Dynamic change of neutrophil-to-lymphocyte ratio and its predictive value of prognosis in acute ischemic stroke.

OBJECTIVE: The present research aimed to explore the dynamic change of the neutrophil-to-lymphocyte ratio (NLR) and its relationship with functional outcome following an acute ischemic stroke (AIS), whether receiving intravenous thrombolysis (IVT) or not. METHODS: We retrospectively analyzed data that were prospectively acquired from patients with AIS treated with IVT or not. For patients receiving IVT, the NLR was based on a blood test performed prior to IVT (d0) and at different time points after disease onset (d1, d3, d7). In addition, in the non-IVT group, the NLR was obtained at different time points after disease onset (d1, d3, d7). Follow-ups were performed 3 months after onset via telephone. In addition, a good outcome was defined as a modified Rankin scale (mRS) ≤1; a poor outcome means 2 ≤ mRS ≤ 6. RESULTS: A total of 204 AIS patients were included in this study. The NLR presented a dynamic change as it increased to its peak at day 1 and gradually declined to its baseline at day 7, no matter whether patients were receiving IVT or not. Patients with poor outcomes have a higher NLR at various time points. The results of multivariate logistic regression analysis demonstrated that the National Institutes of Health Stroke Scale (NIHSS), NLR d1, NLR d3, and NLR d7 were independently associated with functional outcomes. The area under the receiver operating characteristic curve of NLR in predicting outcomes was as follows: NLR d3 demonstrated robust predictive power within the IVT therapy cohort, whereas NLR d7 was predictive in the non-IVT cohort. However, the most potent predictor emerged as the combination of NIHSS and NLR. CONCLUSION: NLR has the potential to predicate diagnosis for AIS, especially when combined with the NIHSS score.

Comparison of the Clinical Outcomes Between Reperfusion and Non-Reperfusion Therapy in Elderly Patients with Acute Ischemic Stroke.

Purpose: To investigate the benefit (90-day mRS score) and rate of major complications (early symptomatic intracranial hemorrhage-SICH) after reperfusion therapy (RT) (including intravenous thrombolysis -IVT and mechanical thrombectomy -MT) in patients over 80 years with acute ischemic stroke (AIS). Patients and Methods: AIS patients aged over 80 admitted to Huizhou Central People's Hospital from September 2018 to 2023 were included in this study. Data on SICH, NIHSS, and mRS were analyzed. A good prognosis was defined as a mRS ≤ 2 or recovery to pre-stroke status at 90 days. Results: Of 209 patients, 80 received non-RT, 100 received IVT and 29 underwent MT. The non-RT group had the lowest baseline NIHSS while the MT group had the highest (non-RT 6.0 vs IVT 12.0 vs MT 18.0, P <0.001). Higher NIHSS was associated with increased SICH risk (OR 1.083, P=0.032), while RT was not (OR 5.194, P=0.129). The overall SICH rate in the RT group was higher but not significantly different after stratification by stroke severity. Poor prognosis was associated with higher admission NIHSS, stroke due to large artery atherosclerosis (LAA) combined with cardioembolism (CE), and stroke-associated pneumonia (SAP) (OR 0.902, P<0.001; OR 0.297, P=0.029; OR 0.103, P<0.001, respectively). The RT group showed a greater reduction in NIHSS (delta NIHSS) than the non-RT group (non-RT 2.0 vs IVT 4.0 vs MT 6.0, P<0.005). For severe AIS, the IVT group had a better prognosis at 90 days (non-RT 0% vs IVT 38.2%, P=0.039). No 90-day mortality difference was found between groups after stratification. Conclusion: Stroke severity, rather than RT, is an independent risk factor for SICH in AIS patients over 80. RT in severe stroke patients improves NIHSS at 90 days, suggesting RT is safe and effective in this demographic. Further studies with larger samples are required to confirm these findings.

Thrombolysis in acute retinal ischemia treated with tenecteplase.

Central retinal artery occlusion (CRAO), a type of acute retinal arterial ischemia, analogous to an ocular stroke, is a medical emergency that warrants immediate diagnosis and treatment. CRAO usually presents with sudden, painless, monocular vision loss. Ipsilateral carotid artery disease is an important associated finding in these patients. The primary limitation to effective treatment of CRAO is that patients are rarely seen in the acute stage. Moreover, there are no guidelines for effective treatment. We report a patient with right CRAO whose treatment with intravenous thrombolysis with tenecteplase and anterior chamber paracentesis with ocular massage resulted in a good clinical outcome.

Combined Intracoronary Prourokinase Thrombolysis on Myocardial Perfusion and Vascular Endothelial Function in STEMI.

BACKGROUND: This study aimed to investigate the effects of intracoronary prourokinase thrombolysis combined with emergency percutaneous coronary intervention (PCI) on myocardial perfusion and vascular endothelial function in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 104 patients with STEMI were collected from August 2020 to August 2022, and were divided into control group and observation group in a random manner. The control group received PCI directly, and the observation group received intracoronary prourokinase thrombolytic therapy before PCI. The treatment effects were evaluated by measuring the cardiac function indexes, including left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF), the TIMI myocardial perfusion grade, the vascular endothelial indexes, including soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), the von Willebrand factor (vWF), the myocardial injury indexes, including cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), and lactate dehydrogenase (LDH), and the inflammatory factors, including myeloperoxidase (MPO), C-reactive protein (CRP), and interleukin-6 (IL-6). Furthermore, the treatment safety was assessed by recording the incidence of major MACE events, 6 months after the operation. RESULTS: After treatment, LVEDD and LVESD were lower in the observation group than in the control group, and LVEF was higher (p < 0.05). The TIMI myocardial perfusion grade in the observation group was higher than in the control group, after treatment (p < 0.05). The levels of sICAM-1, sVCAM-1, and vWF were higher in the observation group than in the control group (p < 0.05). The levels of cTnI, CK-MB, and LDH in the observation group were lower than those in the control group, 24 hours after surgery. At 3 days after surgery, MPO was lower in the observation group than in the control group, and CRP and IL-6 were higher (p < 0.05). The incidence of major MACE events in the observation group was lower than that in the control group, 6 months after surgery (p < 0.05). There was 1 case of puncture site bleeding in the observation group, 1 case of puncture site bleeding and 1 case of subcutaneous ecchymosis in the control group, but no serious bleeding events, such as internal bleeding or cerebral hemorrhage, in the two groups. CONCLUSIONS: Intracoronary prourokinase thrombolytic therapy combined with emergency PCI can promote the recovery of cardiac function, improve myocardial perfusion and vascular endothelial function, and reduce inflammation and the incidence of major postoperative MACE events in acute STEMI patients.

Which one is the best in treating deep venous thrombosis -- percutaneous mechanical thrombectomy, catheter-directed thrombolysis or combination of them?

OBJECTIVE: To compare the treatment outcomes among percutaneous mechanical thrombectomy (PMT) with AngioJet, Catheter-directed thrombolysis (CDT), and a combination of both. METHODS: One hundred forty nine patients with acute or sub-acute iliac-femoral vein thrombosis accepting CDT and/or PMT were divided into three groups respectively: PMT group, CDT group, PMT + CDT group (PMT followed by CDT). The severity of thrombosis was evaluated by venographic scoring system. Technical success was defined as restored patent deep venous blood flow after CDT and/or PMT. Clinical follow-up were assessed by ultrasound or venography imaging. The primary endpoints were recurrence of DVT, and severity level of post-thrombotic syndrome (PTS) during the follow-up. RESULTS: Technical success and immediate clinical improvements were achieved on all patients. The proportion of sub-acute DVT and the venographic scoring in PMT + CDT group were significantly higher than that in CDT group and PMT group (proportion of sub-acute DVT: p = 0.032 and p = 0.005, respectively; venographic scoring: p < 0.001, respectively). The proportion of May-Thurner Syndrome was lower in PMT group than that in CDT and PMT + CDT group (p = 0.026 and p = 0.005, respectively). The proportion of DVT recurrence/stent thrombosis was significantly higher in CDT group than that in PMT + CDT group (p = 0.04). The severity of PTS was the highest in CDT group ( χ2 = 14.459, p = 0.006) compared to PMT group (p = 0.029) and PMT + CDT group (p = 0.006). CONCLUSION: Patients with sub-acute DVT, high SVS scoring and combined May-Thurner Syndrome were recommended to take PMT + CDT treatment and might have lower rate of DVT recurrence/stent thrombosis and severe PTS. Our study provided evidence detailing of PMT + CDT therapy.

Parallel activation of helicopter and ground transportation after dispatcher identification of suspected anterior large vessel occlusion stroke in rural areas: a proof-of-concept case with modeling from the LESTOR trial.

