Journal of Investigative Medicine最新文献

Background: Distal embolisation (DE) is a common complication following endovascular treatment (EVT) for acute ischaemic stroke. Thrombus magnetic susceptibility may offer predictive insights into DE risk. In this study, we employed quantitative susceptibility mapping (QSM) to measure thrombus susceptibility in patients undergoing EVT and examined its association with DE occurrence.

Methods: Patients with confirmed intracranial large vessel occlusion were consecutively enrolled from a participating centre in the RESCUE-RE study (a registration study for Critical Care of Acute Ischaemic Stroke After Recanalisation). Thrombus magnetic susceptibility was quantitatively measured using three-dimensional multiecho QSM imaging. DE was defined as the appearance of new downstream occlusions on postinterventional digital subtraction angiography. The association between thrombus susceptibility metrics and the occurrence of DE was analysed using multivariable logistic regression, adjusting for relevant clinical and procedural variables.

Results: Among the 61 patients included, DE occurred in 29.5% of patients. Thrombi from patients with DE showed significantly higher mean susceptibility values (0.28±0.11 parts per million (ppm) vs 0.22±0.08 ppm, p=0.029). Multivariable analysis identified increased thrombus susceptibility as an independent predictor of DE, with an OR of 2.38 per 0.1 ppm (95% CI 1.04 to 5.45, p=0.039), after adjusting for potential confounders such as National Institutes of Health Stroke Scale score, stroke aetiology, occlusion site, intravenous thrombolysis and time from onset to groin puncture.

Conclusion: This study identifies thrombus magnetic susceptibility, as quantified by QSM, as a novel imaging biomarker predictive of DE during EVT. These findings highlight the potential of QSM to guide treatment decisions and stratify DE risk preoperatively, although validation in larger cohorts is warranted.

Objective: To develop an MRI habitat atlas that is robust across different haemorrhage stages for haemorrhagic brainstem cavernous malformations (BSCMs) and to integrate habitat-derived imaging biomarkers with clinical variables for precise prediction of symptomatic re-haemorrhage.

Methods: A retrospective cohort of 205 eligible patients from Huashan Main Campus (2015-2020) was randomly divided into a discovery set (n=147) for model development and an internal validation set (n=58). External validation was performed using a prospective temporal cohort from Huashan West Campus (2021-2023, n=94). Each lesion was segmented into six biologically distinct habitats via unsupervised clustering of multiparametric MRI. Habitat-derived radiomic features were combined with clinical variables into a multimodal logistic regression model, which was rigorously validated both internally and temporally.

Results: The 2-year cumulative re-haemorrhage rate was 81% in high-risk lesions versus 26% in low-risk lesions. The combined habitat-clinical model achieved an area under the curve (AUC) of 0.833 (95% CI 0.777 to 0.889) in the training set and 0.851 in the external validation set, significantly outperforming both imaging-only (∆AUC+0.07, p=0.008) and clinical-only models (∆AUC+0.17, p<0.001). The model demonstrated excellent calibration and provided net clinical benefit across decision thresholds of 5%-75%.

Conclusion: The multimodal MRI habitat atlas provides a robust and reproducible tool for individualised re-haemorrhage risk stratification in BSCMs, facilitating clinical decision-making for surveillance or intervention while reducing the likelihood of overtreatment.

Background: Transradial access has become an increasingly preferred approach for cerebral angiography. However, embolic events, often clinically silent, remain a frequent concern. Despite routine use, the efficacy and safety of heparin strategies in this setting lack randomised clinical trial evidence.

Methods: In this investigator-initiated, single-centre, prospective, open-label, outcome-blinded randomised clinical trial, adult patients undergoing transradial cerebral angiography with a negative diffusion-weighted imaging (DWI) scan within the past month were enrolled. Participants were randomised (1:1:1) to receive no heparin (heparin-free), systemic heparinisation alone or systemic heparinisation followed by continuous heparinised saline flush. A follow-up DWI was performed within 24 hours postprocedure to identify new ischaemic lesions. The primary efficacy outcome was the incidence of new embolic events. Safety outcomes included bleeding and other procedure-related adverse events.

Results: Between March and December 2024, 472 patients were randomised. Embolic events were detected in 24 of 158 patients (15.2%) in the heparin-free group, 24 of 157 patients (15.3%) in the heparinisation group (adjusted risk ratio (RR) 0.93; 95% CI 0.54 to 1.61; p=0.802) and 35 of 157 patients (22.3%) in the heparinisation followed by heparinised saline flush group (adjusted RR 1.22; 95% CI 0.74 to 2.03; p=0.437). Bleeding complications occurred in one (0.6%) patient in the heparin-free group, three (1.9%) patients in the heparinisation group and nine (5.7%) patients in the heparinisation followed by heparinised saline flush group (p=0.02). Overall adverse events were reported in two (1.3%), four (2.5%) and 11 (7.0%) patients across the respective groups (p=0.018).

Conclusions: Systemic heparinisation did not reduce embolic events, while continuous heparinised saline flush increased bleeding and adverse events without added benefit. These findings suggest that routine use of heparinised flush warrants reconsideration, emphasising the need to balance procedural anticoagulation strategies against safety risks in clinical practice.

Trial registration number: ChiCTR2400080902.

Background: In addition to infectious fever, stroke-related disturbances in thermoregulation, referred to as central fever, are frequently observed in patients with stroke, particularly in those with intracerebral haemorrhage (ICH). Rapid identification of the underlying cause of fever is crucial for treatment decisions. This study aims to identify clinical, laboratory and radiological parameters that differentiate central fever from infectious fever in patients with ICH.

Methods: We included 547 ICH patients in this retrospective, single-centre cohort study. Fever was defined as a body temperature exceeding 38.3°C for at least 2 consecutive days. Central fever was characterised by the absence of an infection diagnosis, cultured pathogens and any other identified cause of fever. CT scans were assessed visually and with a 3D nn-UNet for segmentation and subsequent quantification of all ICH components. Voxel-based lesion-symptom mapping was performed to identify lesion locations related to central fever. Univariate analyses and multiple logistic regression were conducted.

Results: Fever occurred in 213 patients: 54 with central fever, 156 with infectious fever and 3 with other causes. Central fever was linked to higher scores on the National Institutes of Health Stroke Scale and worse outcomes (p<0.01). It had an earlier onset (median day 2 (1-3) vs 6 (4-9) p<0.01) and was more frequent in patients with lesions affecting the left midbrain and hypothalamic region (p<0.01). In contrast, infectious fever was associated with higher levels of infectious parameters (ie, C reactive protein, procalcitonin and leucocyte count). Its early onset (p<0.001) and affection of the left hypothalamic region (OR=9.7 (1.6 to 58.837), p=0.013) emerged as independent predictors of central fever.

Conclusions: Early onset and hypothalamic involvement are the strongest indicators of central fever, which may help guide evidence-based treatment decisions for patients with fever following ICH.

Background: Stem cell (SC) transplantation is a promising therapeutic approach for ischemic stroke (IS). However, the current literature lacks robust evidence substantiating its efficacy and safety. This systematic review aims to evaluate the efficacy and safety profile of SC therapy in patients who had an IS.

Methods: References up to November 2025 were sourced from OVID Medline, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, Web of Science and ClinicalTrials.gov. Eligibility criteria followed a Population, Intervention, Comparator, Outcome framework: adult patients with image-confirmed IS, any human SC therapy (non-neural or neural), placebo or standard medical care and functional or neurological outcomes (modified Rankin Scale (mRS), Barthel Index (BI), National Institutes of Health Stroke Scale (NIHSS)), mortality or adverse events at ≥6 months. Only randomised controlled trials were considered. Random-effects meta-analyses compared efficacy and safety between SC and control groups. Study heterogeneity was measured using the I² statistic, and risk of bias was assessed using the Cochrane Risk-of-Bias V.2 tool.

Results: 17 RCTs involving 999 patients (SC therapy: 495; control: 504) were included. A pooled analysis showed that SC therapy was associated with significant improvements in mRS scores (mean difference (MD)=-0.27, 95% CI -0.51 to -0.03, p=0.027, I²=42.2%), BI scores (MD=7.78, 95% CI 0.50 to 15.06, p=0.036, I²=53.0%) as well as reduced mortality rates (relative risk=0.64 (95% CI 0.42 to 0.98), p=0.040, I²=0%). No significant effect was observed for NIHSS scores. The incidence of AE was comparable between groups. The included trials exhibited moderate heterogeneity and a moderate risk of bias.

Conclusion: SC therapy shows potential to improve functional outcomes and survival in patients who had an IS without significant safety concerns. However, the observed effect on disability is fragile, as statistical significance was lost in leave-one-out analyses, and the substantial heterogeneity and moderate methodological quality limit definitive conclusions.

Prospero registration number: CRD42024567397.

Background: Predicting futile recanalisation following endovascular treatment (EVT) in patients with large core infarctions is crucial for guiding clinical decisions, optimising perioperative management and improving healthcare resource allocation. This study aimed to compare four machine learning (ML) algorithms and identify the most effective model for preinterventional prediction of futile recanalisation.

Methods: Patients achieving successful reperfusion (expanded Thrombolysis in Cerebral Infarction Score≥2b) from the EVT in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core trial were stratified into two groups: no-futile recanalisation (90-day modified Rankin Scale (mRS) 0-3) and futile recanalisation (mRS 4-6). The least absolute shrinkage and selection operator regression method was used for feature selection, and four ML algorithms, including logistic regression, support vector machine (SVM), decision tree and random forest, were applied. Model performance was evaluated using receiver operating characteristic curves, calibration plots and decision curve analysis. Feature importance was ranked using SHapley Additive exPlanation (SHAP) values.

Results: Among 146 patients, 74 experienced futile recanalisation. Eight predictors were identified and ranked by SHAP analysis from highest to lowest importance: sex, age, National Institutes of Health Stroke Scale, glucose, systolic blood pressure, neutrophil-to-lymphocyte ratio, fibrinogen and occlusion site. Among the four models, the SVM model achieved the highest area under the curve of 0.891 (95% CI 0.837 to 0.945), along with good calibration (Hosmer-Lemeshow test, p=0.103) and clinical utility.

Conclusion: The SVM model emerges as the optimal predictive tool for futile recanalisation following EVT in patients with large core infarction. Nevertheless, external validation is required to confirm its performance before clinical application.

Trial registration number: NCT04551664.

Background: Hyperacute prehospital blood pressure (BP)-lowering in randomised trial setting improves outcomes for intracerebral haemorrhage (ICH) but worsens outcomes for acute cerebral ischaemia. Consequently, hyperacute antihypertensive therapy could potentially aid prehospital patients identified as likely having ICH by clinical scales and diagnostic technologies. The required diagnostic performance characteristics needed to yield net benefit have not been well-delineated.

Methods: We modelled 3-month global disability (modified Rankin Scale, mRS) outcomes using magnitude of beneficial and harmful effects of BP-lowering in the INTERACT 4 trial to develop a two-stage algorithm. In stage 1, positive predictive values (PPVs) are converted to net treatment effect for different ordinal/dichotomised and utility-weighted mRS outcomes. In stage 2, for continuously varied prehospital diagnostic test sensitivity, specificity and disease prevalence, PPVs for ICH are output.

Results: As PPVs increase, progressively enriching the test-positive population with actual ICH patients, the effect of treating likely ICH patients changes from net harm to neutrality to net benefit for all analysed 3-month outcomes: For the functional independence outcome, treating test-positive likely ICH patients with BP-lowering reached minimal clinically important difference (MCID) desirable for a very simple intervention in mRS 0-2 increase at PPV of 39% and the outcome-specific MCID increase at PPV of 67%. At 67% PPV, among every 1000 patients treated, 130 would have less disabled outcome, including 50 more achieving functional independence.

Conclusions: This study developed an analytic framework to determine, for all possible combinations of test sensitivity, specificity and ICH prevalence, the effect on global disability outcomes of prehospital BP-lowering among patients identified as likely ICH.

Background and purpose: Evidence on whether add-on early antiplatelet therapy may improve functional outcome in acute ischaemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) remains inconsistent. This study aims to evaluate the efficacy and safety of oral ticagrelor plus aspirin within 6 hours of symptom onset in IVT-treated AIS patients.

Methods and design: Efficacy and Safety of Ticagrelor with Aspirin Dual Antiplatelet Therapy Combined with Intravenous Thrombolysis in Patients with Ischemic Stroke (TAPIS) is a multicentre, randomised, double-blind, parallel-group, placebo-controlled trial. The study will enrol 1380 AIS patients with a pre-IVT National Institutes of Health Stroke Scale (NIHSS) score of 4-10 who have received/are intended to receive IVT with alteplase or tenecteplase within 4.5 hours of onset. Eligible participants will be randomised at a 1:1 ratio within 6 hours of onset, before, during or after IVT. The intervention group will receive a loading dose of ticagrelor tablets (180 mg) and aspirin tablets (100 mg) on day 1, and ticagrelor (90 mg two times per day) plus open-label aspirin (100 mg daily) for days 2-7. The control group will receive ticagrelor placebo and aspirin placebo on day 1, and ticagrelor placebo plus open-label aspirin for days 2-7. Both groups will receive open-label aspirin (100 mg daily) for days 8-90.

