Thrombocytopenia and In-hospital outcomes in patients with acute ischemic stroke undergoing intravenous thrombolysis: Findings from a nationwide registry study in China.

BACKGROUND AND OBJECTIVE: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis. METHODS: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 109/L), mild thrombocytopenia (100 ≤ PC < 150 × 109/L), normal PC (150 ≤ PC ≤ 450 × 109/L), and thrombocythemia (PC > 450 × 109/L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes. RESULTS: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 109/L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02). CONCLUSIONS: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 109/L, especially PC < 100 × 109/L. It indicated that PC < 100 × 109/L is a reasonable contraindication to thrombolysis.

Establishing reliable selection criteria for performing fibrinolytic therapy in patients with intracerebral haemorrhage based on prognostic tools.

OBJECTIVES: Minimally invasive surgery combined with fibrinolytic therapy is a promising treatment option for patients with intracerebral haemorrhage (ICH), but a meticulous patient selection is required, because not every patient benefits from it. The ICH score facilitates a reliable patient selection for fibrinolytic therapy except for ICH-4. This study evaluated whether an additional use of other prognostic tools can overcome this limitation. MATERIALS AND METHODS: A consecutive ICH patient cohort treated with fibrinolytic therapy between 2010 and 2020 was retrospectively analysed. The following prognostic tools were calculated: APACHE II, ICH-GS, ICH-FUNC, and ICH score. The discrimination power of every score was determined by ROC-analysis. Primary outcome parameters regarding the benefit of fibrinolytic therapy were the in-hospital mortality and a poor outcome defined as modified Rankin scale (mRS) > 4. RESULTS: A total of 280 patients with a median age of 72 years were included. The mortality rates according to the ICH score were ICH-0 = 0 % (0/0), ICH-1 = 0 % (0/22), ICH-2 = 7.1 % (5/70), ICH-3 = 17.3 % (19/110), ICH-4 = 67.2 % (45/67), ICH-5 = 100 % (11/11). The APACHE II showed the best discrimination power for in-hospital mortality (AUC = 0.87, p < 0.0001) and for poor outcome (AUC = 0.79, p < 0.0001). In the subgroup with ICH-4, APACHE II with a cut-off of 24.5 showed a good discriminating power for in-hospital mortality (AUC = 0.83, p < 0.001) and for poor outcome (AUC = 0.87, p < 0.001). CONCLUSIONS: An additional application of APACHE II score increases the discriminating power of ICH score 4 enabling a more precise appraisal of in-hospital mortality and of functional outcome, which could support the patient selection for fibrinolytic therapy.

Complications of Carotid Interventions for Symptomatic Lesions after Systemic Thrombolysis.

BACKGROUND: Series detailing complications after carotid endarterectomy (CEA) and transfemoral carotid stenting (tfCAS) for patients presenting with neurologic symptoms that are treated with systemic thrombolysis (ST) are sparse. We sought to determine if treatment with ST was associated with a higher rate of post-carotid intervention complications. METHODS: A multispecialty, institutional, prospectively maintained database was queried for symptomatic patients treated with CEA or tfCAS from 2007 to 2019. The primary outcomes of interest were bleeding complications (access/wound complications, hematuria, intracranial hemorrhage) or need for reintervention, stroke, and death. We compared rates of these outcomes between patients who were and were not treated with ST. To adjust for preoperative patient factors and confounding variables, propensity scores for assignment to ST and non-ST were calculated. RESULTS: There were 1,139 patients included (949 [82%] CEA and 190 [17%] tfCAS. All treated lesions were symptomatic (550 [48%] stroke, 603 [52%] transient ischemic attack). Fifty-six patients (5%) were treated with ST. Fifteen of 56 patients also underwent catheter-based intervention for stroke. ST was administered 0 to 1 day preoperatively in 21 (38%) patients, 2 to 6 days preoperatively in 27 (48%) patients, and greater than 6 days preoperatively in 8 (14%) patients. ST patients were more likely to present with stroke (93% vs. 45%; P < 0.001) and have higher preoperative Rankin scores. Unadjusted rate of bleeding/return to operating room was 3% for ST group and 3% for non-ST group (P = 0.60). Unadjusted rate of stroke was 4% for ST group and 3% for the non-ST group (P = 0.91), while perioperative mortality was 5% for ST group and 1% for non-ST group (P = 0.009). After adjusting for patient factors, preoperative antiplatelet/anticoagulation, and operative factors, ST was not associated with an increased odds of perioperative bleeding/return to the operating room (odds ratio 0.37; 95% confidence interval: 0.02-1.63; P = 0.309) or stroke (odds ratio 0.62; 95% confidence interval: 0.16-2.40; P = 0.493). CONCLUSIONS: ST does not convey a higher risk of complications after CEA or tfCAS. After controlling for other factors, patients that received ST had similar rates of local complications and stroke when compared to non-ST patients. Early carotid intervention is safe in patients that have received ST, and delays should be avoided in symptomatic patients given the high risk of recurrent stroke.

