Significance of aphasia after first-ever acute stroke: Impact on early and late outcomes

Background: We assessed the incidence and determinants of aphasia attributable to first-ever acute stroke. We also investigated early and long-term mortality and 1-year dependence in post-stroke patients. Methods: A 10-year prospective hospital-based study was conducted in the prefecture of Athens, Greece. Results: In total, 2,297 patients were included in the study, of whom 806 (35.1%) had aphasia. The presence of aphasia was independently associated with increasing age (OR: 1.19 per 10-year increase, 95% CI: 1.12-1.21) and atrial fibrillation (OR: 1.35, 95% CI: 1.08-1.67), and inversely associated with Scandinavian Stroke Scale (SSS) score (OR: 0.55 per 10-point increase, 95% CI: 0.52-0.59) and hypertension (OR: 0.77, 95% CI: 0.63-0.96). One-year dependence score (calculated with the modified Rankin score) was higher in aphasic patients compared to non-aphasics (p < 0.001). Moreover, severity of aphasia (estimated with a subscale of SSS) was found as an independent predictor of 1-year dependence. Most of the deaths in the aphasic patients were attributed to infections and neurological damage. Using the Kaplan-Meier limit method, the unadjusted probability of 10-year mortality was demonstrated to increase with the severity of aphasia (log-rank test: 233.9, p < 0.001) and, even after adjustment for several other factors, severity of aphasia remained an independent predictor of 10-year mortality. Conclusions: Increasing age, atrial fibrillation and severity of stroke were associated with the risk of aphasia after stroke. Severity of aphasia is a strong predictor of long-term mortality and dependence of post-stroke patients. Copyright © 2009 S. Karger AG

In Vitro and in Vivo Preclinical Effects of Type i IFNs on Gliomas

The interferons (IFNs) are a family of cytokines with diverse cellular actions such as control of cell proliferation and regulation of immune responses; therefore, they have been extensively studied as antitumor agents for a variety of malignancies, including gliomas. Type I IFNs exert their antitumor effects either directly, by targeting the tumor cells or the tumor stem cells, or indirectly, by regulating the anticancer activities of the immune system. More specifically, IFN-beta and IFN-alpha exhibit antiproliferative effects by p53 induction, CD8+ T-lymphocyte and macrophage activation, chemokine secretion, and miR-21 downregulation. In vitro and in vivo studies provide evidence that immunotherapy could have a role in glioma treatment, especially when first-line therapeutic interventions fail to produce durable responses. These effects are more obvious when combining IFN-beta with classical antitumor therapies such as temozolamide, an oral chemotherapeutic, for both newly diagnosed and recurrent gliomas. However, further clinical studies are needed to determine whether IFNs will have a definite place in the management of gliomas. © Copyright Mary Ann Liebert, Inc. 2017

Type 1 blue copper protein amicyanin from Thiobacillus versutus: line-broadening effects of chromium(III) complexes and related studies

The effect of redox-inactive cationic and anionic paramagnetic chromium(III) complexes on the H-1 NMR spectrum of the reduced type 1 blue copper protein amicyanin, AmCu1, from Thiobacillus versutus has been studied as a means of defining sites for association at the protein surface. With [Cr(CN)(6)](3-) two sites are detected, one at the adjacent hydrophobic patch close to the exposed imidazole of the co-ordinated His-96, and the other at Phe-92 which has Lys-59, Lys-60, Arg-69 and Arg-100 in close proximity and is adjacent to the active site-co-ordinated Cys-93. In contrast, the cationic complexes [Cr(NH3)(6)](3+) and [Cr(en)(3)](3+) (en = ethane-2,2-diamine) cause no significant line broadening and no preferred sites for association are detected. Kinetic stopped-flow studies on the competitive inhibition by [Cr(CN)(6)](3-) of the [Fe(CN)(6)](3-) oxidation of AmCu1 indicate that [Fe(CN)(6)](3-) reacts at two sites, one of which is inhibited by [Cr(CN)(6)](3-) and the other is unaffected by [Cr(CN)(6)](3-). It is suggested that the first of these corresponds to reaction at the Phe-92 site, contributing 25% to the reaction, and the second to reaction at His-96. Therefore, in its reaction with [Fe(CN)(6)](3-) amicyanin has adjacent and remote binding sites.Macromolecular Biochemistr

