Peripheral Artery Disease in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy; Results From the MR CLEAN Registry

Background and Purpose: Though peripheral artery disease (PAD) is a well-known risk factor for ischemic events, better outcomes have been described in acute ischemic stroke patients with co-existing PAD. This paradoxical association has been attributed to remote ischemic preconditioning (RIPC) and might be related to better collateral blood flow. The aim of this study is to compare outcomes after endovascular thrombectomy (EVT) in acute stroke patients with and without PAD and to assess the relation between PAD and collateral grades. Methods: We analyzed acute ischemic stroke patients treated with EVT for an anterior circulation large artery occlusion, included in the Dutch, prospective, multicenter MR CLEAN Registry between March 2014 and November 2017. Collaterals were scored on CT angiography, using a 4-point collateral score. We used logistic regression analysis to estimate the association of PAD with collateral grades and functional outcome, assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included mortality at 90 days, symptomatic intracranial hemorrhage, and stroke progression. Results: We included 2,765 patients for analysis, of whom 254 (9.2%) had PAD. After adjustment for potential confounders, multivariable regression analysis showed no association of PAD with functional outcome [mRS cOR 0.90 (95% CI, 0.7-1.2)], collateral grades (cOR 0.85, 95% CI 0.7-1.1), or safety outcomes. Conclusion: In the absence of an association between the presence of PAD and collateral scores or outcomes after EVT, it may be questioned whether PAD leads to RIPC in patients with acute ischemic stroke due to large vessel occlusion

Peripheral Artery Disease in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy; Results From the MR CLEAN Registry

Background and Purpose: Though peripheral artery disease (PAD) is a well-known risk factor for ischemic events, better outcomes have been described in acute ischemic stroke patients with co-existing PAD. This paradoxical association has been attributed to remote ischemic preconditioning (RIPC) and might be related to better collateral blood flow. The aim of this study is to compare outcomes after endovascular thrombectomy (EVT) in acute stroke patients with and without PAD and to assess the relation between PAD and collateral grades. Methods: We analyzed acute ischemic stroke patients treated with EVT for an anterior circulation large artery occlusion, included in the Dutch, prospective, multicenter MR CLEAN Registry between March 2014 and November 2017. Collaterals were scored on CT angiography, using a 4-point collateral score. We used logistic regression analysis to estimate the association of PAD with collateral grades and functional outcome, assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included mortality at 90 days, symptomatic intracranial hemorrhage, and stroke progression. Results: We included 2,765 patients for analysis, of whom 254 (9.2%) had PAD. After adjustment for potential confounders, multivariable regression analysis showed no association of PAD with functional outcome [mRS cOR 0.90 (95% CI, 0.7-1.2)], collateral grades (cOR 0.85, 95% CI 0.7-1.1), or safety outcomes. Conclusion: In the absence of an association between the presence of PAD and collateral scores or outcomes after EVT, it may be questioned whether PAD leads to RIPC in patients with acute ischemic stroke due to large vessel occlusion

Imatinib and Nilotinib Inhibit Hematopoietic Progenitor Cell Growth, but Do Not Prevent Adhesion, Migration and Engraftment of Human Cord Blood CD34+ Cells

Background: The availability of tyrosine kinase inhibitors (TKIs) has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib is also known to inhibit the tyrosine kinase of the stem cell factor receptor, c-Kit. Nilotinib is 30 times more potent than imatinib towards BCR-ABL in vitro. Studies in healthy volunteers and patients with chronic myelogenous leukemia or gastrointestinal stromal tumors have shown that therapeutic doses of nilotinib deliver drug levels similar to those of imatinib. The aim of this study was to compare the inhibitory effects of imatinib and nilotinib on proliferation, differentiation, adhesion, migration and engraftment capacities of human cord blood CD34+ cells. Design and Methods: After a 48-hour cell culture with or without TKIs, CFC, LTC-IC, migration, adhesion and cell cycle analysis were performed. In a second time, the impact of these TKIs on engraftment was assessed in a xenotransplantation model using NOD/SCID/IL-2Rc (null) mice. Results: TKIs did not affect LTC-IC frequencies despite in vitro inhibition of CFC formation due to inhibition of CD34+ cell cycle entry. Adhesion of CD34+ cells to retronectin was reduced in the presence of either imatinib or nilotinib but only at high concentrations. Migration through a SDF-1a gradient was not changed by cell culture in the presence of TKIs. Finally, bone marrow cellularity and human chimerism were not affected by daily doses of imatinib and nilotinib in a xenogenic transplantation model. No significant difference was seen between TKIs given the equivalent affinity of imatinib and nilotinib for KIT. Conclusions: These data suggest that combining non-myeloablative conditioning regimen with TKIs starting the day of the transplantation could be safe

Cost-effectiveness of CT perfusion for the detection of large vessel occlusion acute ischemic stroke followed by endovascular treatment:a model-based health economic evaluation study

OBJECTIVES: CT perfusion (CTP) has been suggested to increase the rate of large vessel occlusion (LVO) detection in patients suspected of acute ischemic stroke (AIS) if used in addition to a standard diagnostic imaging regime of CT angiography (CTA) and non-contrast CT (NCCT). The aim of this study was to estimate the costs and health effects of additional CTP for endovascular treatment (EVT)-eligible occlusion detection using model-based analyses. METHODS: In this Dutch, nationwide retrospective cohort study with model-based health economic evaluation, data from 701 EVT-treated patients with available CTP results were included (January 2018-March 2022; trialregister.nl:NL7974). We compared a cohort undergoing NCCT, CTA, and CTP (NCCT?+?CTA?+?CTP) with a generated counterfactual where NCCT and CTA (NCCT?+?CTA) was used for LVO detection. The NCCT?+?CTA strategy was simulated using diagnostic accuracy values and EVT effects from the literature. A Markov model was used to simulate 10-year follow-up. We adopted a healthcare payer perspective for costs in euros and health gains in quality-adjusted life years (QALYs). The primary outcome was the net monetary benefit (NMB) at a willingness to pay of €80,000; secondary outcomes were the difference between LVO detection strategies in QALYs (?QALY) and costs (?Costs) per LVO patient. RESULTS: We included 701 patients (median age: 72, IQR: [62-81]) years). Per LVO patient, CTP-based occlusion detection resulted in cost savings (?Costs median: €?-?2671, IQR: [€?-?4721; €?-?731]), a health gain (?QALY median: 0.073, IQR: [0.044; 0.104]), and a positive NMB (median: €8436, IQR: [5565; 11,876]) per LVO patient. CONCLUSION: CTP-based screening of suspected stroke patients for an endovascular treatment eligible large vessel occlusion was cost-effective. CLINICAL RELEVANCE STATEMENT: Although CTP-based patient selection for endovascular treatment has been recently suggested to result in worse patient outcomes after ischemic stroke, an alternative CTP-based screening for endovascular treatable occlusions is cost-effective. KEY POINTS: • Using CT perfusion to detect an endovascular treatment-eligible occlusions resulted in a health gain and cost savings during 10 years of follow-up. • Depending on the screening costs related to the number of patients needed to image with CT perfusion, cost savings could be considerable (median: €?-?3857, IQR: [€?-?5907; €?-?1916] per patient). • As the gain in quality adjusted life years was most affected by the sensitivity of CT perfusion-based occlusion detection, additional studies for the diagnostic accuracy of CT perfusion for occlusion detection are required