Marianna Leite

To compare efficacy and safety outcomes of DWI–FLAIR mismatch versus CT/MR perfusion-based selection for intravenous thrombolysis (IVT) in extended-window acute ischemic stroke (AIS), we performed a systematic review and meta-analysis of randomized controlled trials enrolling adults with acute ischemic stroke treated with imaging-selected IVT beyond 4.5 h from last known well or with unknown onset. Trials using DWI–FLAIR mismatch or CT/MR perfusion selection were included. Outcomes were excellent functional outcome, functional independence, symptomatic intracranial hemorrhage (sICH), parenchymal hematoma, major bleeding, and mortality. Random-effects pairwise meta-analysis and Bucher-type indirect comparison were performed. Eight randomized trials including 2,546 patients were analyzed. Compared with best medical treatment, IVT improved excellent functional outcome (mRS 0–1: RR 1.27, 95% CI 1.14–1.40) and functional independence (mRS 0–2: RR 1.15, 95% CI 1.07–1.23), but increased sICH (RR 5.21, 95% CI 2.25–12.04). In imaging-stratified analyses, functional outcome RRs favored IVT in both perfusion-based and DWI–FLAIR mismatch-selected trials, with wider confidence intervals in the DWI–FLAIR subgroup. Hemorrhagic risk was increased with intravenous thrombolysis in both imaging subgroups, but subgroup interaction testing and a Bucher-type indirect comparison did not detect a statistically significant between-paradigm difference; the indirect comparison re-expresses the subgroup contrast rather than adding independent evidence. In AIS patients not planned for routine endovascular therapy, imaging-selected IVT beyond 4.5 h was associated with improved functional outcomes but increased sICH risk. No definitive superiority or equivalence was established between imaging strategies; imaging choice should be guided by clinical context, time window, EVT eligibility, local workflow, and patient-level factors. Graphical abstract This meta-analysis included eight randomized controlled trials involving 2,546 patients and compared imaging-selected intravenous thrombolysis (IVT) with best medical treatment (BMT) beyond 4.5 hours from last known well or with unknown onset. Overall pairwise meta-analysis showed improved excellent functional outcome (mRS 0–1; RR 1.27, 95% CI 1.14–1.40) and functional independence (mRS 0–2; RR 1.15, 95% CI 1.07–1.23) with IVT, with an increased risk of symptomatic intracranial hemorrhage (RR 5.21, 95% CI 2.25–12.04). Imaging-stratified analyses showed treatment effects favoring IVT in both perfusion-based and DWI–FLAIR mismatch-selected trials. Subgroup interaction tests and the Bucher-type indirect comparison did not demonstrate a statistically significant difference between imaging-selection strategies. Abbreviations: IVT, intravenous thrombolysis; BMT, best medical treatment; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; mRS, modified Rankin Scale; RR, risk ratio; CI, confidence interval; sICH, symptomatic intracranial hemorrhage

Purpose: This systematic review and meta-analysis evaluates endovascular therapy (EVT) versus best medical treatment (BMT) in pediatric acute ischemic stroke (AIS) due to large-vessel occlusion. Methods: Systematic searches were conducted across PubMed, Cochrane, and Embase, inception July-2025. Comparative studies of EVT versus BMT in pediatric AIS were included. Efficacy outcomes assessed were Modified Rankin Scale (mRS) 0–2, mRS 0–1 and Pediatric Stroke Outcome Measure (PSOM). Safety outcomes included mortality, symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (aICH), hospital stay length and need for craniectomy. Results: 10 studies ( n = 20,083) were included. In the primary analysis restricted to confirmed large-vessel occlusion (LVO), EVT was associated with significantly higher odds of achieving a good functional outcome (mRS 0–2: OR 2.08; 95% CI 1.07–4.03) and showed no significant difference in all-cause mortality (OR 2.01; 95% CI 0.34–12.01) compared to BMT. In the all-comers analysis, EVT was associated with higher all-cause mortality (OR 3.00; 95% CI 2.23–4.02) and increased risk of aICH (OR 3.12; 95% CI 1.78–5.47); however, these signals were heavily confounded by baseline stroke severity. Conclusion: When restricted to confirmed LVO, EVT demonstrates a potential functional benefit over BMT in pediatric AIS. The increased risks of aICH and mortality observed in broader analyses are likely confounded by indication, reflecting the selection of the most severe cases for intervention. Based on GRADE assessments, the certainty of evidence remains very low, highlighting the critical need for prospective studies incorporating standardized reperfusion metrics.

