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Background: Mechanical thrombectomy (MT) has significantly reduced morbidity and mortality in acute ischemic stroke (AIS). This study aims to analyze the outcomes and factors associated with decompressive hemicraniectomy (DHC) in AIS patients who underwent MT. Methods: We retrospectively analyzed data from an ongoing, multicenter database to investigate AIS patients who underwent MT for ICA, M1, or M2 occlusion. We compared clinical and procedural variables between patients who underwent DHC and those who did not. Propensity score (PS) matching between the two groups was conducted using age, sex, admission NIHSS, occluded vessel, ASPECTS, time from symptoms onset to arterial puncture, intracranial hemorrhage (ICH), and symptomatic ICH (sICH). Results: Among the 3,135 MT patients who met our inclusion criteria, 113 underwent DHC. A 1:3 propensity matching yielded a well-matched cohort of 113 in the DHC group versus 339 in the non-DHC group. The DHC group had a significantly higher rate of successful recanalization (mTICI ≥ 2C) (175 [51.6%] versus 36 [31.9%], P < 0.001) and a longer procedure duration, with a median of 30 minutes (IQR: 17-54) compared to 44 minutes (IQR: 25-78) in the non-DHC group (P = <0.001). Further comparison of patients with low ASPECTS (≤ 5) who underwent DHC (n = 36) with those who did not (n = 99) showed no significant difference in successful recanalization rates (15 [41.7%] versus 43 [43.4%], P > 0.90). However, procedure duration was significantly longer in the DHC group with a median of 29 minutes (IQR: 13-52), compared to 39 minutes (IQR: 27-86) in the non-DHC group (P = 0.02). Conclusions: Successful recanalization can help in preventing DHC in AIS patients with high ASPECTS, but not those with low ASPECTS. Procedure duration is independently related to DHC following MT, especially in low ASPECTS patients.

Introduction: The first-pass effect (FPE), defined as a complete or near-complete recanalization after a single pass of a mechanical thrombectomy (MT) device, has been linked to favorable clinical outcomes. However, its effectiveness in acute ischemic stroke (AIS) patients with low ASPECTS (Alberta Stroke Program Early CT Score 2-5) has not been validated. Method: We utilized data from STAR, a multicenter database of 84 centers worldwide, to conduct a retrospective, cohort study on patients who underwent MT for internal carotid artery (ICA) or M1 occlusion presenting with ASPECTS 2-5. We compared the outcomes of patients who achieved FPE (successful recanalization with an mTICI score of 2c or higher in one pass) to those who did not. The primary outcome was a 90-day favorable outcome, defined as mRS 0-3. Secondary outcomes included any intracranial hemorrhage (ICH), symptomatic ICH (sICH), and 90-day mortality. Results: Out of 10,229 patients in the STAR database, 250 patients met our inclusion criteria. Among those, 60 (24%) achieved FPE. There were no significant differences between the two groups in baseline, imaging, and procedural characteristics. FPE was significantly associated with higher odds of 90-day mRS 0-3 (adjusted odds ratio (aOR): 2.17, 95% confidence interval (CI): 1.04 - 4.20; P-value: 0.04) and lower rates of ICH (OR: 0.49, 95% CI: 0.25 - 0.93, P-value: 0.03). However, there was no significant difference in sICH rates (OR: 0.84, 95% CI: 0.31 - 2.04, P-value: 0.70). Conclusion: Achieving FPE in AIS stroke patients with low ASPECTS was associated with significantly higher rates of good functional outcomes and lower rates of ICH.

Introduction: Real-world data showed that less than half of the acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) presenting with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (2-5) achieved favorable outcomes at 90 days after mechanical thrombectomy (MT). In this study, we aim to investigate the relationship between the number of MT passes at which successful recanalization is obtained and outcomes in LVO-related AIS patients with low ASPECTS. Methods: This retrospective cohort study was performed on the data from 31 thrombectomy-capable centers between 2013 to 2022. Successful recanalization was defined as modified Thrombolysis in Cerebral Ischemia Score≥ 2b. The primary outcome was a 90-day modified Rankin Scale (mRS) of 0-3. Secondary outcomes were symptomatic intracranial hemorrhage and intracranial hemorrhage within 24 hours and mortality at 90 days. Outcomes were compared among patients with unsuccessful recanalization, and successful recanalization at first, second, third, and more than four passes. Results: A total of 297 patients with a median age of 70 [IQR 59-78] years were included and 140 (47.1%) were female. In 239 (80.4%) patients, successful recanalization was achieved: 88 patients (29.6 %) with 1 pass, 59 patients (19.9 %) with 2 passes, 35 patients(11.8%) with 3 passes, and 57 patients (19.2%) with more than 4 passes. Compared to unsuccessful recanalization, successful recanalization at first pass (adjusted OR 5.25, 95% CI 1.78 - 17.1), second passes (adjusted OR 5.20, 95% CI 1.68 - 17.6), and passes 4 (adjusted OR 4.90, 95% CI 1.68 - 17.6) was related to 90-day mRS 0-3. Recanalization status and MT attempt number were not related to secondary outcomes except for 90-day mortality. Compared to unsuccessful recanalization, successful recanalization at second and third passes were inversely related to 90-day mortality (adjusted OR 0.37, 95% CI 0.14 - 0.93; adjusted OR 0.33, 95% CI 0.11 - 0.95, respectively). Conclusion: The present results indicated that successful recanalization was related to 90-day good outcome regardless of the number of MT passes but the odds of achieving favorable outcome declines with each pass.

Introduction: The combination of intravenous or intra-arterial thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) has been thoroughly investigated. However, no study has explored the outcomes of combining both intravenous and intra-arterial thrombolysis with MT. Methods: Data from Stroke Thrombectomy and Aneurysm Registry (STAR) from 2013 to 2023 was utilized. We compared AIS patients with LVO who underwent MT with combined intra-venous and intra-arterial thrombolysis (IV+IA) and with intra-venous thrombolysis alone (IV). We performed propensity score (PS) matching between the two groups using age, sex, premorbid mRS, admission NIHSS, occluded vessel, ASPECTS score, time from symptoms onset to arterial puncture, and frontline technique. Primary outcomes were any intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Secondary outcomes included successful recanalization (mTICI ≥2C), early neurological improvement (defined as 4 or more points improvement in NIHSS score in 24 hours), 90-day modified Rankin Scale (mRS) 0-2, mRS 0-1, and mortality. Results: A total of 2495 LVO-related AIS patients were included, consisting of the IA+IV group (n = 266) and the IV group (n = 2228). Propensity matching yielded 192 well-matched patients in each group. No significant differences were observed between the groups in either ICH or sICH (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.61-1.52, p = 0.60; OR: 0.92, 95% CI: 0.42-2.03, p > 0.90, respectively). The IA+IV group had a significantly lower proportion of successful recanalization (OR: 0.41, 95% CI: 0.27-0.62, p < 0.001), and early neurological improvement (OR: 0.55, 95% CI: 0.30-1.00). However, 90-day mRS 0-2, mRS 0-1, and mortality rates showed no significant differences between the two groups. Conclusion: The findings of this study suggest that the combined use of IA and IV thrombolysis in AIS patients undergoing MT is safe. Although the IA+IV group demonstrated lower rates of recanalization and early neurological improvement, long-term functional outcomes and mortality rates were comparable to the IV-thrombolysis group, indicating a potential delayed benefit of additional IA thrombolysis therapy.

