Risultati per: Il dolore neuropatico: review

Stroke, Volume 56, Issue Suppl_1, Page AWP127-AWP127, February 1, 2025. Introduction:Cognitive impairment, mood disorders, and reduced serum BDNF levels are common in stroke patients. Previous studies suggest that aerobic exercise improves these outcomes by enhancing oxygenation. Herein, the authors compare the effectiveness of high-intensity interval training (HIIT) with low (LIT) and moderate (MIT) intensities and usual activity (UA) in stroke patients.Methods:We systematically searched PubMed, Cochrane, Embase, and Scopus databases for studies comparing HIIT with LIT, MIT, or UA in stroke patients. We evaluated change from baseline in cognitive improvement, mood disorders including anxiety and depression, and serum BDNF levels. Subgroup analyses were conducted based on stroke onset and exercise intensity, and separate analyses compared HIIT with each control group to assess cognitive improvement at different intensity levels.Results:A total of ten non-randomized and randomized studies were included in the analysis. Seven studies involving 373 patients showed no statistically significant difference in cognitive improvement between HIIT and the control group (std. MD 0.09; 95% CI -0.13 to 0.30; p=0.43). Separate analyses also revealed no significant differences between HIIT and LIT (std. MD -0.06; 95% CI -0.54 to 0.41; p=0.60), HIIT and MIT (std. MD 0.03; 95% CI -0.30 to 0.37; p=0.85), and HIIT and UA (std. MD 0.20; 95% CI -0.13 to 0.53; p=0.23). Subgroup analysis for chronic stroke did not show significant differences either (std. MD 0.07; 95% CI -0.19 to 0.34; p=0.58). Additionally, an analysis of four studies involving 281 patients found no significant difference in mood disorders (std. MD -0.21; 95% CI -0.62 to 0.21; p=0.33). A separate analysis of four studies with 130 patients also revealed no significant difference in serum BDNF levels between the two groups (std. MD 3.65; 95% CI -0.37 to 7.67; p=0.08). However, subgroup analysis indicated that serum BDNF levels were 3.32 ng/mL higher in the MIT group compared to the HIIT group.Conclusion:High-intensity-interval training does not demonstrate a significant advantage in cognitive improvement, mood disorders, or serum BDNF levels when compared to different exercise intensities. However, MIT is associated with increased serum BDNF levels compared to HIIT. Future robust RCTs are needed to compare different exercise intensities and durations to provide more conclusive results.

Stroke, Volume 56, Issue Suppl_1, Page AWP292-AWP292, February 1, 2025. Background:Intracranial atherosclerosis (ICAS) is a common stroke cause, with a recurrent stroke risk of up to 18% per year despite treatment advances. Although lipid-lowering therapies reduce cardiovascular events, their effect on stroke risk in ICAS remains unclear.Objective:To perform a systematic review and meta-analysis assessing the efficacy of lipid-lowering therapies in improving stroke outcomes among patients with ICAS.Methods:A systematic search of PubMed, Embase, Web of Science, Cochrane, and other databases was conducted from inception to November 2023. Eligible studies compared lipid-lowering therapies (Statins and PCSK9i) to standard care or placebo in patients with ICAS. The primary outcome was the incidence of stroke. Pooled relative risks (RR) with 95% confidence intervals (CI) were calculated using a random-effects model, and forest plots were constructed. Chi-square and I 2 statistics were used to assess heterogeneity.Results:Seven observational studies and two randomized controlled trials involving 1,902 ICAS patients were included. Of these, 801 received lipid-lowering therapy, and 1,101 received standard care or placebo. The weighted mean follow-up was 17.6 months (IQR 9.75-25.5). The weighted mean age was 63.7 years (range 55-68) for the lipid-lowering group and 64.0 years (range 50-66) for controls. Females comprised 42% of both groups. Hypertension was present in 74% of the intervention group and 71% of controls. A history of stroke was reported in 32% of the intervention group and 29% of controls. The weighted mean baseline LDL level was 105 mg/dL in the intervention group and 107 mg/dL in controls. The weighted mean change in LDL pre- and post-treatment in the intervention group was -47.18 mg/dL, compared to -12.39 mg/dL in controls. The incidence of ischemic stroke was 5.0% (40/801) in the lipid-lowering group versus 13.0% (143/1,101) in controls (RR 0.40; 95% CI 0.24-0.64; P

