Cutting-edge advances in nano/biomedicine: A review on transforming thrombolytic therapy.

Thrombotic blockages within blood vessels give rise to critical cardiovascular disorders, including ischemic stroke, venous thromboembolism, and myocardial infarction. The current approach to the therapy of thrombolysis involves administering Plasminogen Activators (PA), but it is hindered by fast drug elimination, narrow treatment window, and the potential for bleeding complications. Leveraging nanomedicine to encapsulate and deliver PA offers a solution by improving the efficacy of therapy, safeguarding the medicine from proteinase biodegradation, and reducing unwanted effects in in vivo trials. In this review, we delve into the underlying venous as well as arterial thrombus pathophysiology and provide an overview of clinically approved PA used to address acute thrombotic conditions. We explore the existing challenges and potential directions within recent pivotal research on a variety of targeted nanocarriers, such as lipid, polymeric, inorganic, and biological carriers, designed for precise delivery of PA to specific sites. We also discuss the promising role of microbubbles and ultrasound-assisted Sono thrombolysis, which have exhibited enhanced thrombolysis in clinical studies. Furthermore, our review delves into approaches for the strategic development of nano-based carriers tailored for targeting thrombolytic action and efficient encapsulation of PA, considering the intricate interaction in biology systems as well as nanomaterials. In conclusion, the field of nanomedicine offers a valuable method for the exact and effective therapy of severe thrombus conditions, presenting a pathway toward improved patient outcomes and reduced complications.

Ten-year trends, disparities, and clinical impact of stroke thrombectomy and thrombolysis: A single center experience 2012-2021.

OBJECTIVES: As indications for acute ischemic stroke treatment expand, it is unclear whether disparities in treatment utilization and outcome still exist. The main objective of this study was to investigate disparities in acute ischemic stroke treatment and determine impact on outcome. MATERIALS AND METHODS: Retrospective observational cohort study of consecutive ischemic stroke admissions to a comprehensive stroke center from 2012-2021 was performed. Primary exposure was intravenous thrombolysis and/or endovascular thrombectomy. Primary end points were discharge modified Rankin Scale, home disposition, and expired/hospice. Multivariable logistic regression analyses were conducted to elucidate disparities in treatment utilization and determine impact on outcome. RESULTS: Of 517,615 inpatient visits, there were 7,540 (1.46 %) ischemic stroke admissions, increasing from 1.14 % to 1.79 % from 2012-2021. Intravenous thrombolysis significantly decreased from 14.4 % to 9.8 % while endovascular thrombectomy significantly increased from 0.8 % to 10.5 %. Both intravenous thrombolysis and endovascular thrombectomy increased odds of discharge home and modified Rankin Scale 0-2, and thrombectomy decreased odds of expired/hospice. After adjusting for covariates, decreased odds of thrombectomy was associated with Medicaid insurance (Odds Ratio [95 % Confidence Interval] 0.55 [0.32-0.93]), age 80+ (0.49 [0.35-0.69]), prior stroke (0.49 [0.31-0.77]), and diabetes mellitus (0.55 [0.39-0.79]), while low median household income (<$80,000/year) increased odds of no acute treatment (1.34 [1.16-1.56]). No sex or racial disparities were observed. Medicaid and low-income were not associated with worse clinical outcomes. CONCLUSIONS: Less endovascular thrombectomy occurred in Medicaid, older, prior stroke, and diabetic patients, while low-income was associated with no treatment. The observed socioeconomic disparities did not impact discharge outcome.

Temporal trends of sex differences in acute reperfusion therapy and early outcomes of acute ischemic stroke in South Korea: 10-year analysis of the nationwide stroke registry.