Introduction: While balloon guide catheters (BGCs) enhance safety and efficacy of mechanical thrombectomy in large vessel occlusions, their impact on distal medium vessel occlusion (DMVO) remains underexplored. This study aimed to compare the outcomes of BGC vs non-BGC in DMVO thrombectomy. Methods: This retrospective study focused on DMVO cases defined as occlusions in M2-M4 middle cerebral artery, anterior cerebral artery, and posterior cerebral artery. Baseline characteristics and technical and clinical outcomes were compared between the two groups, with subgroup analysis in first-line thrombectomy techniques, including ADAPT, stent retriever, and Solumbra. First pass effect (FPE) was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score ≥ 2C after the first pass. Results: A total of 1,508 patients were included, of whom 231 (15.3%) were in the BGC group and 1,277 (84.7%) were in the Non-BGC group. The BGC group was associated with a lower mTICI score ≥ 2C (overall: 43.2% vs. 52.7%, p = 0.01; ADAPT: 42.2% vs. 57.1%, p = 0.01; Solumbra: 32.4% vs. 51.4%, p = 0.005), longer puncture to intracranial access time (overall: 15 vs. 8 min, p < 0.001; ADAPT: 17 vs. 8 min, p < 0.001; Solumbra: 12 vs. 8 min, p = 0.02), and longer puncture to recanalization time (overall: 97 vs. 35 min, p < 0.001; ADAPT: 100 vs. 28 min, p < 0.001; Solumbra: 78 vs. 46 min, p < 0.001; Stent retriever: 95 vs. 45 min, p < 0.001 ). The BGC group also had a lower FPE rate (17.4% vs. 30.7%, p = 0.03) in the Solumbra subgroup. In terms of clinical outcomes, the BGC group had a lower rate of distal embolization (overall: 8.8% vs. 14.9%, p = 0.02), but there were no significant differences in other clinical outcomes between the two groups in first-line thrombectomy techniques. Conclusions: Our findings showed that the use of BGC in DMVO had a lower mTICI score, reduced FPE rates, decreased distal embolization, and longer procedure times. Figure 1: Figure 2:

Introduction: The efficacy of mechanical thrombectomy (MT) for tandem vertebrobasilar occlusion (tVBO) is not well established in patients with basilar artery occlusion (BAO). Objective: To investigate the treatment outcomes of MT in tVBO. Method: This international, multicenter, retrospective cohort included patients with MT for tVBO and isolated BAO from 2013 to 2023. The primary outcome was the 90-day modified Rankin Scale (mRS) score 0-2. Secondary outcomes included complete recanalization (modified Thrombolysis in Cerebral Ischemia [mTICI] ≥ 2C) and 90-day mortality rate. These outcomes were compared between tVBO and isolated BAO groups. Adjustment factors were age, sex, admission National Institutes of Health Stroke Scale (NIHSS), pre-morbid mRS, onset to groin duration, and intravenous tissue plasminogen activator. Results: Among 10,229 patients, 689 had BAO. Of those, 61 (9.7%) had a tVBO. Median age was 61 [IQR 53-74] years and 29 (47.5%) patients were female. Compared to isolated BAO, tVBO group had lower age (61 [53-74] versus 68 [58-79], P<0.001) and lower admission NIHSS (15 [7 - 22] versus 17 [9-26], P≤0.05). There was no significant difference in the rate of complete recanalization between the two groups (adjusted odds ratio [aOR]: 0.83; 95% CI: 0.39-1.79; P=0.60) However, the tVBO group had significantly lower odds of a favorable outcome compared to the isolated BAO group (aOR: 0.35; 95% CI: 0.13-0.83; P=0.023) and higher odds of 90-day mortality (aOR: 3.51; 95% CI: 1.59-7.85; P=0.002). Binary regression analysis revealed that age (OR 0.98; 95% CI 0.96 - 1.00; P=0.019), admission NIHSS (OR 0.90; 95% CI 0.87-0.93; P<0.001), premorbid mRS (OR 0.71; 95% CI 0.53-0.93; P=0.016), successful recanalization (OR 2.94; 95% CI 1.71-5.15; P<0.001), and tVBO (OR 0.33; 95% CI 0.11-0.86; P=0.031) were significant predictors of 90-day favorable outcome. Conclusion: tVBO was associated with poor outcomes. Further efforts should be aimed at improving outcomes for this subpopulation.