BACKGROUND: When stroke patients with suspected anterior large vessel occlusion (aLVO) happen to live in rural areas, two main options exist for prehospital transport: (i) the drip-and-ship (DnS) strategy, which ensures rapid access to intravenous thrombolysis (IVT) at the nearest primary stroke center but requires time-consuming interhospital transfer for endovascular thrombectomy (EVT) because the latter is only available at comprehensive stroke centers (CSC); and (ii) the mothership (MS) strategy, which entails direct transport to a CSC and allows for faster access to EVT but carries the risk of IVT being delayed or even the time window being missed completely. The use of a helicopter might shorten the transport time to the CSC in rural areas. However, if the aLVO stroke is only recognized by the emergency service on site, the helicopter must be requested in addition, which extends the prehospital time and partially negates the time advantage. We hypothesized that parallel activation of ground and helicopter transportation in case of aLVO suspicion by the dispatcher (aLVO-guided dispatch strategy) could shorten the prehospital time in rural areas and enable faster treatment with IVT and EVT. METHODS: As a proof-of-concept, we report a case from the LESTOR trial where the dispatcher suspected an aLVO stroke during the emergency call and dispatched EMS and HEMS in parallel. Based on this case, we compare the provided aLVO-guided dispatch strategy to the DnS and MS strategies regarding the times to IVT and EVT using a highly realistic modeling approach. RESULTS: With the aLVO-guided dispatch strategy, the patient received IVT and EVT faster than with the DnS or MS strategies. IVT was administered 6 min faster than in the DnS strategy and 22 min faster than in the MS strategy, and EVT was started 47 min earlier than in the DnS strategy and 22 min earlier than in the MS strategy. CONCLUSION: In rural areas, parallel activation of ground and helicopter emergency services following dispatcher identification of stroke patients with suspected aLVO could provide rapid access to both IVT and EVT, thereby overcoming the limitations of the DnS and MS strategies.

[Therapeutic effect of intravenous thrombolysis with tenecteplase on patients with post awakening branch atheromatous disease].

Objective: To investigate the efficacy and safety of intravenous thrombolysis with Tenecteplase (TNK) in patients with post-awakening branch atheromatous disease (BAD). Methods: A retrospective collection was conducted on 178 patients with post-awakening BAD admitted to the Stroke Centre of Zhengzhou People's Hospital from January 2017 to June 2023, who had a mismatch in DWI/FLAIR on magnetic resonance imaging. The patients were divided into thrombolysis group (60 patients) and control group (118 patients) according to whether or not they were applied to intravenous thrombolysis by TNK. Propensity score matching (PSM) was used to pair and balance the confounding factors at 1∶1 between the two groups, and the 90-d long-term prognosis of the patients was assessed using the modified Rankin Scale (mRS) and the Barthel Index (BI). The National Institutes of Health Stroke Scale (NIHSS) score was used to compare the early neurological changes between the two groups.The differences in clinical outcomes were compared between the two groups. Results: Fifty-two pairs of patients, 65 males and 39 females, aged (60±9) years, were successfully matched by PSM. The thrombolysis group had lower NIHSS score than that of the control group at 24 h, 7 d, 14 d after treatment or at discharge [3(2, 5) vs 4(3, 7), 3(2, 5) vs 4(3, 5), and 2(1, 4) vs 3(2, 4)], and shorter hospital stay than that of the control group [9(7, 12) d vs 11(9, 13) d], and at the same time, the thrombolysis group was less likely to experience early neurological deterioration (END) [9.6% (5/52) vs 28.9% (15/52)], and the proportion of 90 d mRS≤1, mRS≤2, and BI scores were higher than those in the control group [63.5% (33/52) vs 30.8% (16/52), 82.7% (43/52) vs 59.6% (31/52), and (91±8) points vs (82±8) points ], all differences were statistically significant (P<0.05). The percentage of mRS≥4 points was higher in the control group than that in the thrombolysis group [23.1% (12/52) vs 7.7% (4/52)]. One case of intracranial haemorrhage occurred in the thrombolysis group, and 1 case in the control group died of pulmonary infection within 90 d of follow-up, with a case-fatality rate of 1.9% (1/52). Conclusion: In the patients with post-awakening BAD screened by MRI, TNK intravenous thrombolysis can significantly reduce the risk of END, improving long-term prognosis and has a high safety.

In ischemic stroke, adding IV thrombolysis ≤2 h after symptom onset to thrombectomy was associated with benefit.

SOURCE CITATION: Kaesmacher J, Cavalcante F, Kappelhof M, et al; IRIS Collaborators. Time to treatment with intravenous thrombolysis before thrombectomy and functional outcomes in acute ischemic stroke: a meta-analysis. JAMA. 2024;331:764-777. 38324409.

Sex difference in the association between triglyceride and intracerebral bleeding risk after intravenous thrombolysis for acute ischemic stroke, a multi-center retrospective study.

Background: Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA). Methods: This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors. Results: Of 957 participants (median age 68 (interquartile range, 59-75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors (vs lowest tertile, medium tertile OR 0.39, 95% CI [0.17-0.91], top tertile OR 0.33, 95% CI [0.13-0.84], overall p = 0.021; per point increase, adjusted OR 0.29, 95% CI [0.13-0.63], p = 0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH. Conclusions: This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed.

Predicting ineffective thrombolysis in acute ischemic stroke with clinical and biochemical markers.

**Ischemic stroke remains a leading cause of morbidity and mortality globally. Despite the advances in thrombolytic therapy, notably recombinant tissue plasminogen activator (rtPA), patient outcomes are highly variable. This study aims to introduce a novel predictive model, the Acute Stroke Thrombolysis Non-Responder Prediction Model (ASTN-RPM), to identify patients unlikely to benefit from rtPA within the critical early recovery window. We conducted a retrospective cohort study at Baoding No.1 Central Hospital including 709 adult patients diagnosed with acute ischemic stroke and treated with intravenous alteplase within the therapeutic time window. The ASTN-RPM was developed using Least Absolute Shrinkage and Selection Operator (LASSO) regression technique, incorporating a wide range of biomarkers and clinical parameters. Model performance was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and Decision Curve Analysis (DCA). ASTN-RPM effectively identified patients at high risk of poor response to thrombolysis, with an AUC of 0.909 in the training set and 0.872 in the validation set, indicating high sensitivity and specificity. Key predictors included posterior circulation stroke, high admission NIHSS scores, extended door to needle time, and certain laboratory parameters like homocysteine levels. The ASTN-RPM stands as a potential tool for refining clinical decision-making in ischemic stroke management. By anticipating thrombolytic non-response, clinicians can personalize treatment strategies, possibly improving patient outcomes and reducing the burden of ineffective interventions. Future studies are needed for external validation and to explore the incorporation of emerging biomarkers and imaging data.

Spontaneous intracerebral hemorrhage - patients retrospectively consent to fibrinolytic surgery despite poor neurological outcome and reduced health-related quality of life.

Spontaneous intracerebral hemorrhage (ICH) might lead to devastating consequences. Nonetheless, subjective interpretation of life circumstances might vary. Recent data from ischemic stroke patients show that there might be a paradox between clinically rated neurological outcome and self-reported satisfaction with quality of life. Our hypothesis was that minimally invasive surgically treated ICH patients would still give their consent to stereotactic fibrinolysis despite experiencing relatively poor neurological outcome. In order to better understand the patients' perspective and to enhance insight beyond functional outcome, this is the first study assessing disease-specific health-related quality of life (hrQoL) in ICH after fibrinolytic therapy. We conducted a retrospective analysis of patients with spontaneous ICH treated minimally invasive by stereotactic fibrinolysis. Subsequently, using standardized telephone interviews, we evaluated functional outcome with the modified Rankin Scale (mRS), health-related Quality of Life with the Quality of life after Brain Injury Overall scale (QOLIBRI-OS), and assessed retrospectively if the patients would have given their consent to the treatment. To verify the primary hypothesis that fibrinolytic treated ICH patients would still retrospectively consent to fibrinolytic therapy despite a relatively poor neurological outcome, we conducted a chi-square test to compare good versus poor outcome (mRS) between consenters and non-consenters. To investigate the association between hrQoL (QOLIBRI-OS) and consent, we conducted a Mann-Whitney U-test. Moreover, we did a Spearman correlation to investigate the correlation between functional outcome (mRS) and hrQoL (QOLIBRI-OS). The analysis comprised 63 data sets (35 men, mean age: 66.9 ± 11.8 years, median Hemphill score: 3 [2-3]). Good neurological outcome (mRS 0-3) was achieved in 52% (33/63) of the patients. Patients would have given their consent to surgery retrospectively in 89.7% (52/58). These 52 consenting patients comprised all 33 patients (100%) who achieved good functional outcome and 19 of the 25 patients (76%) who achieved poor neurological outcome (mRS 4-6). The mean QOLIBRI-OS value was 49.55 ± 27.75. A significant association between hrQoL and retrospective consent was found (p = 0.004). This study supports fibrinolytic treatment of ICH even in cases when poor neurological outcome would have to be assumed since subjective perception of deficits could be in contrast with the objectively measured neurological outcome. HrQoL serves as a criterion for success of rtPa lysis therapy in ICH.

