Clinical pregenetic screening for stroke monogenic diseases: Results from lombardia GENS registry

BACKGROUND AND PURPOSE: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease METHODS: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis. RESULTS: In 209 patients (57.4\ub114.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. CONCLUSIONS: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series

Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study.

74sinonenonePaciaroni M; Inzitari D; Agnelli G; Caso V; Balucani C; Grotta JC; Sarraj A; Sung-Il S; Chamorro A; Urra X; Leys D; Henon H; Cordonnier C; Dequatre N; Aguettaz P; Alberti A; Venti M; Acciarresi M; D'Amore C; Zini A; Vallone S; Dell'Acqua ML; Menetti F; Nencini P; Mangiafico S; Barlinn K; Kepplinger J; Bodechtel U; Gerber J; Bovi P; Cappellari M; Linfante I; Dabus G; Marcheselli S; Pezzini A; Padovani A; Alexandrov AV; Shahripour RB; Sessa M; Giacalone G; Silvestrelli G; Lanari A; Ciccone A; De Vito A; Azzini C; Saletti A; Fainardi E; Orlandi G; Chiti A; Gialdini G; Silvestrini M; Ferrarese C; Beretta S; Tassi R; Martini G; Tsivgoulis G; Vasdekis SN; Consoli D; Baldi A; D'Anna S; Luda E; Varbella F; Galletti G; Invernizzi P; Donati E; De Lodovici ML; Bono G; Corea F; Sette MD; Monaco S; Riva M; Tassinari T; Scoditti U; Toni D.Paciaroni, M; Inzitari, D; Agnelli, G; Caso, V; Balucani, C; Grotta, Jc; Sarraj, A; Sung Il, S; Chamorro, A; Urra, X; Leys, D; Henon, H; Cordonnier, C; Dequatre, N; Aguettaz, P; Alberti, A; Venti, M; Acciarresi, M; D'Amore, C; Zini, A; Vallone, S; Dell'Acqua, Ml; Menetti, F; Nencini, P; Mangiafico, S; Barlinn, K; Kepplinger, J; Bodechtel, U; Gerber, J; Bovi, P; Cappellari, M; Linfante, I; Dabus, G; Marcheselli, S; Pezzini, Alessandro; Padovani, Alessandro; Alexandrov, Av; Shahripour, Rb; Sessa, M; Giacalone, G; Silvestrelli, G; Lanari, A; Ciccone, A; De Vito, A; Azzini, C; Saletti, A; Fainardi, E; Orlandi, G; Chiti, A; Gialdini, G; Silvestrini, M; Ferrarese, C; Beretta, S; Tassi, R; Martini, G; Tsivgoulis, G; Vasdekis, Sn; Consoli, D; Baldi, A; D'Anna, S; Luda, E; Varbella, F; Galletti, G; Invernizzi, P; Donati, E; De Lodovici, Ml; Bono, G; Corea, F; Sette, Md; Monaco, S; Riva, M; Tassinari, T; Scoditti, U; Toni, D

Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study.

The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0-2) or unfavourable (score of 3-6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88-1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40-0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5-6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86-1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 %) (adjusted OR 1.75, 95 % CI 1.00-3.03, p = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed

Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancer: a HuGE-GSEC review

The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html ). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9-3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9-1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4-2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3-3.1; ORm1m2 or [infi]m2m2: 1.3, 95% confidence interval: 1.1-1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1-4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer