Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.
The aim of this study was to determine whether initial shock index (SI) was independently associated with the requirement for massive transfusion (MT) in emergency department (ED) patients with primary postpartum hemorrhage (PPH). A retrospective cohort study of ED patients with primary PPH was performed at a university-affiliated, tertiary referral center between January 2004 and May 2012. Patients were classified to two groups: MT group (patients who received ≥10 U of packed red blood cells within 24 h of ED admission) and non-MT group (patients who received <10 U). Variables of the two groups were compared using univariate and multivariate analyses. A total of 126 patients were included in this study. Of these patients, 26 (20.6%) were included in MT group and 100 (79.4%) in non-MT group. Patients in MT group had significantly lower blood pressure and higher heart rate compared with patients in non-MT group (P < 0.01). Initial SI was significantly higher in MT group than in non-MT group (1.3 vs 0.8, P < 0.01). In multivariate logistic regression analysis, initial SI and heart rate were the only variables associated with the requirement for MT, with an odds ratio of 9.47 (95% confidence interval, 1.75-51.28; P < 0.01) and 1.06 (95% confidence interval, 1.02-1.09; P < 0.01), respectively. In conclusion, initial SI was independently associated with the requirement for MT in ED patients with primary PPH. Routine calculation of initial SI can help clinicians to identify patients who may benefit from timely and appropriate use of MT to improve clinical outcomes.
Point-of-care testing of lactate concentrations in the emergency department may be useful to predict massive transfusion requirements in primary postpartum haemorrhage. Combining initial lactate concentrations with the shock index improves the predictive performance for massive transfusion requirements and may contribute to rapid risk stratification of patients with primary postpartum haemorrhage in need of transfusion and further focus on early interventions to control bleeding.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.