Stroke, Volume 56, Issue Suppl_1, Page ATP285-ATP285, February 1, 2025. Introduction:Previous studies have observed an increased risk of stroke in head and neck cancer (HNC) survivors. However, whether this risk is amplified with exposure to various treatment modalities including radiotherapy is less certain, as are any potential mechanisms by which this increase in risk is mediated. This study aims to investigate the risk of stroke in patients with HNC and whether cancer type and treatment modalities have varying effects.Methods:This PRISMA-adherent systematic review involved a systematic search of PubMed, SCOPUS and Embase for studies reporting stroke incidence in patients with HNC and without prior strokes since inception to April 25,2024. The study protocol was registered prospectively on PROSPERO. The hazard ratios extracted from the studies were pooled for meta-analyses. Random effects meta-analyses and meta-regressions were used for primary analysis. Subgroup analyses and meta-regression were performed to determine if key categorical and hierarchical variables influenced the results. Risk of bias was performed using the Newcastle Ottawa Scale.Results:22 studies [EL1] with 5,093,445 patients were included. The meta-analyses of nine studies showed that the risk of stroke was increased in patients with HNC compared to healthy controls (HR=1.45; 95%CI: 1.27-1.65, I2: 20%). Subgroup analyses demonstrated that the risk of stroke was significantly increased in HNC patients treated with radiotherapy alone compared to those treated with surgery alone (HR=1.66; 95%CI: 1.35-2.03, I2: 0%). Subgroup analyses also revealed an increased risk of stroke in HNC patients who had undergone any radiotherapy compared to HNC patients who had not undergone radiotherapy in the past (HR=1.47; 95%CI: 1.29-1.68, I2: 60%).Additionally, HNC patients who had undergone definitive chemoradiotherapy had increased risk of stroke compared to HNC patients who had undergone definitive surgery with or without adjuvant chemoradiotherapy (HR=1.28; 95%CI: 1.09-1.49, I2: 86%).Conclusion:We report an increased risk of stroke in HNC patients, which is consistently raised when compared with the general population. This risk is more significant in patients who had undergone radiotherapy. Future research should aim to understand the pathogenesis of stroke in HNC patients and the effect of different treatment modalities on stroke risk to develop effective preventive strategies, thereby guiding the management for patients with HNC.

Stroke, Volume 56, Issue Suppl_1, Page ATP246-ATP246, February 1, 2025. Introduction:Mechanical thrombectomy (MT) is a primary treatment for acute ischemic stroke due to large vessel occlusions. While effective, 20-40% of patients experience hemorrhagic transformation (HT), and around 50% fail to achieve favorable functional outcomes. Transcranial Doppler (TCD) is a non-invasive and cost-effective method for real-time monitoring of hemodynamic status following MT. However, the prognostic value of TCD parameters in predicting HT and poor functional outcome is unclear. We performed a systematic review and meta-analysis of 4 TCD parameters (mean flow velocity (MFV), MFV index, peak systolic velocity (PSV), and pulsatility index (PI) in patients with and without HT and favorable vs poor functional recovery (modified Rankin Scale (mRS) 0-2 vs 3-6).Methods:PubMed, Embase, and Scopus were searched on July 25, 2024 to identify observational studies in which TCD parameters were measured within 48 hours from successful MT (Thrombolysis in Cerebral Infarction 2b–3) of anterior circulation. Risk of bias assessment was performed using a standardized tool tailored for TCD studies. The standardized mean difference (Hedges’ g) with 95% CI and risk ratios (RRs) with 95% CI were calculated using random-effects models. The review was prospectively registered on PROSPERO (registration number CRD42024575381).Results:Eleven studies met inclusion criteria. No study had high risk of bias. MFV and MFV index were higher in patients with HT+ compared with HT- (Hedges’ g = 0.42 and 0.54, p = 0.015 and 0.005, respectively). Patients with MFV index ≥1.3 showed a higher risk of all HT (RR = 2.01, 95% CI = 1.27–3.17, p = 0.003), symptomatic HT (RR, 4.68; 95% CI,1.49–14.65, p=0.008), and poor functional recovery at 90 days (RR, 1.66; 95% CI,1.32–2.08, p

