Abstract WP138: Collateral Status Measured by Hypoperfusion Intensity Ratio Correlates With Infarct Core Size and Growth Rate in MCA Medium Vessel Occlusions <6 Hours and 6-24 Hours Post Onset

Stroke, Volume 55, Issue Suppl_1, Page AWP138-AWP138, February 1, 2024. Purpose:Hypoperfusion intensity ratio (HIR) derived from CT perfusion (CTP) has shown to be a useful surrogate marker of collateral status, but prior studies focused on ICA/M1 large vessel occlusions (LVO). We aimed to determine: associations between HIR and clinical/imaging metrics of stroke severity for M2 and M3 medium vessel occlusions (MVO), any differences between 10mL/h (fast progressor).Methods:We retrospectively analyzed consecutive patients arriving within 24h from onset, with M2 or M3 occlusion on CTA, and had concurrent CTP. RAPID generated maps of infarct core defined as rCBF10s/Tmax >6s. IGR was defined as core size/onset-to-CTP time. ASPECTS and NIHSS data were also collected. Correlations were tested using Spearman’s rank analysis, for the cohort and separately for 10mL/h was determined by ROC analysis.Results:78 patients included with median (IQR) age of 79 (64-84), onset of 7.5h (2.5-14.5), NIHSS of 12 (7-18), ASPECTS of 7 (9-10), core size of 4 mL (0-22), and IGR of 0.57 mL/h (0-2.8). 63 M2 and 15 M3 occlusions identified with median HIR of 0.35 (0.06-0.52). For the cohort, HIR was highly correlated to core size r=0.740 and IGR r=0.710, moderately correlated to NIHSS r=0.474 and ASPECTS r=-0.331 (all p

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Febbraio 2024

Abstract WMP64: Late Lesion Growth Following Endovascular Therapy: Is 24 Hours Too Early to Assess Acute Infarct Size Including the Effects of Secondary Injury?

Stroke, Volume 55, Issue Suppl_1, Page AWMP64-AWMP64, February 1, 2024. Background:Measurement of “final” lesion volume at 24hr following endovascular therapy (post-EVT) has been used in multiple studies as a surrogate for clinical outcome. However, despite successful recanalization, a significant proportion of patients do not experience favorable clinical outcome.Methods:This is a prospective study of acute ischemic stroke patients at two stroke centers who met the following criteria: i) anterior large vessel occlusion (LVO) acute ischemic stroke, ii) attempted EVT, iii) written informed consent obtained, and iv) had MRI post-EVT at 24hr and 5-day. We defined “Early” and “Late” lesion growth as ≥10mL lesion growth between baseline and 24hr DWI, and between 24hr DWI and 5-day FLAIR, respectively.Results:One hundred fourteen patients met study criteria with median age 67 years, 56% female, median admit NIHSS 19, 54% received IV or IA thrombolysis, 67% with M1 occlusion, and median baseline DWI volume 28.2mL. Successful recanalization was achieved in 86% and 67% had complete reperfusion, with an overall favorable clinical outcome rate of 54%. Nearly two thirds (65%) of the patients did not have Late lesion growth with a median volume change of -0.2mL between 24hr and 5-days and an associated high rate of favorable clinical outcome (65%). However, ~1/3 of patients (35%) did have significant Late lesion growth despite successful recanalization (85% TICI 2b/3). Late lesion growth patients had a 26.2mL change in Late lesion volume and 19.9mL change in Early lesion volume. These patients had an increased hemorrhagic transformation rate of 68% with only 1 in 3 patients having favorable clinical outcome. Late lesion growth was independently associated with incomplete reperfusion, hemorrhagic transformation, and unfavorable outcome even after adjusting for admit NIHSS and Early lesion growth.Conclusions:Approximately 1 out of 3 patients had Late lesion growth following EVT, with a favorable clinical outcome occurring in only 1 out of 3 of these patients. Identification of patients with Late lesion growth could be critical to guide clinical management and inform prognosis post-EVT. Additionally it can serve as an imaging biomarker for the development of adjunctive therapies to mitigate reperfusion injury.

