Determination of Uric Acid in the Presence of Ascorbic Acid Using Poly(3,4-ethylenedioxythiophene)-Modified Electrodes

A poly(3,4-ethylenedioxythiophene) (PEDOT) modified glassy carbon electrode (GCE) was used to determine uric acid in the presence of ascorbic acid at physiological pH facilitating a peak potential separation of ascorbic acid and uric acid oxidation (ca. 365 mV), which is the largest value reported so far in the literature. Also, an analytical protocol involving differential pulse voltammetry has been developed using a microchip electrode for the determination of uric acid in the concentration range of 1 to 20 mM in presence of excess of ascorbic acid

Clinical performance review for 3-D Deep Learning segmentation of stroke infarct from diffusion-weighted images

Introduction: During the subacute phase of ischemic stroke, MR diffusion-weighted imaging (DWI) is used to assess the extent of tissue injury. Segmentation of DWI infarct is challenging due to disease variability, but Deep Learning (DL) provides a solution, outperforming existing methods on small datasets. However, a lack of clinically meaningful performance evaluation hinders clinical translation. Here we develop a DL DWI segmentation tool and provide clinical performance review. Methods: Subjects in this retrospective study presented with stroke symptoms and later underwent DWI imaging. DL architectures U-Net and DenseNet were used to develop a DWI segmentation tool. The Dice Similarly Coefficient (DSC) was used to select the best- and worst-performing model. Clinical experts reviewed these models on the clinical test set, agreeing with the model if no 'significant’ error was present. The average agreement with the model and interrater agreement was also derived. Results: In total, 573 participants with an ischemic stroke were included. The DenseNet delivered the best model (DSC = 0.831 ± 0.064) with a mean inference time of 0.07 s. Clinicians compared this with the worst model (U-Net, DSC = 0.759 ± 0.122), agreeing with the DenseNet predictions more than the U-Net (83.8 % vs. 79.3 %). Clinicians also agreed with each other more over performance interpretation when evaluating the DenseNet over the U-Net (87.9 % vs. 72.7 %). Conclusion: Our DWI segmentation tool achieved high performance with clinical review providing meaningful performance evaluation. Model development will continue towards prospective deployment before which clinical review will be repeated. This work will benefit physicians in assessing patient prognosis

Association of Ischemic Core Hypodensity With Thrombectomy Treatment Effect in Large Core Stroke: A Secondary Analysis of the SELECT2 Randomized Controlled Trial

Background: We aimed to determine whether extensive severe computed tomography (CT) hypodensity, representing blood-brain barrier injury, would be associated with a reduced benefit of endovascular therapy (EVT) in patients presenting with large core stroke. Methods: This study is an exploratory analysis of SELECT2 (Randomized Controlled Trial to Optimize Patient\u27s Selection for Endovascular Treatment in Acute Ischemic Stroke), a randomized controlled trial of EVT versus medical management in patients with large ischemic core who presented to 31 comprehensive stroke centers across the United States, Canada, Europe, Australia, and New Zealand. Visible CT hypodensity was outlined, and a threshold of severe CT hypodensity was defined as the lower 99% CI of contralateral thalamic gray matter in Hounsfield units (HU). The association between the volume of severe CT hypodensity and modified Rankin Scale (mRS) score of 0 to 3 was evaluated using logistic regression models, with adjustment for age, National Institutes of Health Stroke Scale, total noncontrast CT core volume, and a volume-by-treatment interaction. The relationship between severe CT hypodensity volume and the probability of an mRS score of 0 to 3 was used to select clinically relevant volume cut points for further evaluation. The treatment effect of EVT versus medical management on independent ambulation and hemicraniectomy was assessed in 2 subgroups based on these volume cut points. Results: In 322 patients, the median CT density was 31 HU (interquartile range, 28-34). The selected threshold of severe CT hypodensity was 26 HU. The volume of ischemic core ≤26 HU (per 1 mL increase) was associated with lower odds of mRS score of 0 to 3 after EVT (adjusted odds ratio [aOR], 0.96 [95% CI, 0.94-0.99]), but not medical management (aOR, 1.01 [95% CI, 0.98-1.03]; Pinteraction\u3c 0.01). In 101 patients with ≥26 mL of severe CT hypodensity, EVT, compared with medical management, was not associated with mRS score of 0 to 3 (aOR, 0.98 [95% CI, 0.33-2.88]) and was associated with hemicraniectomy (≥26 mL: aOR, 3.45 [95% CI, 1.09-10.86] versus \u3c 26 mL: aOR, 0.74 [95% CI, 0.31-1.75]; Pinteraction=0.03), whereas among 221 patients with \u3c 26 mL of severe hypodensity EVT was associated with mRS score of 0 to 3 (aOR, 7.20 [95% CI, 3.55-15.47]; Pinteraction\u3c 0.01). Conclusions: Severe hypodensity within large ischemic regions modifies the thrombectomy treatment effect and increases the likelihood of hemicraniectomy, independent of lesion volume. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03876457

Benchmark dataset for clot detection in ischemic stroke vessel-based imaging: CODEC-IV

We present an annotated dataset for the purposes of creating a benchmark in Artificial Intelligence for automated clot detection. While there are commercial tools available for automated clot detection on computed tomographic (CT) angiographs, they have not been compared in a standardized manner whereby accuracy is reported on a publicly available benchmark dataset. Furthermore, there are known difficulties in automated clot detection - namely, cases where there is robust collateral flow, or residual flow and occlusions of the smaller vessels - and it is necessary to drive an initiative to overcome these challenges. Our dataset contains 159 multiphase CTA patient datasets, derived from CTP and annotated by expert stroke neurologists. In addition to images where the clot is marked, the expert neurologists have provided information about clot location, hemisphere and the degree of collateral flow. The data is available on request by researchers via an online form, and we will host a leaderboard where the results of clot detection algorithms on the dataset will be displayed. Participants are invited to submit an algorithm to us for evaluation using the evaluation tool, which is made available at together with the form at https://github.com/MBC-Neuroimaging/ClotDetectEval

Bridging thrombolysis with tenecteplase versus endovascular thrombectomy alone for large-vessel anterior circulation stroke: a target trial emulation analysis

Published Online First 22 January 2025Background Whether bridging thrombolysis with tenecteplase is beneficial compared with thrombectomy alone in patients who had a stroke with large-vessel occlusion remains unclear. Methods This is a causal inference study of observational data from the trials SWIFT DIRECT and EXTEND-IA TNK Parts 1 and 2 applying target trial emulation. We compared patients receiving thrombectomy alone to patients receiving tenecteplase 0.25mg/kg or 0.40mg/kg before thrombectomy. The primary outcome was functional independence (modified Rankin Scale (mRS) of 0–2) at 90 days. Secondary outcomes included improvement over the full ordinal mRS scale, freedom of disability (mRS 0–1), mortality and occurrence of symptomatic intracranial haemorrhage. The average causal treatment effect was estimated via inverse probability of treatment weighting and GComputation. We calculated standardised risk differences (SRDs) and adjusted (common) ORs (a(c)ORs). Results Of 377 patients included in the target trial, 187 received thrombectomy alone and 190 tenecteplase before thrombectomy. Tenecteplase before thrombectomy did not increase the probability of patients achieving functional independence (SRD 0.04 (95% CI –0.06 to 0.13)) but resulted in a significant improvement in the mRS overall (acOR 1.56 (95% CI 1.07 to 2.23)) and in a higher probability of freedom from disability (SRD 0.10 (95% CI 0.01 to 0.20)). The probability for improvement of functional outcomes was further increased in patients treated within 140min after onset (ordinal mRS acOR 1.63 (95% CI 1.04 to 2.56)). No significant differences in safety outcomes were observed between the two groups. Conclusion Tenecteplase before thrombectomy compared with thrombectomy alone did not increase the probability of functional independence but resulted in significant improvement over the full mRS scale. This improvement was most evident in patients treated early.Valerian L Altersberger, Johannes Kaesmacher, Leonid Churilov, Vignan Yogendrakumar, Jan Gralla, Daniel Strbian, David J Seiffge, Peter J Mitchell, Timothy J Kleinig, Bruce CV Campbell, Urs Fische

Safety and Efficacy of Tenecteplase in Older Patients with Large Vessel Occlusion: A Pooled Analysis of the EXTEND-IA TNK Trials

Background and Objectives Detailed study of tenecteplase (TNK) in patients older than 80 years is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients older than 80 years with large vessel occlusion. Methods We performed a pooled analysis of the EXTEND-IA TNK randomized controlled trials (n = 502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25 mg/kg, TNK 0.40 mg/kg, and alteplase 0.90 mg/kg, stratifying for patient age (>80 years). Outcomes evaluated include 90-day modified Rankin Scale (mRS) score, all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIH Stroke Score, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. Results In patients >80 years (n = 137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, adjusted common odds ratio (acOR) 2.70, 95% CI 1.23–5.94) and reduced mortality (acOR 0.34, 95% CI 0.13–0.91) vs 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, acOR 2.28, 95% CI 1.03–5.05) vs alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, 1 patient treated with alteplase, and 0 patients treated with TNK 0.25 mg/kg. In patients ≤80 years, no differences in 90-day mRS, mortality, or symptomatic ICH were observed among TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg. Discussion TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients older than 80 years. No differences among the doses were observed in younger patients. Trial Registration Information NCT02388061, NCT03340493. Classification of Evidence This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients >80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.No Full Tex