Prevalence and predictors of atrial fibrillation in patients with embolic stroke of undetermined source: a real-life single-center retrospective study.

INTRODUCTION: Up to one-third of ischemic strokes remained cryptogenic despite extensive investigations. Atrial fibrillation may be detected in a significant proportion of patients with embolic stroke of undetermined source, particularly after the introduction of implantable loop recorder in clinical practice. METHODS: We retrospectively included all the consecutive patients with embolic stroke of undetermined source referred to our units in the period November 2013 to December 2018 and in which an implantable loop recorder was positioned within 6 months from stroke event. Prevalence and predictors of atrial fibrillation were investigated. RESULTS: One hundred thirty-eight patients with embolic stroke of undetermined source fulfilling inclusion criteria were identified. The crude prevalence of atrial fibrillation at the end of observation period was of 45.7%. Incidence rates at 6, 12, 18, 24, and 36 months resulted, respectively, 31.8% (95% CI, 30.4-46.7), 38.0% (95% CI, 30.4-46.9), 42.6% (95% CI, 34.5-51.6), 46.6% (95% CI, 38.2-55.8), and 50.4% (95% CI, 41.6-59.9). On multivariate analysis, only excessive supraventricular electric activity and left atrial enlargement resulted to be significant predictors of atrial fibrillation (p = 0.037 and p < 0.0001, respectively). CONCLUSIONS: Atrial fibrillation may be detected in a relevant proportion (up to 50%) of patients with embolic stroke of undetermined source if a careful and extensive diagnostic work-up is employed. Excessive supraventricular electric activity and left atrial enlargement are significant predictors of the occurrence of atrial fibrillation in these patients.

Chronic cerebrospinal venous insufficiency is not associated with chronic venous disorders: A case-control study.

OBJECTIVES: To evaluate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and the presence of a Chronic Venous Disorder (CVD). METHOD: We included 55 subjects with CCSVI aged >18 years, and 186 controls without CCSVI. Each subject was evaluated with color Doppler sonography in accordance with Zamboni's five criteria, examined by two neurologists and interviewed with an ad-hoc designed form. The neurologists and the sonographers were mutually blinded. CVD were classified according to CEAP. RESULTS: Mean age was 42 years (SD = 9) in cases and 43 years (10) in controls (p = ns). The odds ratios in subjects CCSVI were 0.6 (0.2-2.2) for CEAP 1, 0.9 (0.2-4.5) for CEAP 2, and 1.0 (0.6-1.9) for family history of varicose veins. The prevalence of CVD and, family history of varicose veins, was similar between cases and controls for each Zamboni criterion. CONCLUSIONS: We found no association of CCSVI with the presence of CVD or family history of varicose veins.

Chronic cerebrospinal venous insufficiency in multiple sclerosis: a sonographer-blinded case-control study.

OBJECTIVES: To evaluate the presence of chronic cerebrospinal venous insufficiency (CCSVI) and cerebral venous anomalies in a consecutive series of patients with multiple sclerosis (MS), other neurologic diseases (NEU) and healthy controls (HC). METHODS: A consecutive series of 80 MS patients, 41 HC and 26 NEU cases underwent a transcranial and extracranial echo-color Doppler (ECD) evaluation of cerebrospinal venous return in a sonographer-blinded fashion. According to the original Dr. Zamboni's protocol, CCSVI was diagnosed in presence of ≥2 ECD venous criteria. RESULTS: We did not observe any association between CCSVI and MS. CCSVI was detected in 17.5% of MS cases, 7.3% of HC and 11.5% of NEU patients (p=0.333). The prevalence of internal jugular vein stenosis (IJV) and the proportion of patients with any positive ECD criterion differed significantly among groups, being higher in MS cases versus HC (67.5% and 76.2% versus 48.8% and 41.5%, respectively; p=0.005 and p=0.006). No relationship between CCSVI and MS type and severity was evidenced. CONCLUSIONS: The present study argues against a positive link between CCSVI and MS risk or severity. Interestingly, a weak association between venous ECD anomalies (in particular IJV stenosis) and MS was observed in our population. This finding should be interpreted with caution due to the possible confounders and needs to be confirmed in large controlled studies.

Intracellular accumulation and cytotoxicity of doxorubicin with different pharmaceutical formulations in human cancer cell lines.

The structure of both carrier and anticancer drug affects the intracellular fate of a transported drug. The study investigated in vitro intracellular accumulation and cytotoxic activity of doxorubicin-loaded solid lipid nanoparticles (SLN), doxorubicin in pegylated liposomes (Caelyx) and free doxorubicin. Intracellular doxorubicin levels and cytotoxic activity were determined by high performance liquid chromatography with fluorescence detection, and by the trypan blue dye exclusion assay, respectively. Doxorubicin-loaded SLN inhibited cell growth more strongly than either free or liposomal doxorubicin, in human colorectal adenocarcinoma, HT-29, retinoblastoma Y79, and glioblastoma U373 cell lines. The IC50 values for doxorubicin-loaded SLN were significantly lower after 24 h exposure than those for free doxorubicin in all cell lines; after 48 h exposure they were lower than those for liposomal doxorubicin in HT-29 and Y79 cells. The enhanced cytotoxic activity of doxorubicin-loaded SLN was associated with increased drug incorporation in cells: intracellular doxorubicin levels were significantly enhanced after exposure to drug-loaded SLN versus either free or liposomal drug. Rate of intracellular accumulation and cytotoxic activity also differed among different cell lines; in particular, cells of epithelial origin were found to be more sensitive to doxorubicin-loaded SLN. In conclusion, the greater sensitivity of HT-29, Y79, and U373 cells to doxorubicin-loaded SLN than to the other drug formulations may be due to the capability of the delivery system to enhance drug action, through a marked uptake and accumulation of SLN within the cell.

Molecular genetic changes in a series of neuroepithelial tumors of childhood.

Amplification of the EGFR, mdm2, CDK4 and PDGFR A genes has been widely demonstrated in adult malignant gliomas, almost exclusively glioblastomas. To determine the role of these mutational events in pediatric astrocytic gliomas we investigated the presence of EGFR, mdm2, CDK4 and PDGFR A gene amplification in 38 childhood brain tumor biopsies, including 24 low-grade astrocytomas and 14 malignant tumors. We used differential PCR assay on DNA extracted either from paraffin embedded or frozen tissues. EGFR gene amplification was detected in 4 out of 14 malignant tumors; no low-grade astrocytoma showed amplification. Tumors with EGFR gene amplification were negative for the presence of p53 mutations, as observed in a previous study. One glioblastoma showed PDGFR A amplification, while no amplifications were observed for mdm2 and CDK4 genes. These data are in line with those obtained from studies on gliomas of adults and suggest the existence of two different subsets of malignant gliomas also in pediatric brain tumors: one carrying EGFR gene amplification, the other showing p53 mutations.