BACKGROUND: Sex differences in stroke outcomes are notable, with women experiencing higher incidence rates, greater disability-adjusted life years, and poorer recovery compared to men, even after adjusting for age and comorbidities. Despite the disproportionate burden in women, studies have reported that women are less likely to receive appropriate stroke treatment than men. AIM: This study investigated temporal trends of sex differences in acute reperfusion therapy and early outcomes in patients with acute ischemic stroke over 10 years in South Korea. METHODS: A retrospective analysis of Korean Stroke Registry included patients with acute ischemic stroke from 2012 to 2021. The study outcomes were the temporal trends of acute reperfusion therapy and early outcomes over 10 years in men and women, respectively. In addition, this study analyzed the temporal trends of sex differences in these parameters during the same period. Early outcomes include the proportions of favorable functional outcomes at discharge, discharge patterns, and in-hospital mortality. RESULTS: A total of 93,692 patients (68.4 years, 40.1% women) with acute ischemic stroke were finally enrolled. Women had a higher age at stroke onset, a higher prevalence of atrial fibrillation, and more severe strokes than men. Women had lower proportion of favorable functional outcomes at discharge and higher proportion of in-hospital mortality compared to men each year. The proportion of patients who received intravenous thrombolysis was lower or similar in women compared to men in most years, and the proportion of patients who received endovascular thrombectomy did not significantly differ between sexes annually. Sex differences in acute reperfusion therapy remained unchanged over 10 years. CONCLUSION: Women have received acute reperfusion therapy at similar or lower rates than men and experienced poorer outcomes, despite having more stroke risk factors and often more severe strokes.

Neuroendovascular Rescue 2025: Trends in Stroke Endovascular Therapy.

Neuroendovascular rescue of patients with acute ischemic stroke caused by a large arterial occlusion has evolved throughout the first quarter of the present century, and continues to do so. Starting with the intra-arterial instillation of thrombolytic agents via microcatheters to dissolve occluding thromboembolic material, the current status is one that includes a variety of different techniques such as direct aspiration of thrombus, removal by stent retriever, adjuvant techniques such as balloon angioplasty, stenting, and tactical intra-arterial instillation of thrombolytic agents in smaller branches to treat no-reflow phenomenon. The results have been consistently shown to benefit these patients, irrespective of whether they had already received intravenous tissue-type plasminogen activator or not. Improved imaging methods of patient selection and tactically optimized periprocedural care measures complement this dimension of the practice of neurointervention.

Door to needle time trends after transition to tenecteplase: A Multicenter Texas stroke registry.

BACKGROUND: Tenecteplase (TNK) is considered a promising option for the treatment of acute ischemic stroke (AIS) with the potential to decrease door-to-needle times (DTN). This study investigates DTN metrics and trends after transition to tenecteplase. METHODS: The Lone Star Stroke (LSS) Research Consortium TNK registry incorporated data from three Texas hospitals that transitioned to TNK. Subject data mapped to Get-With-the-Guidelines stroke variables from October 1, 2019 to March 31, 2023 were limited to patients who received either alteplase (ALT) or TNK within the 90 min DTN times. The dataset was stratified into ALT and TNK cohorts with univariate tables for each measured variable and further analyzed using descriptive statistics. Logistic regression models were constructed for both ALT and TNK to investigate trends in DTN times. RESULTS: In the overall cohort, the TNK cohort (n = 151) and ALT cohort (n = 161) exhibited comparable population demographics, differing only in a higher prevalence of White individuals in the TNK cohort. Both cohorts demonstrated similar clinical parameters, including mean NIHSS, blood glucose levels, and systolic blood pressure at admission. In the univariate analysis, no difference was observed in median DTN time within the 90 min time window compared to the ALT cohort [40 min (30-53) vs 45 min (35-55); P = .057]. In multivariable models, DTN times by thrombolytic did not significantly differ when adjusting for NIHSS, age (P = .133), or race and ethnicity (P = .092). Regression models for the overall cohort indicate no significant DTN temporal trends for TNK (P = .84) after transition; nonetheless, when stratified by hospital, a single subgroup demonstrated a significant DTN upward trend (P = 0.002). CONCLUSION: In the overall cohort, TNK and ALT exhibited comparable temporal trends and at least stable DTN times. This indicates that the shift to TNK did not have an adverse impact on the DTN stroke metrics. This seamless transition is likely attributed to the similarity of inclusion and exclusion criteria, as well as the administration processes for both medications. When stratified by hospital, the three subgroups demonstrated variable DTN time trends which highlight the potential for either fatigue or unpreparedness when switching to TNK. Because our study included a multi-ethnic cohort from multiple large Texas cities, the stable DTN times after transition to TNK is likely applicable to other healthcare systems.

Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results From the Nationwide Inpatient Sample.

BACKGROUND: Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status. METHODS AND RESULTS: We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey-weighted logistic regression. We calculated odds ratios for IVT for each category in 2002 to 2008 (period 1) and 2009 to 2015 (period 2). IVT use for acute ischemic stroke increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio, 1.15). Individuals aged ≥85 years had the most pronounced increase during 2002 to 2015 (adjusted annual relative ratio, 1.18) but were less likely to receive IVT compared with 18- to 44-year-olds in period 1 (adjusted odds ratio [aOR], 0.23) and period 2 (aOR, 0.36). Women were less likely than men to receive IVT, but the disparity narrowed over time (period 1: aOR, 0.81; period 2: aOR, 0.94). Inequities in IVT resolved for Hispanic individuals in period 2 (aOR, 0.96) but not for Black individuals (period 2: aOR, 0.81). The disparity in IVT for Medicare patients, compared with privately insured patients, lessened over time (period 1: aOR, 0.59; period 2: aOR, 0.75). Patients treated in rural hospitals remained less likely to receive IVT than in urban hospitals; a more dramatic increase in urbanity widened the inequity (period 2, urban nonteaching versus rural: aOR, 2.58, period 2, urban teaching versus rural: aOR, 3.90). CONCLUSIONS: IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.

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.

Reflection on the Past, Present, and Future of Thrombolytic Therapy for Acute Ischemic Stroke.

More than 25 years have passed since the US Food and Drug Administration approved IV recombinant tissue plasminogen activator (alteplase) for the treatment of acute ischemic stroke. This landmark decision brought a previously untreatable disease into a new therapeutic landscape, providing inspiration for clinicians and hope to patients. Since that time, the use of alteplase in the clinical setting has become standard of care, continually improving with quality measures such as door-to-needle times and other metrics of specialized stroke unit care. The past decade has seen more widespread use of alteplase in the prehospital setting with mobile stroke units and telestroke and beyond initial time windows via the use of CT perfusion or MRI. Simultaneously, the position of alteplase is being challenged by new lytics and by the concept of its bypass altogether in the era of endovascular therapy. We provide an overview of alteplase, including its earliest trials and how they have shaped the current therapeutic landscape of ischemic stroke treatment, and touch on new frontiers for thrombolytic therapy. We highlight the critical role of thrombolytic therapy in the past, present, and future of ischemic stroke care.

Changes in Stroke Hospital Care During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

[Figure: see text].

Advanced management of intermediate-high risk pulmonary embolism.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

National Trends in Telestroke Utilization in a US Commercial Platform Prior to the COVID-19 Pandemic.

OBJECTIVES: Most data on telestroke utilization come from single academic hub-and-spoke telestroke networks. Our objective was to describe characteristics of telestroke consultations among a national sample of telestroke sites on one of the most commonly used common vendor platforms, prior to the COVID-19 public health emergency. MATERIALS AND METHODS: A commercial telestroke vendor provided data on all telestroke consultations by two specialist provider groups from 2013-2019. Kendall's τ ß nonparametric test was utilized to assess time trends. Generalized linear models were used to assess the association between hospital consult utilization and alteplase use adjusting for hospital characteristics. RESULTS: Among 67,736 telestroke consultations to 132 spoke sites over the study period, most occurred in the emergency department (90%) and for stroke indications (final clinical diagnoses: TIA 13%, ischemic stroke 39%, hemorrhagic stroke 2%, stroke mimics 46%). Stroke severity was low (median NIHSS 2, IQR 0-6). Alteplase was recommended for 23% of ischemic stroke patients. From 2013 to 2019, times from ED arrival to NIHSS, CT scan, imaging review, consult, and alteplase administration all decreased (p<0.05 for all), while times from consult start to alteplase recommendation and bolus increased (p<0.01 for both). Transfer was recommended for 8% of ischemic stroke patients. Number of patients treated with alteplase per hospital increased with increasing number of consults and hospital size and was also associated with US region in unadjusted and adjusted analyses. Longer duration of hospital participation in the network was associated with shorter hospital median door-to-needle time for alteplase delivery (39 min shorter per year, p=0.04). CONCLUSIONS: Among spoke sites using a commercial telestroke platform over a seven-year time horizon, times to consult start and alteplase bolus decreased over time. Similar to academic networks, duration of telestroke participation in this commercial network was associated with faster alteplase delivery, suggesting practice improves performance.

Dynamic Neutrophil-Lymphocyte Ratios Predict Short-term Prognostic Outcome of Thrombolysis in Patients with Acute Ischemic Stroke.

AIM: The main purpose of this study was to investigate the dynamic changes of neutrophils-lymphocytes ratios (NLRs) in patients with acute ischemic stroke (AIS) and their relationships with 3-month prognostic outcomes. METHODS: Two hundred ninety-one patients with AIS were included in this study, followed up for 3 months. At admission, 1 and 7 days after recombinant tissue plasminogen activator (r-tPA) injection, blood samples were obtained. Outcome events included excellent outcome, good outcome, and death defined as modified Rankin Scale (mRS) scores of 0-1, 0-2, and 6 respectively. RESULTS: NLRs measured in admission and 7 days after r-tPA treatment were associated with prognosis outcome after 3 months. Twenty-four-hour NLR is an excellent indicator in forecasting (excellent outcome's the areas under the curve (AUC) = 0.725; good outcome AUC = 0.742; death AUC = 0.759). In addition, we were surprised to find that dynamic increase in NLR within 24 h is significantly related to excellent and good outcomes. CONCLUSIONS: Twenty-four-hour NLR is related to the severity of AIS and poor prognosis, which can help early risk stratification. SIGNIFICANCE: We can predict the prognosis of AIS more accurately. Compared with previous studies, our study has shown the dynamic changes of NLR and its relationship with NIHSS and multiple prognostic.

Ischemic Stroke in Patients With Pulmonary Arteriovenous Fistulas.

BACKGROUND AND PURPOSE: Pulmonary arteriovenous fistulas (PAVFs) are a treatable cause of acute ischemic stroke (AIS), not mentioned in current American Heart/Stroke Association guidelines. PAVFs are recognized as an important complication of hereditary hemorrhagic telangiectasia. METHODS: The prevalence of PAVF and hereditary hemorrhagic telangiectasia among patients admitted with AIS in the United States (2005-2014) was retrospectively studied, utilizing the Nationwide Inpatient Sample database. Clinical factors, morbidity, mortality, and management were compared in AIS patients with and without PAVF/hereditary hemorrhagic telangiectasia. RESULTS: Of 4 271 910 patients admitted with AIS, 822 (0.02%) were diagnosed with PAVF. Among them, 106 of 822 (12.9%) were diagnosed with hereditary hemorrhagic telangiectasia. The prevalence of PAVF per million AIS admissions rose from 197 in 2005 to 368 in 2014 (Ptrend, 0.026). Patients with PAVF were younger than AIS patients without PAVF (median age, 57.5 versus 72.5 years), had lower age-adjusted inpatient morbidity (defined as any discharge other than home; 39.6% versus 46.9%), and had lower in-hospital case fatality rates (1.8% versus 5.1%). Multivariate analyses identified the following as independent risk markers (odds ratio [95% CI]) for AIS in patients with PAVF: hypoxemia (8.4 [6.3-11.2]), pulmonary hemorrhage (7.9 [4.1-15.1]), pulmonary hypertension (4.3 [4.1-15.1]), patent foramen ovale (4.2 [3.5-5.1]), epistaxis (3.7 [2.1-6.8]), venous thrombosis (2.6 [1.9-3.6]), and iron deficiency anemia (2 [1.5-2.7]). Patients with and without PAVF received intravenous thrombolytics at a similar rate (5.9% versus 5.8%), but those with PAVF did not receive mechanical thrombectomy (0% versus 0.7%). CONCLUSIONS: Pulmonary arteriovenous fistula-related ischemic stroke represents an important younger demographic with a unique set of stroke risk markers, including treatable conditions such as causal PAVFs and iron deficiency anemia.

