Dual antiplatelet therapy versus intravenous tissue plasminogen activator with acute minor ischemic stroke: A systematic review and meta-analysis of safety and efficacy.

OBJECTIVES: To compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS). MATERIALS AND METHODS: Following Cochrane and PRISMA guidelines, we analyzed observational studies and clinical trials comparing DAPT and IV t-PA in patients with minor AIS. Databases included PubMed, Scopus, and Web of Science. Data extraction included study characteristics, patient demographics, and analyzed outcomes. RevMan 5.3 and OpenMetaAnalyst 2021 were used to analyze the data and assess heterogeneity, respectively. The risk of bias was determined using RoB 2.0 and the Newcastle-Ottawa scale. RESULTS: This meta-analysis included five studies with 3,978 DAPT-treated patients and 2,224 IV t-PA-treated patients. We found no significant differences in achieving modified Rankin scale (mRS) scores of 0-1 (OR 1.11, 95 % CI: 0.79, 1.55, p = 0.56) and 0-2 (OR 0.90, 95 % CI: 0.61, 1.31, p = 0.57), as well as combined mRS scores (OR 1.05, 95 % CI: 0.82, 1.34, p = 0.72). Similarly, there were no significant disparities between the two treatment groups in NIHSS score change from baseline (MD 0.32, 95 % CI: -0.35, 0.98, p = 0.35) and in mortality rates (OR 0.87, 95 % CI: 0.26, 2.93, p = 0.83). Notably, in comparison to the IV t-PA group, the DAPT group exhibited a significantly lower incidence of bleeding (OR 0.31, 95 % CI: 0.14, 0.69, p = 0.004) and symptomatic intracranial hemorrhage (sICH) (OR 0.10, 95 % CI: 0.04, 0.26, p < 0.00001). CONCLUSIONS: Our meta-analysis found no significant differences in efficacy between DAPT and IV t-PA. However, DAPT demonstrated a significantly lower risk of sICH and bleeding compared with IV t-PA.

Safety and efficacy of clot-dissolving therapies for submassive pulmonary embolism: A network meta-analysis of randomized controlled trials.

BACKGROUND: Acute pulmonary embolism (PE) is a serious condition that needs quick and effective treatment. Anticoagulation therapy is the usual care for most PE patients but may not work well for higher-risk ones. Thrombolysis breaks the clot and improves blood flow. It can be given systemically or locally. Ultrasound-assisted catheter-directed thrombolysis (USAT) is a new technique that boosts clot-busting drugs. This network meta-analysis compares death, bleeding, and benefits of four treatments in acute submassive PE. METHODS: We comprehensively searched relevant databases up to July 2023 for RCTs. The outcomes encompassed all-cause mortality, major and minor bleeding, PE recurrence, and hospital stay duration. Bayesian network meta-analysis computed odds ratios (OR) and 95 % CI estimates. RESULTS: In this network meta-analysis of 23 RCTs involving 2521 PE patients, we found that SCDT had the most favorable performance for mortality, as it had the lowest odds ratio (OR) among the four interventions (OR 5.41e-42; 95 % CI, 5.68e-97, 1.37e-07). USAT had the worst performance for major bleeding, as it had the highest OR among the four interventions (OR 4.73e+04; 95 % CI, 1.65, 9.16e+13). SCDT also had the best performance for minor bleeding, as it had the lowest OR among the four interventions (OR 5.68e-11; 95 % CI, 4.97e-25, 0.386). CONCLUSION: Our meta-analysis suggests that SCDT is the most effective treatment intervention in improving the risks of All-cause mortality and bleeding. Thrombolytic therapy helps in improving endpoints including the risk of PE recurrence and the duration of hospital stay.

Institutional trends over a decade in catheter-directed interventions for pulmonary embolism.