Prognostic value of combining 24-hour ASPECTS and hemoglobin to red cell distribution width ratio to the THRIVE score in predicting in-hospital mortality among ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND: Acute ischemic stroke (AIS) is a significant global health issue, directly impacting mortality and disability. The Totaled Health Risks in Vascular Events (THRIVE) score is appreciated for its simplicity and ease of use to predict stroke clinical outcomes; however, it lacks laboratory and neuroimaging data, which limits its ability to predict outcomes precisely. Our study evaluates the impact of integrating the 24-hour Alberta Stroke Program Early CT Score (ASPECTS) and hemoglobin-to-red cell distribution width (HB/RDW) ratio into the THRIVE score using the multivariable fractional polynomial (MFP) method (combined THRIVE-MFP model) compared to the THRIVE-c model. We aim to assess their added value in predicting in-hospital mortality (IHM) prognosis. MATERIALS AND METHODS: A retrospective study from January 2015 to July 2022 examined consecutive AIS patients receiving intravenous thrombolysis. Data on THRIVE scores, 24-hour ASPECTS, and HB/RDW levels were collected upon admission. The model was constructed using logistic regression and the MFP method. The prognostic value was determined using the area under the receiver operating characteristic curve (AuROC). Ischemic cerebral lesions within the middle cerebral artery territory were evaluated with non-contrast computed tomography (NCCT) after completing 24 hours of intravenous thrombolysis (24-hour ASPECTS). RESULTS: Among a cohort of 345 patients diagnosed with AIS who received intravenous thrombolysis, 65 individuals (18.8%) experienced IHM. The combined THRIVE-MFP model was significantly superior to the THRIVE-c model in predicting IHM (AuROC 0.980 vs. 0.876, p<0.001), 3-month mortality (AuROC 0.947 vs. 0.892, p<0.001), and 3-month poor functional outcome (AuROC 0.910 vs. 0.853, p<0.001). CONCLUSION: The combined THRIVE-MFP model showed excellent predictive performance, enhancing physicians' ability to stratify patient selection for intensive neurological monitoring and guiding treatment decisions. Incorporating 24-hour ASPECTS on NCCT and HB/RDW proved valuable in mortality prediction, particularly for hospitals with limited access to advanced neuroimaging resources.

Analysis of the Effect of Superselective Ophthalmic Artery Thrombolysis for Central Retinal Artery Occlusion.

INTRODUCTION: The aim of the study was to investigate the clinical efficacy of superselective ophthalmic artery thrombolysis for central retinal artery occlusion (CRAO). METHODS: Retrospective study of CRAO patients who attended the Department of Ophthalmology of Affiliated Hospital of Weifang Medical University from January 2022 to July 2023, 138 CRAO patients with onset time of 1-3 days were selected for the study. Among them, 86 patients refused thrombolytic treatment and chose to adopt traditional treatment, which was categorized as the control group; 52 patients adopted superselective ophthalmic artery thrombolytic treatment, which was categorized as the observation group. The visual acuity of the patients treated with traditional modality on the 4th day after the onset of the disease and the visual acuity of the patients treated with superselective ophthalmic artery thrombolysis on the 1st postoperative day were recorded, and the visual acuity improvement after different modalities of treatment was compared between the two groups. RESULTS: In the control group, 77 (89.5%) of the treated patients had no improvement in visual acuity, 9 (10.5%) had improvement, 0 (0.0%) had significant improvement, and the total improvement was 9 (10.5%); in the observation group, 18 (34.6%) of the treated patients had no improvement in visual acuity, 21 (40.4%) had improvement, 13 (25.0%) had significant improvement, and the total improvement was 34 (65.4%). The total improvement rate of treatment in the observation group was 65.4%, which was significantly higher than the 10.5% in the control group, and the difference was statistically significant (p < 0.05). CONCLUSION: Superselective ophthalmic artery thrombolysis for patients with CRAO is clinically effective, promotes improvement in patient vision, and has a high safety profile.

