Citations

BACKGROUND AND OBJECTIVES: We aimed to develop and validate a prediction score for futile recanalization (FR) for large vessel occlusion (LVO) presenting low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) for patients who underwent endovascular thrombectomy (EVT). METHODS: Patients with anterior circulation LVO with low ASPECTS (<6) who underwent successful EVT (modified treatment in cerebral ischemia score ≥2b) from Stroke Thrombectomy and Aneurysm Registry were retrospectively analyzed. FR was defined as 90-day modified Rankin Scale (mRS) scores ≥4 despite successful EVT. Multivariable logistic regression was used to identify independent predictors of FR, and they were used to create a clinical score. The performance of the score was assessed by receiver operating characteristic curve analyses. RESULTS: Of 219 patients, 170 and 49 patients were randomly assigned to the training and validation cohort, respectively. Independent predictors of FR identified in the training cohort were used to construct the SNAP score: site of occlusion (middle cerebral artery = 0, internal carotid artery = 1), National Institutes of Health Stroke Scale score at admission (≤10 = 0, 10 to 19 = 1, ≥20 = 2), age (<75 = 0, ≥75 = 2), and prestroke mRS score (0-3). Receiver operating characteristic curve analyses of the SNAP score in the training and validation cohorts showed areas under the curve of 0.79 (95% CI 0.72-0.86) and 0.79 (95% CI 0.65-0.92) for predicting FR, respectively. A SNAP score ≥5 had a positive predictive value of 92.1% [95% CI 78.8%-97.3%] for FR. CONCLUSION: The SNAP score may be useful in predicting FR after EVT in low-ASPECTS patients with LVO. It can provide patients, family members, and physicians with reliable outcome expectations among patients with acute ischemic stroke with large infarcts.

Abstract Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma‐induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells. It is observed that quiescent MSCs transition into cycling MSCs, subsequently giving rise to chondrogenic (cMSC) and/or osteogenic (oMSC) lineages within the inflammatory microenvironment following muscle or tendon injuries, as revealed through single‐cell RNA sequencing (scRNA‐seq), spatial transcriptome and lineage tracing analysis. Moreover, these investigations demonstrate that neutrophils and natural killer (NK) cells enhance transition of quiescent MSCs into cycling MSCs, which is also controlled by M1 macrophages, a subpopulation of macrophages can also stimulate cMSC and oMSC production from cycling MSCs. Additionally, M2 macrophages, CD4 + and CD8 + T lymphocytes are found to promote chondrogenesis. Further analysis demonstrates that immune cells promotes the activation of signaling transducers and activators of transcription (STAT) pathway and phosphoinositide 3 (PI3K)/protein kinase B (AKT) pathway in MSC proliferation and osteochondral progenitors’ production, respectively. These findings highlight the dynamics of MSC fate within the inflammatory lesion and unveil the molecular landscape of osteoimmunological interactions, which holds promise for advancing HO treatment.

Background A higher number of recanalization attempts reduces the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke secondary to large vessel occlusion (LVO). We assessed the impact of switching EVT techniques after a failed first pass on procedural and clinical outcomes. Methods This multicenter international study, conducted between January 2013 and December 2022, included patients undergoing EVT for anterior circulation LVO (internal carotid artery or M1 segments) with failed first pass recanalization. Propensity score matching identified a 1:1 matched cohort of patients in whom EVT technique was changed after a failed first pass and those with the same technique repeated. The primary outcome was successful recanalization at second attempt defined as Thrombolysis in Cerebral Ischemia (TICI) score of 2B or higher. Secondary outcomes were 90-day modified Rankin Score (mRS) and postprocedural hemorrhage. Results Among 2167 patients, converting to an alternative technique after a failed first pass was associated with higher odds of successful recanalization (adjusted OR (aOR)=1.5, p=0.041), and higher odds of mRS 0–2 at 90 days (aOR=1.6, p=0.005) without additional risk of symptomatic hemorrhage (p=0.379). Using a propensity score matched cohort of 490 patients, technique conversion at second attempt increased odds of successful recanalization at second attempt (aOR=1.32, p=0.006) and 90-day mRS 0–2 (aOR=1.38, p=0.008). Conclusions Early conversion to an alternative EVT technique after a failed first pass recanalization in patients with AIS is associated with better technical success and clinical outcomes.