Stroke, Volume 56, Issue Suppl_1, Page ATP244-ATP244, February 1, 2025. Introduction:Although older patients with subarachnoid hemorrhage (SAH) are often preferentially treated with coiling, in practice, there are insufficient data to support a clear benefit of coiling in this population. We aimed to do a meta-analysis comparing clipping with coil embolization for treatment of SAH in elderly people.Methods:We systematically searched Pubmed, Embase and Cochrane databases for studies that compared clipping with coiling for treatment of patients ≥ 60 years old with SAH. Our main endpoint was a compound unfavorable outcome that included Modified Rankin Score (mRS) >2, Glasgow Outcome Scale (GOS) < 4, death or dependency. Other endpoints were an unfavorable outcome in the GOS, mortality and a favorable outcome in the mRS separately. Heterogeneity was assessed with I2statistics.Results:We included 25 studies, two randomized, with a total of 49,540 patients, of whom 19,263 (38.8%) were treated with coil embolization. In pooled analysis, there was no statistical difference in the compound unfavorable outcome (RR 1.06; 95%CI 0.79-1.01; p = 0.15; I2=56%), GOS (RR 0.88; 95%CI 0.68- 1.14; p = 0.02; I2= 55%) and mRS (RR 0.97; 95%CI 0.88- 1.08; p = 0.61; I2= 20%). However, all-cause mortality was more common in patients treated with coiling (RR 1.14; 95%CI 1.01- 1.28; p = 0.03; I2= 35%). In randomized studies, although not significant, the point estimate seems to favor coiling whereas in observational studies it happened to clipping.Conclusions:The results of our meta-analysis suggest that clipping is a better treatment for SAH in elderly patients regarding all-cause mortality. Otherwise, the endpoints GOS, mRS and compound unfavorable outcome didn't show significant difference between the groups.

Stroke, Volume 56, Issue Suppl_1, Page ATP242-ATP242, February 1, 2025. Background:Symptomatic intracranial hemorrhage (sICH) is the most dreaded complication after reperfusion therapy for acute ischemic stroke. We performed a meta-analysis of randomized controlled trials to estimate and compare risks of sICH after mechanical thrombectomy (MT) depending on the location of the large vessel occlusion, concomitant use of intravenous thrombolysis, timing of treatment, and core size.Methods:Randomized controlled trials were included following a comprehensive search strategy on different databases from inception to March 1, 2024. Random-effect models in a meta-analysis were employed to get the pooled risk ratios (RRs) and their corresponding 95% confidence intervals (95% CI) for sICH with MT, compared to other reperfusion treatment regimens, including best medical treatment and intravenous thrombolysis (IVT).Results:MT in the anterior circulation was associated with a significantly higher risk of sICH as compared with no-MT (RR: 1.46; 95%CI: 1.03-2.07; P = 0.037). Risk of sICH was comparable between the MT and MT+IVT groups (RR: 0.77; 95%CI: 0.57-1.03; P = 0.079). There was no difference in sICH risk with MT as compared with no-MT within 6 hours of last known well (RR: 1.14; 95%CI: 0.78-1.66; P = 0.485) and beyond that time (RR: 1.29; 95%CI: 0.80-2.08; P = 0.252); the risk of sICH was also comparable between MT conducted within 6 hours of last known well and MT conducted beyond that time (P = 0.512). The sICH risk for MT in the posterior circulation (RR: 7.48; 95%CI: 2.27-24.61) was significantly higher than for MT in the anterior circulation (RR: 1.18; 95%CI: 0.90-1.56) (P = 0.003). MT was also associated with a significantly higher sICH risk than no-MT among patients with large-core strokes (RR: 1.71; 95%CI: 1.09-2.66, P = 0.018).Conclusion:When evaluating cumulative evidence from randomized controlled trials, the risk of sICH is increased after MT compared with patients not treated with MT. Yet, the difference is largely driven by the greater risk of sICH in patients treated with MT for posterior circulation occlusions and, to a lesser degree, large core strokes. Concomitant use of intravenous thrombolysis and the use of MT in the extended therapeutic window do not raise the risk of sICH.

