Entropy predicts sensitivity of pseudorandom seeds.

Seed design is important for sequence similarity search applications such as read mapping and average nucleotide identity (ANI) estimation. Although k-mers and spaced k-mers are likely the most well-known and used seeds, sensitivity suffers at high error rates, particularly when indels are present. Recently, we developed a pseudorandom seeding construct, strobemers, which was empirically shown to have high sensitivity also at high indel rates. However, the study lacked a deeper understanding of why. In this study, we propose a model to estimate the entropy of a seed and find that seeds with high entropy, according to our model, in most cases have high match sensitivity. Our discovered seed randomness-sensitivity relationship explains why some seeds perform better than others, and the relationship provides a framework for designing even more sensitive seeds. We also present three new strobemer seed constructs: mixedstrobes, altstrobes, and multistrobes. We use both simulated and biological data to show that our new seed constructs improve sequence-matching sensitivity to other strobemers. We show that the three new seed constructs are useful for read mapping and ANI estimation. For read mapping, we implement strobemers into minimap2 and observe 30% faster alignment time and 0.2% higher accuracy than using k-mers when mapping reads at high error rates. As for ANI estimation, we find that higher entropy seeds have a higher rank correlation between estimated and true ANI.

Intravenous Thrombolysis before Complete Angiographic Reperfusion: Beyond Angiographic Assessment to Target Microvascular Obstruction?

OBJECTIVE: Recent data have suggested that ineffective tissue reperfusion despite successful angiographic reperfusion was partly responsible for unfavorable outcomes after endovascular therapy (EVT) and might be modulated by intravenous thrombolysis (IVT) use before EVT. To specifically decipher the effect played by IVT before EVT, we compared the clinical and safety outcomes of patients who experienced a complete reperfusion at the end of EVT according to IVT use before EVT. METHODS: The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, observational study at 21 centers that perform EVT in France. Patients were included if they had an anterior large vessel occlusion of the intracranial internal carotid artery or middle cerebral artery (M1/M2 segments) and complete reperfusion (expanded Thrombolysis in Cerebral Infarction score = 3) with EVT within 6 hours, between January 2015 and December 2021. The cohort was divided into two groups according to IVT use before EVT, and propensity score matching (PSM) was used to balance the two groups. Primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included favorable outcome (mRS 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Outcomes were estimated with multivariate logistic models adjusted for age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and time from symptom onset to puncture. RESULTS: Among 5,429 patients included in the ETIS registry, 1,093 were included in the study, including 651 patients with complete recanalization treated with IVT before EVT. After PSM, 488 patients treated with IVT before EVT were compared to 337 patients without IVT. In the matched cohort analysis, the IVT+EVT group had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR] = 1.41, 95% confidence interval [CI] = 1.04-1.91, p = 0.023) and higher rates of favorable outcome (61.1% vs 48.7%, aOR = 1.49, 95% CI = 1.02-2.20, p = 0.041) at 90 days compared with the EVT alone group. Rates of symptomatic intracerebral hemorrhage were comparable between both groups (6.0% vs 4.3%, aOR = 1.16, 95% CI = 0.53-2.54, p = 0.709). INTERPRETATION: In clinical practice, even after complete angiographic reperfusion by EVT, prior IVT use improves clinical outcomes of patients without increasing bleeding risk. ANN NEUROL 2024;95:762-773.

Inferring country-specific import risk of diseases from the world air transportation network.

Disease propagation between countries strongly depends on their effective distance, a measure derived from the world air transportation network (WAN). It reduces the complex spreading patterns of a pandemic to a wave-like propagation from the outbreak country, establishing a linear relationship to the arrival time of the unmitigated spread of a disease. However, in the early stages of an outbreak, what concerns decision-makers in countries is understanding the relative risk of active cases arriving in their country-essentially, the likelihood that an active case boarding an airplane at the outbreak location will reach them. While there are data-fitted models available to estimate these risks, accurate mechanistic, parameter-free models are still lacking. Therefore, we introduce the 'import risk' model in this study, which defines import probabilities using the effective-distance framework. The model assumes that airline passengers are distributed along the shortest path tree that starts at the outbreak's origin. In combination with a random walk, we account for all possible paths, thus inferring predominant connecting flights. Our model outperforms other mobility models, such as the radiation and gravity model with varying distance types, and it improves further if additional geographic information is included. The import risk model's precision increases for countries with stronger connections within the WAN, and it reveals a geographic distance dependence that implies a pull- rather than a push-dynamic in the distribution process.

