This study projected the incidence, prevalence, death and disability-adjusted life-years (DALYs) attributable to total strokes and pathological types in people aged ≥ 15 years for 204 countries and territories to 2050. Age- and sex-specific trends in rates were developed using XGBoost models incorporating national human development index, gross domestic product per capita, and demographic data from the Global Burden of Disease study, the World Bank, and the United Nations. Uncertainty intervals were calculated as the 2.5th and 97.5th percentiles of the distribution using a bootstrap-like method. From 2021 to 2050, the global absolute number of incident strokes is anticipated to increase by 31.64

Intracerebral hemorrhage (ICH) is a lethal stroke subtype with limited treatment options, largely due to secondary injury driven by oxidative stress and neuroinflammation. Here, we developed a ruthenium (Ru)-manganese (Mn) composite nanozyme by integrating Ru nanozyme into Mn-doped zeolitic imidazolate framework (Mn-ZIF) to enable cascade catalytic activity for efficient ROS clearance. In vitro, Ru@Mn-ZIF nanozyme reduced LPS-induced microglia activation and H2O2-induced neuronal oxidative damage, showing stronger protective effects than Mn-ZIF nanozyme. In vivo, both intranasal and intravenous administration of Ru@Mn-ZIF nanozyme significantly decreased hematoma volume, preserved blood-brain barrier integrity, suppressed inflammatory responses, and improved neurological recovery in collagenase- and autologous blood-induced ICH models. Biosafety evaluation revealed no pathological or biochemical abnormalities after treatment. These findings highlight Ru@Mn-ZIF nanozyme as a promising therapeutic strategy for mitigating secondary brain injury and improving outcomes after ICH.

The relationship between statin therapy and clinical outcomes after intracerebral hemorrhage (ICH) remains uncertain. Therefore, we performed a post-hoc analysis of the third intensive care bundle with blood pressure reduction in acute cerebral haemorrhage trial study to evaluate the associations of pre-ICH and post-ICH statin use with clinical outcomes. The primary outcome was death or dependency (modified Rankin Scale [mRS] 3–6) at 6 months. Secondary outcomes included death, dependency, hematoma expansion, serious adverse events (SAEs), and cerebral hemorrhagic events. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated. Analysis was performed using generalized linear mixed model. We further examined whether post-ICH statin therapy modified outcomes within the care bundle group. Overall, a total of 7035 patients were included in the study. Pre-ICH (aOR 0.93, 95% CI 0.61–1.42) or post-ICH statin use (aOR 0.97, 95% CI 0.72–1.29) was not associated with death or dependency. However, pre-ICH statin use was associated with lower 6-month mortality (aOR 0.46, 95% CI 0.26–0.80) and a reduced incidence of cerebral hemorrhage (aOR 0.45, 95% CI 0.21–0.97). In stratified analyses, post-ICH statin use was associated with lower odds of 6-month mortality or disability among care bundle recipients (aOR 0.66, 95% CI 0.44–0.99; P = 0.046), with significant effect modification by intervention allocation (P for interaction = 0.019). In summary, statin therapy before or after ICH onset appeared to be safe, without increased risk of SAEs and hematoma expansion. Besides, among patients receiving the care bundle intervention, post-ICH statin use showed a potential association with improved functional outcomes. These exploratory findings require confirmation in future studies.

INTRODUCTION:ICH is a severe form of stroke with increasing global burden. Although more common in older adults, ICH in younger individuals (≤50 years) is a clinically distinct but understudied subgroup. This secondary analysis of the INTERACT3 trial compared baseline characteristics, management and outcomes between younger and older ICH patients. PATIENTS AND METHODS:INTERACT3 was a stepped-wedge, cluster-randomised trial conducted in 122 hospitals across 10 countries (2017-2021), evaluating a bundled care intervention for acute ICH. This sub-study analysed 7031 patients and compared demographics, imaging features, in-hospital treatment and 6-month outcomes between age groups. Primary outcomes were functional status (mRS), mortality and quality of life (EQ-5D-3L). Outcomes were analysed using generalised linear-mixed models accounting for clustering by hospital (random effect) and fixed effects for time period and cluster treatment assignment, with additional adjustment for pre-specified patient-level covariates. RESULTS:Of 7031 patients, 1351 (19.2%) were aged ≤ 50 years. Younger patients were more often male (70.8% vs 62.4%, P < .0001), had higher body mass index (BMI) (25.3 vs 23.8 kg/m2, P < .0001) and were more likely to smoke (36.1% vs 21.4%) and consume alcohol (33.2% vs 13.3%). Despite having slightly larger haematoma volumes (18.0 vs 15.0 mL, P < .0001), younger patients had significantly better outcomes, with lower 6-month mortality (9.1% vs 16.6%; adjusted OR 0.42; 95% CI, 0.33-0.54) and reduced rates of death or disability (46.5% vs 57.8%; OR 0.56; 95% CI, 0.48-0.65). A significant age-by-treatment interaction was observed (P = .0251). CONCLUSION:Younger ICH patients demonstrated a distinct risk profile and better recovery, and benefiting more from bundled care interventions. These findings highlight the importance of early, intensive management and tailored prevention strategies targeting modifiable lifestyle risks in younger populations.

BACKGROUND:Frailty has been widely associated with poor outcomes in mixed stroke cohorts, but evidence specific to intracerebral haemorrhage, particularly from settings in low-income and middle-income countries and regarding treatment-effect modification, remains scarce. We aimed to evaluate the association between frailty and several clinical outcomes and to ascertain whether frailty modifies the treatment effect of a care bundle in individuals with acute intracerebral haemorrhage. METHODS:We conducted a post-hoc analysis of the third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral haemorrhage (INTERACT3) international, stepped-wedge, cluster-randomised controlled trial (NCT03209258; Chinese Clinical Trial Registry ChiCTR-IOC-17011787), which enrolled individuals with acute spontaneous intracerebral haemorrhage at 121 hospitals in nine low-income and middle-income countries and one high-income country. Frailty was quantified using a 30-item cumulative-deficit frailty index; individuals were categorised as non-frail (frailty index ≤0·10), pre-frail (frailty index >0·10 to <0·21), or frail (frailty index ≥0·21). The primary outcome was 6-month all-cause mortality. Mixed-effects regression models, adjusted for key prognostic variables and clustering by hospital site, were used to estimate associations and treatment interactions across frailty strata. FINDINGS:Of the 7036 individuals enrolled in INTERACT3, 7035 with available frailty data were included in this analysis (mean age 62·0 years; 2533 [36·0%] women and 4502 [64·0%] men). 3185 (45·3%) were non-frail, 3000 (42·6%) were pre-frail, and 850 (12·1%) were frail. Increasing frailty was associated with higher 6-month mortality and poorer functional outcomes. These associations were attenuated but persisted after multivariable adjustment (mortality: adjusted hazard ratio [HR] 1·48 [95% CI 1·20-1·83]; major disability among survivors: adjusted odds ratio 1·73 [1·40-2·14] for frail vs non-frail individuals). The care bundle was associated with lower mortality point estimates across frailty groups (non-frail adjusted HR 0·66 [95% CI 0·46-0·94], pre-frail adjusted HR 0·80 [0·61-1·05], and frail adjusted HR 0·65 [0·43-0·98]; p for interaction=0·30). Absolute mortality rate reductions were larger among individuals with frailty (116·9 events per 1000 person-years) than among individuals without frailty (44·1 events per 1000 person-years). No clear evidence of treatment-by-frailty interaction was observed for death or major disability at 6 months (p for interaction=0·27). INTERPRETATION:Frailty showed a graded association with poor prognosis in acute intracerebral haemorrhage, and these associations were attenuated but generally persisted after adjustment for age, baseline neurological severity, and other prognostic factors. We found no clear evidence that frailty modified the effect of the INTERACT3 care bundle on mortality. Mortality estimates favoured the care bundle across frailty strata, with larger absolute mortality reductions observed among individuals with frailty. These findings support offering protocolised acute care to individuals with imaging-confirmed spontaneous intracerebral haemorrhage who present within 6 h of symptom onset, irrespective of frailty status, while also maintaining individualised clinical judgement regarding prognosis and functional recovery. FUNDING:None.

BACKGROUND AND OBJECTIVES:While moderate and rapid systolic blood pressure (SBP) lowering was associated with better functional outcomes after intracerebral hemorrhage (ICH), large reductions in SBP within 1 hour, for example, reductions from >200 to <140 mm Hg, diminished or even reversed these beneficial effects. We aimed to define the optimal trajectory of SBP control in relation to favorable functional outcomes after acute ICH. METHODS:We conducted a pooled analysis of individual patient-level data from all 4 Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) and second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trials, which were international, randomized, open-label, blinded, end point-assessed, controlled trials that determined the effectiveness of early intensive SBP control in acute ICH. Latent class analysis grouped SBP trajectories over the first 24 hours (9 measurements) into defined clusters. The primary outcome was functional recovery at 90 days after randomization, defined as modified Rankin Scale (mRS) scores of 3-6. Logistic regression models with adjustment for baseline covariates and trial were used to determine associations between SBP cluster trajectories and outcomes in INTERACT, with validation in ATACH-II. RESULTS:A total of 11,269 patients (INTERACT n = 10,269; ATACH-II n = 1,000; mean age 62.4 years; female 36.4%) with at least 1 postrandomization SBP reading were included. Six SBP trajectories were identified: low, moderate-to-low, moderate, high, high-to-moderate, and high-to-low. Compared with the low SBP group, associations with poor functional outcome (mRS scores 3-6) increased progressively across other groups in INTERACT (p = 0.04 for trend). Adjusted odds ratios (95% CI) for groups 2 to 6 were 1.16 (0.98-1.37), 1.44 (1.18-1.75), 1.46 (1.15-1.87), 1.90 (1.32-2.73), and 1.28 (1.02-1.60), respectively. A similar albeit nonsignificant trend was observed in ATACH-II due to limited power. DISCUSSION:Distinct SBP trajectories over 24 hours defined prognosis after ICH, with a severe hypertensive group having the highest odds of death or disability, regardless of the BP-lowering strategy used. These findings highlight the importance of well-controlled but tailored SBP management strategies after ICH. CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that distinct SBP trajectories over 24 hours are associated with prognosis after acute ICH, with a severe hypertensive group having the highest odds of poor functional outcome, regardless of the BP-lowering strategy used. TRIAL REGISTRATION INFORMATION:(INTERACT1 NCT00226096; INTERACT2 NCT00716079; INTERACT3 NCT03209258; INTERACT4 NCT03790800; ATACH-2 NCT01176565).

INTRODUCTION:As the management of intracerebral hemorrhage (ICH) shifts from historical inertia to more proactive, evidence-based care, ensuring sex-equitable access to best-practice stroke care is increasingly important. Data on sex differences in access to care for ICH remains limited and often conflicting. More robust evidence is required to understand where disparities may exist to inform targeted interventions. AIMS:We aimed to determine sex differences in the clinical and surgical management of patients with acute ICH who participated in the third Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3). METHODS:We performed a post hoc analysis of INTERACT3, an international stepped-wedge, cluster-randomised trial undertaken in 121 hospitals across 9 low- to middle-income countries and 1 high-income country. The trial aimed to evaluate a care bundle composed of intensive blood-pressure lowering, rapid correction of hyperglycemia, fever control, and reversal of anticoagulation; in adults presenting within 6 h of ICH onset. We used mixed-effects logistic regression to evaluate sex differences in access to surgical interventions, admission to an intensive care unit or acute stroke unit, assisted feeding, physiotherapy, occupational therapy, withdrawal of care, and use of pharmacological therapies (antiepileptic drugs, mannitol, dexamethasone, and statins). Patterns of care were further evaluated using latent class analysis, with sex differences analyzed using the same regression framework. RESULTS:Of 7036 patients with ICH, 2533 (36%) were female. Females were older and had more severe neurological deficits. Overall care provision was similar across sexes. However, females were more likely to receive assisted feeding (odds ratio [OR] 1.15, 95% CI = 1.02-1.31), and were less likely to withdraw from active care (OR 0.41, 95% CI = 0.19-0.87) than males. Surgical interventions were accessed at similar rates among sexes, a finding that persisted in analyses restricted to supratentorial ICH with hematoma volumes ⩾ 30 mL. Three distinct care classes were identified: high-intensity, high-rehabilitation, and low-intensity, with females and males having comparable distributions within the classes. CONCLUSION:Following acute ICH, females generally receive similar active acute care interventions as males, except for observed differences in access to assisted feeding and decision to withdraw from active care. These findings suggest that equal access to ICH interventions for females and males is feasible and exists in some settings. However, disparities in certain key interventions remain and present actionable opportunities for improvement. Further research is needed to explore not only access but also the timing and frequency of these interventions.Data access statement:Individual, de-identified participant data used in these analyses will be shared on request from any qualified investigator after the approval of a protocol and signed data access agreement via both the trial steering committee and the research office of The George Institute for Global Health (Sydney, NSW, Australia).

OBJECTIVE:The objective of this study was to assess the heterogeneity in treatment effect of intensive blood pressure (BP)-lowering across hematoma volume after acute intracerebral hemorrhage (ICH). METHODS:We undertook a pooled analysis of individual patient data from the pivotal trials of early intensive BP-lowering in ICH (the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 4 [INTERACT4] and Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 [ATACH-2] studies). The primary outcome was functional recovery, defined by the distribution of scores on modified Rankin scale (mRS). Secondary outcomes were hematoma expansion (HE) over 24 hours, defined by absolute (<0, 0-6, 6-12.5, and >12.5 ml) and relative HE (<0, 0-33, 33-66, and >66%). Generalized linear mixed models with trial as a random effect were conducted. We further assessed effect modification by hematoma volume and plotted the treatment effect curve. RESULTS:Among 6,125 individuals with available hematoma volume, intensive BP-lowering improved functional recovery (odds ratio [OR] for unfavorable shift in mRS score = 0.90, 95% confidence interval [CI] = 0.82 to 0.99, p = 0.027). In 3,897 participants with available HE, intensive BP-lowering reduced the risk of absolute (OR = 0.88, 95% CI = 0.78 to 0.99, p = 0.043) and relative (OR = 0.88, 95% CI = 0.78 to 0.99, p = 0.034) HE. We found effect modification of treatment on functional outcome and absolute HE by hematoma volume (p for interaction = 0.043 and 0.025, respectively). U-shaped curves were observed, with benefits seen in cases with hematoma volume of 7.5 to 27.5 and 7.0 to 32.5 ml, respectively, both peaking at 20 ml. INTERPRETATION:Early intensive BP-lowering improves functional outcome and reduces HE in ICH. Heterogeneity by hematoma volume indicates the importance of patient selection in future trials and clinical practice. ANN NEUROL 2026;100:171-179.

Intracerebral hemorrhage (ICH) is associated with high mortality and disability, and ineffective hematoma resolution contributes substantially to secondary brain injury and poor functional recovery. Although macrophage-mediated erythrophagocytosis has been recognized as an important mechanism for endogenous hematoma clearance, strategies that simultaneously enhance hematoma resolution and remodel the toxic perihematomal milieu remain limited. Herein, we developed a synergistic nanotherapeutic platform based on natural polyphenol-derived nanofibers fabricated through the co-assembly of bexarotene (Bex) and epigallocatechin gallate (EGCG). In this formulation, Bex was incorporated to promote macrophage-mediated erythrophagocytosis, while the EGCG-derived polyphenol scaffold provided antioxidant, anti-inflammatory, and ironmodulating functions to alleviate perihematomal microenvironmental stress. The Bex-EGCG nanofibers enhanced endogenous hematoma clearance, reduced inflammation and oxidative stress, attenuated secondary brain injury, and improved neurological recovery after ICH. Overall, this study presents a dual-functional nanofiber delivery strategy that combines Bex-mediated erythrophagocytosis promotion with polyphenolmediated perihematomal milieu remodeling, providing a multifunctional therapeutic approach for ICH.

BACKGROUND:Early intensive blood pressure (BP) lowering improves outcome after acute intracerebral hemorrhage (ICH), but the optimal degree of early systolic blood pressure (SBP) reduction remains uncertain. AIMS:We aimed to identify relative SBP reduction thresholds associated with the most favorable functional outcome after ICH. METHODS:We performed an individual participant data meta-analysis of five randomized trials of acute BP lowering in ICH (INTERACT1-4 and ATACH-II). The relative reduction measurements in SBP were defined as the percentage decrease (a) from baseline SBP to the lowest SBP in 1 h (primary) and (b) from baseline SBP to the achieved mean of SBP between 1 and 24 h. Associations with functional outcome, assessed as an unfavorable shift in scores on the modified Rankin scale (mRS) at the end of follow-up (90 or 180 days), were examined in multivariable ordinal logistic regression models and tested for non-linearity using restricted cubic splines. Heterogeneity of associations between the 1-hrelative SBP reduction and functional outcome by age, sex, history of hypertension, history of diabetes, baseline SBP, and hematoma volume was further explored by including each interaction term into the models. RESULTS:Among 11,283 participants (mean age, 62.6 years; 36.0% female; mean baseline SBP, 176.9 mmHg), the association between 1-h relative SBP reduction and unfavorable functional outcome was U-shaped with an inflection nadir at around 20%. Associations differed by sex, baseline SBP, and history of diabetes (all p for interaction <0.05). A similar U-shaped association was also observed in relation to the relative SBP reduction from baseline to the achieved level in 1-24 h, with the greatest apparent benefit at approximately 30%. CONCLUSION:In acute ICH, a first-hour relative SBP reduction of around 20% and a 24-h reduction target of 30%, individualized to the presenting SBP, were associated with the most favorable functional outcome. Larger reductions may attenuate the benefit and should be applied cautiously, particularly in patients with very high baseline SBP.

Abstract Background and aims The location-specific optimal cut point of ultra-early hematoma growth speed (UHG) for prognosticating acute intracerebral hemorrhage (ICH) is unknown. Methods Secondary analyses of participant data are from the INTERACT (Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trials) 1-3 studies. UHG was defined as hematoma volume (mL) divided by onset-to-CT time (hours). Cutoffs for UHG in whole and location-specific ICH with optimal sensitivity and specificity for 90-day or 180-day clinical outcomes (death or major disability [defined as modified Rankin Scale scores 3-6], and death alone) were identified using receiver operating characteristic curves. Results There were 4109 ICH patients (age, 62.8 ± 12.6 years; female, 36.0%; UHG, 5.55 [0.69-29.65] mL/h; location [lobar 10.9%, deep 82.2%, infratentorial 6.9%]) included in the main analyses. Receiver operating characteristic curve analysis identified an optimal UHG cutoff of 6.04 mL/h for death or major disability (area under the curve [AUC]=0.81) and 8.74 mL/h for death alone (AUC=0.79). Location-specific optimal UHG cutoffs for death or major disability were 8.73 mL/h (AUC=0.82) for lobar, 5.77 mL/h (AUC=0.79) for deep, and 4.35 mL/h (AUC=0.81) for infratentorial ICH, whereas corresponding cutoffs for death alone were 7.07 mL/h (AUC=0.74), 12.77 mL/h (AUC=0.81), and 7.91 mL/h (AUC=0.83), respectively. Conclusions In patients with ICH, baseline UHG cutoffs of 6.04 mL/h and 8.74 mL/h were optimal for predicting death or major disability and death alone, respectively, at 90 or 180 days, with values varying by hematoma location. Conflict of interest Dr You holds the National Natural Science Foundation of China (82471226), Discipline Construction Program of the Second Affiliated Hospital of Soochow University (XKTJ-XK202401 and XKTJ-RC202412). Dr Anderson holds a the National Health and Medical Research Council (NHMRC) of Australia Senior Investigator Fellowship and reports grant funding from NHMRC, Penumbra, and Takeda China. The other authors have nothing to disclose.

Statistics indicate that brain metastases occur in nearly 30% of patients with solid tumors, with lung cancer, breast cancer, and melanoma being the three most common primary sources. Brain metastasis is characterized by the co-evolution of tumor cells co-evolve with the brain microenvironment, inducing changes in the phenotype of brain stromal cells that facilitate the colonization, survival, and growth of tumors. The prognosis for brain metastases remains poor, with 2-year and 5-year survival rates for patients diagnosed with brain metastases of 8.1% and 2.4%, respectively. Notably, more than half of brain metastases patients die from neurological diseases. Current treatment options for brain metastases include radiotherapy, neurosurgery, systemic chemotherapy, targeted therapy, and immunotherapy, which are often used in combination to improve therapeutic outcomes. In recent years, the use of nanomaterials for brain metastases treatments has been progressively developed to enhance the efficiency and precision of drug delivery. In the future, with a deeper understanding of the mechanisms underlying brain metastases and further development of treatment strategies, patient outcomes are expected to improve. This review, summarizes the current understanding of brain metastasis mechanisms and therapeutic approaches, and outlines an outlook on future research directions in the field.

