Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke

BACKGROUND: There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes. AIMS: We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications. METHODS: From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected. RESULTS: The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p < 0.01; OR 1.82, 95% CI: 1.21-2.73) and large vessel occlusion site (carotid-T, p < 0.03; OR 3.05, 95% CI: 1.13-8.19; M2-segment-MCA, p < 0.01; OR 4.54, 95% CI: 1.66-12.44) were associated with a higher risk of subarachnoid hemorrhage/arterial perforation. Thrombectomy alone (p < 0.01; OR 0.50, 95% CI: 0.31-0.83) and younger age (p < 0.04; OR 0.98, 95% CI: 0.97-0.99) revealed a lower risk of developing dissection. M2-segment-MCA occlusion (p < 0.01; OR 0.35, 95% CI: 0.19-0.64) and hypertension (p < 0.04; OR 0.77, 95% CI: 0.6-0.98) were less related to clot embolization. Higher NIHSS at onset (p < 0.01; OR 1.04, 95% CI: 1.02-1.06), longer groin-to-reperfusion time (p < 0.01; OR 1.05, 95% CI: 1.02-1.07), diabetes (p < 0.01; OR 1.67, 95% CI: 1.25-2.23), and LVO site (carotid-T, p < 0.01; OR 1.96, 95% CI: 1.26-3.05; M2-segment-MCA, p < 0.02; OR 1.62, 95% CI: 1.08-2.42) were associated with a higher risk of developing symptomatic intracerebral hemorrhage compared to no/asymptomatic intracerebral hemorrhage. The subgroup of patients treated with thrombectomy alone presented a lower risk of symptomatic intracerebral hemorrhage (p < 0.01; OR 0.70; 95% CI: 0.55-0.90). Subarachnoid hemorrhage/arterial perforation and symptomatic intracerebral hemorrhage after endovascular thrombectomy worsen both functional independence and mortality at three-month follow-up (p < 0.01). Distal embolization is associated with neurological deterioration (p < 0.01), while arterial dissection did not affect clinical outcome at follow-up. CONCLUSIONS: Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits

A tablet app for handwriting skill screening at the preliteracy stage: Instrument validation study

Background: Difficulties in handwriting, such as dysgraphia, impact several aspects of a child\u2019s everyday life. Current methodologies for the detection of such difficulties in children have the following three main weaknesses: (1) they are prone to subjective evaluation; (2) they can be administered only when handwriting is mastered, thus delaying the diagnosis and the possible adoption of countermeasures; and (3) they are not always easily accessible to the entire community. Objective: This work aims at developing a solution able to: (1) quantitatively measure handwriting features whose alteration is typically seen in children with dysgraphia; (2) enable their study in a preliteracy population; and (3) leverage a standard consumer technology to increase the accessibility of both early screening and longitudinal monitoring of handwriting difficulties. Methods: We designed and developed a novel tablet-based app Play Draw Write to assess potential markers of dysgraphia through the quantification of the following three key handwriting laws: isochrony, homothety, and speed-accuracy tradeoff. To extend such an approach to a preliteracy age, the app includes the study of the laws in terms of both word writing and symbol drawing. The app was tested among healthy children with mastered handwriting (third graders) and those at a preliterate age (kindergartners). Results: App testing in 15 primary school children confirmed that the three laws hold on the tablet surface when both writing words and drawing symbols. We found significant speed modulation according to size (P&lt;.001), no relevant changes to fraction time for 67 out of 70 comparisons, and significant regression between movement time and index of difficulty for 44 out of 45 comparisons (P&lt;.05, R2&gt;0.28, 12 degrees of freedom). Importantly, the three laws were verified on symbols among 19 kindergartners. Results from the speed-accuracy exercise showed a significant evolution with age of the global movement time (circle: P=.003, square: P&lt;.001, word: P=.001), the goodness of fit of the regression between movement time and accuracy constraints (square: P&lt;.001, circle: P=.02), and the index of performance (square: P&lt;.001). Our findings show that homothety, isochrony, and speed-accuracy tradeoff principles are present in children even before handwriting acquisition; however, some handwriting-related skills are partially refined with age. Conclusions: The designed app represents a promising solution for the screening of handwriting difficulties, since it allows (1) anticipation of the detection of alteration of handwriting principles at a preliteracy age and (2) provision of broader access to the monitoring of handwriting principles. Such a solution potentially enables the selective strengthening of lacking abilities before they exacerbate and affect the child\u2019s whole life

Functionally defined therapeutic targets in diffuse intrinsic pontine glioma

Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNAseq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated efficacy in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat with histone demethylase inhibitor GSKJ4 revealed synergy. Together, these data suggest a promising therapeutic strategy for DIPG

Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke

Background: There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes. Aims: We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications. Methods: From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected. Results: The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p &lt; 0.01; OR 1.82, 95% CI: 1.21–2.73) and large vessel occlusion site (carotid-T, p &lt; 0.03; OR 3.05, 95% CI: 1.13–8.19; M2-segment-MCA, p &lt; 0.01; OR 4.54, 95% CI: 1.66–12.44) were associated with a higher risk of subarachnoid hemorrhage/arterial perforation. Thrombectomy alone (p &lt; 0.01; OR 0.50, 95% CI: 0.31–0.83) and younger age (p &lt; 0.04; OR 0.98, 95% CI: 0.97–0.99) revealed a lower risk of developing dissection. M2-segment-MCA occlusion (p &lt; 0.01; OR 0.35, 95% CI: 0.19–0.64) and hypertension (p &lt; 0.04; OR 0.77, 95% CI: 0.6–0.98) were less related to clot embolization. Higher NIHSS at onset (p &lt; 0.01; OR 1.04, 95% CI: 1.02–1.06), longer groin-to-reperfusion time (p &lt; 0.01; OR 1.05, 95% CI: 1.02–1.07), diabetes (p &lt; 0.01; OR 1.67, 95% CI: 1.25–2.23), and LVO site (carotid-T, p &lt; 0.01; OR 1.96, 95% CI: 1.26–3.05; M2-segment-MCA, p &lt; 0.02; OR 1.62, 95% CI: 1.08–2.42) were associated with a higher risk of developing symptomatic intracerebral hemorrhage compared to no/asymptomatic intracerebral hemorrhage. The subgroup of patients treated with thrombectomy alone presented a lower risk of symptomatic intracerebral hemorrhage (p &lt; 0.01; OR 0.70; 95% CI: 0.55–0.90). Subarachnoid hemorrhage/arterial perforation and symptomatic intracerebral hemorrhage after endovascular thrombectomy worsen both functional independence and mortality at three-month follow-up (p &lt; 0.01). Distal embolization is associated with neurological deterioration (p &lt; 0.01), while arterial dissection did not affect clinical outcome at follow-up. Conclusions: Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits