Journal of Investigative Medicine最新文献

Objective: Given China's rapid population ageing and substantial stroke burden, understanding the epidemiology of vascular cognitive impairment (VCI) is critical. This study aimed to systematically evaluate VCI prevalence and incidence in China from 1980 to 2023, and explore demographic and geographic disparities.

Methods: A systematic review and meta-analysis of 81 observational studies (73 on prevalence, 10 on incidence) was conducted, analysing data from 784 846 participants for prevalence. Data were extracted from multiple databases, and studies were selected based on predefined inclusion criteria. Meta-analysis was performed using random-effects models due to high heterogeneity (I²>90%). Machine learning models (including gradient boosting machine, random forest) were employed to assess associations between demographic factors and VCI prevalence, with SHapley Additive exPlanations analysis for interpretability.

Results: Overall pooled prevalence was estimated at 1.54% (95% CI: 1.14% to 1.93%), varying significantly with age, education and region, peaking at 2.91% in those ≥80 years. Temporal trends revealed increasing prevalence from 1980 to 2023, while incidence was estimated at 0.29 per 100 person-years (95% CI: 0.21% to 0.41%), with regional disparities. Machine learning identified age, sex and survey period as key determinants of prevalence, aligning with meta-regression findings.

Conclusions: VCI poses a growing burden in China, particularly among older and less-educated populations. This analysis provides the most comprehensive assessment of VCI in China to date, underscoring demographic and regional variations. These findings highlight the need for targeted public health strategies, improved diagnostics and lifestyle interventions to address the growing burden of VCI, particularly amidst China's ageing population. Future longitudinal research integrating clinical data, biomarkers and potentially neuroimaging is warranted to better understand VCI progression and refine intervention efficacy.

Background: Dual antiplatelet therapy (DAPT) is often necessary following endovascular treatment for ruptured cerebral aneurysms; however, the optimal drug combination and treatment duration remain uncertain.

Method: Patients with subarachnoid haemorrhage secondary to ruptured cerebral aneurysms were identified from the TriNetX database. Subjects were categorised based on DAPT regimen (aspirin+clopidogrel vs aspirin+ticagrelor) and duration (≥1 month, ≥3 months, ≥6 months). Propensity score matching was performed, and outcomes including new onset intracranial haemorrhage, ischaemic stroke and overall survival were compared.

Results: A total of 2775 patients were included in the regimen analysis, with 725 matched in each group. At the 1-month follow-up, the ORs for new intracranial haemorrhage and ischaemic stroke in the aspirin+clopidogrel group were 1.11 (95% CI 0.71 to 1.75) and 0.97 (95% CI 0.59 to 1.59), respectively, with no significant differences at mid-term or long-term follow-up. However, survival analysis revealed a statistically significant difference at the 6-month follow-up favouring the clopidogrel group (OR 0.65; 95% CI, 0.44 to 0.97). In the duration analysis, 465 patients were matched for the 1-month versus 3-month groups, and 355 for the 3-month versus 6-month groups. ORs for ischaemic stroke were 1.06 (95% CI 0.67 to 1.67) and 1.24 (95% CI 0.76 to 2.01), respectively. No significant differences in survival were observed based on log-rank tests.

Conclusion: Our real-world data analysis revealed no significant differences in ischaemic or haemorrhagic outcomes between the aspirin+clopidogrel and aspirin+ticagrelor regimens. However, the observed differences in survival suggest the need for more refined patient selection strategies. In addition, the appropriate duration of DAPT is still unknown, although our results suggest that a shorter DAPT duration may offer comparable safety and efficacy.

Introduction: Cerebral venous thrombosis (CVT) is a rare but serious disease. Despite anticoagulation being the cornerstone therapy, some patients experience worsening disease, necessitating alternative treatment. Endovascular treatment is an anticipated option with an uncertain clinical relevance. The aim of this study was to assess the clinical effects and efficacy of endovascular therapy and identify patient populations that may benefit from treatment.

Patients and methods: This retrospective study examined patient data from April 2014 to March 2022 that were extracted from a nationwide Japanese Diagnosis Procedure Combination database. The primary outcome was in-hospital mortality. The secondary outcomes included modified Rankin Scale (mRS) scores and post-hospitalisation complications of cerebral infarction and intracranial haemorrhage. Severity was adjusted using a generalised linear mixed model, and propensity-score matching was employed to compare outcomes between treatment groups.