OBJECTIVE: Catheter-directed interventions (CDIs) are commonly performed for acute pulmonary embolism (PE). The evolving catheter types and treatment algorithms impact the use and outcomes of these interventions. This study aimed to investigate the changes in CDI practice and their impact on outcomes. METHODS: Patients who underwent CDIs for PE between 2010 and 2019 at a single institution were identified from a prospectively maintained database. A PE team was launched in 2012, and in 2014 was established as an official Pulmonary Embolism Response Team. CDI annual use trends and clinical failures were recorded. Clinical success was defined as physiologic improvement in the absence of major bleeding, perioperative stroke or other procedure-related adverse event, decompensation for submassive or persistent shock for massive PE, the need for surgical thromboembolectomy, or death. Major bleeding was defined as requiring a blood transfusion, a surgical intervention, or suffering from an intracranial hemorrhage. RESULTS: There were 372 patients who underwent a CDI for acute PE during the study period with a mean age of 58.9 ± 15.4 years; there were males 187 (50.3%) and 340 patients has a submassive PE (91.4%). CDI showed a steep increase in the early Pulmonary Embolism Response Team years, peaking in 2016 with a subsequent decrease. Ultrasound-assisted thrombolysis was the predominant CDI technique peaking at 84% of all CDI in 2014. Suction thrombectomy use peaked at 15.2% of CDI in 2019. The mean alteplase dose with catheter thrombolysis techniques decreased from 26.8 ± 12.5 mg in 2013 to 13.9 ± 7.5 mg in 2019 (P < .001). The mean lysis time decreased from 17.2 ± 8.3 hours in 2013 to 11.3 ± 8.2 hours in 2019 (P < .001). Clinical success for the massive and the submassive PE cohorts was 58.1% and 91.2%, respectively; the major bleed rates were 25.0% and 5.3%. There were two major clinical success peaks, one in 2015 mirroring our technical learning curve and one in 2019 mirroring our patient selection learning curve. The clinical success decrease in 2018 was primarily derived from blood transfusions owing to acute blood loss during suction thrombectomy. CONCLUSIONS: CDIs for acute PE have rapidly evolved with high success rates. Multidisciplinary approaches among centers with appropriate expertise are advisable for the safe and successful implementation of catheter interventions.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

In-Hospital Acute Ischemic Stroke is Associated with Worse Outcome: Experience of a Single Center in Santiago Chile.

OBJECTIVES: In-hospital acute ischemic stroke (HIS) accounts for 2-17% of all acute ischemic strokes (AIS) seen in hospital and they have worse prognosis. In this study we aimed to identify the frequency of HIS and their characteristics in our center. MATERIALS AND METHODS: Retrospective analysis of a prospective register of patients with AIS seen at Clínica Alemana de Santiago, between January 2017 and January 2019. HIS and community onset ischemic strokes patients (CIS) were compared, univariate analysis was performed, covariates with p < 0.25 were selected for multivariate analysis. Differences between, proportion of strokes treated with thrombolytic therapy, door to needle time were compared between HIS and CIS patients, as also mortality rates at 90 days. RESULTS: During the study period 369 patients with AIS were seen; of these 20 (5.4%, 95 CI%, 3.5-8.2) corresponded to HIS. In univariate analysis, HIS compared to patients arriving form the community to the emergency room, suffered more frequently from, heart failure (p = 0.04), and active malignancies (p < 0.001). HIS patients had longer times from symptom onset to non-contrast brain tomography (540 ±150 minutes); they were also less frequently treated with intravenous thrombolysis compared to community AIS: 15% versus 30% respectively (p = 0.08). Mortality rates at 90 days were higher in HIS: 30 versus 5% (p = 0.001). CONCLUSIONS: In this cohort, HIS patients suffered delays in their neuroimaging studies and received less intravenous thrombolysis; this underscores the need for a standardized approach to the recognition and management of inhospital acute ischemic stroke.

Outcomes of Homeless Ischemic Stroke Patients Receiving Intravenous Thrombolysis in the United States.

BACKGROUND: Morbidity and mortality among homeless people with cardiovascular diseases and stroke in the United States is high. Adverse outcomes within the homeless population may be the result of seeking care too late to receive time-sensitive interventions. We sought to investigate the impact of homelessness on ischemic stroke patients who received intravenous thrombolysis (IVT). METHODS: We determined rates of post-thrombolytic intracranial hemorrhage (ICH), in-hospital death, and development of moderate to severe disability among homeless ischemic stroke patients treated with IVT. Patients were identified using the Nationwide (National) Inpatient Sample between 2002 and 2017. We compared rates of the various outcomes to non-homeless ischemic stroke patients treated with IVT. RESULTS: There were 514 homeless (mean age 54.7 ± 10.2 years, 20.4% women) and 364,408 non-homeless (mean age 68.6 ± 14.7 years, 49.7% women) ischemic stroke patients who received IVT. There was no difference in post-thrombolytic ICH rates between the two groups (6.6% homeless versus 8.8% non-homeless, p = 0.09). Homeless patients were more frequently discharged to self-care (p = 0.003). Homeless patients were less likely than non-homeless patients to suffer in-hospital death (AOR 0.499 [95% CI 0.30-0.84], p = 0.009) and moderate to severe disability (AOR 0.423 [95% CI 0.29 - 0.62], p < 0.001). CONCLUSION: Homeless ischemic stroke patients who receive IVT are not at an increased risk of developing post-thrombolytic ICH or in-hospital death. Efforts are needed to encourage this unique population to seek medical attention as soon as possible for time-sensitive interventions that may decrease the risk of permanent disability or death associated with ischemic stroke.

Ischemic Stroke in the Very Elderly: Experience from an Italian Stroke Unit Hub Over a Period of 8 Years in the Era of Thrombectomy.

OBJECTIVE: The goal of this study is to understand how very elderly patients (VEP) after ischemic stroke are currently treated in a Stroke Unit (SU) Hub in Italy. We designed a retrospective monocentric study on patients admitted in the SU of "AO San Camillo Forlanini" over an 8-year period. MATERIAL AND METHODS: Data were collected among patients with acute ischemic stroke admitted to SU between January 2012 and December 2019. Patients were divided into three sub-groups: Adults (18-65 years); Elderly (66-85 years); and VEP (>85 years). Vascular risk factors and clinical variables as predictors of short-term clinical outcome were compared among age groups. RESULTS: A total of 1979 patients were enrolled, 254 were VEP (12.8%). The proportion of VEP showed no significant modifications during the 8-year period (11.9% in 2012-2015 and 13.7% in 2016-2019; p=0.93). The proportion of women, hypertension and atrial fibrillation was significantly higher in VEP compared to other age groups (p<0.001). The rate of VEP being treated with rt-PA increased from 2012-2015 to 2016-2019 (from 12.8% to 25.5%, p<0.001). Endovascular thrombectomy was rarely performed in VEP (1.5% of VEP). Rt-PA treatment was associated with favorable outcome for all three age groups (p<0.05). CONCLUSIONS: We showed that VEP present different vascular risk factor profiles, clinical features, and prognostic elements for short-term stroke outcome. Future studies will reveal whether we will observe an increasing trend in the use of rt-PA and endovascular thrombectomy and whether it will result in improved functional outcome for VEP.

Reperfusion Therapy in Acute Ischemic Stroke with Active Cancer: A Meta-Analysis Aided by Machine Learning.

OBJECTIVES: While the prevalence of active cancer patients experiencing acute stroke is increasing, the effects of active cancer on reperfusion therapy outcomes are inconclusive. Thus, we aimed to compare the safety and outcomes of reperfusion therapy in acute stroke patients with and without active cancer. MATERIALS AND METHODS: A comprehensive literature search was conducted for studies comparing the effects of intravenous thrombolysis (IVT) or endovascular treatment (EVT) in ischemic stroke patients with and without active cancer. The literature was screened using both a manual and machine learning algorithm approach. The outcomes evaluated were symptomatic intracerebral hemorrhage (sICH), all-type intracerebral hemorrhage (aICH), successful recanalization, favorable outcomes (modified Rankin Scale, 0-2), and mortality. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) using the random-effects model from the included studies. RESULTS: Seven studies were analyzed in this meta-analysis. IVT (n = 1012) was associated with an increased risk of sICH (OR, 9.80; 95% CI, 3.19-30.13) in the active cancer group. However, no significant differences in aICH, favorable outcomes, and mortality were found between groups. Although sICH and successful recanalization in the EVT group (n = 2496) were similar, we observed fewer favorable outcomes (OR, 0.55; 95% CI, 0.33-0.93) and a high prevalence of mortality (OR, 2.91; 95% CI, 1.89-4.47) in the active cancer group. CONCLUSIONS: Reperfusion therapy may benefit selected patients with acute ischemic stroke with active cancer, considering the comparable clinical outcomes of IVT and procedure-related outcomes of EVT. These results should be cautiously interpreted and confirmed in future well-designed large-scale studies.