Complex atheromatous plaques in the descending aorta and the risk of stroke: A systematic review and meta-analysis

Background and Purpose: Proximal aortic plaques, especially in the aortic arch, have already been established as an important cause of stroke and peripheral embolism. However, aortic plaques situated in the descending thoracic aorta have recently been postulated as a potential embolic source in patients with cryptogenic cerebral infarction through retrograde aortic flow. The aim of the present study was to evaluate the potential association of descending aorta atheromatosis with cerebral ischemia. METHODS-: We conducted a systematic review and meta-analysis of all available prospective observational studies reporting the prevalence of complex atheromatous plaques in the descending aorta in patients with stroke and in unselected populations undergoing examination with transesophageal echocardiography. RESULTS-: We identified 11 eligible studies including a total of 4000 patients (667 patients with stroke and 3333 unselected individuals; mean age, 65 years; 55% men). On baseline transesophageal echocardiograpic examination, the prevalence of complex atheromatous plaques in the descending aorta was higher (P=0.001) in patients with stroke (25.4%; 95% confidence interval, 14.6-40.4%) compared with unselected individuals (6.1%; 95% confidence interval, 3.4-10%). However, no significant difference (P=0.059) in the prevalence of complex atheromatous plaques in the descending aorta was found between patients with cryptogenic (21.8%; 95% confidence interval, 17.5-26.9%) and unclassified (28.3%; 95% confidence interval, 23.9-33.1%) cerebral infarction. CONCLUSIONS-: Our findings indicate that the presence of complex plaques in the descending aorta is presumably a marker of generalized atherosclerosis and high vascular risk. The present analyses do not provide any further evidence for a direct causal relationship between descending aorta atherosclerosis and cerebral embolism. © 2014 American Heart Association, Inc

Cerebral arterial infarction in inflammatory bowel diseases

It has been estimated that up to 10% of hypercoagulable state manifestations in patients with inflammatory bowel disease (IBD) are ischemic strokes. The literature search through MEDLINE and EMBASE highlighted 33 case reports of IBD patients complicated with cerebral arterial infarction during the course of their disease. Most of these patients presented with either left or right sided hemiparesis on admission, while the most common site of arterial infarction was either the right or the left middle cerebral artery. Thrombocytosis and anemia were the most commonly observed potential risk factors for stroke in the laboratory analysis. Other coagulation abnormalities, hereditary thrombotic mutations, hyperhomocysteinemia, hyperlipidemia, structural cardiac abnormalities, endocarditis and cerebral artery vasculitis have also been reported in some of the cases that were reviewed. Even though many of these findings are commonly observed in IBD patients, literature data is still controversial about their causal relationship to ischemic stroke. Similarly, there is also lack of steady evidence and official guidelines for stroke management in both children and adults with IBD comorbidity. Finally, an algorithm based on both the American Heart Association and European Stroke Organization guidelines for stroke management and prevention in the general population, is presented as a reference point for the treatment of IBD patients who are complicated by an ischemic cerebral event. © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved

Multiple sclerosis and inflammatory bowel diseases: a systematic review and meta-analysis

The association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) has been suggested, apart from their common epidemiological and immunological patterns, also due to observations of increased incidence of both IBD among MS patients and MS among IBD patients. We estimated the risk of concurrent IBD and MS comorbidity, using data from all available case–control studies. We calculated the corresponding Risk ratios (RRs) in each included case–control study to express the risk of IBD and MS concurrence at a given population. We performed additional subgroup analyses according to the type of registry from which the data of the cases were exported (IBD or MS registry) and the IBD type (Crohn’s disease, CD or Ulcerative colitis, UC). We included 10 studies, comprising a total of 1,086,430 patients (0.08% of them with concurrent IBD and MS). Pooled RR for IBD/MS comorbitity was 1.54 (95% CI 1.40–1.67; p < 0.0001) with no differences (p = 0.91) among IBD and MS registries (RR 1.53, 95% CI 1.36–1.72, p < 0.001 for MS comorbidity in IBD patients vs. RR 1.55, 95% CI 1.32–1.81, p < 0.001 for IBD comorbidity in MS patients). No difference was also found on the risk of MS comorbidity among patients with CD or UC (RR 1.52, 95% CI 1.34–1.72, p < 0.001 vs. RR 1.55, 95% CI 1.38–1.74, p < 0.001; p for subgroup differences: 0.84). In all analyses no evidence of heterogeneity or publication bias was detected. Both IBD and MS patients seem to have a fifty-percent increased risk of MS or IBD comorbidity, respectively, with no apparent differences between patients with CD or UC. © 2016, Springer-Verlag Berlin Heidelberg