Intravenous thrombolysis (IVT) improves outcomes in acute ischemic stroke (AIS), yet many patients remain disabled. Earlier studies suggested potential benefits of adjunctive tirofiban with smaller samples and pooled heterogeneous reperfusion strategies, limiting conclusions about comparison with IVT alone. With new evidence available focused specifically on IVT-treated patients, we conducted an updated meta-analysis with a larger sample comparing tirofiban plus IVT versus IVT alone. We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) comparing tirofiban plus IVT versus IVT alone in AIS. The primary outcome was favorable functional status at 90 days (modified Rankin Scale [mRS] 0-2). Secondary outcomes included excellent recovery (mRS 0-1), moderate-to-severe disability (mRS 3-5), early neurological improvement (NIHSS change at 24 h and 7 days), symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), and all-cause mortality. Risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Six RCTs involving 1,793 patients were included. Compared with IVT alone, tirofiban improved favorable functional status (RR 1.14; 95% CI 1.07-1.20) and excellent recovery (RR 1.19; 95% CI 1.09-1.30), while reducing moderate-to-severe disability (RR 0.57; 95% CI 0.44-0.72). NIHSS scores at 7 days favored tirofiban (MD - 2.22; 95% CI - 4.21 to - 0.23), with no difference at 24 h. Safety analyses showed no significant differences in sICH (RR 1.70; 95% CI 0.58-4.97), any ICH (RR 1.17; 95% CI 0.75-1.81), or all-cause mortality (RR 0.98; 95% CI 0.51-1.85). This study provides focused evidence on tirofiban in IVT-treated AIS patients. Our results highlight that adjunctive tirofiban improves 90-day functional outcomes without increasing hemorrhagic or mortality risk. These findings strengthen the rationale for considering the potential role of tirofiban as an adjuvant therapy in IVT and may inform future clinical guidelines.

Background: Arterial calcification is commonly found in patients with cerebrovascular disease and may negatively affect outcomes following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). This systematic review and meta-analysis aimed to evaluate the impact of intracranial or aortic arch calcification on procedural success and functional outcomes in AIS patients undergoing anterior circulation EVT. Methods: We systematically searched the PubMed, EMBASE, and Cochrane databases to identify studies comparing EVT outcomes between AIS patients with and without arterial calcification. Outcomes assessed included first-pass effect (FPE), successful reperfusion at the end of the procedure, modified Rankin scale (mRS), mortality, and symptomatic intracerebral hemorrhage (sICH). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random effects models, with heterogeneity evaluated with I ² statistics. Results: A total of six observational studies were included, with a total of 3834 patients (2303 with calcification and 1531 controls). Arterial calcification was associated with a lower chance of achieving FPE (RR: 0.50, 95% CI: 0.36–0.69, p < 0.001) and successful reperfusion (RR: 0.90, 95% CI: 0.86–0.94, p < 0.001). Patients with calcification had a greater risk of poor outcome (mRS 3–6) (RR: 1.29, 95% CI: 1.16–1.43, p < 0.001), mortality (RR: 1.51, 95% CI: 1.14–2.00, p < 0.001), and sICH (RR: 1.29, 95% CI: 1.16–1.43, p < 0.001). Heterogeneity was low, with I ² ≤ 34%. Conclusion: Arterial calcification may be indicative of advanced vascular disease, potentially leading to diminished technical success and worse functional outcomes following EVT for AIS. These findings underscore that vascular calcification acts as an associative marker of procedural complexity and advanced vascular disease in EVT candidates.