Efficacy and Safety of the Telestroke Drip-And-Stay Model: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare outcomes between two models of acute ischemic stroke care. Namely 1) "drip-and-stay", i.e. IV tissue plasminogen activator (tPA) administered at a spoke hospital in a telestroke network, with the patient remaining at the spoke, versus 2) "drip-and-ship", i.e. tPA administered at a spoke hospital with subsequent patient transfer to a hub hospital, and 3) "hub", i.e. tPA and subsequent treatment at a hub hospital. MATERIALS AND METHODS: We performed a systematic review and meta-analysis according to PRISMA guidelines. Literature searches of MEDLINE, Embase, and Cochrane from inception-October 2019 included randomized control trials and observational cohort studies comparing the drip-and-stay model to hub and drip-and-ship models. Outcomes of interest were functional independence (modified Rankin Scale ≤ 1), symptomatic intracranial hemorrhage (sICH), mortality, and length of stay. Pooled effect estimates were calculated using a fixed-effects meta-analysis and random-effects Bayesian meta-analysis. Non-inferiority was calculated using a fixed-margin method. RESULTS: Of 2806 unique records identified, 10 studies, totaling 4,164 patients, fulfilled the eligibility criteria. Meta-analysis found no significant difference in functional outcomes (mRS0-1) (6 studies, RR=1.09, 95%CI 0.98-1.22, p=0.123), sICH (8 studies, RR=0.98, 95%CI 0.64-1.51, p=0.942), or 90-day mortality (5 studies, RR=0.98, 95%CI 0.73-1.32, p=0.911, respectively) between patients treated in a drip-and-stay model compared to patients treated in drip-and-ship or hub models. There was no significant heterogeneity in these outcomes. Drip-and-stay outcomes (mRS 0-1, sICH) were non-inferior when compared to the combined group. CONCLUSIONS: Our findings indicate that drip-and-stay is non-inferior to current models of drip-and-ship or hub stroke care, and may be as safe and as effective as either.

Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Taking Warfarin with Subtherapeutic INR.

INTRODUCTION: Current guidelines allow the administration of intravenous recombinant tissue plasminogen activator (IV r-tPA) to warfarin-treated patients with acute ischemic stroke (AIS) who have an international normalized ratio (INR) of ≤1.7. However, concerns remain about the safety of using IV r-tPA in this situation due to a conceivable risk of symptomatic intracranial hemorrhage (sICH), lack of dedicated randomized controlled trials and the conflicts in the available data. We aimed to determine the risk of sICH in warfarin-treated patients with subtherapeutic INR who received IV r-tPA for AIS in our large volume comprehensive center. METHODS: Patients who had received IV r-tPA for AIS in a 9.6-year period were retrospectively investigated (n = 834). Patients taking warfarin prior to presentation were identified (n = 55). One patient was excluded due to elevated INR beyond the acceptable range for IV r-tPA treatment. Because of the significant difference in the sample size (54 vs 779), warfarin group was matched with 54 non-warfarin patients adjusted for independent risk factors for sICH (age, admission NIHSS, history of diabetes). Good outcome was defined as mRS of 0-2 on discharge and sICH was defined as an ICH causing increase in NIHSS ≥4 or death. Warfarin-treated group was further dichotomized based on INR (1-1.3 vs 1.3-1.7) and safety and outcome measures were compared between resultant groups. RESULTS: No significant difference was found between warfarin-treated and the non-warfarin groups in terms of chance of good outcome on discharge (27.8% in warfarin group vs 26.4% in non-warfarin group; p-value >0.05), or the rate of occurrence of sICH (3.7% in warfarin group vs 11.1% in non-warfarin group; p-value >0.05). Furthermore, rate of sICH (5.1% in patients with INR <1.3 versus 0.0% in patients with INR 1.3-1.7; p-value >0.05) or chance of good outcome on discharge (28.2% of patients with INR <1.3 versus 26.7% in patients with INR 1.3-1.7; p-value >0.05) were not found to be different after the warfarin-treated group was dichotomized. CONCLUSION: Administration of IV r-tPA for AIS in warfarin-treated patients with subtherapeutic INR <1.7 does not increase the risk of sICH.