Analysis of Thrombolytic Agents in Intraventricular Hemorrhage: A Systematic Review and Meta-Analysis.

AIM: To determine the effectiveness of extraventricular drainage (EVD) combined with fibrinolytics in reducing morbidity and mortality rates associated with intraventricular cerebral hemorrhage (IVH). MATERIAL AND METHODS: A literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration number: CRD42022332152). Articles were selected from various sources, including PubMed, Trip Database, LILACS, Cochrane Library, and ScienceDirect. Clinical trials focusing on IVH treatment using EVD and/or fibrinolytics were considered. The Risk of Bias in Non-randomized Studies of Interventions (ROB 2) tool was employed for bias assessment. A fixed-effects regression model was used following heterogeneity analysis. Treatment effectiveness was evaluated based on mortality outcomes. RESULTS: A total of 531 patients from four studies were included. The use of fibrinolytics significantly decreased IVH mortality compared with a placebo. The odds ratio (OR) for recombinant tissue plasminogen activator (rtPA) or alteplase was 0.54 [0.36; 0.82]. For urokinase (UK), the OR was 0.21 [0.03; 1.54], rendering it statistically non-significant. The overall OR was 0.52 [0.35; 0.78], and the heterogeneity I2 was 0% (indicating low heterogeneity). CONCLUSION: While EVD alone is a common approach for managing hydrocephalus, its effectiveness is limited by potential blockages and infections. Combining EVD with UK or rtPA demonstrated improved patient outcomes. rtPA stands out as a reliable and effective option, while limited data are available regarding UK's effectiveness in reducing IVH mortality.

Comparison of functional and safety outcomes between the extended versus early time window after intravenous thrombolysis and endovascular thrombectomy.

INTRODUCTION: Based on recent trials regarding the early time window, omitting intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) in eligible patients seems unjustified. Whether this also concerns the extended time window, 4.5 to 9 h from last seen well, is yet unclear. PATIENTS AND METHODS: All consecutive patients treated with IVT, EVT, or IVT plus EVT in the extended time window at Helsinki University Hospital (HUS) between 1/2021 and 12/2022 were compared with matched controls treated in the early time window between 1/2016 and 12/2020. Regression analysis was applied on functional outcome at 90 days, evaluated on modified Rankin Scale (mRS), and on the occurrence of symptomatic intracerebral hemorrhage (sICH), adjusted for potential confounders. RESULTS: Altogether 134 patients and 134 matching controls were included. Functional outcomes did not significantly differ between the extended versus early time window. Among patients with IVT plus EVT, the adjusted odds ratio (aOR) for a favorable outcome shift on mRS was 1.15, 95% confidence interval (CI) 0.54-2.43. Although sICH occurred more frequently (2.2% versus 3.0%) in the extended time window, regression analysis did not show a significant difference, aOR 0.96, 95% CI 0.14-6.87. DISCUSSION AND CONCLUSION: We found no significant differences in the functional or safety outcomes between the extended versus early time window among patients with either IVT, EVT, or IVT plus EVT. There were no signals indicating, that IVT or EVT should be avoided in eligible patients in the extended time window which aligns with the current clinical treatment guidelines of HUS.