Ischemic stroke during pregnancy and postpartum represents a rare but severe clinical event. Although reperfusion therapies like intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are standard in the general population, their use in pregnant and postpartum patients remains controversial due to limited data. Therefore, this study aims to evaluate the safety and efficacy of reperfusion therapy in pregnant and postpartum women with acute ischemic stroke. Systematic review and single-arm meta-analysis of studies reporting outcomes in pregnant or postpartum women undergoing IVT or MT. Outcomes included maternal and fetal events, intracerebral hemorrhage (ICH), symptomatic ICH (sICH), functional recovery (mRS 0-2), and mortality. Six studies comprising 275 patients were included. The pooled proportion of good maternal outcomes at discharge was 50% (95% CI: 44%-56%), and 85% (95% CI: 53%-100%) achieved functional recovery at 3 months. In-hospital mortality was 0% (95% CI: 0%-1%). Hemorrhagic complications included 10% ICH (95% CI: 1%-20%) and 3% sICH (95% CI: 0%-9%). Good fetal outcomes were observed in 78% (95% CI: 50%-100%) of cases. Although limited, the results suggest that reperfusion therapy in pregnancy-related ischemic stroke is safe and potentially effective, with favorable maternal and fetal outcomes and low mortality rates. These findings support the use of reperfusion therapies associated with individualized decision-making-in line with European Stroke Organisation guidelines -, emphasizing that pregnancy and post-partum period should not be a contraindication to IVT or MT.

Computer vision models for chest X-ray interpretation hold significant promise for global healthcare, but their clinical value depends on equitable development across diverse populations. We conducted a scientometric analysis to examine authorship patterns, geographic distribution, and dataset origins to assess potential disparities that could affect clinical applicability. We systematically reviewed literature on computer vision applications for chest X-rays published between 2017-2025 across multiple databases, including PubMed, Embase and SciELO databases. Using Dimensions API and manual extraction, we analyzed 928 eligible studies, examining first and senior author affiliations, institutional contributions, dataset provenance, and collaboration patterns across different income classifications based on World Bank categories. High-income countries dominated research leadership, representing 55.6% of first authors and 59.7% of senior authors; no first authors were affiliated with low-income countries. China (16.93%) and the United States (16.72%) led in first authorship positions. Most datasets (73.6%) originated from high-income settings, with the United States being the largest contributor (40.45%). Private datasets were most frequently used (20.52%). Cross-income collaborations were rare, with only 3.9% of publications involving partnerships between high-income and lower-middle-income countries. Findings reveal substantial disparities in who shapes computer vision research on chest X-rays and which populations are represented in training data. These imbalances risk developing AI systems that perform inconsistently across diverse healthcare settings, potentially exacerbating healthcare inequities. Addressing these disparities requires coordinated efforts to develop globally representative datasets, establish equitable international collaborations, and implement policies that promote inclusive research practices. Author Summary: In this study, we examined the global landscape of research involving computer vision applied to chest X-rays. While these technologies have the potential to significantly improve healthcare worldwide, their effectiveness depends on being developed and tested using data from diverse populations. We analyzed nearly one thousand scientific articles and found that research leadership and data sources are heavily concentrated in high-income countries, particularly the United States and China. Our findings reveal a concerning gap because people in low-income regions, who often face the highest burden of respiratory diseases, are almost entirely absent from the research process as both authors and data contributors. This imbalance creates a risk that medical artificial intelligence may not perform reliably when used in different parts of the world, which could accidentally worsen existing health inequalities. We argue that the scientific community must prioritize international partnerships that treat researchers from developing nations as equal leaders. By making medical data more diverse and accessible, we can ensure that these powerful diagnostic tools benefit patients everywhere, regardless of their location or economic status.

Background: The susceptibility vessel sign (SVS) on MRI has been linked to functional outcomes and reperfusion success after endovascular treatment (EVT), suggesting its potential as a prognostic marker. This updated systematic review and meta-analysis aimed to evaluate the prognostic and etiological significance of SVS in acute ischemic stroke (AIS). Methods: We conducted a systematic search of PubMed, Embase, and Cochrane in May 2025. Eligible studies included post-hoc analyses of randomized controlled trials (RCTs) and observational studies of AIS patients treated with EVT and/or intravenous thrombolysis (IVT). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Primary outcome was successful reperfusion (mTICI 2b-3). Secondary outcomes included functional independence (modified Rankin Scale [mRS] score 0–2), mortality, stroke etiology, and time metrics. Results: Eighteen studies ( n = 2602) were included. Overall, SVS was not associated with higher reperfusion rates (12 studies; n = 2083; RR: 1.01; 95% CI: 0.93–1.10; p = .832; I ² = 56.0%), except in the SWI subgroup (2 studies; RR: 1.17; 95% CI: 1.02–1.34; p = .022; I ² = 0.0%). SVS ⁺ was linked to lower 90-day mortality in anterior circulation strokes (3 studies; n = 865; RR: 0.52; 95% CI: 0.36–0.74; p < .001; I ² = 0%), improved 90-day functional independence in Western populations (7 studies; n = 1481; RR: 1.22; 95% CI: 1.01–1.47, p = .039; I ² = 37.7%), and in cardioembolic stroke etiology using GRE (9 studies; n = 1058; RR: 1.29; 95% CI: 1.05–1.57; p = .014; I ² = 36.3%). The mean time from onset to treatment was 238.19 minutes ± 147.5. Conclusions: Although SVS ⁺ did not predict reperfusion, it was associated with better functional outcomes in Western populations, particularly in cardioembolic stroke, and lower mortality, thereby reinforcing its prognostic value. MRI protocols did not delay treatment, but high heterogeneity limits certainty, highlighting the need for prospective studies.

