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Monti G.,University of Modena and Reggio Emilia | Monti G.,Neurology Unit | Tondelli M.,University of Modena and Reggio Emilia | Tondelli M.,Neurology Unit | And 9 more authors.
Epilepsy and Behavior

Tau protein is a phosphorylated microtubule-associated protein, principally localized at neuronal level in the central nervous system (CNS). Tau levels in the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal damage. To date, however, no study has specifically evaluated the CSF levels of tau proteins in patients with status epilepticus (SE). We evaluated these established biomarkers of neuronal damage in patients with SE who received a lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to acute structural brain damage, including CNS infection, were excluded. Clinical, biological, therapeutic, and follow-up data were collected. Group comparison between patients stratified according to SE response to antiepileptic drugs (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients were considered for the analyses (mean age 56years): 14 patients had abnormally high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only three patients had abnormally low Aβ1-42 level. Cerebrospinal fluid t-tau value was higher in patients who developed a refractory SE compared to patients with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively correlated with SE duration and were higher in patients treated with propofol anesthesia compared to patients that had not received this treatment. Patients with higher CSF t-tau had higher risk of developing disability (OR=32.5, p=0.004) and chronic epilepsy (OR=12; p=0.016) in comparison with patients with lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed as a biomarker of SE severity and prognosis. Prospective studies are needed to evaluate the effects of propofol on tau pathology in this setting.This article is part of a Special Issue entitled "Status Epilepticus". © 2015 Elsevier Inc. Source

Cariani E.,Clinical Pathology Toxicology | Missale G.,UO Infectious Diseases and Hepatology

Natural killer (NK) cells play a major role in antitumor immune responses. Recent results from our laboratory demonstrate the impact of the immunogenetic background on the activity of NK cells and hence on the outcome of hepatocellular carcinoma, disclosing perspectives for the development of NK-cell based therapies. © 2013 Landes Bioscience. Source

Bruno S.,A.O. Fatebenefratelli e Oftalmico | Thompson A.J.,University of Melbourne | Thompson A.J.,Duke University | Critelli R.,University of Modena and Reggio Emilia | And 9 more authors.
Antiviral Research

Background: Interferon Lambda-3 (IFN-λ3) gene polymorphism is associated with spontaneous clearance of hepatitis C virus (HCV) and response to IFN-based therapy (IFN). However, very few data are available about its value in predicting sustained virologic response (SVR) in patients with cirrhosis, and whether IFN-λ3 genotype influences liver disease progression remains unclear. Methods: We determined IFN-λ3 genotype by PCR in a cohort of patients with compensated HCV-related cirrhosis, enrolled between 1989 and 1992. Person-years follow-up was calculated for each individual from the date of enrolment to the development of first episode of decompensation, HCC, liver transplant, death or end of follow-up. The follow-up of patients who achieved SVR was censored at the time of IFN initiation. Kaplan-Meier curves and Cox regression analyses were used to assess the association between IFN-λ3 genotype and clinical outcome. Results: IFN-λ3 was determined in 264 patients (52% males, mean age 57 ± 8 years, 67% HCV genotype (G)1, while CC, CT and TT genotypes were 36%, 50% and 14%, respectively. During a median follow-up of 14.8 years, 149 (56%) patients received IFN. Overall, SVR was achieved in 31 (21%) patients, 40% among those with CC genotype (22% in G1 and 61% in G2, respectively) compared to 10% and 13% among patients with CT and TT genotypes (p < 0.0001). Univariate and multivariate analyses found no association between IFN-λ3 (CC vs. non-CC genotype) and disease progression. Conclusion: IFN-λ3 determination is fundamental for allocating cirrhotic patients to be treated with IFN, while it has no value in predicting the outcome of the disease. © 2014 Elsevier B.V. All rights reserved. Source

Vandelli L.,University of Modena and Reggio Emilia | Marietta M.,University of Modena and Reggio Emilia | Gambini M.,U.S. Environmental Protection Agency | Cavazzuti M.,University of Modena and Reggio Emilia | And 7 more authors.
Journal of Stroke and Cerebrovascular Diseases

Background Intravenous thrombolysis is an effective treatment in acute stroke patients, but it increases the risk of intracerebral hemorrhages. Our aim is to establish if fibrinogen depletion increases the risk of intracerebral hemorrhage after intravenous thrombolysis for acute ischemic stroke. Methods In 104 ischemic stroke patients, treated with intravenous thrombolysis, we assessed the rate of intracerebral hemorrhages documented by computed tomographic scan at 24 hours and within 7 days post-treatment. Fibrinogen levels were determined at 2 hours after therapy: patients were classified as belonging to "low fibrinogen group" if levels decreased to less than 2 g/L and/or by 25% or more. Fibrinogen levels and other known hemorrhagic risk factors were studied using univariate and multivariate analyses. Results During the first 7 days, an intracerebral hemorrhage was detected in 24 patients (23.1%), and only 6 of these (5.8%) experienced symptomatic bleeding; 41 patients were included in the low fibrinogen group. Among the 24 hemorrhages, 18 occurred in the low fibrinogen group and 6 in the "normal fibrinogen group": the bleeding rate in the low fibrinogen group was significantly higher (43.9%) than that in the normal fibrinogen group (9.5%; odds ratio [OR] 7.43, P <.001). Univariate and multivariate analyses revealed that only clinical severity (OR 1.15, P <.001) and hypofibrinogenemia (OR 7.47, P <.001) were significantly associated with brain bleeding at 7 days and at 24 hours (P =.008). Conclusions An early fibrinogen reduction seems to increase the risk of intracerebral hemorrhage after rtPA treatment in ischemic stroke. Fibrinogen assessment could be a rapid, inexpensive, and widely available tool to help the identification of patients at higher risk of bleeding. © 2015 National Stroke Association. Source

Pecoraro V.,Clinical Pathology Toxicology | Pecoraro V.,Mario Negri Institute for Pharmacological Research | Roli L.,Clinical Pathology Endocrinology | Plebani M.,University of Padua | Trenti T.,Clinical Pathology Toxicology
Clinical Chemistry and Laboratory Medicine

Background: Diagnostic studies usually provide important information about the analytical and diagnostic performances. We investigated the clinical utility of (-2)proPSA in identifying patients with prostate cancer (PCa). Methods: We performed electronic searches in five databases as well as a list of reference literature. Studies were included if they evaluated the diagnostic accuracy of (-2)proPSA in men with PSA value ranged from 2.0 to 10 μg/L. We also analyzed data about total PSA (tPSA), %(-2)proPSa, freePSA (fPSA), its percentage (%fPSA) and the prostate health index (phi). The selection of the studies, the screening of the full texts and the data extraction, as well as the assessment of risk of bias using the QUADAS-2 tool were conducted independently by two authors. Grading the quality of the evidence was carried out according to the GRADE method. The random effects model was used for the meta-analyses. Results: We included 17 studies, including 6912 patients. The pooled sensitivity of (-2)proPSA was 90% and the summary specificity was 13%. The tPSA sensitivity and specificity were 89% and 25%, respectively. Considering (-2)proPSA, 225 men out of 1000 have been identified having PCa true positives (TP). However, 652 persons have been incorrectly identified and undergo biopsy. The majority of studies were judged to carry a moderate risk of bias. Therefore, the overall quality of evidences was deemed to be low. Conclusions: The (-2)proPSA could be useful to identify men at risk of PCa, but its accuracy still remains uncertain and the level of evidence does not support an improved clinical utility. © 2016 by De Gruyter 2016. Source

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