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

Leggi
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.

Leggi
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.

Leggi
Febbraio 2024

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

Leggi
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.

Leggi
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.

Leggi
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.

Leggi
Novembre 2023

Danish Prostate Cancer Consortium Study 1 (DPCC-1) protocol: Multicentre prospective validation of the urine-based three-microRNA biomarker model uCaP

Introduction
The primary objective of the Danish Prostate Cancer Consortium Study 1 (DPCC-1) is to provide validation for a novel urine-based microRNA biomarker, called uCaP, for a diagnosis of prostate cancer.

Methods and analysis
Eligible participants are biopsy naïve men aged ≥18 years with prostate-specific antigen (PSA) levels ≥3 ng/mL, who are referred to prostate MRI due to suspicion of PC at one of the following three major urology/uroradiology centers: Aarhus University Hospital, Herlev & Gentofte University Hospital, or Odense University Hospital, where MRI and targeted biopsy are implemented in clinical use. Exclusion criteria include previous diagnosis of urogenital cancer, contraindication to MRI, gender reassignment treatment or PSA level >20 ng/mL. The participants will be asked to donate a urine sample in connection with their MRI. The study is observational, uses a diagnostic accuracy testing setup and will integrate into the current diagnostic pathway.
We will measure the levels of the three microRNAs in the uCaP model (miR-222–3 p, miR-24–3 p and miR-30c-5p) in extracellular vesicle-enriched cell-free urine samples, to assess if uCaP can improve specificity and retain sensitivity for International Society of Urological Pathology Grade Group ≥2 PC, when used as a reflex test to PSA ≥3 ng/mL. We hypothesise that uCaP can improve selection for prostate MRI and reduce the number of unnecessary scans and biopsies.

Ethics and dissemination
This study is approved by the Central Denmark Region Committee on Health Research Ethics (reference number: 1-10-72-85-22). All participants will provide written informed consent. Study results will be published in peer-reviewed journals and presented in scientific meetings.

Trial registration number
NCT05767307 at clinicaltrials.gov.

Leggi
Novembre 2023

Abstract 13867: Sustained Improvement in Door-to-Balloon Time Over 15 Years: The Aurora St. Luke’s 24×7 STEMI Program With Redefinition of Contemporary Door-to-Balloon Time Less Than 60 Minutes: 60 is the New 90

Circulation, Volume 148, Issue Suppl_1, Page A13867-A13867, November 6, 2023. Background:In April 2004, Aurora St. Luke’s Medical Center implemented an in-house 24×7 interventional cardiology program to improve door-to-balloon time (D2BT) in ST-segment elevation myocardial infarction (STEMI). Previously published data showed a significant reduction in median D2BT, from 98 minutes (January 1, 2002-March 31, 2004) to 55 minutes (April 1, 2004-June 30, 2008), along with a reduction in major adverse cardiovascular events (MACE) and mortality after implementation of the program.Hypothesis:We hypothesized that the continued experience with the 24×7 program would demonstrate further gain in STEMI outcomes in regard to D2BT.Aims:The primary objective was to evaluate the overall median D2BT over a 15-year period. The secondary objectives were to evaluate median D2BT stratified by weekdays and weekends, on- and off-hours, the proportion of D2BT

Leggi
Novembre 2023

Abstract 18004: Impact of a Urine Sodium Guided Treatment Protocol on Acute Heart Failure Length of Stay: A Single Center Quality Improvement Study

Circulation, Volume 148, Issue Suppl_1, Page A18004-A18004, November 6, 2023. Introduction:Inpatient management of acute decompensated heart failure (ADHF) is associated with high costs and in-hospital complications. Traditional methods of assessing response to loop diuretics for ADHF is prone to inaccuracies that may contribute to costs and complications. More objective evidence-based methods of treating ADHF are needed to improve outcomes for these patients.Hypothesis:We hypothesize a treatment algorithm using Una as an objective marker of response to loop diuretics can decrease hospital length of stay (LOS) for patients with ADHF.Methods:This quality improvement study took place at a single urban academic center. 3 plan do study act (PDSA) cycles were performed to study the impact of the intervention on key quality metrics. The first two PDSA cycles took place on two medical teams over the course of two weeks each. The third PDSA cycle took place on all medical teams over the course of 5 months. Median hospital LOS, rates of readmission and acute kidney injury (AKI), and protocol use rates were calculated.Results:An average of 78 patients per month were admitted with ADHF. Protocol implementation rate was 58%. Patients in the first two PDSA cycles with ADHF who were managed with the UNa protocol on average had lower hospital LOS by 1 day and similar rates of acute kidney injury (AKI). Patients in the third PDSA cycle, however, did not experience any change in hospital LOS or AKI. Readmission rates were stable across all PDSA cycles.Conclusions:Protocoling the implementation of spot uNa to diuretic management in a large academic hospital required extensive multi-disciplinary coordination. While there was no observable impact on key quality metrics, maintaining high levels of protocol adherence remains a challenge. The impact of acute and chronic kidney injury on Una-protocol performance should be evaluated. Finally, the efficacy of a Una-based treatment approach across diverse patient demographics must be better understood.

Leggi
Novembre 2023

Abstract 13951: Change in Albuminuria Measured by Urine Albumin-to-Creatinine Ratio (UACR) and Associated Clinical Outcomes in Patients With Chronic Kidney Disease (CKD) Associated With Type 2 Diabetes (T2D)

Circulation, Volume 148, Issue Suppl_1, Page A13951-A13951, November 6, 2023. Introduction:The impact of change in albuminuria measured by UACR on key clinical outcomes (overall survival [OS], a composite cardiovascular [CV] outcome, and kidney disease progression) in patients (pts) with CKD associated with T2D is understudied.Hypothesis:A decreased UACR is associated with a lower risk of clinical outcomes, while an increased UACR is associated with a higher risk of clinical outcomes.Methods:Adult pts with an elevated UACR ≥30 mg/g (initial test) after T2D and CKD diagnosis were identified from the Optum EHR database (1/2007-9/2021). UACR change was categorized as increased ( >30% change), stable (-30% to 30%), or decreased (30% UACR decrease was associated with a lower long-term risk of overall mortality, CV events, and kidney disease progression. These findings highlight the importance of albuminuria monitoring in these pts.

Leggi
Novembre 2023