The Benefit of a Complete over a Successful Reperfusion Decreases with Time.

OBJECTIVE: Time from stroke onset to reperfusion (TSOR) is strongly associated with outcomes after endovascular treatment. A near-to-complete or complete reperfusion (modified Treatment in Cerebral Ischemia [mTICI] 2c-3) is associated with improved outcomes compared with a successful reperfusion (mTICI 2b). However, it is unknown whether this association remains stable as TSOR increases. Therefore, we sought to investigate the association between TSOR and outcomes according to the reperfusion status. METHODS: We analyzed data from the Endovascular Treatment in Ischemic Stroke registry, a prospective, observational, multicentric study of acute ischemic stroke patients treated with endovascular treatment in 21 centers in France. We included patients with anterior occlusions (M1, internal carotid artery, tandem), with a known time of symptom onset. Outcomes were early neurological improvement at 24 hours and favorable outcome (modified Rankin Scale between 0 and 2) at 90 days. RESULTS: Overall, 4,444 patients were analyzed. Compared with a mTICI 2b, a mTICI 2c-3 at 1 hour was associated with higher mean marginal probabilities of early neurological improvement (25.6%, 95% CI 11.7-39.5, p = 0.0003) and favorable outcome (15.2%, 95% CI 3.0-27.4, p = 0.0143), and progressively declined with TSOR. The benefit of a mTICI 2c-3 over a mTICI 2b was no longer significant regarding the rates of early neurological improvement and favorable outcome after a TSOR of 414 and 344 minutes, respectively. INTERPRETATION: The prognostic value of a complete over a successful reperfusion progressively declined with time, and no difference regarding the rates of favorable outcome was observed between a complete and successful reperfusion beyond 5.7 hours. ANN NEUROL 2023;93:934-941.

Thrombectomy with or without Intravenous Thrombolytics in Basilar Artery Occlusion.

OBJECTIVE: Two randomized trials demonstrated the benefit of endovascular therapy (EVT) in patients suffering from a stroke due to a basilar artery occlusion (BAO). However, intravenous thrombolytic (IVT) use before EVT was low in these trials, questioning the added value of this treatment in this setting. We sought to investigate the efficacy and safety of EVT alone compared to IVT + EVT in stroke patients with a BAO. METHODS: We analyzed data from the Endovascular Treatment in Ischemic Stroke registry, a prospective, observational, multicenter study of acute ischemic stroke patients treated with EVT in 21 centers in France between 1 January 2015 and 31 December 2021. We included patients with BAO and/or intracranial vertebral artery occlusion and compared patients treated with EVT alone versus IVT + EVT after propensity score (PS) matching. Variables selected for the PS were pre-stroke mRS, dyslipidemia, diabetes, anticoagulation, admission mode, baseline NIHSS and ASPECTS, type of anesthesia, and time from symptom onset to puncture. Efficacy outcomes were good functional outcome (modified Rankin Scale [mRS] 0-3) and functional independence (mRS 0-2) at 90 days. Safety outcomes were symptomatic intracranial hemorrhages and all-cause mortality at 90 days. RESULTS: Among 385 patients, 243 (134 EVT alone and 109 IVT + EVT) were included after PS matching. There was no difference between EVT alone and IVT + EVT regarding good functional outcome (adjusted odd ratio [aOR] labeling = 1.27, 95% confidence interval [CI], 0.68-2.37, p = 0.45) and functional independence (aOR = 1.50, 95% CI, 0.79-2.85, p = 0.21). Symptomatic intracranial hemorrhage and all-cause mortality were also similar between the two groups (aOR = 0.42, 95% CI, 0.10-1.79, p = 0.24 and aOR = 0.56, 95% CI, 0.29-1.10, p = 0.09, respectively). INTERPRETATION: In this PS matching analysis, EVT alone seemed to lead to similar neurological recovery than IVT + EVT, with comparable safety profile. However, given our sample size and the observational nature of this study, further studies are needed to confirm these findings. ANN NEUROL 2023;94:596-604.

24-Hour Carotid Stent Patency and Outcomes After Endovascular Therapy: A Multicenter Study.