Intravenous Thrombolysis Is Associated with Less Disabling Stroke and Lower Mortality in Multiple-Pass Endovascular Thrombectomy.

BACKGROUND AND PURPOSE: The benefit of bridging intravenous thrombolysis (IVT) in acute ischaemic stroke patients eligible for endovascular thrombectomy (EVT) is unclear. This may be particularly relevant where reperfusion is achieved with multiple thrombectomy passes. We aimed to determine the benefit of bridging IVT in first and multiple-pass patients undergoing EVT ≤6 h from stroke onset to groin puncture. METHODS: We compared 90-day modified Rankin Scale (mRS) outcomes in 187 consecutive patients with large vessel occlusions (LVOs) of the anterior cerebral circulation who underwent EVT ≤6 h from symptom onset and who achieved modified thrombolysis in cerebral ischaemia (mTICI) 2c/3 reperfusion with the first pass to those patients who required multiple passes to achieve reperfusion. The effect of bridging IVT on outcomes was examined. RESULTS: Significantly more first-pass patients had favourable (mRS 0-2) 90-day outcomes (68 vs. 42%, p = 0.001). Multivariate analysis showed an association between first-pass reperfusion and favourable outcomes (OR 2.25; 95% CI 1.08-4.68; p = 0.03). IVT provided no additional benefit in first-pass patients (OR 1.17; CI 0.42-3.20; p = 0.76); however, in multiple-pass patients, it reduced the risk of disabling stroke (mRS ≥4) (OR 0.30; CI 0.10-0.88; p = 0.02) and mortality (OR 0.07; CI 0.01-0.36; p = 0.002) at 90 days. CONCLUSION: Bridging IVT may benefit patients with anterior circulation stroke with LVO who qualify for EVT and who require multiple passes to achieve reperfusion.

Intracerebral Hemorrhage Volume Reduction and Timing of Intervention Versus Functional Benefit and Survival in the MISTIE III and STICH Trials.

BACKGROUND: The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure. OBJECTIVE: To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials. METHODS: Postoperative scans were performed in STICH II, but not in STICH I; therefore, surgical MISTIE III cases with lobar hemorrhages (n = 84) were compared to STICH II all lobar cases (n = 259) for volumetric analyses. All MISTIE III surgical patients (n = 240) were compared to both STICH I and II (n = 722) surgical patients for timing analyses. These were investigated using cubic spline modeling and multivariate risk adjustment. RESULTS: End-of-treatment ICH volume ≤28.8 mL in MISTIE III and ≤30.0 mL in STICH II had increased probability of modified Rankin Scale (mRS) 0 to 3 at 180 d (P = .01 and P = .003, respectively). The effect in the MISTIE cohort remained significant after multivariate risk adjustments. Earlier surgery within 62 h of ictus had a lower probability of achieving an mRS 0 to 3 at 180 d with STICH I and II (P = .0004), but not with MISTIE III. This remained significant with multivariate risk adjustments. There was no impact of timing until intervention on mortality up to 47 h with either procedure. CONCLUSION: Thresholds of ICH removal influenced outcome with both procedures to a similar extent. There was a similar likelihood of achieving a good outcome with both procedures within a broad therapeutic time window.

Prognostic Significance of Stroke-Associated Infection and other Readily Available Parameters in Acute Ischemic Stroke Treated by Intravenous Thrombolysis.

OBJECTIVES: The impact of contracting stroke-associate infection (SAI) that requires antibiotic treatment after an acute ischemic stroke (AIS) treated with alteplase remains unclear. We studied the profiles of SAI in patients with AIS treated with alteplase toward identifying predictive factors and prognostic implications at 90 days post-stroke. METHODS: We analyzed 33 parameters readily available within 24 hours after AIS: demographics, risk factors, and several clinical and biochemical parameters. Outcome measures were mRS ≤ 2 and mortality 90 days post-stroke. RESULTS: 83 (23.6%) of 352 patients developed SAI. Multivariate logistic regression analysis showed that atrial fibrillation, mRS above 0 pre-stroke, lower delta NIHSS (the difference between NIHSS score measured upon admission and 24 hours after later), CRP≥10 mg/L, and elevated WBC count affected SAI risk (model including CRP levels and WBC count) and atrial fibrillation, mRS above 0 pre-stroke, lower delta NIHSS, HT, and elevated fibrinogen levels affected SAI risk (model excluding CRP levels and WBC count). 231 patients (74.1%) had mRS ≤ 2 at day 90. Multivariate logistic regression analysis showed that younger age, no hypertension, mRS=0 pre-stroke, higher delta NIHSS, no HT, no SAI, and CRP<10 mg/L, were associated with mRS≤2 at day 90. 54 (15.3%) patients died within 90 days. Multivariate logistic regression analysis showed that pre-stroke mRS>0, lower delta NIHSS, HT, CRP≥10 mg/L, lower triglyceride levels affected the risk of death within 90 days. CONCLUSIONS: Several markers available within 24 hours post-stroke were predictive of SAI that requires antibiotic treatment. SAI affects long-term outcome but not mortality.