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Febbraio 2024

Abstract 148: Increased Systolic Blood Pressure Variability During the First 24-hours of Hospitalization Associates With Poor 90-day Outcome After Intracerebral Hemorrhage

Stroke, Volume 55, Issue Suppl_1, Page A148-A148, February 1, 2024. Introduction:Prospective studies and secondary analyses from clinical trials have identified increased systolic blood pressure variability (SBPV) as a risk factor for poor outcomes. Evidence of this association in real-world intracerebral hemorrhage (ICH) hospitalization is lacking, however.Methods:Data for adult (≥18) patients with primary ICH were retrieved from the REINAH cerebrovascular research database. Systolic blood pressure measurements from the first 24 hours of admission were retrieved and SBPV was calculated as the Coefficient of Variation (CV) = (standard deviation/mean)*100. Socioeconomic deprivation was assessed using the state Area Deprivation Index (ADI), with high deprivation assessed at ADI ≥ 8. The primary outcome was severe disability or death (SDD; modified Rankin Scale ≥4) at 90-days after discharge. Differences in SBPV across SDD were assessed using the Mann-Whitney U test. Associations between SBPV and SDD were assessed using multivariable logistic regression models adjusted for patient characteristics. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported.Results:Final cohort included 807 patients (median [IQR]: 66 [54-77], 45.6% female), with an ethno-racial distribution of 41.9% White, 25.9% Black, 23.9% Hispanic, 5.7% Asian, and 2.6% Other. The median CV was 12.07 [9.50-15.59] and 485 (60.1%) patients experienced SDD. Patients with SDD showed significantly higher SBPV than non-SDD patients (12.90 [10.33-17.11] vs 10.99 [8.72-13.72]; p

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Febbraio 2024

Abstract WP190: Comparison of Collateral Score to ASPECTS to Exclude “Very Large” Infarct Core Volumes in Anterior Circulation Large Vessel Occlusion Strokes at 0-24 Hours

Stroke, Volume 55, Issue Suppl_1, Page AWP190-AWP190, February 1, 2024. Purpose:ASPECTS100mL) for reperfusion using endovascular thrombectomy (EVT). While specific, ASPECTS100mL while maintaining similar specificity to ASPECTS.Methods:Retrospective analysis included consecutive stroke patients arriving within 24 hours of onset, with intracranial ICA and/or M1 occlusion on CTA, and had concurrent CT perfusion. RAPID AI software estimated ICV using the rCBF0 but =50 but 100mL. Sensitivity and specificity of that CS threshold vs ASPECTS100mL (9.8%) with median of 136mL (105-172). Using ASPECTS

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Febbraio 2024

Abstract 28: Patients Randomised to Glenzocimab Suffered Less Haemorrhagic Transformation at 24 Hours Compared to Placebo: AI-Imaging Sub-Analysis of the ACTIMIS Trial

Stroke, Volume 55, Issue Suppl_1, Page A28-A28, February 1, 2024. Introduction:ACTIMIS (NCT03803007) was a randomized phase 1b/2a clinical trial evaluating glenzocimab, a monoclonal antibody fragment targeting platelet receptor glycoprotein VI in patients with acute ischemic stroke treated by thrombolysis. Primary analysis demonstrated a reduction in intracranial hemorrhage occurrence stroke-related mortality. In this sub-analysis, volumetric imaging biomarkers were used to assess efficacy of glenzocimab.Methods:In the phase 2a study, patients were randomized (1:1) with 1000mg glenzocimab or placebo. CT or MRI was acquired at baseline with CT at 24 hours and MRI at 7 days for safety and efficacy analysis. Baseline and follow up imaging were processed as post-hoc analysis using AI core lab software (Brainomix, Oxford, UK). Automated output was reviewed for accuracy by an expert clinician (DC) blinded to treatment allocation.Results and Conclusions:Follow up imaging data were available from 103/106 patients (51 glenzocimab, 52 placebo) at 24 hours. Of these, 54 underwent mechanical thrombectomy (MT, 27 glenzocimab, 27 placebo). Day-7 imaging was available for 9 fewer placebo patients and 1 glenzocimab patient. All except 2 patients (1 placebo, 1 glenzocimab) with missing data at Day-7 died during the study. Preliminary analysis showed smaller volume of hemorrhagic transformation (HT) in the glenzocimab group at 24 hours compared to placebo and a trend towards smaller volume of ischemic injury. Exploratory analysis also highlighted an interaction effect between risk of HT following MT and glenzocimab (lower risk in patients treated with glenzocimab). The full results of the imaging sub-analysis of the ACTIMIS study will be presented at the conference and discussed in the context of current literature.

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Febbraio 2024

Abstract 24: Differences in Door to Needle and Door In Door Out Times for Tenecteplase vs Alteplase in Acute Ischemic Stroke: Findings From Get With the Guidelines Stroke

Stroke, Volume 55, Issue Suppl_1, Page A24-A24, February 1, 2024. Introduction:Tenecteplase (TNK) has arisen as an alternative to alteplase (ALT) for emergent treatment of acute ischemic stroke. Shorter times to prepare and administer TNK raises the possibility that TNK use leads to faster treatment and transfer times.Hypothesis:We hypothesized that treatment with TNK is associated with shorter door-to-needle (DTN) and door-in-door-out (DIDO) times.Methods:Using the US Get With The Guidelines-Stroke registry, we performed a retrospective, observational cohort study of consecutive patients treated with either TNK or ALT between July 1, 2020 and June 30, 2022. The exposure was treatment with TNK vs ALT. The primary endpoints were DTN and DIDO. We fit generalized linear mixed models to determine the association between TNK (vs ALT) and endpoints after adjustment for key demographic, clinical, and hospital-level variables. A secondary analysis compared changes in DTN among hospitals that switched to TNK in 2021 with at least 10 cases per year pre and post switch.Results:From 2092 sites, 133,228 patients received intravenous thrombolysis. Among the 13,988 (10%) treated with TNK, median age was 70 yrs, median NIHSS 7, 47% female, 21% received endovascular thrombectomy (EVT), and 9% were transferred from the hospital emergency department after receiving lytic. Among 119,240 (90%) treated with ALT, median age was 69 yrs, median NIHSS 7, 48% female; 17% received EVT, and 12% were transferred after lytic. In the primary DTN analysis, time to treatment was shorter with TNK, with mean 47.0 vs 52.7 minutes and DTN ≤60 mins in 77.5% vs 70.7% (TABLE). In the primary DIDO analysis, time to departure was shorter with TNK, 108.3 vs 114.1 minutes. In centers that changed from ALT to TNK during this period DTN times were significantly lower after switching.Conclusions:In this largest study of TNK vs ALT workflow time intervals in ischemic stroke using population-based data, TNK use was associated with more favorable DTN and DIDO times relative to ALT use.

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Febbraio 2024

COMPARING REAL-WORLD OUTCOMES, MEASURED AS 12 AND 24-MONTH IBD-RELATED SURGERIES, BETWEEN INFLIXIMAB DOSE OPTIMIZED PATIENTS USING THERAPEUTIC DRUG MONITORING (TDM) VS AN UNOPTIMIZED CONTROL GROUP, IN A LARGE US COMMUNITY-BASED GASTROENTEROLOGY PRACTICES

Anti-TNFs such as infliximab (IFX) continue to be the standard of care to treat moderate-to-severe IBD. Remission and reducing detrimental outcomes are achievable goals when therapeutic drug monitoring (TDM) is implemented to assist with IFX therapy optimization. TDM aids in achieving & maintaining adequate drug exposure to avoid loss of response by offering actionable information to guide treatment adjustments. The value of TDM has been described in numerous studies which show that optimization of anti-TNFs correlates with improved clinical outcomes & the use of TDM is recommended by IBD guidelines and expert consensus.