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.

Outcomes of acute ischemic stroke among patients with renal cell carcinoma: A nationwide analysis.

INTRODUCTION: Renal cell carcinoma (RCC) has been associated with an increased risk for acute ischemic stroke (AIS). As individuals with cancer who experience AIS tend to face higher mortality rates compared to AIS patients without cancer, recognizing the implications of RCC in AIS is crucial for identifying high-risk patients for major complications and directing management strategies. OBJECTIVE: To examine risk factors, interventions, and outcomes for patients with AIS stratified by their RCC diagnosis. METHODS: The National Inpatient Sample (NIS) database was queried for the period 2010-2019 using International Classification of Disease 10th Edition (ICD-10) codes for acute ischemic stroke and renal malignancies. We assessed demographic information, comorbidities, and clinical interventions between patients presenting with AIS, with and without renal malignancies. A logistic regression model was employed to further examine mortality outcomes. RESULTS: Among 1,609,817 patients identified with AIS, 2,068 (0.12%) had a concomitant diagnosis of RCC. AIS patients with RCC were older (72.09 yrs. vs. 70.9 yrs., p < 0.01), more often white (72.05% vs. 68.16%, p < 0.01), and had similar stroke severity scores. RCC patients received less tissue plasminogen activator (tPA; 4.98% vs. 6.2%, p = 0.02) but underwent endovascular mechanical thrombectomy (MT) at similar rates. RCC patients had more complications (p < 0.01) as well as longer hospital stays (8.19 days vs. 5.98 days, p < 0.01), and higher rates of mortality (11.27% vs. 5.63%, p < 0.01), when compared to their non-RCC counterparts. Propensity score-adjusted analysis largely confirmed these findings, with RCC being positively associated with in-hospital mortality (OR: 1.373, p < 0.01) and longer stays (OR: 2.591, p < 0.01). CONCLUSION: In addition to describing the demographics and clinical course of AIS patients diagnosed with RCC, our study underscores the substantial impact of RCC on AIS outcomes. Despite experiencing strokes of similar severity, AIS patients diagnosed with RCC are at a heightened risk of complications, including thromboembolic events and infections, leading to elevated in-hospital mortality rates and prolonged hospital stays.

Intravenous thrombolysis for ischemic stroke in the posterior circulation: A systematic review and meta-analysis.

OBJECTIVES: Intravenous thrombolysis (IVT) is recommended in patients with ischemic stroke in the anterior and posterior circulation. Neurological outcomes due to posterior circulation strokes (PCS) without treatment remain poor. Our aim was to overview the literature on outcomes of IVT and conservative treatment in PCS, based on a systematic review and meta-analysis. METHODS: A systematic literature search was performed on February 27th 2023. Outcome measures included favorable functional outcome at 90 days (modified Rankin Scale [mRS] 0-2), mortality at 90 days, and symptomatic intracranial hemorrhages (sICH). Weighted averages with DerSimonian-Laird approach was used to analyze the data. Subgroup analyses by time window were performed: standard time window (<4.5 hours after symptom onset) and extended time window (>4.5 hours). Analyses were performed using R. RESULTS: Eight prospective and four retrospective cohort studies were included (n = 1589 patients); no studies with conservative treatment were eligible. The pooled weighted probability regarding favorable functional outcome after IVT was 63 % (95 %CI:0.45-0.78), for mortality 19 % (95 %CI:0.11-0.30), and for sICH 4 % (95 %CI:0.02-0.07). Subgroup analyses showed higher probabilities on achieving favorable functional outcomes for patients treated in the standard (77 %; 95 %CI:0.62-0.88) compared to the extended time window (38 %; 95 %CI:0.29-0.48) with RR = 1.93 (95 %CI:1.66-2.24). Lower probabilities regarding mortality at 90 days and sICH were seen in patients treated in standard compared to extended time window (RR = 0.42, 95 %CI:0.34-0.51 and RR = 0.27, 95 %CI:0.16-0.45, respectively). CONCLUSIONS: IVT in patients with PCS seems to be safe and effective in standard and extended time window. The effect of IVT is higher in the standard time window.

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.

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.

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.

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.

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.

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.