Contemporary nationwide trends and in-hospital outcomes of adjunctive stenting in patients undergoing catheter-directed thrombolysis for proximal deep venous thrombosis.

OBJECTIVE: Outflow venous stenting as an adjunct to catheter-directed thrombolysis (CDT) is performed to prevent recurrent thrombosis and to reduce the risk of post-thrombotic syndrome. Historical data show that stenting improves outcomes of surgical thrombectomy in patients with iliofemoral deep venous thrombosis (DVT), and recent observational data suggest that stenting improves long-term outcomes of CDT. However, the impact of stenting during CDT on acute safety outcomes is unknown. We sought to investigate the contemporary trends, safety outcomes, and resource utilization of adjunctive stent placement in patients undergoing CDT. METHODS: Patients with proximal lower extremity and caval DVT were identified within the National Inpatient Sample from January 2005 to December 2013. From this data set, we stratified our patients into three groups: patients who received CDT alone, patients who received CDT plus angioplasty, and patients who received CDT plus angioplasty with stenting. We used an inverse probability treatment weighting algorithm to create three weighted cohorts. Cochran-Armitage test was used to evaluate the trends of stent placement among patients treated with CDT. The primary outcome was a composite end point of all-cause mortality, gastrointestinal bleed, or intracranial hemorrhage. RESULTS: A total of 138,049 patients were discharged with a principal diagnosis of proximal and caval DVT; 7097 of these patients received CDT (5.1%). From this group, 2854 (40.2%) were treated with CDT alone, 2311 (32.6%) received adjunctive angioplasty alone, and 1932 (27.2%) received adjunctive angioplasty and stent. Adjunctive stenting had a significantly lower rate of primary composite outcome compared with CDT alone (2.7% vs 3.8%; P = .04). Stent placement was associated with a similar length of stay compared with angioplasty and CDT alone groups (6.8 vs 6.9 vs 7.1 days, respectively; P = .94) and higher in-hospital charges ($115,164.01 ± $76,985.31 vs $98,089.82 ± $72,921.94 vs $80,441.63 ± $74,024.98; P < .001). CONCLUSIONS: This nationwide study suggests that one in four patients undergoing CDT is treated with adjunctive stent placement in the United States. This observational study showed that adjunctive stenting does not adversely affect the acute safety outcomes of CDT; however, it was associated with increased hospital charges.

Propofol administration during catheter-directed interventions for intermediate-risk pulmonary embolism is associated with major adverse events.

