Journal of Investigative Medicine最新文献

Background: Prehospital delay in acute ischaemic stroke (AIS) remains prevalent in China. We aimed to assess the status of the onset-to-door time (ODT) in AIS and analyse its influencing factors.

Methods: Data were collected from a prospective multicentre hospital-based registry (China National Cerebrovascular Disease Prevention and Control Project Management Special Database) of patients with AIS involving 21 hospitals across different economic and geographical regions in China in 2022. The Mann-Whitney U test or t-test was used for between-group comparisons. Factors influencing ODT ≤3 hours were analysed using a binary logistic regression model.

Results: Of the included 12 484 patients (attended middle school or below, 69.2%), females had a higher illiteracy rate (13.1%) than males (4.8%); 94.8% were living with others at illness onset; 22.5% of patients/family members were aware of the stroke emergency map (SEM, but only 7.3% were transported by SEM; 76.8% lived within 20 km of the first visited hospital. Significant differences occurred in modes of arrival at hospitals among cities of different sizes (χ²=74.882, p<0.001). Being in a medium-sized (OR 0.65, 95% CI 0.50 to 0.86); large (OR 0.61, 95% CI 0.47 to 0.79) or extralarge city (OR 0.60, 95% CI 0.46 to 0.78); experiencing cardiogenic embolism (OR 0.65, 95% CI 0.50 to 0.86) or stroke of undetermined aetiology (OR 0.69, 95% CI 0.52 to 0.92); stroke onset between 18:00 and 23:59 (OR 0.71, 95% CI 0.60 to 0.85); distance <20 km from onset location to the hospital (OR 0.47, 95% CI 0.41 to 0.54); being transported by SEM (OR 0.31, 95% CI 0.26 to 0.36) and having initial National Institutes of Health Stroke Scale scores of 5-15 (OR 0.63, 95% CI 0.57 to 0.71) or 16-42 (OR 0.32, 95% CI 0.27 to 0.39) were independent factors favouring ODT ≤3 hours. Conversely, being transferred between hospitals during transportation (OR 3.31, 95% CI 2.66 to 4.14); experiencing wake-up stroke (OR 2.00, 95% CI 1.67 to 2.38); symptom-onset including dizziness (OR 1.28, 95% CI 1.10 to 1.47) and prestroke modified Rankin scale (mRS) score of 2-3 (OR 1.58, 95% CI 1.30 to 1.92) or 4-5 (OR 1.48, 95% CI 1.02 to 2.15) tended to indicate ODT >3 hours.

Conclusions: Urban scale, stroke type, onset time, distance from initial location to the first hospital visit, transportation method, stroke symptoms, prestroke mRS score and stroke severity significantly influenced prehospital delay. Our findings can facilitate the development of targeted policies.

Introduction: Venous thromboembolic events (VTEs) like deep vein thrombosis or pulmonary embolism are frequent complications in (neuro) critical ill patients. Anticoagulation for VTE after space-occupying brain infarction is a therapeutic dilemma. The aim of this retrospective study was to investigate the frequency of clinically apparent VTE in patients with acute ischaemic stroke (AIS) due to large vessel occlusion (LVO), its treatment, and the rate of complications.

Methods: Patients with first AIS due to LVO were assigned to one of the following groups: space-occupying brain infarction with (1) or without (2) decompressive craniectomy (DC), AIS comprising more than 2/3 (3) or less than 2/3 (4) of the middle cerebral artery territory. Clinically obtained parameters included risk factors for VTE, type of thromboprophylaxis, treatment of VTE and treatment-associated complications.

Results: 15 of 173 (8.7%) patients had a VTE, which was diagnosed 10.9 ± 7.2 days after admission. Patients with a space-occupying brain infarction and DC had significantly more VTE (n=11/63; 17.5%) than patients with a space-occupying brain infarction without DC (0/26; p =0.023) or patients without DC (4/110; 3.6%; p = 0.004). Younger age, DC and cumulative duration of central venous catheter were identified as risk factors for VTE. Only three patients had major bleeding events while being anticoagulated (one asymptomatic cerebral and two extracranial bleedings).

Discussion: Patients with space-occupying brain infarction and DC hold a high risk for VTE. Despite extensive infarct size and DC, therapeutic anticoagulation required for VTE appeared to be safe regarding intracranial bleeding complications.