BACKGROUND: Management of extracranial internal carotid artery steno-occlusive lesion during endovascular therapy remains debated. Stent occlusion within 24 hours of endovascular therapy is a frequent event after acute carotid artery stenting, and we currently lack large population results. We investigated the incidence, predictors, and clinical impact of stent occlusion after acute carotid artery stenting in current clinical practice. METHODS: Patients treated by endovascular therapy with acute carotid artery stenting between 2015 and 2019 in 5 large-volume endovascular-capable centers were retrospectively analyzed. Patients were separated in 2 groups according to the stent patency at 24 hours after carotid artery stenting. We compared baseline characteristics, treatment modalities, and clinical outcome depending on 24-hour stent patency. Primary end point was favorable outcome, defined as a modified Rankin Scale score 0-2 at 3 months. RESULTS: A stent occlusion was observed in 47/225 patients (20.9%). Patients with stent patency had a lower baseline National Institutes of Health Stroke Scale (median [interquartile range]: 13 [7-17] versus 18 [12-21]) and had more often stroke of atherothrombotic origin (77.0% versus 53.2%). A higher stent patency rate was found for patients treated with P2Y12 antagonists at the acute phase (odds ratio [OR]' 2.95 [95% CI' 1.10-7.91]; P=0.026) and treated with angioplasty (OR' 2.42 [95% CI' 1.24-4.67]; P=0.008). A better intracranial angiographic reperfusion was observed in patients with 24-hour stent patency compared with patients without stent patency (OR' 8.38 [95% CI' 3.07-22.78]; P<0.001). Patients with a stent patency at 24 hours had a higher chance of favorable outcome (OR' 3.29 [95% CI, 1.66-6.52]; P<0.001) and a lower risk of death (OR' 0.32 [95% CI, 0.13-0.76]; P=0.009). CONCLUSIONS: One out of 5 patients treated with carotid artery stenting during endovascular therapy presented a stent occlusion within 24 hours. This event was associated with worse functional outcome. Stroke etiology, P2Y12 antagonist administration, quality of intracranial reperfusion, and angioplasty were associated with 24-hour stent patency.

Role of Brain Imaging in the Prediction of Intracerebral Hemorrhage Following Endovascular Therapy for Acute Stroke.

Currently most acute ischemic stroke patients presenting with a large vessel occlusion are treated with endovascular therapy (EVT), which results in high rates of successful recanalization. Despite this success, more than half of EVT-treated patients are significantly disabled 3 months later partly due to the occurrence of post-EVT intracerebral hemorrhage. Predicting post-EVT intracerebral hemorrhage is important for individualizing treatment strategies in clinical practice (eg, safe initiation of early antithrombotic therapies), as well as in selecting the optimal candidates for clinical trials that aim to reduce this deleterious outcome. Emerging data suggest that brain and vascular imaging biomarkers may be particularly relevant since they provide insights into the ongoing acute stroke pathophysiology. In this review/perspective, we summarize the accumulating literature on the role of cerebrovascular imaging biomarkers in predicting post-EVT-associated intracerebral hemorrhage. We focus on imaging acquired before EVT, during the EVT procedure, and in the early post-EVT time frames when new therapeutic therapies could be tested. Accounting for the complex pathophysiology of post-EVT-associated intracerebral hemorrhage, this review may provide some guidance for future prospective observational or therapeutic studies.

Stochastic dynamics of Type-I interferon responses.

Interferon (IFN) activates the transcription of several hundred of IFN stimulated genes (ISGs) that constitute a highly effective antiviral defense program. Cell-to-cell variability in the induction of ISGs is well documented, but its source and effects are not completely understood. The molecular mechanisms behind this heterogeneity have been related to randomness in molecular events taking place during the JAK-STAT signaling pathway. Here, we study the sources of variability in the induction of the IFN-alpha response by using MxA and IFIT1 activation as read-out. To this end, we integrate time-resolved flow cytometry data and stochastic modeling of the JAK-STAT signaling pathway. The complexity of the IFN response was matched by fitting probability distributions to time-course flow cytometry snapshots. Both, experimental data and simulations confirmed that the MxA and IFIT1 induction circuits generate graded responses rather than all-or-none responses. Subsequently, we quantify the size of the intrinsic variability at different steps in the pathway. We found that stochastic effects are transiently strong during the ligand-receptor activation steps and the formation of the ISGF3 complex, but negligible for the final induction of the studied ISGs. We conclude that the JAK-STAT signaling pathway is a robust biological circuit that efficiently transmits information under stochastic environments.