Stroke, Volume 56, Issue Suppl_1, Page ATP257-ATP257, February 1, 2025. Background:Clinical trial designs have evolved due to changes in therapies, populations, and statistical methods.Objective:We aimed to analyze the designs of acute endovascular therapy trials in ischemic stroke over time, and how mechanical thrombectomy has evolved, particularly in patient selection and statistical methods.Methods:A systematic search was conducted in PubMed, EMBASE, Cochrane, CINAHL, and SCOPUS for phase 3 or 4 randomized clinical trials of endovascular reperfusion therapy for acute ischemic stroke. Trials with functional outcomes measured at 3 months were included. Data extracted included year of publication, estimated and actual sample sizes, observed outcomes, and statistical methods used. The studies were classified in 3 periods by publication date: Period 1: before 2015, pre-stent retriever; Period 2: 2015-2019, early thrombectomy era; and Period 3: 2020-2024, recent period.Results:Of 2693 references, 21 trials met inclusion criteria, 3 in Period 1, 10 in Period 2, 8 in Period 3. Median sample sizes were 150 in Period 1, 206 in Period 2, and 300 in Period 3. Dichotomized Rankin were primary outcomes in 100% in Period 1, 80% in Period 2, and 60% in Period 3, with remainder analyzed by Rankin shift or proportional odds. Early termination occurred in 0% in Period 1, 40% in Period 2, and 0% in Period 3. 7 studies met or almost met their estimated sample size.14 studies did not meet their estimated sample size, due to early terminations (for efficacy or futility), slow recruitment, or positive findings from other trialsConclusion:The trials published during the 2015–2019 period had early terminations and positive results for thrombectomy. More recent trials have larger sample sizes and more commonly used methods to analyze the full range of Rankin categories, such as mRS shift or proportional odds models. This might reflect a shift toward capturing more nuanced outcomes in stroke populations.

Stroke, Volume 56, Issue Suppl_1, Page ATP269-ATP269, February 1, 2025. Background:Patients with active cancer and ischemic stroke have significantly higher morbidity and mortality compared to stroke patients without cancer. Elevated d-dimer levels are a key finding for determining cancer coagulopathy as the likely etiology for stroke. Studies that examined d-dimer as a surrogate marker of outcomes in cancer-associated stroke are limited by small sample sizes. Our objective was to conduct a systematic review&meta-analysis for the prognostic value of serum d-dimer measured at the time of ischemic stroke in cancer patients. We hypothesize that high d-dimer is associated with high rates of recurrent stroke, death,&poor functional outcomes.Methods:MEDLINE, Embase, and the Web of Science were searched (until July 2024) for cohort studies of patients with cancer-associated ischemic stroke that assessed the prognostic value of elevated d-dimer levels (measured at the time of stroke onset) for recurrent stroke, mortality, and poor functional outcome (modified Rankin Scale [mRS] score of 3-6). For the primary analysis, we conducted meta-analyses of median differences in d-dimer levels between patients with vs. without the outcomes of interest, using the random-effects method. Meta-analyses of studies reporting odds ratios or hazard ratios could not be performed due to the variable d-dimer cutoffs used across the studies; associations from these studies are summarized narratively.Results:From 4522 titles, there were 19 eligible studies. Elevated serum d-dimer was significantly associated with an increased risk of recurrent stroke (pooled median difference 14.54 [95% CI, 2.09 to 26.99], p=0.022), and mortality (pooled median difference, 11.18 [95% CI, 9.67 to 12.70], p