Background and aim: Recently, long-term outcomes in patients with spontaneous intracerebral haemorrhage (sICH) have gained increasing attention besides acute-phase characteristics. Predictive models for long-term outcomes are valuable for risk stratification and treatment strategies. This study aimed to develop and validate an explainable model for predicting long-term recurrence and all-cause death in patients with ICH, using clinical and imaging markers of cerebral small vascular diseases from MRI.

Method: We retrospectively analysed data from a prospectively collected large-scale cohort of patients with acute ICH admitted to the Neurology Department of The Second Affiliated Hospital of Zhejiang University between November 2016 and April 2023. After comprehensive variable selection using least absolute shrinkage and selection operator and stepwise Cox regression, we constructed Cox proportional hazards models to predict recurrence and all-cause death. Model performance was evaluated using the concordance index, integrated Brier score and time-dependent area under the curve. Global and local interpretability were assessed using variable importance calculated as SurvSHAP(t) and SurvLIME methods for the entire training set and individual patients, respectively.

Results: A total of 842 eligible patients were included. Over a median follow-up of 36 months (IQR: 12-51), 86 patients (9.1%) died, and 62 patients (6.6%) experienced recurrence of ICH. The concordance indexes for the all-cause death and recurrence models were 0.841 (95% CI 0.767 to 0.913) and 0.759 (95% CI 0.651 to 0.867), respectively, with integrated Brier scores of 0.079 and 0.063. The interpretability maps highlighted age, aetiology of ICH and low haemoglobin as key predictors of long-term death, while cortical superficial siderosis and previous haemorrhage were crucial for predicting recurrence.

Conclusions: This model demonstrates high predictive accuracy and emphasises the crucial factors in predicting long-term outcomes of patients with sICH.

Background: MLC1501, consisting of four herbs, that is, Radix Astragali, Radix Angelicae sinensis, Rhizoma Chuanxiong, Radix Polygalae, has the same pharmacological properties as its precursors MLC601 and MLC901 which contain extracts of nine herbs and showed neuroprotective, anti-inflammatory and neurorestorative properties in non-clinical models, as well as clinical benefits in improving functional and neurological recovery after brain injuries.

Aims: To determine the efficacy of MLC1501 on motor recovery as measured by Fugl-Meyer motor Assessment (FMA) total score at 24 weeks in patients with ischaemic stroke (IS).

Design: A total of 300 patients aged >18 years, diagnosed with IS in the prior 2-10 days, with National Institute of Health Stroke Scale (NIHSS) total score of 8-18 and a combined score of ≥3 on NIHSS motor items 5A, 5B, 6A and/or 6B, will be randomised in a 1:1:1 ratio to receive oral placebo, MLC1501 low dose or MLC1501 high dose for 6 months. The study is governed by a Steering Committee. An independent Data Monitoring Committee oversees patient safety.

Outcomes: The primary outcome is mean change from baseline in FMA total score at 24 weeks. Efficacy outcomes evaluated in person at baseline, 12 weeks and 24 weeks include the FMA (total, upper extremity and lower extremity motor scores), modified Rankin Scale (mRS), Patient-Reported Outcomes Measurement Information System-Global Health (PROMIS-10) and NIHSS. Additionally, telephone assessment at week 4 includes the simplified mRS and PROMIS-10.Safety will be evaluated by standard assessments and occurrence of adverse events over the duration of the study.

Discussion: Interventions that enhance recovery beyond the acute period of stroke are needed. MLC1501 has a good safety profile as well as potential to be a treatment for recovery after brain injury. The results of this study will provide objective level B evidence on the efficacy of MLC1501 on long-term recovery and safety of 24 weeks of treatment among patients with IS.

Trial registration number: NCT05289947.

Background: Cervical artery dissection (CAD) is a rare cause of stroke. This is an update of an earlier systematic review, which focuses on the risk of CAD in the general population. The objective was to identify the risk factors for CAD.

Methods: A comprehensive search was conducted in MEDLINE, EMBASE and Web of Science on 20 September 2024. Observational studies (cohort, case-control studies and case-crossover studies) that studied patients with CAD and a control group were included. Risk of bias was assessed with the ROBINS-E tool, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). The results were stratified by healthy controls (primary analyses) and other control groups, notably ischaemic non-CAD stroke (secondary analyses).