Effect of small vessel disease severity on blood pressure management after endovascular therapy in the BP TARGET trial.

BACKGROUND AND PURPOSE: Acute ischaemic stroke patients with cerebral small vessel disease (CSVD), including cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs), have worse outcomes. The effect was investigated of two blood pressure strategies (intensive vs. standard) and blood pressure variability (BPV) after reperfusion according to CSVD burden in the BP TARGET trial. METHODS: Patients with available magnetic resonance imaging at baseline were included. CMBs were described as absent or present and WMH severity was described according to the Fazekas classification (0-1, absent-mild; 2-3, moderate to severe). Outcomes consisted of any intracerebral hemorrhage (ICH) at 24 h and favorable outcome at 90 days (modified Rankin Scale score between 0 and 2). RESULTS: In all, 246 patients were included. The intensive systolic blood pressure target was not associated with lower rates of ICH or favorable outcome according to CSVD subgroups (all p values >0.35). Several BPV parameters were associated with increased odds of ICH in patients with CMBs but not in patients without CMBs (diastolic blood pressure coefficient of variation, odds ratio 2.06, 95% confidence interval [CI] 1.13-3.77, in patients with ≥1 CMB vs. 0.94, 95% CI 0.68-1.31, in patients without CMBs, phet  = 0.026). Several diastolic BPV parameters were associated with worse outcomes in patients with severe WMHs but not in patients without WMHs (diastolic blood pressure coefficient of variation, odds ratio 0.32, 95% CI 0.17-0.61, in patients with severe WMHs vs. 1.09, 95% CI 0.67-1.79, in patients without WMHs; phet  = 0.003). CONCLUSION: No effect of the intensive systolic blood pressure management strategy was found on ICH occurrence or functional outcome according to CSVD burden. BPV was associated with higher odds of ICH in patients with CMBs and worse outcome in patients with moderate-to-severe WMHs.

Estimating the share of SARS-CoV-2-immunologically naïve individuals in Germany up to June 2022.

After the winter of 2021/2022, the coronavirus disease 2019 (COVID-19) pandemic had reached a phase where a considerable number of people in Germany have been either infected with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, vaccinated or both, the full extent of which was difficult to estimate, however, because infection counts suffer from under-reporting, and the overlap between the vaccinated and recovered subpopulations is unknown. Yet, reliable estimates regarding population-wide susceptibility were of considerable interest: Since both previous infection and vaccination reduce the risk of severe disease, a low share of immunologically naïve individuals lowers the probability of further severe outbreaks, given that emerging variants do not escape the acquired susceptibility reduction. Here, we estimate the share of immunologically naïve individuals by age group for each of the sixteen German federal states by integrating an infectious-disease model based on weekly incidences of SARS-CoV-2 infections in the national surveillance system and vaccine uptake, as well as assumptions regarding under-ascertainment. We estimate a median share of 5.6% of individuals in the German population have neither been in contact with vaccine nor any variant up to 31 May 2022 (quartile range [2.5%-8.5%]). For the adult population at higher risk of severe disease, this figure is reduced to 3.8% [1.6%-5.9%] for ages 18-59 and 2.1% [1.0%-3.4%] for ages 60 and above. However, estimates vary between German states mostly due to heterogeneous vaccine uptake. Excluding Omicron infections from the analysis, 16.3% [14.1%-17.9%] of the population in Germany, across all ages, are estimated to be immunologically naïve, highlighting the large impact the first two Omicron waves had until the beginning of summer in 2022. The method developed here might be useful for similar estimations in other countries or future outbreaks of other infectious diseases.

COVID-19 lockdown induces disease-mitigating structural changes in mobility networks.