Stroke, Volume 56, Issue Suppl_1, Page ATP251-ATP251, February 1, 2025. Background:Transradial access has become increasingly favored over the traditional transfemoral approach for neurointerventional procedures, however radial artery spasm (RAS) and radial artery occlusion (RAO) pose challenges to this approach. RAS is one of the most common complications associated with the transradial approach that can impede procedural success and cause significant pain to patients. A promising strategy to mitigate RAS is the use of hydrophilic-coated (HC) introducer sheaths. The lubricious surface facilitates smoother insertion and manipulation within the radial artery, potentially reducing friction that contributes to RAS. Prior studies have reported conflicting results regarding the utility of HC sheaths in reducing the risk of RAS. Thus, the clinical benefit of HC sheaths is not fully understood.Objective:The purpose of this study is to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing HC introducer sheaths with non-coated (NC) introducer sheaths during transradial procedures and their impact on RAS, RAO, periprocedural pain, and complications.Methods:PubMed, Embase, and Cochrane Library were searched for RCTs utilizing HC sheaths in their intervention arm and NC sheaths in their control arm in patients undergoing a transradial procedure. Outcomes included incidence of RAS, RAO, pain/discomfort during the procedure, pseudoaneurysm, and hematoma. RevMan 5.4 software was used to calculate pooled risk ratios and mean differences with 95% confidence intervals.Results:Seven RCTs were included in this study. HC sheaths were associated with a significant reduction in the risk of RAS and periprocedural pain/discomfort compared to NC sheaths (RR = 0.38, 95% CI [0.24, 0.60], I2= 19% and RR = 0.45, 95% CI [0.34, 0.60], I2= 14%, respectively). The use of HC sheaths had no significant effect on the risk of RAO, hematoma, or pseudoaneurysm.Conclusion:The use of HC sheaths is associated with a reduced risk of RAS and periprocedural pain/discomfort compared to NC sheaths with no significant effect on RAO, procedure duration, hematoma, or pseudoaneurysm. HC sheaths improve the overall patient experience and reduce the risk of spasm. These findings may provide valuable insights for neurointerventionalists seeking to optimize transradial techniques and improve patient care.

Stroke, Volume 56, Issue Suppl_1, Page ATP295-ATP295, February 1, 2025. Background:It is suggested that survivors of different types of cancer may have an increased risk of stroke. Our study aims to evaluate cancer patients and non-cancer controls by analyzing stroke events in each group. Previous studies concluded that certain types of cancer increased stroke risk, however, their results had significant heterogeneity and statistical concerns.Methods:Medline, Embase, and Cochrane databases were systematically searched until February 18th, 2024, assessing stroke in cancer survivor patients compared to the global population. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed using I2statistics. Review Manager 5.4 was used for statistical analysis.Results:A total of 18 studies were included, and stroke was reported in both cancer and non-cancer groups. Breast cancer (HR 1.09; 95% CI 1.02-1.17; p=0.01; I2= 0%), Central Nervous System cancers (HR 2.47; 95% CI 1.01-6.01; p=0.05; I2= 78%), cervical cancers (HR 1.58; 95% CI 1.19-2.09; p=0.001; I2= 0%), head and neck cancers (HR 1.34; 95% CI 1.07-1.68; p=0.01; I2= 59%), lung cancers (HR 1.60; 95% CI 1.40-1.83; p