Objective: To determine whether first pass effect (FPE) after mechanical thrombectomy (MT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) is modified by procedural time (PT). Methods: The Stroke Thrombectomy and Aneurysm Registry (STAR), a multi-center international dataset, was retrospectively analyzed for anterior circulation LVO-AIS treated by MT who achieved excellent reperfusion (TICI 2c/3). The primary outcome was good functional outcome as defined by a 90-day modified Rankin Scale (mRS) 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. Logistic regression models were fit-adjusted and marginal effects used to assess the interaction of PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from last known well to start of MT. Results: A total of 1,310 patients had excellent reperfusion. These patients were divided into two cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and > 30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant (p=0.018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs. 46.7%, p=0.001). However, there was no significant difference in the adjusted predicted probability of good outcome based on FPS in individuals with PT >30 minutes (p=0.763). This relationship appeared identical in models with PT treated as a continuous variable. Conclusion: In a large, real-world, multi-national dataset, we find that FPE is importantly modified by PT. The added clinical benefit of FPE is lost in longer procedures (>30 minutes). These data argue for a new metric for MT procedures, namely, FPE 30 , that better represents the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

While the cure rate of pediatric acute lymphoblastic leukemia (ALL) now exceeds ~90% with contemporary combination chemotherapy, the prognosis for adults with ALL remains significantly inferior with long-term overall survival ranging from 50% to 70%. Recent studies have uncovered marked differences in ALL genomics between children and adults, with some high-risk subtypes becoming more prevalent with age. However, the underlying biology of age-related disparities in ALL is not fully understood, especially with regard to differences in leukemia sensitivity to chemotherapy. To address this knowledge gap, we performed ex vivo drug sensitivity profiling (i.e., pharmacotyping) of 21 anti-leukemia agents on primary B-ALL diagnostic samples from 767 pediatric (age, 0-18 years) and 309 adult (19-84 years) patients. Drug sensitivity was measured as LC 50: the concentration of drug required to kill 50% of the leukemia cells (PMID: 36604538). A total of 7,975 unique LC 50 values were experimentally determined. RNA-seq was used for subtype classification and gene expression analysis. Among 21 drugs, seven showed significant differences in overall LC 50 between children and adults ( P&lt;0.05 after Bonferroni correction): children displayed higher sensitivity to asparaginase, prednisolone, mercaptopurine, daunorubicin, and inotuzumab, while adults showed higher sensitivity to dasatinib and nelarabine. In multivariate models adjusting for 23 ALL molecular subtypes, only mercaptopurine remained significantly associated with age ( P=1.5×10 -5), suggesting that age-related differences in drug sensitivity can be primarily attributed to the variation in ALL subtypes between children and adults. For mercaptopurine, within KMT2A, CRLF2, and DUX4 subtypes, pediatric samples consistently showed a lower LC 50 than adults carrying the same genomic abnormality ( P=0.032, 0.0045, and 0.02, respectively). To explore intra-subtype heterogeneity, we performed unsupervised clustering using gene expression data for each of these three subtypes. Remarkably, within each of these subtypes, we identified two clusters with distinct transcriptomic profiles that were also largely segregated by age group, i.e., an adult-dominated cluster (C-a) and a pediatric-dominated cluster (C-p). In the KMT2A subtype, cases in C-a exhibited an over-representation of the KMT2A:: AFF1 fusion, and resistance to mercaptopurine ( P=0.029), prednisolone ( P=0.0039), vincristine ( P=0.046) and cytarabine ( P=0.0037). Within CRLF2 ALL, cases in C-a were associated with the presence of BCR:: ABL1-like signature and IGH:: CRLF2 rearrangements, and were more resistant to mercaptopurine ( P=0.0073) and prednisolone ( P=0.00036) compared to those in C-p. For DUX4 ALL, C-a was characterized by an under-representation of ERG deletions and resistance to mercaptopurine ( P=0.0056) and prednisolone ( P=0.0031), compared to C-p within DUX4. To explore the clinical relevance of this heterogeneity, we analyzed the in vivo treatment response of KMT2A (N=35), CRLF2 (N=59) and DUX4 (N=118) B-ALL enrolled in six frontline ALL trials. Compared to cases in C-p (usually drug-sensitive), those in C-a (usually drug-resistant) consistently had significantly poorer initial treatment responses as measured by persistent end-of-induction minimal residual disease (≥0.01%) in KMT2A (58% vs 9%; P=0.0063), CRLF2 (74% vs 41%; P=0.030), and DUX4 (66% vs 40%; P=0.0058) ALL. In conclusion, these studies have revealed important new insights into the pharmacogenomic basis of age-related differences in B-ALL treatment response. These results indicate that both inter- and intra-subtype heterogeneity contribute to inferior prognosis in adults with ALL, but also point to therapeutic opportunities to improve their outcomes.