In the wake of the COVID-19 pandemic many countries implemented containment measures to reduce disease transmission. Studies using digital data sources show that the mobility of individuals was effectively reduced in multiple countries. However, it remains unclear whether these reductions caused deeper structural changes in mobility networks and how such changes may affect dynamic processes on the network. Here we use movement data of mobile phone users to show that mobility in Germany has not only been reduced considerably: Lockdown measures caused substantial and long-lasting structural changes in the mobility network. We find that long-distance travel was reduced disproportionately strongly. The trimming of long-range network connectivity leads to a more local, clustered network and a moderation of the "small-world" effect. We demonstrate that these structural changes have a considerable effect on epidemic spreading processes by "flattening" the epidemic curve and delaying the spread to geographically distant regions.

Magnitude of Blood Pressure Change After Endovascular Therapy and Outcomes: Insight From the BP-TARGET Trial.

BACKGROUND AND PURPOSE: To assess the association between systolic blood pressure change (ΔSBP) at different time intervals after successful reperfusion with radiographic and clinical outcomes. METHODS: This is a post hoc analysis of the BP-TARGET multicenter trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy). ΔSBP was defined as end of procedure SBP minus mean SBP at different time intervals (15-60 minutes, 1-6 hours, and 6-24 hours postprocedure). The primary outcome was the poor functional outcome (90-day modified Rankin Scale score 3-6). RESULTS: We included a total of 267 patients (130 in the intensive treatment group). Compared with patients with favorable outcome, patients with poor outcome had lower ΔSBP (less SBP reduction) at all times intervals. After adjusting for potential confounders including baseline SBP, both ΔSBP15-60M and ΔSBP6-24H were associated with lower odds of poor outcome (adjusted odds ratio per 5 mm Hg SBP reduction, 0.89 [95% CI, 0.81-0.99], and adjusted odds ratio 0.82 [95% CI, 0.73-0.92], respectively). Concerning safety outcomes, patients with intraparenchymal hemorrhage had lower ΔSBP at all time intervals. ΔSBP15-60M was associated with lower odds of any intraparenchymal hemorrhage (adjusted odds ratio per 5 mm Hg SBP reduction 0.91 [95% CI, 0.83-0.99]). Conversely, ΔSBP was not associated with mortality or neurological deterioration at any time interval. CONCLUSIONS: After successful reperfusion, ΔSBP had a linear relationship with poor outcome and the risk of poor outcome was higher with less reduction from the baseline SBP. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03160677.

Effect of Baseline Antihypertensive Treatments on Stroke Severity and Outcomes in the BP TARGET Trial.

BACKGROUND: Acute ischemic stroke (AIS) patients with a history of hypertension experience worse outcomes, which may be explained by a deleterious impact of the renin-angiotensin system (RAS) overactivation. We sought to investigate whether prestroke antihypertensive treatments (AHT) influenced baseline stroke severity and neurological outcomes, in patients with AIS successfully treated by endovascular therapy. METHODS: We performed a post hoc analysis of the BP TARGET trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) and included hypertensive patients with available data regarding AHT at admission, categorized as RAS inhibitors (ACE [angiotensin-converting enzyme] inhibitors, ARBs [angiotensin 2 receptor blockers], and ß-blockers) and non-RAS inhibitors (calcium channel blockers and diuretics). Associations of each AHT with National Institutes of Health Stroke Scale (NIHSS) score at baseline were investigated in linear mixed model adjusted for the number of treatments and center. Associations of each AHT with 24-hour NIHSS change, intracranial hemorrhage were performed using linear mixed model adjusted for baseline NIHSS, the number of treatments, center, age, and sex and adjusted for age, sex, diabetes, and current smoking for favorable outcome. All analyses were performed on cases-available data regarding the low number of missing data. RESULTS: Overall, 203 patients with at least one AHT were included. Patients under non-RAS inhibitor treatments had a higher NIHSS score at baseline (adjusted mean difference=3.28 [95% CI, 1.33-5.22]; P=0.001). Conversely, patients under RAS inhibitor treatments had a lower baseline NIHSS score (adjusted mean difference=-2.81 [95% CI, -5.37 to -0.25]; P=0.031). Intracranial hemorrhage occurrence was significantly more frequent in patients under non-RAS inhibitor treatments (adjusted odds ratio of 2.48 [95% CI, 1.12-5.47]; P=0.025). Conversely, the use of RAS inhibitor treatments before AIS was not associated with higher odds of radiographic intracranial hemorrhage. Patients with non-RAS inhibitor treatments had less improvement of NIHSS at 24 hours compared with patients without (adjusted mean difference, 2.83 [95% CI, -0.16 to 5.81]; P=0.063). Baseline RAS inhibitor or noninhibitor treatments were not associated with favorable outcome. CONCLUSIONS: We showed an opposite effect of baseline AHT, based on their effect on the RAS. Patients treated with RAS inhibitor agents before AIS exhibited less severe AIS compared with patients under non-RAS inhibitor treatments, developed less intracranial hemorrhage at 24 hours and had a trend toward better NIHSS score at 24 hours. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03160677.