Stroke, Volume 56, Issue Suppl_1, Page ATP253-ATP253, February 1, 2025. Background:Angiographic shape of occlusion, like the clot meniscus sign and the claw-sign, have been reported to potentially impact recanalization rate and clinical outcome in patient undergoing mechanical thrombectomy for acute ischemic strokes.Method:Following PRISMA guidelines, a systematic literature search was conducted across PubMed, Scopus, and Web of Science databases. Patients were grouped into clot meniscus/claw sign positive and negative groups based on the definitions obtained from each study. Primary outcomes included technical success, with a meta-analysis performed using a random-effects model to calculate proportions and odds ratios (OR) with 95% confidence intervals (Cl).Results:We included seven studies recruiting 1572 patients. The results indicated that the positive and negative groups had comparable first-pass effect (OR: 1.95; 95%CI: 0.76 – 5.01; P = 0.167) and final recanalization (OR: 1.36; 95%CI: 0.81 – 2.27; P = 0.248) rates. However, the rate of having a favorable functional outcome was significantly higher in the positive than negative sign groups (OR: 1.91; 95%CI: 1.25 – 2.92; P < 0.003). Within the sign-positive population, the use of contact aspiration was associated with a significantly higher rate of recanalization compared to using a stent retriever (OR: 0.18; 95%CI: 0.07 – 0.49; P < 0.001). This result did not translate into a clinical impact, as both stent retriever and contact aspiration showed comparable rates of functional independence at three months (OR: 0.22; 95%CI: 0.02 – 2.33; P = 0.210).Conclusion:The presence of the clot meniscus/claw sign is not associated with recanalization outcomes after thrombectomy. However, it might be a good sign to predict which thrombectomy technique might be associated with better recanalization, although current evidence might need further confirmation.

Stroke, Volume 56, Issue Suppl_1, Page ATP60-ATP60, February 1, 2025. Background:Due to limited diagnostic accuracy in the symptom-based tools currently used by paramedics, triage nurses, and emergency physicians, up to 35% of strokes are missed at initial clinician contact. As a result, there has been a push to identify blood biomarkers that could aid in stroke recognition at triage. There is evidence to suggest stroke is more frequently mistriaged in minority patients than White patients; to avoid perpetuating these disparities as stroke biomarkers move towards clinical use, it is important that involved investigations meaningfully account for race and ethnicity. However, it is unclear how commonly this occurs in practice.Purpose:This systematic review and meta-analysis aimed to quantify the degree that race and ethnicity information was reported in prior acute stroke blood biomarker investigations, and assess the effect of racial and ethnic heterogeneity on reported diagnostic performance.Methods:An electronic database search to identify published human acute stroke blood biomarker investigations yielded 14,253 articles. After abstract and full-text screening, 189 articles reporting 705 unique diagnostic comparisons were analyzed. For each diagnostic comparison, the reported primary diagnostic statistics were manually extracted, along with the racial and ethnic composition of the study sample if available. Diagnostic statistics were converted to a single diagnostic odds ratio, and race and ethnicity information was used to calculate a Gini diversity index value to represent the demographic heterogeneity of the sample.Results:Subject race or ethnicity was only described for 21.8% of diagnostic comparisons. For diagnostic comparisons reporting this information, study populations showed high homogeneity with median Gini diversity indices of 0.33 for race and 0 for ethnicity. We found a negative correlation between Gini diversity index for race and diagnostic odds ratio (Spearman’s rho= -0.17, p=0.14), indicating to some degree that that more homogenous study samples are more likely to produce higher diagnostic performance estimates.Conclusions:Findings from acute stroke biomarker investigations are at risk for poor generalizability to the diverse clinical populations that stroke triage serves. To reduce this risk, future work needs to address race and ethnicity more meaningfully in terms of both sampling methods and reporting.

