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Upamostat is an orally available small-molecule serine protease inhibitor that is a highly potent inhibitor of trypsin 1, trypsin 2, trypsin 3 (PRSS1/2/3), and the urokinase-type plasminogen activator (uPA). These enzymes are expressed in many cancers, especially during tissue remodeling and subsequent tumor cell invasion. Opaganib (ABC294640), a novel, orally available small molecule is a selective inhibitor of the phosphorylation of sphingosine to sphingosine-1-phosphate (S-1-P) by sphingosine kinase 2 (SPHK2). Both sphingosine kinase 1 (SPHK1) and SPHK2 are known to regulate the proliferation-inducing compound S-1-P. However, SPHK2 is more critical in cancer pathogenesis. The goal of this project was to investigate the potential antitumor effects of upamostat and opaganib, individually and in combination, on cholangiocarcinoma (CCA) xenografts in nude mice. PAX165, a patient-derived xenograft (PDX) from a surgically resected CCA, expresses substantial levels of SPHK2, PRSS1, PRSS2, and PRSS3. Four groups of 18 mice each were treated with upamostat, opaganib, both, or vehicle. Mouse weights and PAX165 tumor volumes were measured. Tumor volumes in the upamostat, opaganib, and upamostat plus opaganib groups were significantly decreased compared to the control group.

OBJECTIVE Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Introduction: Acute ischemic stroke (AIS) patients often require multiple passes during mechanical thrombectomy (MT) to open the vessel. Yet, at times, even numerous passes are unsuccessful. This study aims to investigate the impact of the number of passes on the outcomes of patients who underwent failed MT. Methods: We used Data from the Stroke Thrombectomy and Aneurysm Registry (STAR) from 2013 to August 2023. Patients who underwent MT for ICA, M1, or M2 with unsuccessful recanalization (modified Thrombolysis in Cerebral Infarction ≤ 2a) were included. Primary outcome was 90- day modified Rankin Scale (mRS) 0-2. Secondary outcomes included any intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Outcomes were compared among patients who received ≤ 2, 3, 4, and ≥ 5 MT passes. Results: 736 patients met inclusion criteria. 90-day mRS 0-2 was found to decrease with number of passes (Figure 1). Multivariate logistic regression analysis revealed that 3 passes (OR: 0.48, 95% CI: 0.23 -0.96, P-value: 0.04), 4 passes (OR: 0.46, 95% CI: 0.19 -1.03, P-value: 0.07), and ≥ 5 passes (OR: 0.22, 95% CI: 0.08 -0.50, P-value: <0.001) were associated with lower odds of mRS 0-2 compared to ≤ 2 passes. However, there were no significant differences between groups in ICH, sICH, or 90-day mortality. Conclusion: The number of passes affects functional outcomes among stroke patients who underwent failed MT.

Introduction: Recent randomized control trials suggested that mechanical thrombectomy (MT) was associated with good functional outcomes after acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in patients presenting with low Alberta Stroke Program Early CT Score (ASPECTS) (defined as ASPECTS 2-5). The aim of this study is to develop and validate a stroke prediction tool for outcome in MT for AIS patients with low ASPECTS using data from an ongoing international multicenter registry, the Stroke Thrombectomy and Aneurysm Registry (STAR). Methods: 236 AIS patients with low ASPECTS caused by LVO who undertook MT between January 2010 and December 2022 were retrospectively investigated. Univariate and multivariate logistic regression results were used to screen model predictors and construct nomograms of 90-day modified Rankin Scale scores (mRS) 0-3. The performance of the model was detected by using receiver operating characteristic analysis. The bootstrap resampling method was considered internal validation of the model. Results: Age (< 70 years), premorbid status (mRS 0), National Institutes of Health Stroke Scale (NIHSS) (< 20), and recanalization status after the MT (modified Thrombolysis in Cerebral Ischemia [mTICU] ≥2b) were related to 90-day mRS 0-3. Predictive score was calculated by adding 1 point for age (< 70 years), premorbid status (mRS 0), and NIHSS < 20 and 3 points for a mTICI ≥2b (ranging 0-6). 90-day mRS 0-3 was observed in 0% of patients with a score of 0 or 1, 6.3% with a score of 2, 17.7% with a score of 3, 22.2% with a score of 4, 45.7% with a score of 5, and 73.7% with a score of 6. The score showed relatively high performance in predicting 90-day mRS0-3 (area under the curve: 0.79 [95% CI 0.73-0.79] and 0.78 [95% CI 0.78-0.78] for derivation and validation cohorts, respectively). Conclusions: This study indicates the STAR score can be calculated with baseline and periprocedural characteristics to predict the 90-day outcome after MT in AIS patients with low ASPECTS.