Patient Characteristics and Outcomes Associated with Decline in Stroke Volumes During the Early COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Delayed evaluation of stroke may contribute to COVID-19 pandemic-related morbidity and mortality. This study evaluated patient characteristics, process measures and outcomes associated with the decline in stroke presentation during the early pandemic. METHODS: Volumes of stroke presentations, intravenous thrombolytic administrations, and mechanical thrombectomies from 52 hospitals from January 1-June 30, 2020 were analyzed with piecewise linear regression and linear spline models. Univariate analysis compared pandemic (case) and pre-pandemic (control) groups defined in relation to the nadir of daily strokes during the study period. Significantly different patient characteristics were further evaluated with logistic regression, and significantly different process measures and outcomes were re-analyzed after propensity score matching. RESULTS: Analysis of 7,389 patients found daily stroke volumes decreased 0.91/day from March 12-26 (p < 0.0001), reaching a nadir 35.0% less than expected, and increased 0.15 strokes/day from March 27-June 23, 2020 (p < 0.0001). Intravenous thrombolytic administrations decreased 3.3/week from February 19-March 31 (p = 0.0023), reaching a nadir 33.4% less than expected, and increased 1.4 administrations/week from April 1-June 23 (p < 0.0001). Mechanical thrombectomy volumes decreased by 1.5/week from February 19-March 31, 2020 (p = 0.0039), reaching a nadir 11.3% less than expected. The pandemic group was more likely to ambulate independently at baseline (p = 0.02, OR = 1.60, 95% CI = 1.08-2.42), and less likely to present with mild stroke symptoms (NIH Stroke Scale ≤ 5; p = 0.04, OR = 1.01, 95% CI = 1.00-1.02). Process measures and outcomes of each group did not differ, including door-to-needle time, door-to-puncture time, and successful mechanical thrombectomy rate. CONCLUSION: Stroke presentations and acute interventions decreased during the early COVID-19 pandemic, at least in part due to patients with lower baseline functional status and milder symptoms not seeking medical care. Public health messaging and initiatives should target these populations.

Pulmonary Embolism Response Team utilization during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 (n = 74) compared to the same period in 2019 (n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.

A meta-analysis of the global impact of the COVID-19 pandemic on stroke care & the Houston Experience.

OBJECTIVE: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston. METHODS: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times. RESULTS: A total of 32,640 stroke admissions from 29 studies were assessed. Compared to prepandemic period, the mean ratio of stroke admissions during the pandemic was 70.78% [95% CI, 65.02%, 76.54%], ICH cases was 83.10% [95% CI, 71.01%, 95.17%], tPA cases was 81.74% [95% CI, 72.33%, 91.16%], and MT cases was 88.63% [95% CI, 74.12%, 103.13%], whereas DTN time was 104.48% [95% CI, 95.52%, 113.44%] and DTG was 104.30% [95% CI, 81.99%, 126.61%]. In Houston, a total of 4808 cases were assessed. There was an initial drop of ~30% in cases at the pandemic onset. Compared to 2019, there was a significant reduction in mild strokes (NIHSS 1-5) [N (%), 891 (43) vs 635 (40), P = 0.02]. There were similar mean (SD) (mins) DTN [44 (17) vs 42 (17), P = 0.14] but significantly prolonged DTG times [94 (15) vs 85 (20), P = 0.005] in 2020. INTERPRETATION: The COVID-19 pandemic led to a global reduction in stroke admissions and treatment interventions and prolonged treatment time metrics.

The association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio with post-thrombolysis early neurological outcomes in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). METHODS: AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI. RESULTS: Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238-1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009-1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560-0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643-0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively. CONCLUSIONS: NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.