RESULTS: ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2-overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA.
METHODS: The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2-overexpressing cell line and ARG inhibitor, N (omega)-hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA).
CONCLUSIONS: ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2.
METHODOLOGY: We collected data of patients with ICH diagnosed via a plain computed tomography of the brain (CT brain) with thrombocytopenia and positive Dengue virus type 1 nonstructural protein (NS1) antigen test or positive dengue serology IgM from January 2014 till June 2015 at our center. Nine patients were included and all 20 other remaining patients reported in literature so far are discussed.
DISCUSSION: We found that all patients in our center requiring neurosurgical intervention died. Another interesting observation is that detection of Dengue IgG usually meant more severe ICH and poorer outcomes. From our series, platelet levels did not seem to influence the outcome.
CONCLUSION: We recommend that for early detection of ICH, Dengue IgG should be routinely screened and a high index of suspicion be maintained. Future research should be focused on determining predictors of ICH in patients with dengue fever so that preventive steps can be taken as mortality is high and no treatment seems beneficial at the moment once severe ICH occurs.
OBJECTIVE: We hypothesized that the risk of infections after primary cranioplasty in adult patients who underwent craniectomies for non-infection-related indications are no different when performed early or delayed. We tested this hypothesis in a prospective, multicenter, cohort study.
METHODS: Data were collected prospectively from 5 neurosurgical centers in the United Kingdom, Malaysia, Singapore, and Bangladesh. Only patients older than 16 years from the time of the non-infection-related craniectomy were included. The recruitment period was over 17 months, and postoperative follow-up was at least 6 months. Patient baseline characteristics, rate of infections, and incidence of hydrocephalus were collected.
RESULTS: Seventy patients were included in this study. There were 25 patients in the early cranioplasty cohort (cranioplasty performed before 12 weeks) and 45 patients in the late cranioplasty cohort (cranioplasty performed after 12 weeks). The follow-up period ranged between 16 and 34 months (mean, 23 months). Baseline characteristics were largely similar but differed only in prophylactic antibiotics received (P = 0.28), and primary surgeon performing cranioplasty (P = 0.15). There were no infections in the early cranioplasty cohort, whereas 3 infections were recorded in the late cohort. This did not reach statistical significance (P = 0.55).
CONCLUSIONS: Early cranioplasty in non-infection-related craniectomy is relatively safe. There does not appear to be an added advantage to delaying cranioplasties more than 12 weeks after the initial craniectomy in terms of infection reduction. There was no significant difference in infection rates or risk of hydrocephalus between the early and late cohorts.
MATERIALS/METHODS: Multivariable models developed to predict atomised and generalised urinary symptoms, both acute and late, were considered for validation using a dataset representing 754 participants from the TROG 03.04-RADAR trial. Endpoints and features were harmonised to match the predictive models. The overall performance, calibration and discrimination were assessed.
RESULTS: 14 models from four publications were validated. The discrimination of the predictive models in an independent external validation cohort, measured using the area under the receiver operating characteristic (ROC) curve, ranged from 0.473 to 0.695, generally lower than in internal validation. 4 models had ROC >0.6. Shrinkage was required for all predictive models' coefficients ranging from -0.309 (prediction probability was inverse to observed proportion) to 0.823. Predictive models which include baseline symptoms as a feature produced the highest discrimination. Two models produced a predicted probability of 0 and 1 for all patients.
CONCLUSIONS: Predictive models vary in performance and transferability illustrating the need for improvements in model development and reporting. Several models showed reasonable potential but efforts should be increased to improve performance. Baseline symptoms should always be considered as potential features for predictive models.