Introduction: Despite comparable outcomes for different frontline techniques in mechanical thrombectomy (MT) for acute ischemic stroke (AIS), there are sparse data regarding if and when to switch techniques if the first pass is unsuccessful. We aimed to investigate the impact of converting from one MT technique to another on the second MT attempt for AIS among patients with large vessel occlusion (LVO). Methods: This was a retrospective observational study using data from the large multicenter international Stroke Thrombectomy and Aneurysm Registry (STAR). Data from 29 stroke centers for 10,229 AIS patients treated with MT for LVO between January 2010 and December 2022 was investigated. The primary outcome measure was successful recanalization defined as modified Thrombolysis in Cerebral Ischemia (mTICI) score of 2b or higher. 90-day modified Rankin score (mRS) 0-2, mortality and symptomatic hemorrhage were used as secondary outcomes. Clinical and technical outcomes after the second MT attempt were compared between those with or without technique conversion. Results: Among 10,229 AIS patients, 1,797 AIS patients with LVO failed first pass recanalization and were included in this retrospective analysis. 927 patients were female (52%) and median (interquartile range) age was 72 (61-81) years. Converting to alternative techniques following a first failed attempt was more likely to be associated with successful recanalization at the second attempt (adjusted odds ratio 2.30, 95% CI: 1.37-3.86, P = 0.002) and 90-day good clinical outcome (adjusted odds ratio 2.10, 95% CI: 1.15-3.85, P = 0.02) after multivariate adjustment. Conclusions: This study demonstrates better clinical and technical outcomes with conversion of MT technique for the second attempt in AIS patients with LVO who failed first pass recanalization.

Introduction: The benefits of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with unsuccessful mechanical thrombectomy (MT) are not well established. Methods: This study included patients from the Stroke Thrombectomy and Aneurysm Registry (STAR) who underwent MT for ICA, M1, or M2 occlusions with unsuccessful MT (mTICI score ≤ 2a). Patients who received IVT prior to MT were compared to those who received MT alone. Propensity score (PS) matching was performed using age, sex, premorbid modified Rankin Scale (mRS), admission National Institute of Health Stroke Scale (NIHSS), occluded vessel, ASPECTS score, mTICI score, and symptom onset to groin puncture time. The primary outcome was favorable 90-day outcomes (mRS 0-2). Results: Of 610 patients with unsuccessful MT, 219 were matched in each group. Median ages were 70 [IQR: 61 - 80] and 73 [IQR: 62 - 81] in the IVT + MT and MT alone groups, respectively. In the IVT + MT group. Final TICI scores of 0, 1, and 2a were achieved in 92 (42.0%), 33 (15.1%), and 94 (42.9%) patients, respectively, compared to 76 (34.7%), 29 (13.2%), and 114 (52.1%) in the MT alone group. The IVT + MT group showed a significantly. higher 90-day mRS of 0-2 (aOR: 2.54, 95% CI: 1.53-4.32) and mRS of 0-3 (aOR: 2.05, 95% CI: 1.36-3.12). There were no significant differences between the groups in intracranial hemorrhage (ICH), symptomatic ICH, or 90-day mortality rates. Conclusions: IVT is associated with improved functional outcomes in patients with unsuccessful MT. Ensuring that IVT is provided to all eligible stroke patients should remain a priority.

Introduction: Up to 50% of acute ischemic stroke (AIS) patients who undergo successful mechanical thrombectomy (MT) fail to achieve favorable outcomes (futile recanalization). In this study we aim to develop a machine learning (ML) model to predict futile recanalization (FR) in AIS patients who undergo MT. Methods: We used data from an ongoing large, multicenter database from 2013 to 2023. We included AIS patients treated with MT for ICA, M1, or M2 occlusion with successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] score ≥ 2C) and procedure durations under 60 minutes. FR was defined as successful recanalization with 90-day modified Rankin Scale (mRS) 3-6. The dataset was divided into 75% for training and 25% for external validation. Using the Caret Package in R, multiple models were tested, and their performances were evaluated by the area under the curve (AUC) of receiver operating. Both baseline and pre-interventional characteristics were incorporated into the model. The selected model was then externally validated on a 25% validation dataset. Results: Among 2,546 qualified patients, FR occurred in 1,342 (52.7%). In univariate analysis, baseline characteristics were significantly different between FR and non-FR groups. The M5P model demonstrated the highest performance (AUC: 0.833; 95% CI: 0.7989-0.852; PPV: 0.8101) in comparison to other tested models such as logistic regression (AUC: 0.74), RF (AUC: 0.78), J48 (AUC: 0.78), SVM (AUC: 0.79), and GB (AUC: 0.79). The external validation of the model showed satisfactory results (AUC: 75.25; 95% CI: 70-80; PPV: 76.87). Conclusion: Utilizing clinical, pre-procedural, and imaging parameters, the M5P model can efficiently predict F) in AIS patients before attempting MT. This tool can assist neurointerventionalists in adequately choosing their MT candidates.