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Gennaio 2024

Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study

Introduction
Non-alcoholic fatty liver disease (NAFLD) affects approximately one in four individuals and its prevalence continues to rise. The advanced stages of NAFLD with significant liver fibrosis are associated with adverse morbidity and mortality outcomes. Currently, liver biopsy remains the ‘gold-standard’ approach to stage NAFLD severity. Although generally well tolerated, liver biopsies are associated with significant complications, are resource intensive, costly, and sample only a very small area of the liver as well as requiring day case admission to a secondary care setting. As a result, there is a significant unmet need to develop non-invasive biomarkers that can accurately stage NAFLD and limit the need for liver biopsy. The aim of this study is to validate the use of the urine steroid metabolome as a strategy to stage NAFLD severity and to compare its performance against other non-invasive NAFLD biomarkers.

Methods and analysis
The TrUSt-NAFLD study is a multicentre prospective test validation study aiming to recruit 310 patients with biopsy-proven and staged NAFLD across eight centres within the UK. 150 appropriately matched control patients without liver disease will be recruited through the Oxford Biobank. Blood and urine samples, alongside clinical data, will be collected from all participants. Urine samples will be analysed by liquid chromatography-tandem mass spectroscopy to quantify a panel of predefined steroid metabolites. A machine learning-based classifier, for example, Generalized Matrix Relevance Learning Vector Quantization that was trained on retrospective samples, will be applied to the prospective steroid metabolite data to determine its ability to identify those patients with advanced, as opposed to mild-moderate, liver fibrosis as a consequence of NAFLD.

Ethics and dissemination
Research ethical approval was granted by West Midlands, Black Country Research Ethics Committee (REC reference: 21/WM/0177). A substantial amendment (TrUSt-NAFLD-SA1) was approved on 26 November 2021.

Trial registration number
ISRCTN19370855.

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Gennaio 2024

Experiences and perceptions of urine sampling for tuberculosis testing among HIV patients: a multisite qualitative descriptive study

Objectives
Evidence on the acceptability of urine-based assays for tuberculosis (TB) diagnosis among patients remains limited. We sought to describe patients’ experiences and perceptions of urine sampling for TB testing at point of care.

Setting
Study sites in Kenya, Uganda, Mozambique and South Africa.

Participants
Adult ambulatory HIV patients enrolled in a TB diagnostic study were selected purposively.

Intervention
For this qualitative descriptive study, audiorecorded individual interviews conducted with consenting participants were translated, transcribed and analysed using content analysis. Ethical agreement was obtained from relevant ethical review committees.

Results
Fifty-eight participants were interviewed. Three domains were identified. Overall, participants described urine sampling as easy, rapid and painless, with the main challenge being lacking the urge. Urine was preferred to sputum sampling in terms of simplicity, comfort, stigma reduction, convenience and practicality. While perceptions regarding its trustworthiness for TB diagnosis differed, urine sampling was viewed as an additional mean to detect TB and beneficial for early diagnosis. Participants were willing to wait for several hours for same-day results to allay the emotional, physical and financial burden of having to return to collect results, and would rather not pay for the test. Facilitators of urine sampling included cleanliness and perceived privacy of sampling environments, comprehensive sampling instructions and test information, as well as supplies such as toilet paper and envelopes ensuring confort and privacy when producing and returning samples. Participants motivation for accepting urine-based TB testing stemmed from their perceived susceptibility to TB, the value they attributed to their health, especially when experiencing symptoms, and their positive interactions with the medical team.

Conclusions
This study suggests that urine sampling is well accepted as a TB diagnostic method and provides insights on how to promote patients’ uptake of urine-based testing and improve their sampling experiences. These results encourage the future broad use of urine-based assays at point of care.

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Novembre 2023