Results: The study included 2901 patients; 240 patients in the endovascular treatment group were matched with 240 patients in the standard treatment group. After adjusting for background factors, endovascular treatment did not improve in-hospital mortality (adjusted OR 1.45; 95% CI 0.74 to 2.16) or the mRS score (adjusted OR 0.89, 95% CI 0.56 to 1.23). No subpopulations that could benefit from endovascular treatment were identified. Post-hospitalisation cerebral infarction and intracranial haemorrhage did not increase with endovascular treatment (0.8% in the endovascular treatment group vs 1.2% in the standard treatment group).

Conclusion: Endovascular treatment showed no significant benefit for patients with CVT, indicating that treatment guidelines need to be refined. Our findings can guide clinical decisions and suggest the necessity of further research on potential benefits in specific subpopulations.

Mild stroke symptoms are cited as the reason for not using tissue-type plasminogen activator in 29-43% of time-eligible patients. Previous studies suggested that not all of these patients had a good recovery or even survival to hospital discharge. Since then, stroke guidelines worldwide recommended thrombolysis in minor but disabling strokes.Dual antiplatelet treatment with aspirin and clopidogrel was more effective than aspirin alone for reducing subsequent events in patients with minor stroke if started within 24 hours of onset in both CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischaemic Stroke) trials. Recently, both PRISMS (The Potential of rtPA for Ischemic Strokes With Mild Symptoms) trial and TEMPO-2 (Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) trial showed that treatment with thrombolysis versus antiplatelet did not increase the likelihood of favourable functional outcome at 90 days among patients with minor non-disabling acute ischaemic strokes. Therefore, a narrative review on thrombolysis for patients with minor strokes from published studies may help practicing clinicians.

Rationale: Neuroprotective strategies based on reperfusion therapy hold substantial promise for acute ischaemic stroke (AIS). Preclinical research indicates that tocilizumab, an interleukin-6 receptor antagonist, can attenuate ischaemia-reperfusion damage by exerting anti-inflammatory and neuroprotective effects.

Aim: To determine tocilizumab's efficacy and safety when combined with endovascular thrombectomy (EVT) in patients with acute anterior circulation large vessel occlusion (LVO).

Sample size estimates: To determine a 30% decrease in average infarct core volume comparing the intervention and historical control groups (mean increase of 18.7 mL (SD=9.7 mL) post-thrombectomy) via a two-sided test (alpha=0.05, power=80%), accounting for a 10% drop-out rate, we plan to recruit 108 participants.

Methods and design: This trial is designed as a randomised, multicentre, double-blind, placebo-controlled trial. Patients will be randomly and evenly allocated to the tocilizumab or placebo groups.

Study outcomes: The primary endpoint is the change in infarct core volume between baseline and 72 hours post-treatment. Secondary outcomes include the 90-day modified Rankin scale score (0-2, indicating functional independence). The key safety endpoints include 90-day mortality and symptomatic intracerebral haemorrhage within 72 hours after EVT.

Discussion: Administering tocilizumab within 24 hours of stroke as an adjunct to EVT may effectively reduce the infarct core volume for patients experiencing AIS with anterior circulation LVO, potentially improving functional outcomes in these patients.

Background and purpose: The low-field MRI is a promising tool to accurately diagnose strokes. We here report our study on the accuracy of a 0.23-Tesla (0.23-T) MRI using the haematoma enhanced inversion recovery (HEIR) sequence to detect acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) within 24 hours of symptom onset.

Methods: A novel HEIR sequence based on fluid-attenuated inversion recovery T1-weighted, with a scanning time of 1 min and 17 s, was developed using an ICH and AIS pig model on a 0.23-T MRI. Images of the pig model were obtained hourly for 24 hours in order to monitor value changes on T1/T2 and verify the differential diagnosis of AIS and ICH. Then, 30 patients with AIS and 30 patients with ICH with confirmed diagnoses by 3T-MRI/CT were included. Diagnostic criteria on a 0.23-T MRI for ICH was the hyperintensity signal on both the diffusion-weighted imaging (DWI) and HEIR sequence, while for AIS was the hyperintensity on DWI and isointensity on the HEIR sequence. Two blinded raters independently assessed the images obtained by the 0.23-T MRI for the presence of ICH/AIS.

Results: In the pig model, setting the inversion time to 800 ms enabled clear differentiation of ICH from brain parenchymal tissue and AIS. In real patients, a correct 0.23-T MRI diagnosis of either an AIS or ICH was made in all 60 patients within 24 hours of symptom onset (100% overall accuracy). No adverse events occurred.

Conclusions: The 0.23-T MRI may have the potential to differentiate cerebral haemorrhage from cerebral infarction with both speed and accuracy, making brain MRI scans easier, faster and cheaper. It might be possible to improve the screening imaging process for strokes in the emergency room. Further multicentre studies are needed to validate our findings.