Mechanical thrombectomy failure in anterior circulation strokes: Outcomes and predictors of favorable outcome.

BACKGROUND AND PURPOSE: Despite continuous improvement and growing knowledge in the endovascular therapy of large vessel occlusion stroke (LVOS), mechanical thrombectomy (MT) still fails to obtain satisfying intracranial recanalization in 10% to 15% of cases. However, little is known regarding clinical and radiological outcomes among this singularly underexplored subpopulation undergoing failed MT. We aimed to investigate the outcome after failed MT and identify predictive factors of favorable outcome despite recanalization failure. METHODS: We conducted a retrospective analysis of consecutive patients prospectively included in the ongoing observational multicenter Endovascular Treatment in Ischemic Stroke registry from January 2015 to September 2020. Patients presenting with anterior circulation LVOS treated with MT but experiencing failed intracranial recanalization defined as final modified Thrombolysis In Cerebral Infarction (mTICI) score of 0, 1 and 2a were included. Clinical and radiological outcomes were assessed along with the exploration of predictive factors of Day-90 favorable outcome. RESULTS: The study population comprised 533 patients. Mean age was 68.8 ± 16 years, and median admission National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were 17 (IQR 12-21) and 7 (IQR 5-8), respectively. Favorable outcomes were observed in 85 patients (18.2%) and 186 died (39.0%). The rate of symptomatic intracranial hemorrhage was 14.1%. In multivariable analysis, younger age (odds ratio [OR] 0.96, 95% CI 0.94-0.98, p < 0.001), a lower admission NIHSS (OR 0.87, 95% CI 0.83-0.91, p < 0.001), a lower number of MT passes (OR 0.77, 95% CI 0.77-0.87, p < 0.001), a lower delta ASPECTS between initial and Day-1 imaging (OR 0.83, 95% CI 0.71-0.98, p = 0.026) and stroke etiology [significant difference among etiological subtypes (p = 0.024) with a tendency toward more favorable outcomes for dissection (OR 2.01, 95% CI 0.71-5.67)] were significantly associated with a 90-day favorable outcome. CONCLUSIONS: In this large retrospective analysis of a multicenter registry, we quantified the poor outcome after MT failure. We also identified factors associated with favorable outcome despite recanalization failure that might influence therapeutic management.

Effect of blood pressure variability in the randomized controlled BP TARGET trial.

BACKGROUND AND PURPOSE: The Blood Pressure Target in Acute Ischemic Stroke to Reduce Hemorrhage After Endovascular Therapy (BP TARGET) trial evaluated whether an intensive systolic blood pressure (SBP) target resulted in reduced rates of intracranial hemorrhage (ICH) after successful endovascular therapy (EVT) but did not assess the effect of blood pressure variability (BPV) on functional outcomes and ICH occurrence. We sought to evaluate this question in the BP TARGET trial. METHODS: We performed a post hoc analysis of the BP TARGET trial and included patients with at least 50% of blood pressure (BP) recordings during the first 24 h after EVT. BPV parameters were SBP and diastolic BP (DBP) coefficient of variation (CV), standard deviation (SD), maximum-minimum (max-min), successive variation (SV), and time rate. The primary outcome was favorable functional outcome (3-month modified Rankin Scale between 0 and 2); the secondary outcome was the rate of ICH at 24 h. RESULTS: We included 290 patients (mean number of BP measures = 30.4, SD = 8.0). BPV parameters (SBPSD , SBPmax-min , SBPCV ) were higher in the intensive SBP target group. Only DBP BPV parameters were associated with worse functional outcomes in the unadjusted model (DBPSD , DBPmax-min , DBPCV , and DBPSV ), but not after adjustment. Higher SBPmax-min was associated with worse functional outcomes in Thrombolysis in Cerebral Infarction 2B patients (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.38-1.02), but not in patients with complete reperfusion (OR = 1.27, 95% CI = 0.80-2.02, p for heterogeneity (phet =0.037). None of the BPV parameters was associated with ICH, regardless of the randomization group or the reperfusion grade. CONCLUSIONS: BPV was significantly higher in the intensive SBP target group but was not associated with functional outcome or ICH.