Findings: In total, 128 study reports were identified, of which 54 used one or more healthy control groups. Of these reports, 49 (91%) used a case-control design. The risk of bias was generally high (93%). For the following categories, effects were identified: (1) genetic factors or factors with a familial predisposition: migraine, methylenetetrahydrofolate reductase (MTHFR), TT homozygosity, matrix metalloproteinases (MMP) concentration, and connective tissue disorders; (2) external factors: recent infection, winter or autumn-winter season and oral contraceptive use; (3) minor trauma; (4) cardiovascular factors: hypertension, hypercholesterolaemia, relative vasodilatation of internal carotid, coronary artery disease and other cardiac diseases. For other risk factors (5), there were no significant pooled estimates. The certainty of the evidence was moderate for migraine and MTHFR TT, low for minor trauma and very low certainty for all others.

Interpretation: This is the first review that comprehensively examined the risk of CAD in the general population. Genetic factors, cardiovascular risk factors, recent infection and minor trauma are risk factors for CAD. Caution is needed in interpretation as the evidence is overall low to very low certainty, except for migraine and MTHFR TT homozygosity.

Background: Endovascular treatment (EVT) is safe and effective in treating acute ischaemic stroke due to basilar artery occlusion (AIS-BAO); nonetheless, the impact of intravenous thrombolysis (IVT) on its efficacy remains unclear.

Objective: To compare the effectiveness and safety of EVT with or without prior IVT in treating AIS-BAO patients within 4.5 hours after stroke onset.

Methods and design: A multicentre, prospective, randomised, open-label controlled clinical trial with blinded assessment of endpoints. 340 patients will be consecutively randomised to receive IVT plus EVT or direct EVT in a ratio of 1:1 from about 100 hospitals in China. An interim analysis is planned when one-third (114) of the patients have completed the primary endpoint follow-ups. It anticipates that IVT plus EVT demonstrates superiority over direct EVT. If the superiority of IVT plus EVT over direct EVT is less than expected, the sample size may be expanded by up to 20% of the original size. If the efficacy of the two groups is similar, it will shift to a non-inferiority hypothesis, aiming to evaluate whether direct EVT is non-inferior to IVT plus EVT.

Outcome: The primary endpoint is the proportion of independent neurological function defined as a modified Rankin Scale score of 0 to 2 at 90±14 days after stroke onset.

Discussion: This trial is expected to provide novel evidence of the superiority or non-inferiority between EVT with or without IVT in the treatment of patients with AIS-BAO.

Trial registration: NCT05631847 at ClinicalTrials.gov and ChiCTR2300070584 at Chictr.org.cn.

Background: The role of adiponectin (ADPN) in stroke remains debatable, despite its significant impact as a major adipocytokine on cardiovascular (CV) diseases. This study aimed to assess the association between ADPN and 5-year mortality, functional outcome and recurrence in Chinese individuals with first ischaemic stroke (IS).

Methods: This prospective, multicentre study recruited IS patients from 201 hospitals in China between August 2015 and March 2018. Multivariable Cox regression evaluated ADPN's association with mortality/recurrence, while logistic regression analysed poor functional outcomes (modified Rankin Scale score 3-6 and 3-5).

Results: Among 8086 patients (median age 62; 31.8% female), there were 710 deaths, 1134 recurrences and 1223 poor functional outcomes (modified Rankin Scale 3-6). Higher baseline ADPN levels were significantly associated with increased risk of 5-year non-CV mortality (adjusted HR _{Q4 vs Q1}=1.47 (95% CI 1.10 to 1.96), p=0.06) after adjustment for age, sex, body mass index and National Institutes of Health Stroke Scale. No independent associations were found between ADPN and CV mortality, stroke recurrence or poor functional outcome. Subgroup analysis revealed a significant association between ADPN and 5-year mortality from various causes among patients with cardioembolism (adjusted HR _{Q4 vs. Q1}=2.39 (95% CI 1.24 to 4.62), p=0.007) and large artery atherosclerosis (adjusted HR _{Q4 vs Q1}=2.16 (95% CI 1.34 to 3.47), p=0.004).