Stroke, Volume 56, Issue Suppl_1, Page ATP25-ATP25, February 1, 2025. Background:Previous study found that compared with thrombolysis, antiplatelet did not improve outcomes but reduce the risk of symptomatic intracranial hemorrhage(sICH) for mild acute ischemic stroke(AIS) defined as National Institutes of Health Stroke Scale score 0 to 5. As relevant studies have been released recently, the benefits and risks of the two treatments are still unclear based on latest evidences.Objective:To compare the efficacy/effectiveness and safety of antiplatelet with thrombolysis for mild AIS in the first update of a living systematic review and meta-analysis.Methods:MEDLINE, Embase and Cochrane Library were systematically searched from July 2023 until August 2024. Randomized clinical trials(RCTs) and observational studies were selected and checked eligibility for inclusion based on the same criteria as before. The primary outcome was 90-day functional outcome measured by the modified Rankin Scale(mRS). Data extraction and certainty of evidence assessment were conducted in duplicate. This study was registered in the PROSPERO.Results:Since July 2023, two new studies were added, for a total of three RCTs and five observational studies with 5526 patients(3333 treated with antiplatelet and 2193 treated with thrombolysis). There were no significant differences between antiplatelet and thrombolysis in 90-day functional outcome(mRS 0-1, odds ratio, 0.96 [95% CI, 0.68 to 1.35]; mRS 0-2, odds ratio, 1.06 [95% CI, 0.73 to 1.51]), and stroke recurrence(odds ratio, 1.19 [95% CI, 0.73 to 1.93]). Compared with thrombolysis, antiplatelet was significantly associated with reduced risks on death(odds ratio, 0.36 [95% CI, 0.18 to 0.71]), and sICH(odds ratio, 0.21 [95% CI, 0.08 to 0.56]).Conclusions:In patients with mild AIS, antiplatelet was similar in functional outcomes and stroke recurrence against thrombolysis, but reduced the risks of death and sICH. Thrombolysis should be used with caution in such patients in clinical practice.

Stroke, Volume 56, Issue Suppl_1, Page ATP85-ATP85, February 1, 2025. Background and Purpose:Due to limitations associated with the symptom-based tools currently used for triage, up to 35% of strokes are missed at initial clinician contact in emergency medicine settings. As a result, there has been a decades-long push to identify blood biomarkers with utility for stroke recognition. Despite numerous studies reporting candidates with seemingly high levels of diagnostic performance, none have made their way into clinical use. It is possible this discrepancy is linked to translational limitations in how these prior biomarker discovery investigations have been designed and implemented. Thus, we performed a nontraditional systematic review and meta-analysis spanning 30 years of published acute stroke blood biomarker data in which we sought to explicitly quantify the effects of study design and reporting considerations on diagnostic performance estimates, and correct said estimates for such effects in order to provide better projections of how the candidate biomarkers that have been studied to date would perform in a true clinical use scenario.Methods and Results:A electronic database search was performed to identify previously reported human acute stroke blood biomarker investigations, which yielded 14,253 potential articles. 189 were included in our final analysis based on subsequent abstract and full-text screening. From each article, detailed methodological information for all reported diagnostic comparisons was manually extracted. Collectively, data from 705 different diagnostic comparisons involving 355 unique single analytes or multi-analyte panels were captured. The raw diagnostic performance estimates reported in the literature inferred that as high as 40% of previously investigated candidate biomarkers could be clinically useful for stroke recognition. However, multiple regression revealed that 47.2% of the variance in these diagnostic performance estimates could be attributed to a small number of confounding study design and reporting factors related to population sampling, timing of blood collection, blinding, and conflicts of interest. After using the model residuals to correct for these factors, not a single candidate biomarker displayed adequate evidence to suggest true clinical utility.Conclusions:Our results clarify the current state of the search for an acute stroke blood biomarker, and identify several translational limitations that need to addressed in future investigations if one is to be realized.