Background The benefit of intravenous thrombolysis (IVT) is well established. We aim to study the benefits of IVT in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) who underwent unsuccessful mechanical thrombectomy (MT). Methods We included AIS patients who underwent MT for anterior circulation LVO with failed recanalization (modified treatment in cerebral ischemia [mTICI] score ≤ 2A). Patients who received IVT prior to MT were compared to those who received MT alone. Propensity score matching using demographic, clinical, radiographic and procedural variables was used to match patients with and without IVT. The primary outcome was favorable 90-day good functional outcome (defined as modified Rankin scale of 0–2), and secondary outcomes included intracranial hemorrhage (ICH), symptomatic ICH (sICH), and 90-day mortality. Results Totally, 610 AIS patients with unsuccessful MT were included. After propensity matching, 219 patients were identified in each group. Median age was 70 years and 73 years in the IVT + MT and MT alone groups, respectively. In the IVT + MT group, final mTICI scores of 0, 1, and 2A were achieved in 92 (42.0%), 33 (15.1%), and 94 (42.9%) patients, respectively, versus 76 (34.7%), 29 (13.2%), and 114 (52.1%) in the MT alone group. The IVT + MT group had greater odds of 90-day good functional outcome (adjusted odds ratio 2.54, 95% confidence interval 1.53–4.32). There were no significant differences in secondary outcomes. Conclusions IVT is associated with improved functional outcomes in AIS patients with LVO despite unsuccessful MT.

PURPOSE Imlunestrant is a next-generation oral selective estrogen receptor (ER) degrader designed to deliver continuous ER target inhibition, including in ESR1- mutant breast cancer. This phase Ia/b trial determined the recommended phase II dose (RP2D), safety, pharmacokinetics, and efficacy of imlunestrant, as monotherapy and in combination with targeted therapy, in ER-positive (ER+) advanced breast cancer (ABC) and endometrial endometrioid cancer. The ER+/human epidermal growth factor receptor 2–negative (HER2–) ABC experience is reported here. METHODS An i3+3 dose-escalation design was used, followed by dose expansions of imlunestrant as monotherapy or in combination with abemaciclib with or without aromatase inhibitor (AI), everolimus, or alpelisib. Imlunestrant was administered orally once daily and with the combination partner per label. RESULTS Overall, 262 patients with ER+/HER2– ABC were treated (phase Ia, n = 74; phase Ib, n = 188). Among patients who received imlunestrant monotherapy (n = 114), no dose-limiting toxicities or discontinuations occurred. At the RP2D (400 mg once daily), patients (n = 51) reported grade 1-2 nausea (39.2%), fatigue (39.2%), and diarrhea (29.4%). Patients at RP2D had received previous cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; 92.2%), fulvestrant (41.2%), and chemotherapy (29.4%) for ABC and achieved a median progression-free survival (mPFS) of 7.2 months (95% CI, 3.7 to 8.3). Among patients who received imlunestrant + abemaciclib (n = 42) and imlunestrant + abemaciclib + AI (n = 43), most (69.4%) were treatment-naïve for ABC; all were CDK4/6i-naïve. Patients treated with imlunestrant + everolimus (n = 42)/alpelisib (n = 21) had received previous CDK4/6i (100%), fulvestrant (34.9%), and chemotherapy (17.5%) for ABC. No new safety signals or interactions with partnered drugs were observed. The mPFS was 19.2 months (95% CI, 13.8 to not available) for imlunestrant + abemaciclib and was not reached for imlunestrant + abemaciclib + AI. The mPFS with imlunestrant + everolimus/alpelisib was 15.9 months (95% CI, 11.3 to 19.1)/9.2 months (95% CI, 3.7 to 11.1). Antitumor activity was evident regardless of ESR1 mutation status. CONCLUSION Imlunestrant, as monotherapy or in combination with targeted therapy, had a manageable safety profile with evidence of preliminary antitumor activity in ER+/HER2– ABC.

Background A combination of intravenous (IVT) or intra-arterial (IAT) thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) has been investigated. However, there is limited data on patients who receive both IVT and IAT compared with IVT alone before MT. Methods STAR data from 2013 to 2023 was utilized. We performed propensity score matching between the two groups. The primary outcomes were symptomatic intracranial hemorrhage (sICH) and 90-day modified Rankin Scale (mRS) score 0–2. Secondary outcomes included successful recanalization (modified treatment in cerebral infarction (mTICI) ≥2B, ≥2C), early neurological improvement, any intracranial hemorrhage (ICH), and 90-day mortality. Results A total of 2454 AIS-LVO patients were included. Propensity matching yielded 190 well-matched patients in each group. No significant differences were observed between the groups in either ICH or sICH (odds ratio (OR): 0.80, 95% confidence interval (CI) 0.51–1.24, P=0.37; OR: 0.60, 95% CI 0.29 to 1.24, P=0.21, respectively). Rates of successful recanalization and early neurological improvement (ENI) were significantly lower in MT+IVT + IAT. mRS 0–1 and mortality were not significantly different between the two groups. However, the MT+IVT + IAT group demonstrated superior rates of good functional outcomes (90-day mRS 0–1) compared with patients in the MT+IVT group who had mTICI ≤2B, (OR: 2.18, 95% CI 1.05 to 3.99, P=0.04). Conclusion The combined use of IAT and IVT thrombolysis in AIS-LVO patients undergoing MT is safe. Although the MT+IVT+ IAT group demonstrated lower rates of recanalization and early neurological improvement, long-term functional outcomes were favorable in this group suggesting a potential delayed benefit of IAT.