OBJECTIVE: Catheter-directed interventions (CDIs) have been increasingly used for selected patients with acute intermediate-risk (submassive) pulmonary embolism (sPE) to prevent decompensation, mortality, and potentially long-term sequelae. The purpose of the present study was to determine whether the choice of anesthetic during these interventions has an effect on the postprocedural outcomes. METHODS: Patients who had undergone CDI for acute sPE from 2009 to 2019 were identified and grouped according to the intraprocedural use of propofol. The primary outcome was in-hospital intra- or postprocedural major adverse events, defined as the need for intubation, progression to massive pulmonary embolism, and in-hospital death. Major bleeding events (ie, intracerebral hemorrhage, transfusion of ≥2 U, the need for reintervention) were also assessed. Multivariate logistic regression analysis was used to evaluate the predictors of the studied outcomes. RESULTS: During the study period, 340 patients (age, 58.74 ± 15.22 years; 51.2% men) had undergone CDI for sPE (85 standard thrombolysis, 229 ultrasound-assisted thrombolysis, 26 suction thrombectomy). Propofol had been used for 36 patients (10.6%); the remaining 304 patients (89.4%) had received midazolam plus fentanyl, morphine, or hydromorphone for anesthesia. The baseline characteristics of both groups were similar, except for age, hypertension, American Society of Anesthesiologists class, and procedure type, with ultrasound-assisted thrombolysis the predominant procedure for the no-propofol group (74%). Overall, 18 patients had experienced ≥1 events of the composite outcome (ie, 10 intubations, 11 decompensations, 2 surgical conversions, 3 deaths). The propofol group had a significantly greater adverse event rate (13.8%; n = 5) compared with the no-propofol group (4.2%; n = 13; P = .015). On multivariate analysis, propofol was still a predictive factor for adverse events (odds ratio, 3.79; 95% confidence interval, 1.11-12.93; P = .03). A total of 16 patients had experienced major bleeding or other procedure-related events, including stroke in 4 (1.17%), coronary sinus perforation in 1, tricuspid valve rupture in 1, and the need for transfusion in 10 patients. The type of intervention (ie, standard thrombolysis, ultrasound-assisted thrombolysis, suction thrombectomy) was not a predictive factor for any studied outcome. CONCLUSIONS: CDIs are low-risk procedures with minimal postoperative morbidity and mortality in the setting of acute sPE. However, the use of propofol for intraprocedural sedation should be avoided because it can have detrimental effects.

Association of Admission Hyperglycemia with Clinical Outcomes in Japanese Patients with Acute Large Vessel Occlusion Stroke: A post hoc Analysis of the Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2.

INTRODUCTION: Admission hyperglycemia is an indicator of poor functional prognosis in acute stroke, but investigations of its prevalence and effects on the outcomes of acute large vessel occlusion in real-world, large-scale studies are limited, especially in Asian population. OBJECTIVE: We aimed to elucidate the relationship between admission hyperglycemia and outcomes in a prospective multicenter registry in Japan. METHODS: We analyzed data from the Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism (RESCUE) Japan Registry 2, which was a prospective, multicenter registry that enrolled patients from 46 centers in Japan. Admission hyperglycemia was defined as blood glucose level >140 mg/dL. The relationships between clinical outcomes and admission hyperglycemia were analyzed in all 1,932 assessable patients. A favorable functional outcome, defined as a modified Rankin Scale score of 0-2 at day 90, as well as mortality within 90 days and symptomatic intracranial hemorrhage (SICH) within 72 h, was analyzed. We performed subgroup analyses of the adjusted variables to investigate the association between hyperglycemia and favorable outcome in relation to each variable. RESULTS: Admission hyperglycemia was present in 687 (35.6%) of the assessable patients and in 420 (26.9%) of the 1,561 patients without diabetes. A favorable outcome was significantly less frequent in the hyperglycemia group than in the no-hyperglycemia group (33.2% vs. 47.6%, adjusted odds ratio [OR]: 0.60, 95% confidence interval [CI]: 0.47-0.76). The mortality rates were 12.8% and 6.8% in the hyperglycemia and no-hyperglycemia groups, respectively. The incidence of SICH within 72 h was higher in the hyperglycemia group than in the no-hyperglycemia group (4.4% vs. 1.9%, adjusted OR: 2.54, 95% CI: 1.36-4.82). Hyperglycemia was associated with unfavorable outcomes in almost all subgroups. CONCLUSIONS: Admission hyperglycemia in Japanese patients with large vessel occlusion stroke is associated with an unfavorable functional outcome at 90 days, mortality within 90 days, and the occurrence of SICH within 72 h.

Intravenous Thrombolysis before Thrombectomy may Increase the Incidence of Intracranial Hemorrhage inTreating Carotid T Occlusion.