Study outcomes: The primary efficacy outcome is excellent functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 0-1. Secondary efficacy outcomes include mRS score of 0-2 at 90 days, distribution of mRS scores at 90 days, NIHSS score at 7 days decreasing by ≥4 points from baseline and recurrent ischaemic stroke within 90 days. The primary safety outcome is symptomatic intracerebral haemorrhage within 36 hours.

Discussion: This trial will evaluate whether early dual antiplatelet therapy with ticagrelor plus aspirin could improve functional outcomes of IVT-treated AIS patients.

Trial registration number: NCT06316570.

Background: Intracerebral haemorrhage (ICH) is a critical condition that leads to significant mortality or profound disability. Surgery serves as an important intervention that can save lives; however, the surgical techniques employed globally exhibit considerable variability, and their efficacy remains ambiguous.

Methods: PubMed, Embase, Web of Science and CENTRAL were searched for randomised controlled trials (RCTs). Two independent reviewers extracted data, assessed bias (Cochrane Risk of Bias Tool, V.2) and evidence certainty (Confidence in Network Meta-Analysis). Frequentist network meta-analysis calculated relative risks (RRs) and 95% CIs.

Results: A total of 26 RCTs with 4892 patients with ICH were included. The very-low-certainty evidence network meta-analysis demonstrated that, compared with standard medical care, both endoscopic surgery (mortality: RR 0.66; 95% CI 0.50 to 0.87) and minimally invasive puncture surgery (mortality: RR 0.77; 95% CI 0.64 to 0.93) were associated with decreased mortality. Moreover, low-certainty evidence showed that endoscopic surgery (functional independence: RR 1.62; 95% CI 1.28 to 2.05) and minimally invasive puncture surgery (functional independence: RR 1.53; 95% CI 1.34 to 1.76) were associated with a higher likelihood of functional independence. In contrast, conventional craniotomy (mortality: RR 0.86; 95% CI 0.72 to 1.02; functional independence: RR 1.07; 95% CI 0.90 to 1.28) showed no statistically significant differences.

Conclusions: This systematic review and network meta-analysis found that endoscopic surgery and minimally invasive puncture surgery were associated with lower mortality and better functional outcomes compared with other interventions. However, the certainty of evidence was limited due to heterogeneity in patient populations and treatment protocols. More definitive conclusions will require future large-scale, rigorously designed RCTs that standardise protocols and minimise confounding factors.

Background: Infarct volume growth (IVG) correlates with outcomes and may represent a prognostic imaging biomarker in acute ischaemic stroke due to anterior circulation large vessel occlusion (LVO). This study aims to identify factors associated with IVG after mechanical thrombectomy (MT) in patients with large core infarction.

Methods: This is a post hoc analysis of the Endovascular Therapy in Anterior Circulation Large Vessel Occlusion with a Large Infarct randomised trial. IVG was calculated as final infarct volume minus baseline infarct volume (BIV). The optimal IVG threshold for predicting 90-day favourable outcomes (modified Rankin Scale score 0-3) was determined using receiver operating characteristic (ROC) curve analysis, maximising both sensitivity and specificity. Factors associated with IVG were identified using multivariate logistic regression analyses.

Results: Among 228 included patients, ROC analysis identified an optimal IVG threshold of 105 mL for predicting favourable 90-day outcomes (area under the curve=0.71; specificity=0.85, sensitivity=0.53). Patients were stratified into mild (IVG <105 mL, n=150) and severe (IVG ≥105 mL, n=78) groups. Multivariate logistic regression identified BIV (OR 1.02, 95% CI 1.00 to 1.03; p<0.01), admission blood glucose (OR 1.20, 95% CI 1.04 to 1.37; p=0.01), time from puncture to recanalisation (OR 1.01, 95% CI 1.00 to 1.02; p=0.049) and recanalisation at 36 hours (±12 hours) (OR 0.19, 95% CI 0.05 to 0.72; p=0.01) as independent factors associated with IVG.

Conclusion: IVG after MT significantly correlates with clinical outcomes. Identification of modifiable IVG determinants after MT may inform periprocedural management strategies in patients with large infarct due to LVO.

Trial registration number: NCT04551664.