Objective: Systolic blood pressure (SBP) affects the risk of early neurological deterioration (END). This subgroup analysis of Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke (ATAMIS) trial aimed to explore whether SBP at admission affected the efficacy of different antiplatelet therapies in preventing END.

Methods: Based on the modified intention-to-treat analysis set of the ATAMIS trial, patients were divided into two subgroups according to whether SBP at admission was equal to or higher than 140 mm Hg, which were further subdivided into clopidogrel plus aspirin and aspirin alone treatments according to the randomised assignment. We conducted multivariable regression analyses to detect relationship between SBP at admission and END, as well as efficacy of different antiplatelet therapies in each SBP subgroup. Primary endpoint was END defined as ≥2-point increase in 7-day National Institutes of Health Stroke Scale score. Safety endpoints included intracranial haemorrhage and bleeding events during the trial.

Results: This study included 2915 patients. Risk of END raised by 16% as SBP at admission increased by every 10 mm Hg (p<0.001). Clopidogrel plus aspirin resulted in significantly lower risk of END than aspirin alone in patients with SBP≥140 mm Hg (5.5% vs 7.9%; adjusted risk difference (RD) and 95% CI -2.5% (-4.1% to -1.0%)), but not in those with SBP<140 mm Hg (3.4% vs 4.2%; adjusted RD and 95% CI -0.8% (-3.2% to 1.7%)). Efficacy of different antiplatelet therapies and SBP did not show significant interaction (p=0.50). Safety endpoints were similar between treatments in SBP subgroups.

Conclusion: The risk of END increases with elevated SBP at admission among patients with acute mild-to-moderate ischaemic stroke who are not suitable for reperfusion treatments. Fewer END occurred following clopidogrel plus aspirin compared with aspirin alone across different SBP levels. The finding should be interpreted cautiously.

Background: Despite successful reperfusion after thrombectomy for large vessel occlusion (LVO) stroke, up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to demonstrate safety and efficacy of administering adjunct intra-arterial (IA) tenecteplase in anterior circulation LVO patients who have achieved successful reperfusion defined as eTICI 2b50 to 3.

Methods: ANGEL-TNK is a multicentre, open-label, assessor-blinded endpoint, prospective randomised, controlled trial that will enrol up to 256 patients. Patients who meet inclusion criteria with anterior circulation LVO stroke and successful reperfusion will be randomised to receive IA tenecteplase or best medical management at 1:1 ratio.

Results: The primary endpoint is a 90-day excellent outcome defined as modified Rankin Scale (mRS) 0-1. The primary safety endpoint is symptomatic intracranial haemorrhage within 48 hours from randomisation. Secondary endpoints include 90-day ordinal mRS, mRS 0-2, mRS 0-3, all-cause mortality and any intracranial haemorrhage.

Conclusion: In patients with anterior circulation LVO stroke, the ANGEL-TNK trial will inform whether adjunct IA tenecteplase administered after successful thrombectomy reperfusion improves patient outcomes.

Trial registration number: NCT05624190.

Background: Stroke-induced transient immune suppression is believed to contribute to post-stroke infections. The β-adrenergic receptor antagonist, propranolol, has been shown to prevent stroke-associated pneumonia (SAP) via reversing post-stroke immunosuppression in preclinical studies and in retrospective analysis in stroke patients. However, whether propranolol can reduce the risk of SAP has not been tested in prospective, randomised controlled trials.

Aim: To describe the rationale and design of a multicentre, prospective, open-label, endpoint-blinded, randomised controlled study to evaluate the safety and efficacy of propranolol hydrochloride injection for the prevention of SAP in patients with intracerebral haemorrhage (ICH) (PROCHASE).

Design: In this investigator-initiated trial, we compare the safety of the standard medical treatment to standard medical treatment plus intravenous propranolol hydrochloride administration (5 mg daily on days 1-7) in patients with ICH and the efficacy of this intervention to reduce the occurrence of SAP. All patients will be followed up for 90±7 days.

Study outcomes: The primary efficacy outcome is SAP within 7±1 days diagnosed by the defined algorithm based on a diagnosis of SAP recommendations from the pneumonia in stroke consensus group. The primary safety outcome is defined as severe or moderate bradycardia within 7±1 days. The secondary outcome is a modified Rankin score of 0-3 at 90±7 days after randomisation.

Discussion: The PROCHASE trial aims to generate clinical evidence regarding the safety and efficacy of propranolol in preventing SAP in patients with ICH.