BACKGROUND:Early intensive blood pressure (BP) lowering improves outcomes in acute intracerebral hemorrhage, but its perioperative benefit among patients undergoing surgical hematoma evacuation is uncertain. We evaluated whether earlier achievement of intensive BP targets is associated with improved outcomes in this population. METHODS:Post hoc secondary analysis of the INTERACT3 (the third Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial) pragmatic, international, multicenter, blinded-end point, and stepped-wedge cluster-randomized trial. Among 7036 enrolled intracerebral hemorrhage patients at 121 hospitals, those who underwent surgical hematoma evacuation were included. Patients were categorized by time from hospital arrival to achieving the target systolic BP <140 mm Hg: ≤2 hours versus >2 hours. The primary outcome was 6-month mortality. Key secondary outcomes included death or disability (modified Rankin Scale scores 4-6), modified Rankin Scale score shift, health-related quality-of-life (EuroQol 5-Dimension 3-Level [EQ-5D-3L] domains, visual analog scale, and health utility index), and serious adverse events. Adjusted associations were estimated using Cox, logistic, ordinal logistic, and linear regression models, controlling for age, sex, treatment type, and admission Glasgow Coma Scale. RESULTS:Of 7036 patients with acute intracerebral hemorrhage, 1506 underwent surgical hematoma evacuation (mean [SD] age, 59.7 [11.8] years; 33.9% women). Overall, there was no statistically significant difference in 6-month mortality between patients who achieved target BP within 2 hours of treatment initiation and those who achieved it after 2 hours (adjusted hazard ratio, 0.81 [95% CI, 0.63-1.04]; P=0.09). Early BP achievement was associated with a lower risk of death or disability (adjusted odds ratio [OR], 0.71 [95% CI, 0.56-0.90]; P=0.01), a favorable shift in the distribution of modified Rankin Scale scores (adjusted common OR, 0.73 [95% CI, 0.60-0.89]; P<0.01), and fewer serious adverse events (adjusted OR, 0.73 [95% CI, 0.57-0.94]; P=0.02). EuroQol 5-Dimension 3-Level outcomes also favored the early group, with significant improvements in mobility (adjusted OR, 0.76 [95% CI, 0.60-0.97]; P=0.03), pain/discomfort (adjusted OR, 0.72 [95% CI, 0.54-0.95]; P=0.02), and usual activities (adjusted OR, 0.79 [95% CI, 0.62-1.00]; P=0.05), as well as higher visual analog scale (mean difference, 0.08 [95% CI, 0.002-0.17]; P=0.04) and health utility scores (mean difference, 0.05 [95% CI, 0.02-0.09]; P<0.01). CONCLUSIONS:In patients with intracerebral hemorrhage undergoing surgical hematoma evacuation, perioperative intensive BP reduction appears safe. Achieving systolic BP <140 mm Hg within 2 hours was associated with better functional and quality-of-life outcomes, and fewer serious adverse events. These time-sensitive associations support prioritizing ultra-early perioperative BP control; confirmatory prospective analyses are warranted. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03209258.

Background: Surgical resection remains the primary treatment for carotid body tumors (CBTs), but it carries a considerable risk of postoperative complications. Although several predictors have been identified, no validated tool currently exists to estimate the individualized risk of complications in CBT patients. This study aimed to develop a nomogram for predicting postoperative complications following CBT resection. Methods: We retrospectively analyzed adult patients who underwent surgical resection for CBTs at our institution between 2016 and 2022. Potential predictors of postoperative complications, including stroke and cranial nerve injury, were evaluated using multivariate logistic regression. A nomogram was then constructed and internally validated using bootstrap resampling and 10-fold cross-validation. Model discrimination, calibration, and clinical utility were assessed by the area under the receiver operating characteristic curve, calibration plots, and decision curve analysis. Results: A total of 230 patients (240 tumors) were included. Postoperative complications occurred in 38.3% of tumors, including 9 strokes and 83 cranial nerve injuries. The final nomogram incorporated the Shamblin classification, prior cerebral ischemia, and white blood cell count as independent predictors, achieving an AUC of 0.72 with a cutoff value of 94.6 for predicting postoperative complications. Conclusions: The proposed nomogram demonstrated good discriminative ability and calibration for predicting postoperative complications after CBT surgery. It may assist clinicians in identifying high-risk patients and optimizing perioperative management strategies. Further external validation across diverse populations is warranted to confirm its generalizability.

Background Iodine-enhanced micro-computed tomography (Micro-CT) enables high-resolution three-dimensional imaging of brain architecture. This study aimed to characterize both acute and chronic pathological changes following intracerebral hemorrhage (ICH) using iodine-enhanced micro-CT. Method Experimental ICH was induced in 8- to 10-week-old C57BL/6 mice (n = 76) via stereotaxic injection of either 0.075 U collagenase IV or 30 μl autologous blood. Iodine-enhanced micro-CT imaging was performed at 4 hours, 1, 3, and 7 days after intracerebral hemorrhage post-ICH to evaluate hematoma formation and erythrolysis. Chronic alterations, including ventriculomegaly and ipsilateral lesion, were assessed at 28 days post-ICH. In parallel, MRI was conducted at 1, 7, and 28 days following autologous blood injection, followed by micro-CT, to facilitate cross-modality quantitative analysis. Lesion volumes were compared between imaging modalities over time. Results Micro-CT enabled quantification of hematoma volume and erythrolysis in ICH models. Hematomas extended along perivascular pathways toward the cerebral surface in both collagenase- and autologous blood-induced ICH models. At 28 days post-ICH, micro-CT detected ventriculomegaly and hypodense lesions without concurrent expansion of the choroid plexus. Lesion volume measurements derived from micro-CT correlated with those from MRI, enabling quantitatively assessment of iron deposition and hematoma size alterations after ICH. Conclusion Iodine-enhanced micro-CT provides a robust and high-resolution imaging platform for evaluating hematoma evolution, hemolysis, ventricular enlargement, and chronic brain lesions in experimental ICH. When integrated with MRI, these multimodal imaging approaches enhance the characterization of both hematoma volume and iron deposition following ICH. ### Competing Interest Statement The authors have declared no competing interest.

