BACKGROUND It remains uncertain whether the drip‐and‐ship (DS) strategy (transport to the nearest primary stroke centers) or the mothership (MS) model (direct transportation to the comprehensive stroke center) is the organizational stroke model associated with the best functional outcome in acute stroke patients with large vessel occlusion. In this study, we compared the periprocedural complications and outcomes at 90 days of acute stroke patients with large vessel occlusion of the anterior circulation directly admitted to our comprehensive stroke center compared to those referred from primary stroke centers treated with mechanical thrombectomy. METHODS This is a single‐center prospective observational study where patients with DS and MS were compared regarding the disability at 90 days, as assessed by applying the modified Rankin scale, the rate of successful reperfusion, and the rate of immediate complications postprocedure. RESULTS Of 579 patients, 216 (37.30%) were MS, and 363 (62.7%) were DS. There was no difference regarding the modified Rankin scale at 3 months between the MS (36.4%) and DS (39.3%) groups of patients treated with mechanical thrombectomy ( P =0.362). There was no significant difference regarding the National Institutes of Health Stroke Scale at 24 hours, mortality at 90 days, and rate of successful recanalization postprocedure between the 2 groups. DS was associated with an increased risk of hemorrhagic transformation and symptomatic intracranial hemorrhage (odds ratio, 5.414 [95% CI, 1.572–18.644]; P =0.007). CONCLUSION Our single‐center study showed no difference in terms of functional independence between the DS and MS organizational paradigm. DS was associated with an increased risk of hemorrhagic transformation and symptomatic intracranial hemorrhage.
Background and purpose. Mechanical thrombectomy (MT) is the standard of care for eligible patients with a large vessel occlusion (LVO) acute ischemic stroke. Among patients undergoing MT there has been uncertainty regarding the role of intravenous thrombolysis (IVT) and previous trials have yielded conflicting results regarding clinical outcomes. We aim to investigate clinical, reperfusion outcomes and safety of MT with or without IVT for ischemic stroke due to anterior circulation LVO. Materials and Methods. This observational, prospective, single-centre study included consecutive patients with acute LVO ischemic stroke of the anterior circulation. The primary outcomes were the rate of in-hospital mortality, symptomatic intracranial haemorrhage and functional independence (mRS 0–2 at 90 days). Results. We enrolled a total of 577 consecutive patients: 161 (27.9%) were treated with MT alone while 416 (72.1%) underwent IVT and MT. Patients with MT who were treated with IVT had lower rates of in-hospital mortality (p = 0.037), higher TICI reperfusion grades (p = 0.007), similar rates of symptomatic intracranial haemorrhage (p = 0.317) and a higher percentage of functional independence mRS (0–2) at 90 days (p = 0.022). Bridging IVT with MT compared to MT alone was independently associated with a favorable post-intervention TICI score (>2b) (OR, 1.716; 95% CI, 1.076–2.735, p = 0.023). Conclusions. Our findings suggest that combined treatment with MT and IVT is safe and results in increased reperfusion rates as compared to MT alone.
Background The evidence for mechanical thrombectomy in acute basilar artery occlusion has until now remained inconclusive with basilar artery strokes associated with high rates of death and disability. This systematic review and meta-analysis will summarize the available evidence for the effectiveness of mechanical thrombectomy in acute basilar artery occlusion compared to best medical therapy. Methods A systematic review and meta-analysis was performed and presented in conformity with the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) to test the primary hypothesis that mechanical thrombectomy for basilar artery occlusion is associated with a different rate of good neurological outcome (modified Rankin Scale (mRS) ≤ 3) at day 90. Secondary outcomes included mortality, symptomatic intracranial hemorrhage (sICH) and excellent functional outcome (mRS ≤ 2). We calculated risk ratios (RRs) and 95% confidence intervals (CIs) to summarize the effect estimates for each outcome. Results We performed a random effects (Mantel-Haenszel) meta-analysis of the four included randomized controlled trials comprising a total of 988 participants. We found a statistically significant improvement in the rates of those with a good functional outcome (mRS 0–3, RR 1.54, 1.16–2.06, p = 0.003) and an excellent functional outcome (mRS 0–2, RR 1.69, 1.05–2.71, p = 0.03) in those who were treated with thrombectomy when compared to best medical therapy alone. Thrombectomy was associated with a higher level of sICH (RR 7.12, 2.16–23.54, p = 0.001) but this was not reflected in a higher mortality rate, conversely the mortality rate was significantly lower in the intervention group (RR 0.76, 0.65–0.89, p = 0.0004). Conclusions Our meta-analysis of the recently presented randomized controlled studies is the first to confirm the disability and mortality benefit of mechanical thrombectomy in basilar artery stroke.
Aims Hippo signalling is an evolutionarily conserved pathway that controls organ size by regulating apoptosis, cell proliferation, and stem cell self‐renewal. Recently, the pathway has been shown to exert powerful growth regulatory activity in cardiomyocytes. However, the functional role of this stress‐related and cell death‐related pathway in the human heart and cardiomyocytes is not known. In this study, we investigated the role of the transcriptional co‐activators of Hippo signalling, YAP and TAZ, in human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) in response to cardiotoxic agents and investigated the effects of modulating the pathway on cardiomyocyte function and survival. Methods and results RNA‐sequencing analysis of human heart samples with doxorubicin‐induced end‐stage heart failure and healthy controls showed that YAP and ERBB2 (HER2) as upstream regulators of differentially expressed genes correlated with doxorubicin treatment. Thus, we tested the effects of doxorubicin on hiPSC‐CMs in vitro. Using an automated high‐content screen of 96 clinically relevant antineoplastic and cardiotherapeutic drugs, we showed that doxorubicin induced the highest activation of YAP/TAZ nuclear translocation in both hiPSC‐CMs and control MCF7 breast cancer cells. The overexpression of YAP rescued doxorubicin‐induced cell loss in hiPSC‐CMs by inhibiting apoptosis and inducing proliferation. In contrast, silencing of YAP and TAZ by siRNAs resulted in elevated mitochondrial membrane potential loss in response to doxorubicin. hiPSC‐CM calcium transients did not change in response to YAP/TAZ silencing. Conclusions Our results suggest that Hippo signalling is involved in clinical anthracycline‐induced cardiomyopathy. Modelling with hiPSC‐CMs in vitro showed similar responses to doxorubicin as adult cardiomyocytes and revealed a potential cardioprotective effect of YAP in doxorubicin‐induced cardiotoxicity.
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