Stroke, Volume 56, Issue Suppl_1, Page AWP220-AWP220, February 1, 2025. Background:Several studies have shown that tranexamic acid (TXA), an anti-fibrinolytic agent, may reduce hematoma expansion (HE) in intracerebral hemorrhage (ICH), but its therapeutic time window is unclear. We analyzed the efficacy and safety of TXA based on its time of administration after hemorrhage onset.Methods:We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) published up to July 27, 2024 comparing TXA with placebo in ICH. We excluded trials that used TXA for longer than 3 days which causes delayed vasospasm, increasing the risk of cerebral ischemia. The primary outcomes were HE, 24-hour hemorrhagic volume change, 90-day mortality and poor functional outcome. We grouped the trials into 2 hours, 8 hours or 24 hours of TXA administration after hemorrhage onset. We pooled odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) using Rstudio. Heterogeneity was examined with the I2 test.Results:We included 12 studies with 3,567 patients. Most of the studies used 1 g TXA in patients with Glasgow Coma Scale score ranging from 13-15. TXA reduced HE risk (OR 0.85; 95% CI 0.73 to 0.98; p= 0.03; I2= 0%). This reduction was observed in studies that administered TXA within 8 hours of ICH onset (OR 0.82; 95% CI 0.70 to 0.97; p= 0.02; I2= 0%). TXA slightly reduced 24-hour hemorrhagic volume (MD -1.30 mL; 95% CI -2.51; -0.09; p= 0.04; I2= 47%). This reduction was mainly seen in patients who were administered TXA within 8 hours of hemorrhage onset (MD -1.86 mL; 95% CI -3.15 to -0.58; p< 0.01; I2= 35%). There were no significant differences in poor functional outcome (OR 0.87; 95% CI 0.67 to 1.15; p= 0.34; I2= 24%), 90-day mortality (OR 1.00; 95% CI 0.84 to 1.19; p= 0.96; I2= 0%), major thromboembolic events (OR 1.22; 95% CI 0.82 to 1.82; p= 0.33; I2= 0%), neurosurgical intervention (OR 0.94; 95% CI 0.61-1.45; p= 0.78; I2= 0%) or length of hospital stay (MD -0.49 days; 95% CI -3.27 to 2.29; p= 0.73; I2= 0%).Conclusion:TXA reduced the risk of HE and slightly reduced 24-hour hemorrhagic volume in patients with ICH within 8 hours. Larger RCTs stratifying administration timing are required to establish these findings.

Stroke, Volume 56, Issue Suppl_1, Page AWP270-AWP270, February 1, 2025. Introduction:Patients experiencing a transient ischemic attack (TIA) or minor stroke have a high long-term risk of subsequent stroke that persists for over one year following presentation. While risk stratification tools like the ABCD2score have been used to identify patients at high risk of stroke in the short-term (within the first 90 days), less is known about factors that determine long-term risk. Some studies suggest that traditional predictors of early stroke risk may not be associated with long-term risk, while others have reported conflicting results. We aimed to summarize the association between clinical, demographic, imaging factors and the long-term risk of stroke in patients experiencing TIA or minor stroke.Methods:We searched MEDLINE, Embase, and the Web of Science from inception to June 2024, for observational studies that examined factors associated with subsequent stroke in patients experiencing TIA or minor stroke during a minimum follow-up of one year. Two reviewers independently performed study screening and data extraction. For the primary analysis, we included prognostic factors if they were derived from a multivariable Cox proportional hazards model and reported in at least 2 studies. We contacted the corresponding authors of the studies to obtain adjusted effect estimates when these values could not be extracted from the reported data. We conducted random effects meta-analyses of adjusted hazard ratios and report pooled effect estimates with 95% confidence intervals.Results:Of 13051 citations identified, we included 28 studies examining 85,328 patients including unpublished data from 8 studies that we directly obtained from study authors. Factors associated with an increased risk of stroke at one year or beyond included male sex, older age, hypertension, diabetes mellitus, atrial fibrillation, history of stroke or TIA before the qualifying event, history of coronary artery disease, presence of hemiparesis, aphasia, baseline ABCD2score of 4 or greater, acute infarct on brain imaging, large-artery atherosclerosis, and cardioembolism (Figure 1).Conclusion:We have identified important prognostic factors associated with long-term risk of stroke after a TIA or minor stroke. These findings provide a framework for evidence-based risk stratification of patients who may require extended treatment and vigorous monitoring.