Conclusions: Elevated baseline ADPN levels were independently associated with increased 5-year non-CV mortality in Chinese IS patients, especially among those with mild neurological impairment. These findings suggest ADPN may serve as a prognostic biomarker for systemic vulnerability after stroke.

Background: Studies on futile recanalisation after endovascular therapy (EVT) for anterior circulation large vessel occlusion with large infarct were scarce. The present study aimed to explore the incidence and independent predictors of futile recanalisation in patients with large infarct.

Methods: This is a post-hoc analysis of the ANGEL-Alberta Stroke Program Early CT (ASPECT) trial. A favourable outcome was defined as a 90-day modified Rankin Scale score of 0-3; successful reperfusion was defined as extended thrombolysis in cerebral infarction 2b, 2c and 3 on final angiogram; and futile recanalisation was defined as unfavourable outcome despite successful reperfusion. We performed multivariate analysis to identify the predictors of futile recanalisation after EVT in patients with large infarct.

Results: A total of 183 patients were included: 91 (49.7%) patients had futile recanalisation and 92 (51.3%) had meaningful recanalisation. In multivariable logistic regression analysis, nonmodifiable factors included older age (age ≥68 years, OR=3.4, 95%CI 1.5 to 7.7, p= 0.003), female sex (OR=2.78, 95%CI 1.28 to 7.27, p=0.01), higher National Institutes of Health Stroke Scale score (NIHSS ≥16, OR=3.1, 95%CI 1.2 to 8.3, p=0.035), diabetes (OR=3.1, 95%CI 1.2 to 8.3, p=0.017) and symptomatic intracranial haemorrhage (sICH) (OR=9.1, 95%CI 1.0 to 80.7, p=0.049), and modifiable factors included larger final infarct volume (FIV ≥174.7, OR=6.2, 95%CI 2.5 to 15.7, p<0.001) and postoperative respiratory failure (OR=14.1, 95%CI 1.6 to 124.8, p=0.018), which were independent predictors of futile recanalisation.

Conclusions: Futile recanalisation occurred in approximately half of patients who had an acute stroke with large infarct after EVT in the ANGEL-ASPECT trial. Nonmodifiable factors that included old age, high baseline NIHSS score, diabetes mellitus, sICH and large FIV, and modifiable factors that included respiratory failure were independent predictors of futile recanalisation after EVT for large ischaemic strokes. Stroke-related pneumonia control may improve prognosis.

Background: The efficacy of intravenous thrombolysis (IVT) versus early antiplatelet therapy (APT) in small artery occlusion (SAO) stroke remains debated.

Methods: Ischaemic stroke (IS) patients with SAO who received IVT or early APT without IVT≤4.5 hours from stroke onset were screened from a prospective multicentre IS registry study from 1 January to 1 June 2021. The primary outcome was unfavourable functional outcome (FO) at 3 months. The secondary outcome was early neurological deterioration (END). The safety outcome was symptomatic intracerebral haemorrhage (sICH).

Results: There were 1125 SAO patients with 394 receiving IVT. 411 patients (36.5%) exhibited unfavourable FO, and sICH occurred in 3 cases (0.27%), all in IVT group, at the follow-up. END was observed in 213 patients (18.9%). After propensity score matching and multivariable adjustment, IVT significantly reduced the likelihood of unfavourable FO at 3 months (aOR 0.447, 95% CI 0.305 to 0.656), but no significant difference was found in END (aOR 0.867, 95% CI 0.569 to 1.321). Clustering analysis identified two distinct phenotypes: phenotype 0 (characterised by traditional cardiovascular risk factors) and phenotype 1 (marked by prominent inflammatory markers). A significant treatment-by-phenotype interaction was observed (p=0.002), with a comparable magnitude of benefit in phenotype 0 (aOR 0.405, 95% CI 0.244 to 0.673) compared with phenotype 1 (aOR 0.414, 95% CI 0.218 to 0.783).

Conclusion: IVT significantly reduced the likelihood of unfavourable FO at 3 months in SAO patients but did not significantly reduce END. Patients with traditional risk factors may benefit more from IVT than those with elevated inflammatory markers.

Trial registration number: ChiCTR2100045258.