Showing posts with label Alteplase. Show all posts
Showing posts with label Alteplase. Show all posts
Saturday, May 23, 2026
Monday, May 11, 2026
Development and validation of machine learning models for predicting functional outcome after low-dose alteplase in the extended time window for acute ischemic stroke
Predicting failure to recover never got anyone recovered! Get the hell out of stroke!
Development and validation of machine learning models for predicting functional outcome after low-dose alteplase in the extended time window for acute ischemic stroke
Abstract
Background:
This study aims to develop machine learning (ML) models to predict 90-day functional outcomes for acute ischemic stroke (AIS) patients receiving thrombolysis with low-dose alteplase at 0.6 mg/kg between 4.5 and 9 h after symptom onset.
Methods:
We conducted a retrospective analysis of AIS patients receiving thrombolysis between August 1, 2019 and August 31, 2023. Eligible patients were randomly divided into training and validation sets in a 7:3 ratio. Good functional prognosis at 90 days were defined as modified Rankin scale score (mRS) ≤2. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select optimal features. Five ML algorithms were employed to construct prediction models. Model performance was evaluated using receiver operating characteristic (ROC) curves, area under the curve (AUC) value, decision curve analysis (DCA), and calibration curves. SHapley Additive exPlanations (SHAP) plot was applied to interpret the model predictions.
Results:
A total of 202 patients were randomly divided into training (n = 142) and validation (n = 60) sets. The rate of poor functional prognosis at 90 days was 56.34% in the training set and 56.67% in the validation set. Random Forest (RF) model showed the best discriminative ability with the highest AUC of 0.854 in the validation set. Key predictive features included age, baseline systolic blood pressure, white blood cell count, baseline National Institutes of Health Stroke Scale (NIHSS) score, wake-up stroke, the absolute difference volume between the ischemic infarct and the penumbra, intracranial hemorrhage, hemorrhagic transformation classification, and occurrence of pneumonia.
Conclusion:
The RF-based ML model demonstrated clinical utility for post-intravenous thrombolysis risk stratification by identifying patients at higher risk of poor functional outcomes.
Thursday, March 19, 2026
Improvements in Time-Sensitive Stroke Care and Alteplase Administration: The Iranian Comprehensive Code Stroke Management Program (ICSM Phase III)
WOW! Creating a stroke protocol that not even first world countries are doing!
Improvements in Time-Sensitive Stroke Care and Alteplase Administration: The Iranian Comprehensive Code Stroke Management Program (ICSM Phase III)
Abstract
BACKGROUND:
Timely management of acute stroke in the emergency medical services setting is critical. Systemic challenges in this phase include the absence of evidence-based standards, inconsistent protocols, and coordination delays. This study aimed to implement and evaluate an updated national stroke protocol in northern Iran.METHODS:
This quasi-experimental study evaluated the Iranian Comprehensive Code Stroke Management Program. The intervention group (Babol emergency medical services, n=248) received a multi-faceted empowerment program, while the control group (Mazandaran emergency medical services, n=900) received standard training. Patients' level outcomes were assessed on prehospital time, monthly intravenous alteplase counts, and administration rates before (March–September 2023) and after the intervention (March–September 2024).RESULTS:
Of 1131 suspected stroke codes, 400 (35%) were hospital-confirmed. The intervention significantly reduced most prehospital time intervals (except transport time) and increased the rate of intravenous alteplase administration per hospital-confirmed stroke code from 13.94% preintervention to 39.49% postintervention (absolute increase +25.55%±19.17; P<0.001). Additionally, the mean monthly number of alteplase administrations showed an increasing trend (+4.00±4.64; P=0.07). Conversely, the control group exhibited a significant decrease in the mean number of monthly alteplase administrations (−0.72±0.57; P=0.04) and a nonsignificant reduction in the administration rate (−1.49 percentage points; SD ±6.47; P=0.69).
CONCLUSIONS:
Implementing the updated protocol was associated with significant reductions in critical time intervals and a near-tripling of the intravenous alteplase administration rate in the intervention group. National evaluation should include long-term functional outcomes to confirm effectiveness and establish its value as a model.
Graphical Abstract
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Wednesday, March 18, 2026
Timing-Dependent Cleavage of Interleukin-1 Receptor Antagonist by Alteplase Impairs Neuroprotection in Ischemic Stroke
Will your competent? doctor and hospital do anything with this? Or is head in the sand their response? I'd start asking now so enough time is available to get some competency in your hospital!
Timing-Dependent Cleavage of Interleukin-1 Receptor Antagonist by Alteplase Impairs Neuroprotection in Ischemic Stroke
Abstract
BACKGROUND:
Inflammation contributes significantly to neuronal damage in ischemic stroke, with IL (interleukin)-1 being a key mediator. IL-1Ra (IL-1 receptor antagonist) inhibits IL-1 signaling, successfully reducing inflammation in preclinical and clinical stroke studies. However, in the latest phase II trial of IL-1Ra in ischemic stroke (SCIL-STROKE [Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke]), a secondary mediation analysis uncovered an alternative pathway leading to no overall functional benefit. This was the first IL-1Ra trial where participants (73%) received preceding tPA (tissue-type plasminogen activator), raising the possibility that IL-1Ra and tPA interact negatively in ischemic stroke. We aim to explore this postulated negative interaction.METHODS:
A retrospective analysis of SCIL-STROKE trial data was performed. Next, we used a thromboembolic model of stroke in male wild-type mice (25–35 g; n=10–13), treated with tPA (10 mg/kg, 20–60 minutes poststroke), followed by IL-1Ra (100 mg/kg) either 6 doses, twice daily (after tPA), or 2 doses at 30 minutes (during tPA) and 3 hours poststroke. The primary outcome was lesion volume at 72 hours, measured by T2-magnetic resonance imaging.RESULTS:
Reanalysis of SCIL-STROKE data revealed a 35.8% reduction in plasma IL-1Ra in patients cotreated with preceding tPA, suggesting IL-1Ra degradation. Biochemical assays confirmed IL-1Ra cleavage by plasmin. While replicating the SCIL-STROKE dosing regimen preclinically, no negative interactions were noted. However, when IL-1Ra was administered during thrombolysis, it impaired the beneficial effect of tPA, reducing lesion volume by only 15%, compared with 68% with tPA alone. Acute cotreatment of IL-1Ra and tPA also led to reduced tissue perfusion and increased leukocyte infiltration and neutrophil extracellular traps.
CONCLUSIONS:
We show that IL-1Ra is cleaved by plasmin, and its administration during thrombolysis worsens outcomes poststroke. These studies confirm a negative interaction between the 2 drugs, which can be prevented by tPA preceding IL-1Ra treatment. The findings raise broader concerns about how tPA may interfere with other neuroprotective treatments.
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