The genetic relationship between migraine and stroke remains underexplored, particularly in the context of druggable targets. Previous studies have been limited by small sample sizes and a lack of focus on genetic-targeted therapies for these conditions. We analyzed the association and causality between migraine and stroke using multivariable logistic regression in the UK Biobank cohort and Mendelian randomization (MR) analyses based on genome-wide association study (GWAS) data. Integrating expression quantitative trait loci (eQTLs) data from blood and brain regions, we explored the phenotypic and genetic links between migraine medications, drug target, and stroke. Additionally, we explored novel druggable genes for migraine and evaluated their effects on migraine signaling molecules and stroke risk. Migraine was significantly associated with stroke, particularly ischemic stroke (IS) and intracerebral hemorrhage (ICH), with MR analysis confirming a causal link to ICH. HTR1A emerged as a potential link between antidepressants (preventive medications for migraine) and stroke. We identified 17 migraine-related druggable genes, with 5 genes (HMGCR, TGFB1, TGFB3, KCNK5, IMPDH2) associated with nine existing drugs. Further MR analysis identified correlation of CELSR3 and IMPDH2 with cGMP pathway marker PRKG1, and identified KCNK5, PLXNB1, and MDK as novel migraine-associated druggable genes significantly linked to the stroke risks. These findings established the phenotypic and genetic link between migraine, its medication and stroke, identifying potential targets for single and dual-purpose therapies for migraine and stoke, and emphasized the need for further research to validate these associations.

BACKGROUND:Uncertainty remains about the effects of intensive blood pressure (BP) lowering in acute intracerebral haemorrhage, particularly the impact of treatment timing. This study aimed to assess the safety and effectiveness of early intensive BP-lowering treatment and its dependence on timing in patients with intracerebral haemorrhage. METHODS:We undertook an individual patient-data pooled analysis of the four Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials: INTERACT1 (n=404), INTERACT2 (n=2829), INTERACT3 (n=7036), and INTERACT4 (n=1043). INTERACT1-3 included adults with acute intracerebral haemorrhage who presented within 6 h of the onset of symptoms and had an elevated systolic BP (>150 mm Hg). INTERACT4 included patients with suspected acute stroke that caused a motor deficit and an elevated systolic BP (≥150 mm Hg) within 2 h after the onset of symptoms, among whom 1029 had a haemorrhagic form of stroke. Patients were randomly assigned to receive intensive (target systolic BP <140 mm Hg within 1 h) or guideline-recommended (target systolic BP <180 mm Hg within 1 h) BP-lowering treatment using locally available drugs. The primary outcome was functional recovery, defined by the distribution of scores on the modified Rankin scale (mRS). In a CT substudy, radiological outcomes were relative (≥33%) and absolute (≥6 mL) changes in haematoma volume from baseline to 24 h. The treatment effects were determined in logistic regression models adjusting for trial and baseline haematoma volume. Heterogeneity in the effects across groups by time from onset to randomisation (continuous) and baseline severity according to the intracerebral haemorrhage score were assessed by adding interaction terms to the models. These trials are registered at ClinicalTrials.gov (INTERACT1 NCT00226096; INTERACT2 NCT00716079; INTERACT3 NCT03209258; INTERACT4 NCT03790800). This pooled analysis is registered with PROSPERO (CRD420251001539). FINDINGS:Among 11 312 patients (mean age 63 years [SD 12·7], 4066 [35·9%] female and 7246 [64·1%] male), the median time from the onset of symptoms to randomisation was 2·9 h (IQR 1·8-4·1). At 1 h, the mean systolic BP was 149·6 mm Hg (SD 21·8) in the intensive treatment group and 158·8 mm Hg (22·8) in the guideline group (difference 9·13 mm Hg, 95% CI 8·28-10·00; p<0·0001). Intensive BP-lowering treatment significantly decreased the chances of poor physical function (mRS scores of 3-6; odds ratio [OR] 0·85, 95% CI 0·78-0·91). Compared with guideline treatment, intensive BP-lowering treatment significantly reduced odds of neurological deterioration within 7 days (OR 0·76, 95% CI 0·66-0·88; p=0·0002), death (0·83, 0·75-0·94; p=0·002), and any serious adverse event (0·84, 0·76-0·92; p=0·0003). In the CT substudy involving 2921 patients, there was no apparent effect of intensive treatment on relative (0·85, 0·70-1·03; p=0·09) or absolute (0·84, 0·68-1·04; p=0·12) haematoma growth compared with guidelines treatment. In the same substudy, the treatment effects on functional recovery and relative haematoma growth decreased with increasing time from onset to randomisation, with a cutoff point in the effect crossing unity at 3 h (p=0·002 and p=0·01 for interaction, respectively). INTERPRETATION:Intensive BP-lowering initiated within several hours of intracerebral haemorrhage onset was safe and improved functional recovery, without a clear effect on haematoma growth. The greatest benefits for both outcomes occurred when treatment was commenced within 3 h of symptom onset. These findings underscore the importance of early intervention and inform the design of future trials targeting patients at highest risk of haematoma expansion. FUNDING:National Health and Medical Research Council of Australia (NHMRC); Department of Health and Social Care, the Foreign, Commonwealth & Development Office, Medical Research Council, and Wellcome Trust (all UK); the West China Hospital; Sichuan Credit Pharmaceutical; Takeda Pharmaceuticals China; the George Institute for Global Health; Shanghai East Hospital of Tongji University, National Natural Science Foundation of China, Sichuan Science and Technology Program, Project of Neurology Key Discipline of Sichuan (2018-53), Chengdu Science and Technology Bureau, the talent fund of Sichuan Provincial People's Hospital, and the talent fund of the First Affiliated Hospital of Chengdu Medical College. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