Background As the number of thrombectomy passes increases during endovascular therapy (EVT) for acute stroke, neurointerventionalists must weigh the risks of potential complications against the risk of failing to recanalize the affected vessel. Thus, we investigated the effectiveness and safety of EVT for patients with acute stroke in which ≥5 EVT passes were performed. Methods This retrospective cohort study from January 2013 to December 2022 included 31 thrombectomy‐capable centers. Patients in whom ≥5 EVT passes were made were included in the analysis. The patients with successful recanalization defined as modified Thrombolysis in Cerebral Infarction ≥2b at 5, 6, 7, or more passes were compared with unsuccessful recanalization. We also compared procedure time, separated by 30 minutes. Primary outcome was a favorable 90‐day outcome (modified Rankin scale score of 0–2). Secondary outcomes were intracranial hemorrhage and death. Results A total of 407 patients met the inclusion criteria, of which 175 were women (43.1%); the mean age was 67.3 years. In 265 (65.1%) patients, successful recanalization was achieved: 134 patients with 5 passes, 67 patients with 6 passes, and 64 with ≥7 passes. Intravenous recombinant tissue plasminogen activator administration was more common in the unsuccessful recanalization group (successful recanalization with 5, 6, and ≥7 EVT passes and unsuccessful recanalization: 35.3%, 30.3%, 18.8%, and 45.4%, respectively). Successful recanalization with 5, 6, and ≥7 EVT passes was associated with favorable outcome compared with unsuccessful recanalization group (adjusted odds ratio successful recanalization with 5, 6, and ≥7 EVT passes to unsuccessful recanalization [95% CIs]: 8.29 [2.13–32.3]; 14.0 [3.27–60.3]; and 5.26 [1.12–24.8], respectively). However, symptomatic intracranial hemorrhage was not significantly different between the groups. Regarding procedure time, favorable outcome was not significantly different in each group, while symptomatic intracranial hemorrhage occurred more frequently in the 60 to 89 minutes group compared with the <30 minutes group (adjusted odds ratio, 60–89 minutes group to <30 minutes group [95% CI]: 5.86 [1.09–31.6]). Conclusion These findings suggest that a benefit in outcome persists for recanalization, without significant increase in complications. In addition, there was no significant difference in favorable outcomes among procedure time.

Background Patient's age is an important factor in determining the risk of aneurysm rupture. However, there is limited data on how aneurysm morphology differs among age groups. We studied morphological characteristics of brain aneurysms among age groups in a large cohort. Methods Aneurysms from the Stroke Thrombectomy and Aneurysm Registry (STAR) were analyzed. The following parameters were included: location, size, neck, width, height, aspect ratio, and regular versus irregular morphology. The risk of rupture presentation was estimated using logistic regression. Results A total of 1407 unruptured and 607 ruptured saccular aneurysms were included. The most common locations of ruptured aneurysms in patients younger than 70 years-old were the middle cerebral artery (MCA) and the anterior communicating artery (ACOM). The most common location of ruptured aneurysms in patients older than 70 years-old were the posterior communicating artery (PCOM) and ACOM. The size of unruptured aneurysms increased with age (p < .001). Conversely, the size of ruptured aneurysms was similar among age groups (p = .142). Unruptured and ruptured aneurysms became more irregular at presentation with older age (p < .001 and p .025, respectively). Irregular morphology and location were associated with rupture status across all age groups in multivariate regression. Conclusions Younger patients have small unruptured and ruptured aneurysms, and ruptured aneurysms are mostly located in the MCA and ACOM. Older patients have larger and more irregular unruptured aneurysms, and ruptured aneurysms are mostly located in the PCOM and ACOM. An irregular morphology increases the risk of rupture in all age groups.