Background Whereas mechanical thrombectomy (MT) has become standard-of-care treatment for patients with salvageable brain tissue after acute stroke caused by large-vessel occlusions, the results of MT in patients with medium-vessel occlusions (MEVOs), particularly in the posterior cerebral artery (PCA), are not well known. Methods Using data from the international Stroke Thrombectomy and Aneurysm Registry (STAR), we assessed presenting characteristics and clinical outcomes for patients who underwent MT for primary occlusions in the P2 PCA segment. As a subanalysis, we compared the PCA MeVO outcomes with STAR's anterior circulation MeVO outcomes, namely middle cerebral artery (MCA) M2 and M3 segments. Results Of the 9812 patients in STAR, 43 underwent MT for isolated PCA MeVOs. The patients’ median age was 69 years (interquartile range 61–79), and 48.8% were female. The median NIH Stroke Scale score was 9 (range 6–17). After recanalization, 67.4% of patients achieved successful recanalization (modified treatment in cerebral infarction score [mTICI] ≥ 2b), with a first-pass success rate of 44.2%, and 39.6% achieved a modified Rankin score of 0–2 at 90 days. Nine patients (20.9%) had died by the 90-day follow-up. In comparison with M2 and M3 MeVOs, there were no differences in presenting characteristics among the three groups. Patients with PCA MeVOs were less likely to undergo intra-arterial thrombolysis (4.7% PCA vs. 10.1% M2 vs. 16.2% M3, p = 0.046) or to achieve successful recanalization (mTICI ≥ 2b, 67.4%, 86.7%, 82.3%, respectively, p < 0.001); however, there were no differences in the rates of successful first-pass recanalization (44.2%, 49.8%, 52.3%, respectively, p = 0.65). Conclusions We describe the STAR experience performing MT in patients with PCA MeVOs. Our analysis supports that successful first-pass recanalization can be achieved in PCA MEVOs at a rate similar to that in MCA MeVOs, although further study and possible innovation may be necessary to improve successful PCA MeVO recanalization rates.

Background The optimal duration for dual antiplatelet therapy (DAPT) after stent-assisted coiling (SAC) of intracranial aneurysms is unclear. Longer-term therapy may reduce thrombotic complications but increase the risk of bleeding complications. Methods A retrospective review of prospectively maintained data at 12 institutions was conducted on patients with unruptured intracranial aneurysms who underwent SAC between January 1, 2016 and December 31, 2020, and were followed ≥6 months postprocedure. The type and duration of DAPT, stent(s) used, outcome, length of follow-up, complication rates, and incidence of significant in-stent stenosis (ISS) were collected. Results Of 556 patients reviewed, 450 met all inclusion criteria. Nine patients treated with DAPT <29 days after SAC and 11 treated for 43–89 days were excluded from the final analysis as none completed their prescribed duration of treatment. Eighty patients received short-term DAPT. There were no significant differences in the rate of thrombotic complications during predefined periods of risk in the short, medium, or long-term treatment groups (1/80, 1.3%; 2/188, 1.1%; and 0/162, 0%, respectively). Similarly, no differences were found in the rate of hemorrhagic complications during period of risk in any group (0/80, 0%; 3/188, 1.6%; and 1/162, 0.6%, respectively). Longer duration DAPT did not reduce ISS risk in any group. Conclusions Continuing DAPT >42 days after SAC did not reduce the risk of thrombotic complications or in-stent stenosis, although the risk of additional hemorrhagic complications remained low. It may be reasonable to discontinue DAPT after 42 days following non-flow diverting SAC of unruptured intracranial aneurysms.

Background Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond–Roy classification 1 or 2) remains challenging. Objective Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. Methods We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. Results A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535–0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024–0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer–Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/ . Conclusion The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.