Journal of Investigative Medicine最新文献

Organised stroke care has become a keystone in delivering efficient and effective treatment to patients with stroke with improved outcomes. Delivering timely acute reperfusion therapy to those with acute ischaemic strokes is key to good recovery. Emergency stroke unit (ESU) is a novel organised stroke care system developed in China. It centralises all necessary procedures for the diagnosis and treatment of acute stroke into one unit that can perform clinical assessment, imaging examination and acute treatments. In ESU, artificial intelligence algorithms are used to aid in reading brain images and making clinical decisions. Therefore, ESU can significantly enhance the efficiency of emergent stroke care. In this guideline, we aim to clarify the concept, construction standards and personnel requirements of an ESU, standardise ESU-based acute stroke triage and treatment workflow, establish metrics of quality control, facilitate the construction and promotion of ESU and continue the improvement of the quality of stroke care.

Objective: The Antiplatelet versus R-tPA for Acute Mild Ischaemic Stroke trial has demonstrated the non-inferiority of dual antiplatelet therapy (DAPT) to alteplase in minor non-disabling stroke. This prespecified secondary analysis aimed to investigate whether the treatment effects were similar across stroke territories.

Methods: Participants were divided according to stroke territory, which were subdivided into DAPT and alteplase. An excellent functional outcome at 90 days defined as modified Rankin Scale scoring 0-1 was primary outcome. National Institutes of Health Stroke Scale (NIHSS) score change and early neurological improvement measured by a 2-point decline in NIHSS score at 24 hours were secondary outcomes. Symptomatic intracerebral haemorrhage (sICH) and bleeding events were safety outcomes. Primary analyses adjusted unbalanced baseline characteristics between treatments by multivariate logistic regression.

Results: A total of 719 patients were included: 566 in anterior circulation stroke (ACS) and 153 in posterior circulation stroke (PCS). Primary outcome was 94.1% in DAPT and 91.7% in alteplase among ACS patients (adjusted risk difference (RD) and 95% CI, 1.5% (-1.5% to 4.6%), p=0.32), while 91.2% in DAPT and 91.8% in alteplase among PCS patients (adjusted RD and 95% CI, -2.1% (-8.5% to 4.4%), p=0.53). Compared with alteplase, DAPT was associated with lower risk of sICH (p=0.03) and bleeding events (p<0.001) in ACS, but only lower risk of bleeding events (p=0.007) in PCS. Additionally, among ACS patients, the alteplase was superior to DAPT in terms of decrease in NIHSS score at 24 hours compared with admission (adjusted geometric mean ratio and 95% CI, -0.09 (-0.16 to -0.03), p=0.005) and early neurological improvement (adjusted RD and 95% CI, -7.2% (-11.6% to -2.7%), p=0.001).

Conclusion: Among ischaemic stroke with minor non-disabling symptoms, DAPT was similar with intravenous alteplase regarding long-term functional outcome and better safety regardless of ACS or PCS. The potential benefit of intravenous alteplase regarding early neurological improvement in patients with ACS warrants further investigation.

Trial registration number: NCT03661411.

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 and objective: We investigated the association of APOE alleles with CT-based cerebral amyloid angiopathy (CAA) markers including subarachnoid extension (SAE) and finger-like projection (FLP).

Methods: We included patients with acute primary supratentorial intracerebral haemorrhage (ICH) from a multicentre cohort in China. First, the association of APOE with ICH location (lobar vs non-lobar) was evaluated. Next, the relationships of APOE with SAE, FLP, and the coexistence of the two (SAE+FLP) were evaluated.

Results: 533 patients with supratentorial ICH were enrolled. Among them were 138 patients with lobar ICH and 395 with non-lobar ICH. Compared with the non-lobar group, APOE ε4 (OR 1.894, 95% CI 1.138 to 3.154, p=0.014) and ε2/ε4 (OR 6.098, 95% CI 1.414 to 26.293, p=0.015) were associated with lobar ICH. With regard to CAA markers, APOE ε2 was associated with SAE (OR 2.109, 95% CI 1.167 to 3.810, p=0.013), ε4 was associated with FLP and SAE+FLP (OR 3.026, 95% CI 1.353 to 6.767, p=0.007; OR 3.514, 95% CI 1.485 to 8.316, p=0.004, respectively) and ε2/ε4 was associated with all three factors (SAH: OR 7.599, 95% CI 1.764 to 32.734, p=0.006; FLP: OR 20.333, 95% CI 3.278 to 126.137, p=0.001; SAE+FLP: OR 30.568, 95% CI 4.460 to 209.503, p<0.001) after adjusting for age, and remained significant after adjusting for age and ICH volume.

Conclusion: In patients with spontaneous supratentorial ICH, APOE ε2 and ε4 alleles were associated with SAE and FLP, respectively, suggesting APOE allele-specific effects on CT markers of CAA and their potential mechanisms.

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: 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.

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.

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.

Background: CT is commonly used to image patients with ischaemic stroke but radiologist interpretation may be delayed. Machine learning techniques can provide rapid automated CT assessment but are usually developed from annotated images which necessarily limits the size and representation of development data sets. We aimed to develop a deep learning (DL) method using CT brain scans that were labelled but not annotated for the presence of ischaemic lesions.

Methods: We designed a convolutional neural network-based DL algorithm to detect ischaemic lesions on CT. Our algorithm was trained using routinely acquired CT brain scans collected for a large multicentre international trial. These scans had previously been labelled by experts for acute and chronic appearances. We explored the impact of ischaemic lesion features, background brain appearances and timing of CT (baseline or 24-48 hour follow-up) on DL performance.

Results: From 5772 CT scans of 2347 patients (median age 82), 54% had visible ischaemic lesions according to experts. Our DL method achieved 72% accuracy in detecting ischaemic lesions. Detection was better for larger (80% accuracy) or multiple (87% accuracy for two, 100% for three or more) lesions and with follow-up scans (76% accuracy vs 67% at baseline). Chronic brain conditions reduced accuracy, particularly non-stroke lesions and old stroke lesions (32% and 31% error rates, respectively).

Conclusion: DL methods can be designed for ischaemic lesion detection on CT using the vast quantities of routinely collected brain scans without the need for lesion annotation. Ultimately, this should lead to more robust and widely applicable methods.