Intravenous abciximab as a rescue therapy for immediate reocclusion after successful mechanical thrombectomy in acute ischemic stroke patients.

Immediate reocclusion after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a rare but devastating condition associated with poor functional outcome. The aim of this study was to gain insights into the mechanisms underlying immediate reocclusion, and to evaluate the efficacy and safety of the glycoprotein IIb/IIIa antagonist abciximab, for its treatment. Clinical data were collected from April 2015 to April 2019 in a monocentric prospective registry of AIS patients treated by MT. All patients with immediate reocclusion were retrospectively selected and subdivided into 2 groups according to abciximab treatment status. In vitro, the separate and combined effects of abciximab and alteplase on clot formation in whole blood under flow conditions were further investigated in microfluidic chambers. From 929 MT-treated patients, 21 had post-MT immediate reocclusion. Abciximab treatment in reocclusion patients (n = 10) led to higher rate of final recanalization (p < .001) while it did not increase bleeding complications. Flow chamber experiments revealed that, in contrast to alteplase, abciximab efficiently limits thrombus accretion from flowing blood by blocking platelet aggregation. Our results underscore a key role for platelet aggregation and the potential of Glycoprotein IIb/IIIa antagonists as a rescue therapy in post-MT immediate reocclusion.

Only true and fabricated baseline statements combined might improve lie, but not truth, detection.

OBJECTIVES: We tested the effect of true and fabricated baseline statements from the same sender on veracity judgments. HYPOTHESES: We predicted that presenting a combination of true and fabricated baseline statements would improve truth and lie detection accuracy, while presenting a true baseline would improve only truth detection, and presenting a fabricated baseline would only improve lie detection compared with presenting no baseline statement. METHOD: In a 4 × 2 within-subjects design, 142 student participants (Mage = 23.47 years; 118 female) read no baseline statement, a true baseline statement, a fabricated baseline statement, and a combination of a true and a fabricated baseline statement from 29 different senders. Participants then rated the veracity of a true or fabricated target statement from the same 29 senders. RESULTS: Logistic mixed-effects models with senders and participants as random effects showed no significant differences in overall veracity judgment accuracy between the no-baseline (51%) and either the true-baseline (44%) or the fabricated-baseline (49%) conditions. Equivalence tests failed to show the predicted equivalence of these accuracy rates. Separate analyses of truth and lie detection rates confirmed the assumed improvement of lie detection in the combination-of-true-and-fabricated-baseline condition (accuracy = 39%-61%). No other truth or lie detection rate changed significantly except that, unexpectedly, a true baseline reduced truth detection accuracy (64%-49%). CONCLUSIONS: Baseline statements largely did not affect judgment accuracy and, in the case of true baselines, even had a negative impact on truth detection. The rather small positive effect of two baseline statements on lie detection suggests an avenue for further research, especially with expert raters. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

First-Pass Effect in Basilar Artery Occlusions: Insights From the Endovascular Treatment of Ischemic Stroke Registry.

BACKGROUND AND PURPOSE: In the settings of thrombectomy, the first-pass effect (FPE), defined by a complete recanalization after one pass with no rescue therapy, has been shown to be associated with an improved outcome. As this phenomenon has been predominantly described in anterior circulation strokes, we aimed to study the prevalence, outcomes, and predictors of FPE in patients with a basilar artery occlusion. METHODS: From a prospective multicentric registry, we collected the data of all consecutive basilar artery occlusion patients who underwent thrombectomy and compared the outcomes of patients who achieved FPE and those who did not. We also compared FPE patients with those who achieved a complete recanalization with >1 pass. Finally, a multivariate analysis was performed to determine the predictors of FPE. RESULTS: Data from 280 patients were analyzed in our study, including 84 of 280 patients (30%) with an atheromatous etiology. An FPE was achieved in 93 patients (33.2%), with a significantly higher proportion of good outcomes (modified Rankin Scale score 0-2 at 3 months) and lower mortality than non-FPE patients. An FPE was also associated with improved outcomes compared with patients who went on to have full recanalization with >1 pass. Contact aspiration as first-line strategy was a strong predictor of FPE, whereas baseline antiplatelets and atheromatous etiology were negative predictors. CONCLUSIONS: In our study, an FPE was achieved in approximately one-third of patients with a basilar artery occlusion and was associated with improved outcomes. More research is needed to improve devices and techniques to increase the incidence of FPE. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877.