Introduction: Previous studies have demonstrated the potent anti-inflammatory effects of RvE1 in various diseases, and recent research has shown that it can also promote macrophage phagocytosis. Given that hematoma clearance is crucial for intracerebral hemorrhage (ICH) treatment, while neuroinflammation significantly influences secondary injury, we hypothesize that RvE1/ChemR23 activation, by modulating the polarization of macrophages/microglia, promotes hematoma resolution and alleviates neuroinflammatory responses after ICH. Method: A total of 125 WT C57BL/6 and 67 ChemR23- /- male mice were used. Western blot and immunofluorescence staining assessed the temporal and spatial expression of ChemR23 after ICH. T2WI, T2*WI and behavioral tests were obtained to assess the protective effect of the RvE1/ChemR23 pathway in ICH. Additionally, co-staining of M1 (iNOS) or M2 polarization (Arg-1) markers with Iba-1 was used to explore the polarization status of macrophages/microglia in the perihematomal region. Finally, Akt phosphorylation was validated as a downstream mediator of the RvE1/ChemR23 pathway using an Akt inhibitor. Results: ChemR23 is mainly expressed in activated microglia and infiltrating macrophages, with expression peaking 5-7 days post-ICH. Activation of the RvE1/ChemR23 pathway promotes hematoma resolution, reduces brain edema, and improves neurological deficits in ICH. These effects are likely mediated by promoting M2 polarization of macrophages/microglia after ICH. Furthermore, the use of an Akt inhibitor can counteract the protective effects of RvE1 in ICH. Conclusions: Our study provides the first evidence of the protective role of RvE1/ChemR23 signaling in ICH. This pathway might offer novel therapeutic targets for the clinical management of ICH.

Traumatic brain injury (TBI) is a significant global health issue, characterized by high rates of morbidity and mortality, along with substantial economic strains on healthcare systems. This study explores the potential of Aminophylline (AMP), a medication traditionally used for cardiovascular conditions and bronchiectasis, to enhance TBI outcomes by protecting against neuronal damage. Our findings indicate that AMP treatment significantly reduces neuronal ferroptosis in the cortex, leading to less tissue damage and notable improvements in cognitive and motor functions in mice subjected to controlled cortical impact (CCI). Additionally, we found that TBI resulted in decreased expression of miR-128-3p, a reduction that was further strengthened by AMP treatment. Gain-of-function experiments showed that overexpressing miR-128-3p increases neuronal ferroptosis by targeting Slc7a11, indicating how AMP mitigates cognitive and motor impairments in CCI mice. This study highlights the potential of AMP in treating TBI through the miR-128-3p/Slc7a11 pathway, marking the first report of its protective effects against ferroptosis in TBI.