BACKGROUND AND PURPOSE: Current evidence does not agree on the merits of direct and bridging thrombectomy. This study aimed to compare the safety and efficacy of direct thrombectomy (DT) and bridging thrombectomy (BT) in treating patients with acute ischaemic stroke due to carotid T occlusion. METHODS: Patients with stroke due to carotid T occlusion who were treated with DT or BT were retrospectively collected from four advanced stroke centres. Baseline characteristics and clinical outcomes were compared between the groups. Successful recanalization was defined by a modified thrombolysis in cerebral infarction (mTICI) score of 2b or 3. A favourable outcome was defined by a modified Rankin Scale (mRS) score of 0-2 at 90 days after stroke onset. Multivariable analysis was performed to control for potential confounders. RESULTS: Of the 111 enrolled patients, 57 (51.4%) patients were treated with DT, and 54 (48.6%) were treated with BT. Patients treated with DT had a shorter imaging to puncture (ITP) time (53 min versus 92 min, P<0.001) and symptom onset to puncture (OTP) time (198 min versus 218 min, P=0.045) than patients treated with BT. No significant difference was detected concerning the rate of successful recanalization (80.7% versus 77.8%, P=0.704) or a favourable outcome between patients treated with DT and BT (35.1% versus 33.3%, P=0.846). Patients treated with DT had a lower intracranial haemorrhage (ICH) rate (40.4% versus 59.3%, P=0.046), but the difference was not significant for symptomatic ICH (sICH, 12.3% versus 16.7%, P=0.511) or asymptomatic ICH (aICH, 28.1% versus 42.6%, P=0.109). After adjusting for potential confounding factors, the ratio of favorable prognosis, successful reperfusion, sICH and mortality did not differ between the two groups. However, there was a higher rate of ICH (OR=2.492, 95% CI 1.005 to 6.180, p=0.049) in the BT group as compared with the DT group. CONCLUSIONS: DT seems equivalent to BT in treating stroke due to carotid T occlusion in favorable outcome, successful recanalization, 90-day morality and sICH. However, BT may increase the incidence of ICH in this specific type stroke.

Treatment Approaches and Outcomes for Acute Anterior Circulation Stroke Patients with Tandem Lesions.

OBJECTIVES: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs. MATERIALS AND METHODS: Consecutive tandem lesion and isolated intracranial LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed. RESULTS: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p = 0.003), had less atrial fibrillation (13% vs 40%, p < 0.0001), less adequate reperfusion (TICI 2b-3, 58% vs 82%, p < 0.0001), more intracranial hemorrhage (ICH, 13% vs 5%, p = 0.037), but similar 90-day functional independence (mRS 0-2, 34% vs 43%, p = 0.181). The cervical ICA was treated before intracranial EVT (57%), after (13%), not acutely (22%), or was inaccessible (8%). Acute cervical ICA treatments were stenting (57%) or angioplasty alone (13%). Neither acute stenting nor order of treatment was associated with outcomes (TICI 2b-3, ICH, or 90-day mRS 0-2). Among acutely stented, neither alteplase nor antiplatelets were associated with outcomes or stent patency. CONCLUSIONS: Tandem lesions were associated with less reperfusion, more ICH, but similar 90-day functional independence. No treatment approach was associated with outcomes. These data illustrate the technical challenges of tandem lesion treatment and underscore the importance of developing new approaches.

Neuroinflammation in hemorrhagic transformation after tissue plasminogen activator thrombolysis: Potential mechanisms, targets, therapeutic drugs and biomarkers.

Hemorrhagic transformation (HT) is a common and serious complication following ischemic stroke, especially after tissue plasminogen activator (t-PA) thrombolysis, which is associated with increased mortality and disability. Due to the unknown mechanisms and targets of HT, there are no effective therapeutic drugs to decrease the incidence of HT. In recent years, many studies have found that neuroinflammation is closely related to the occurrence and development of HT after t-PA thrombolysis, including glial cell activation in the brain, peripheral inflammatory cell infiltration and the release of inflammatory factors, involving inflammation-related targets such as NF-κB, MAPK, HMGB1, TLR4 and NLRP3. Some drugs with anti-inflammatory activity have been shown to protect the BBB and reduce the risk of HT in preclinical experiments and clinical trials, including minocycline, fingolimod, tacrolimus, statins and some natural products. In addition, the changes in MMP-9, VAP-1, NLR, sICAM-1 and other inflammatory factors are closely related to the occurrence of HT, which may be potential biomarkers for the diagnosis and prognosis of HT. In this review, we summarize the potential inflammation-related mechanisms, targets, therapeutic drugs, and biomarkers associated with HT after t-PA thrombolysis and discuss the relationship between neuroinflammation and HT, which provides a reference for research on the mechanisms, prevention and treatment drugs, diagnosis and prognosis of HT.