Managing neuropsychiatric symptoms is crucial in dementia. The Neuropsychiatric Inventory-Distress (NPI-D) assesses caregiver distress, and the Zarit Burden Interview (ZBI) evaluates overall burden. Objective: This meta-regression examined the relationship between ZBI and NPI-D with NPI total scores to explore how burden relates to caregiver distress and neuropsychiatric symptoms. Methods: After a systematic review of studies addressing neuropsychiatric symptoms and caregivers’ burden in people with dementia, a meta-regression was conducted to examine the association between NPI-D and ZBI scores and NPI total scores. We used data from five studies reporting NPI-D scores and seven reporting ZBI scores. Single-arm meta-analyses for NPI-D, NPI total, and ZBI scores were performed using a random-effects model. Results: The random-effects model estimated a mean ZBI score of 23.76 [95% confidence interval - 95%CI 14.32-33.20, I2=100%, p=0]. NPI-D scores had a mean of 10.09 [95%CI 6.56-13.63, I2=96%, p<0.01], and the mean NPI total score was 21.84 [95%CI 19.31-24.38, I2=95%, p<0.01]. The meta-regression between NPI-D Mean and NPI total scores showed a statistically significant relationship, with a coefficient of 1.32 [95%CI 0.97-1.68, p=0.000], indicating a strong association between caregiver distress and neuropsychiatric symptoms. Conclusion: Single-arm studies suggest a positive relationship between neuropsychiatric symptoms and caregiver burden. The meta-regression analysis between NPI-D and NPI total demonstrates a significant link between caregiver distress and neuropsychiatric symptoms. Future studies should develop precise tools capturing caregivers’ challenges and burden. PROSPERO: CRD42024567953

Purpose This meta-analysis aimed to evaluate the clinical outcomes and safety of mechanical thrombectomy (MT) in pediatric acute ischemic stroke (AIS). Methods Systematic search of PubMed, Embase and Cochrane Library identified studies on MT in children (≤ 18 years) with AIS. Data on baseline characteristics, procedural details and clinical outcomes, including favorable functional outcome (modified Rankin Scale [mRS] 0–2), National Institutes of Health Stroke Scale (NIHSS) reduction, Pediatric Stroke Outcome Measure (PSOM), symptomatic intracranial hemorrhage (sICH) and mortality were extracted. A single-arm meta-analysis was performed to estimate pooled rates. Results 25 studies, encompassing 885 patients (mean age of included cohorts: 10.2–18 years), were included. The pooled favorable functional outcome was 80% (95% CI, 70%–88%), while the poor functional outcome was 14% (95% CI: 5%-26%). Mean NIHSS reduction was 8.07 (95% CI, 5.93–10.22), PedNIHSS decrease was 14.64 (95% CI: 12.04 to 17.24), and pooled mean PSOM score at follow-up was 1.02 (95% CI, 0.48–1.55). sICH was 2% (95% CI, 0–5%), need for decompressive hemicraniectomy was 7% (95% CI: 2%–14%) and overall mortality was 4% (95% CI, 1%–8%). Successful recanalization was 88% (95% CI: 81%–95%) and no reperfusion and re-occlusion were both 3% (95% CI: 0%–7%). Conclusion MT appears to be a promising and safe treatment option for pediatric AIS, demonstrating high rates of favorable functional outcomes and low mortality/sICH. However, significant heterogeneity among studies highlights the need for further high-quality, standardized research to optimize patient selection and define its effectiveness.