Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Mental substitution investigation test

[No abstract available

Efficacy of idelalisib and rituximab in relapsed/refractory chronic lymphocytic leukemia treated outside of clinical trials. A report of the Gimema Working Group

48nononeBecause the efficacy of new drugs reported in trials may not translate into similar results when used in the real-life, we analyzed the efficacy of idelalisib and rituximab (IR) in 149 patients with relapsed/refractory chronic lymphocytic leukemia treated at 34 GIMEMA centers. Median progression-free survival (PFS) and overall survival were 22.9 and 44.5 months, respectively; performance status (PS) ≥2 and ≥3 previous lines of therapy were associated with shorter PFS and overall survival (OS). 48% of patients were on treatment at 12 months; the experience of the centers (≥5 treated patients) and PS 0–1 were associated with a significantly longer treatment duration (p = 0.015 and p = 0.002, respectively). TP53 disruption had no prognostic significance. The overall response rate to subsequent treatment was 49.2%, with median OS of 15.5 months and not reached in patients who discontinued, respectively, for progression and for toxicity (p < 0.01). Treatment breaks ≥14 days were recorded in 96% of patients and adverse events mirrored those reported in trials. In conclusion, this real-life analysis showed that IR treatment duration was longer at experienced centers, that the ECOG PS and ≥3 lines of previous therapy are strong prognostic factor and that the overall outcome with this regimen was superimposable to that reported in a randomized trial.noneRigolin G.M.; Cavazzini F.; Piciocchi A.; Arena V.; Visentin A.; Reda G.; Zamprogna G.; Cibien F.; Vitagliano O.; Coscia M.; Farina L.; Gaidano G.; Murru R.; Varettoni M.; Paolini R.; Sportoletti P.; Pietrasanta D.; Molinari A.L.; Quaglia F.M.; Laurenti L.; Marasca R.; Marchetti M.; Mauro F.R.; Crea E.; Vignetti M.; Gentile M.; Montillo M.; Foa R.; Cuneo A.; Chiarenza A.; Perbellini O.; Mannina D.; Sancetta R.; Olivieri A.; Molica S.; Pane F.; Patti C.; Iliariucci F.; Gozzetti A.; Califano C.; Galieni P.; Augello A.F.; Vallisa D.; Cura F.; Frustaci A.M.; Fazi P.; Trentin L.; Ferrara F.Rigolin, G. M.; Cavazzini, F.; Piciocchi, A.; Arena, V.; Visentin, A.; Reda, G.; Zamprogna, G.; Cibien, F.; Vitagliano, O.; Coscia, M.; Farina, L.; Gaidano, G.; Murru, R.; Varettoni, M.; Paolini, R.; Sportoletti, P.; Pietrasanta, D.; Molinari, A. L.; Quaglia, F. M.; Laurenti, L.; Marasca, R.; Marchetti, M.; Mauro, F. R.; Crea, E.; Vignetti, M.; Gentile, M.; Montillo, M.; Foa, R.; Cuneo, A.; Chiarenza, A.; Perbellini, O.; Mannina, D.; Sancetta, R.; Olivieri, A.; Molica, S.; Pane, F.; Patti, C.; Iliariucci, F.; Gozzetti, A.; Califano, C.; Galieni, P.; Augello, A. F.; Vallisa, D.; Cura, F.; Frustaci, A. M.; Fazi, P.; Trentin, L.; Ferrara, F