Intracoronary thrombolysis in ST-elevation myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Despite restoration of epicardial blood flow in acute ST-elevation myocardial infarction (STEMI), inadequate microcirculatory perfusion is common and portends a poor prognosis. Intracoronary (IC) thrombolytic therapy can reduce microvascular thrombotic burden; however, contemporary studies have produced conflicting outcomes. OBJECTIVES: This meta-analysis aims to evaluate the efficacy and safety of adjunctive IC thrombolytic therapy at the time of primary percutaneous coronary intervention (PCI) among patients with STEMI. METHODS: Comprehensive literature search of six electronic databases identified relevant randomised controlled trials. The primary outcome was major adverse cardiac events (MACE). The pooled risk ratio (RR) and weighted mean difference (WMD) with a 95% CI were calculated. RESULTS: 12 studies with 1915 patients were included. IC thrombolysis was associated with a significantly lower incidence of MACE (RR=0.65, 95% CI 0.51 to 0.82, I2=0%, p<0.0004) and improved left ventricular ejection fraction (WMD=1.87; 95% CI 1.07 to 2.67; I2=25%; p<0.0001). Subgroup analysis demonstrated a significant reduction in MACE for trials using non-fibrin (RR=0.39, 95% CI 0.20 to 0.78, I2=0%, p=0.007) and moderately fibrin-specific thrombolytic agents (RR=0.62, 95% CI 0.47 to 0.83, I2=0%, p=0.001). No significant reduction was observed in studies using highly fibrin-specific thrombolytic agents (RR=1.10, 95% CI 0.62 to 1.96, I2=0%, p=0.75). Furthermore, there were no significant differences in mortality (RR=0.91; 95% CI 0.48 to 1.71; I2=0%; p=0.77) or bleeding events (major bleeding, RR=1.24; 95% CI 0.47 to 3.28; I2=0%; p=0.67; minor bleeding, RR=1.47; 95% CI 0.90 to 2.40; I2=0%; p=0.12). CONCLUSION: Adjunctive IC thrombolysis at the time of primary PCI in patients with STEMI improves clinical and myocardial perfusion parameters without an increased rate of bleeding. Further research is needed to optimise the selection of thrombolytic agents and treatment protocols.

The impact of intensive blood pressure management in the post-thrombolysis setting: a real-world observational study.

AIM: Systolic blood pressure (SBP) >180mmHg following stroke thrombolysis has been associated with increased bleeding and poorer outcome. Aiming for the guideline SBP of <180mmHg often leads to SBP overshoot, as treatment is only triggered if this threshold is passed. We tested whether a lower target would result in fewer high SBP protocol violations. METHOD: This is a single-centre, sequential comparison of two blood pressure protocols. Between 2013 and 2017, the guideline-based post-thrombolysis SBP target of <180mmHg was compared with a new protocol aiming for 140-160mmHg. The primary outcome was rate of patients with SBPs >180mmHg. Secondary outcomes included rates of SBP <120 mmHg, antihypertensive infusion use, symptomatic intracerebral haemorrhage (sICH) and 3-month functional independence (modified Rankin Score [mRS] 0-2). Results were adjusted for age, baseline function and stroke severity using regression analysis. RESULTS: During the 23 months preceding and 18 months following the transition to the new protocol, 68 and 100 patients were thrombolysed respectively. Baseline characteristics were similar between groups. The odds of one or more SBPs >180mmHg trended lower in the intensive group (adjusted odds ratio [aOR] 0.61; 95% confidence interval [CI] 0.32-1.17; p=0.14). There was a higher rate of SBPs <120mmHg (aOR 3.09; 95% CI 1.49-6.40; p=0.002) in the intensive BP protocol group. sICH rate and 3-month mRS 0-2 were similar between groups. CONCLUSIONS: The more intensive post-thrombolysis BP protocol was associated with a significant increase in sub-optimally low BP events, with a non-significant trend toward fewer high BP protocol violations and unaffected patient outcomes.

Factors influencing the efficacy of recombinant tissue plasminogen activator: Implications for ischemic stroke treatment.

Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization is relatively low and the underlying processes are not completely understood. The goal was to provide insights into clinically important factors potentially limiting rt-PA efficacy such as clot size, rt-PA concentration, clot age and also rt-PA in combination with heparin anticoagulant. We established a static in vitro thrombolytic model based on red blood cell (RBC) dominant clots prepared using spontaneous clotting from the blood of healthy donors. Thrombolysis was determined by clot mass loss and by RBC release. The rt-PA became increasingly less efficient for clots larger than 50 µl at a clinically relevant concentration of 1.3 mg/l. A tenfold decrease or increase in concentration induced only a 2-fold decrease or increase in clot degradation. Clot age did not affect rt-PA-induced thrombolysis but 2-hours-old clots were degraded more readily due to higher activity of spontaneous thrombolysis, as compared to 5-hours-old clots. Finally, heparin (50 and 100 IU/ml) did not influence the rt-PA-induced thrombolysis. Our study provided in vitro evidence for a clot size threshold: clots larger than 50 µl are hard to degrade by rt-PA. Increasing rt-PA concentration provided limited thrombolytic efficacy improvement, whereas heparin addition had no effect. However, the higher susceptibility of younger clots to thrombolysis may prompt a shortened time from the onset of stroke to rt-PA treatment.