Brand-to-generic levetiracetam switch in patients with epilepsy in a routine clinical setting

Purpose The therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution. Methods A prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4 ± 16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded. Results Patients had epilepsy for a mean period of 14.1 ± 10.6 years and the mean daily LEV dose was 2583.3 ± 763.7 mg. The mean AUC ± SD and Cmax ± SD was 288.4 ± 86.3 (mg/L) h and 37.8 ± 10.4 mg/L respectively for brand LEV and 319.2 ± 104.7 (mg/L) h and 41.6 ± 12.3 mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded. Conclusions In our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV. © 2017 British Epilepsy Associatio

Association of TNF-857C>T, TNFRSF1A36A>G, and TNFRSF1B676T>G polymorphisms with ischemic stroke in a greek population

Background: The role of genetic factors in the predisposition to develop ischemic stroke has been assessed by previous studies. The main goal of the current study was to determine any possible role of TNF-857C>T, TNFRSF1A36A>G, and TNFRSF1B676T>G polymorphisms in risk for stroke. Materials and Methods. One hundred seventy-three patients with first ever ischemic stroke of solely atherosclerotic etiology in Northwest Greece and a control group of 179 healthy unrelated subjects were evaluated. Results. TNF-857TT, TNFR136AA, and TNFR2676TT genotypes were significantly increased in the patient group compared to controls (P =.008, OR = 2.47 (1.26-4.84), P =.005, OR = 1.97 (1.22-3.17), and P =.003, OR = 2.2 (1.43-3.37), resp.). In addition, the TNFR136A and the TNFR2676T alleles were found significantly increased in patients compared to controls (P =.009, OR = 1.48 (1.12) and P =.001, OR = 1.75 (1.25-2.46), resp.). Conclusion. The high incidence of these genotypes and alleles in patient group suggests that they are potentially predisposing factors for stroke in the Greek population studied. Large-scale multicenter controlled studies are needed to verify these polymorphisms effects on stroke susceptibility. Copyright © 2011 Sofia Markoula et al

Associations of ESR2 AluI (G/A) polymorphism with ischemic stroke in Caucasians

Raising interest towards genes implicates the effect of estrogen receptor-alpha (ESR1) gene on cerebrovascular disease, but data are lacking regarding the effect of estrogen receptor-beta (ESR2) gene. We assessed the hypothesis that AluI (G/A) polymorphism of the ESR2 gene (rs 4986938) is associated with ischemic stroke in a Caucasian population. Four hundred twenty four consecutive stroke patients and 430 age and gender-matched controls were enrolled in three stroke centers in Greece over one-year period. Patients and controls were compared in regard to the prevalence of the aforementioned polymorphism. No association was found between variations in the ESR2 gene and risk of stroke or stroke subtype in men and women. Of note, a gender-specific association of G allele with the onset of stroke at a younger age in male patients was found (63.68 ± 12.687 years in G allele (GG + AG) carriers vs. 68.95 ± 10.757 years in non-carriers (AA), p = 0.008). Further population independent studies are needed to establish the role of ESR2 gene polymorphisms in relation to ischemic stroke in both genders. Such studies could lead to ERβ agonists being validated in individuals with certain genotypes and/or alleles towards the development of efficient strategies to preventing ischemic stroke in both men and women. © 2012 Elsevier B.V. All rights reserved