Association of Hypotension During Thrombectomy and Outcomes Differs With the Posterior Communicating Artery Patency.

BACKGROUND AND PURPOSE: Hypotension during endovascular therapy for acute ischemic stroke is associated with worse functional outcomes (FO). Given its important role in intracranial hemodynamics, we investigated whether hypotension during endovascular therapy had the same effect on FO according to the posterior communicating artery (PComA) patency. METHODS: We performed a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). Patients were included if they had middle cerebral artery occlusions. Primary outcome was favorable FO, defined by a modified Rankin Scale scores between 0 and 2 at 3 months. RESULTS: One hundred forty-eight patients with middle cerebral artery occlusion were included. In patients with no PComA, an increase in minimum mean arterial pressure was positively associated with favorable FO (odds ratio per 10 mm Hg increase, 1.59 [95%CI, 1.11-2.25]; P=0.010), whereas no association was found in patients with a PComA (odds ratio, 0.77 [95% CI, 0.54-1.08]; P=0.12). Patients with no PComA and longer cumulative time with mean arterial pressure <90 mm Hg or systolic blood pressure <140 mm Hg had significantly lower rates of favorable FO, with an odds ratio per 10-minute increase of 0.75 (95% CI, 0.59-0.94; P=0.010) and 0.74 (95% CI, 0.60-0.91; P=0.003), but not in patients with a PComA. CONCLUSIONS: Hypotension during endovascular therapy for middle cerebral artery occlusion is consistently associated with worse FO in patients with no PComA but not in those with a PComA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02523261.

Thrombectomy Complications in Large Vessel Occlusions: Incidence, Predictors, and Clinical Impact in the ETIS Registry.

BACKGROUND AND PURPOSE: Procedural complications in thrombectomy for large vessel occlusions of the anterior circulation are not well described. We investigated the incidence, risk factors, and clinical implications of thrombectomy complications in daily clinical practice. METHODS: We used data from the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France. The present study is a retrospective analysis of 4029 stroke patients with anterior large vessel occlusions treated with thrombectomy between January 2015 and May 2020 in 18 centers. We systematically collected procedural data, incidence of embolic complications, perforations and dissections, clinical outcome at 90 days, and hemorrhagic complications. RESULTS: Procedural complications occurred in 7.99% (95% CI, 7.17%-8.87%), and embolus to a new territory (ENT) was the most frequent (5.2%). Predictors of ENTs were terminal carotid/tandem occlusion (odds ratio [OR], 5 [95% CI, 2.03-12.31]; P<0.001) and an increased total number of passes (OR, 1.22 [95% CI, 1.05-1.41]; P=0.006). ENTs were associated to worse clinical outcomes (90-day modified Rankin Scale score, 0-2; adjusted OR, 0.4 [95% CI, 0.25-0.63]; P<0.001), increased mortality (adjusted OR, 1.74 [95% CI, 1.2-2.53]; P<0.001), and symptomatic intracerebral hemorrhage (adjusted OR, 1.87 [95% CI, 1.15-3.03]; P=0.011). Perforations occurred in 1.69% (95% CI, 1.31%-2.13%). Predictors of perforations were terminal carotid/tandem occlusions (39.7% versus 27.6%; P=0.028). 40.7% of patients died at 90 days, and the overall rate of poor outcome was 74.6% in case of perforation. Dissections occurred in 1.46% (95% CI, 1.11%-1.88%) and were more common in younger patients (median age, 64.2 versus 70.2 years; P=0.002). Dissections did not affect the clinical outcome at 90 days. Besides dissection, complications were independent of the thrombectomy technique. CONCLUSIONS: Thrombectomy complication rate is not negligible, and ENTs were the most frequent. ENTs and perforations were associated with disability and mortality, and terminal carotid/tandem occlusions were a risk factor. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877.