-rank statistic. A total of 151 054 patients with DVT were included in this analysis. Recurrence of VTE occurred in 17% overall and increased stepwise with each criterion for MetS. All 4 components of MetS had significant adjusted odds ratios (OR) for VTE recurrence, with hyperlipidemia having the largest (OR, 1.8), representing the 4 largest ORs of all possible explanatory variables. All 4 MetS variables were significant on Kaplan-Meier analysis for recurrence of VTE. These data imply a role for appropriate therapies to reduce the effects of MetS as a way to reduce risk of VTE recurrence.
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    Update on clinical gene therapy for hemophilia
    (American Society of Hematology, 2019-01-31) Perrin, George Q.; Herzog, Roland W.; Markusic, David M.; Pediatrics, School of Medicine
    In contrast to other diverse therapies for the X-linked bleeding disorder hemophilia that are currently in clinical development, gene therapy holds the promise of a lasting cure with a single drug administration. Near-to-complete correction of hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) have now been achieved in patients by hepatic in vivo gene transfer. Adeno-associated viral vectors with different viral capsids that have been engineered to express high-level, and in some cases hyperactive, coagulation factors were employed. Patient data support that sustained endogenous production of clotting factor as a result of gene therapy eliminates the need for infusion of coagulation factors (or alternative drugs that promote coagulation), and may therefore ultimately also reduce treatment costs. However, mild liver toxicities have been observed in some patients receiving high vector doses. In some but not all instances, the toxicities correlated with a T-cell response directed against the viral capsid, prompting use of immune suppression. In addition, not all patients can be treated because of preexisting immunity to viral capsids. Nonetheless, studies in animal models of hemophilia suggest that the approach can also be used for immune tolerance induction to prevent or eliminate inhibitory antibodies against coagulation factors. These can form in traditional protein replacement therapy and represent a major complication of treatment. The current review provides a summary and update on advances in clinical gene therapies for hemophilia and its continued development.