Introduction: Impact of race on outcomes in the treatment of intracranial aneurysm (IA) remains unclear. We aimed to investigate the relationship between race classified into White, Black, Hispanic, and other ("other" includes Native American or Alaska Native, Asian or Pacific Islander, and other race) and treatment outcomes in patients with ruptured and unruptured IAs. Methods: Stroke Thrombectomy and Aneurysm Registry (STAR) was a retrospective observational study. Data from 9 centers in the United States, Europe, and Asia for IA patients who undertook endovascular treatment (EVT) or microsurgical treatment (MST) between January 2016 and December 2020 were included for analysis. The primary outcome was 90-day mRS 0-2. Secondary outcomes included periprocedural cerebral infarction and intracranial hemorrhage, perioperative symptomatic cerebral vasospasm in ruptured IA and mortality, and all causes of mortality within 90 days. Results: 2,836 IA patients treated with EVT or MST were included. Among these 2,836 patients, 1,053 patients were White, 350 were Black, 264 were Hispanic, and 1,169 were other. The primary outcome in Hispanic patients was significantly lower than White patients (adjusted odds ratio [aOR] 0.36, 95% CI, 0.23-0.56, P < .001). The periprocedural cerebral infarction, perioperative mortality, and all causes of mortality in Hispanic patients were significantly higher than White patients (aOR 2.53, 95% CI, 1.40-4.58, P = .002, aOR 1.84, 95% CI, 1.00-3.38, P = .049, aOR 1.83, 95% CI, 1.06-3.17, P = .03, respectively). However, these outcomes were not significantly different in Black and other patients compared to White patients. Conclusions: This study demonstrates Hispanic IA patients are more likely to have a poor outcome at 90 days following EVT or MST than White patients.

Introduction: The outcomes of mechanical thrombectomy (MT) for patients with acute ischemic stroke (AIS) caused by medium vessel occlusions (MeVOs) in different vessels remains unknown. The aim of this study is to investigate MT outcomes in AIS patients with isolated MeVOs in different occluded vessel segments using the data from an ongoing international multicenter registry, the Stroke Thrombectomy and Aneurysm Registry (STAR). The aim of this study is to investigate MT outcomes in AIS patients with isolated MeVOs in different occluded vessel segments using the data from an ongoing international multicenter registry, the Stroke Thrombectomy and Aneurysm Registry (STAR). Methods: 110 AIS patients with MeVO who undertook MT between January 2010 and December 2022 were retrospectively investigated. MeVO was defined as isolated occlusion of the A2 or A3 (A23O) segment of the anterior cerebral artery, M3 segment of the middle cerebral artery (M3O), and P2 or P3 segment of the posterior cerebral artery (P23O). The primary outcome measure was a 90-day modified Rankin score (mRS) 0-2. The 90-day mRS 0-1, any intracranial hemorrhage, symptomatic intracranial hemorrhage, and 90-day mortality were used as secondary outcomes. Outcomes were compared between A23O, M3O, and P23O. Results: Median (interquartile range) age was 68.3 (58.4-76.0) years and 49 patients were female (46.7%). MeVO included 17 A23O (15.5%), 60 M3O (54.5%), and 33 P23O (30.0%).Compared to patients with A23O (17.7%), those with M3O (56.7%) and P23O (45.5%) had a higher proportion of 90-day mRS 0-2 (M3O, adjusted odds ratio 10.3, 95% confidence interval 1.71-62.2, p = 0.01; P23O adjusted odds ratio 8.86, 95% confidence interval 1.32-59.3, p =0.02). Other outcomes showed no significant differences. Conclusions: This study indicates A2O might be related to poorer outcomes compared to M3O and P23 in MT treatment for AIS patients due to isolated MeVO. Efforts should be aimed at improving outcomes following A23O to match those at other MeVO locations.

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.