Journal of Investigative Medicine最新文献

Background and objectives: Although left atrial appendage closure (LAAC) is performed in patients with non-valvular atrial fibrillation (NVAF) at increased risk of intracranial haemorrhage (ICH), outcome data are scarce. We assessed the detailed neurological indications for LAAC and outcomes after LAAC in high ICH risk patients.

Methods: Study population included consecutive patients with NVAF who underwent LAAC in a single hospital network between January 2015 and October 2021 because of prior ICH or the presence of high ICH risk imaging markers on brain MRI (cerebral microbleeds (CMBs)). Primary safety and efficacy outcome measures were the occurrence of ICH and thromboembolic events, respectively, after LAAC.

Results: Among 146 patients with NVAF who underwent LAAC for high ICH risk, 122 had a history of ICH, while 24 presented with high ICH risk imaging markers only. Mean age was 75.7±7.61, 42 (28.8%) were women. Mean CHA₂DS₂-VASc score was 5.23±1.52. Of 122 patients with ICH history, 58 (47.5%) had intraparenchymal haemorrhage (IPH), 40 (32.8%) had traumatic ICH (T-ICH) and 18 (14.7%) had non-traumatic subdural haemorrhage. Of 85 patients with brain MRIs including necessary sequences, 43 (50.6%) were related to cerebral amyloid angiopathy and 37 (43.5%) to hypertensive microangiopathy. While 70% of patients were discharged on oral anticoagulants (OAC), 92% were not taking OAC at 1 year. Over 2.12 years mean follow-up, one patient had recurrent non-traumatic IPH (incidence rate (IR) 0.32 per 100 patient-years), five had T-ICH (IR 1.61 per 100 patient-years) and six had an ischaemic stroke (IR 1.94 per 100 patient-years).

Conclusions: Among patients with NVAF at high ICH risk, LAAC demonstrated a low risk of recurrent ICH or ischaemic stroke compared with previously published data. LAAC in high ICH risk populations should be considered in clinical practice per FDA approval and recent guidelines.

Background: Recently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the clinical implications of its haemodynamic features, which were systematically reviewed in this study.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements, we searched PubMed and Embase up to March 2024 and screened for articles reporting clinical implications of haemodynamic parameters in sICAS derived from CFD models.

Results: 19 articles met the inclusion criteria, all studies recruiting patients from China. Most studies used CT angiography (CTA) as the source image for vessel segmentation, and generic boundary conditions, rigid vessel wall and Newtonian fluid assumptions for CFD modelling, in patients with 50%-99% sICAS. Pressure and wall shear stress (WSS) were quantified in almost all studies, and the translesional changes in pressure and WSS were usually quantified with a poststenotic to prestenotic pressure ratio (PR) and stenotic-throat to prestenotic WSS ratio (WSSR). Lower PR was associated with more severe stenosis, better leptomeningeal collaterals, prolonged perfusion time and internal borderzone infarcts. Higher WSSR and other WSS measures were associated with positive vessel wall remodelling, regression of luminal stenosis and artery-to-artery embolism. Lower PR and higher WSSR were both associated with the presence and severity of cerebral small vessel disease. Moreover, translesional PR and WSSR were promising predictors for stroke recurrence in medically treated patients with sICAS and outcomes after acute reperfusion therapy, which also provided indicators to assess the effects of stenting treatment on focal haemodynamics.

Conclusions: CFD is a promising tool in investigating the pathophysiology of ICAS and in risk stratification of patients with sICAS. Future studies are warranted for standardisation of the modelling methods and validation of the simulation results in sICAS, for its wider applications in clinical research and practice.

Background: Stroke is a major cause of global mortality and disability. Currently, the treatment of acute ischaemic stroke through reperfusion has posed several challenges, raising the need for complementary options to protect the ischaemic penumbra. Recent investigations have indicated that certain epigenetic factors, specifically, histone deacetylases (HDACs) and sirtuins, can be promising for ischaemic stroke therapy, with recent studies suggesting that inhibitors of HDACs or sirtuins may provide neuronal protection after ischaemic stroke. However, the impact of specific HDAC/sirtuin isoforms on the survival of neuronal cells following stroke is still uncertain. This study aims to provide a comprehensive overview of the function of HDACs and their modulators in the treatment of acute ischaemic stroke.

Methods: This systematic review and meta-analysis will encompass animal intervention studies that explore the efficacy of modulation of HDACs and sirtuins in the acute phase of ischaemic stroke. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches will be conducted in PubMed, Web of Science and Scopus, with subsequent screening by independent reviewers based on the established eligibility criteria. Methodological quality will be evaluated using the SYRCLE risk of bias tool. The primary outcomes will be infarct volume and functional response, with the secondary outcomes established a priori. Data pertaining to infarct volume will be used for random-effects meta-analysis. Additionally, a descriptive summary will be conducted for the functional response and secondary outcomes.

Discussion: No systematic review and meta-analysis on the treatment of ischaemic stroke through HDAC modulation has been conducted to date. A comprehensive analysis of the available literature on the relevant preclinical investigations can yield invaluable insights in discerning the most effective trials and in further standardisation of preclinical studies.

Systematic review registration: This systematic review has been recorded in the International Prospective Register of Systematic Reviews (PROSPERO), with the assigned reference number: CRD42023381420.

Background: We investigated differences in intracranial embolus distribution through communicating arteries in relation to supra-aortic vessel (SAV) patency.

Methods: For this experimental analysis, we created a silicone model of the extracranial and intracranial circulations using a blood-mimicking fluid under physiological pulsatile flow. We examined the sequence of embolus lodgment on injecting 104 frangible clot analogues (406 emboli) through the right internal carotid artery (CA) as SAV patency changed: (a) all SAV patent (baseline), (b) emboli from a CA occlusion, (c) emboli contralateral to a CA occlusion and (d) occlusion of the posterior circulation. The statistical analysis included a descriptive analysis of thrombi location after occlusion (absolute and relative frequencies). Sequences of occlusions were displayed in Sankey flow charts for the four SAV conditions. Associations between SAV conditions and occlusion location were tested by Fisher's exact test. Two-sided p values were compared with a significance level of 0.05.

Results: The total number of emboli was 406 (median fragments/clot: 4 (IQR: 3-5)). Embolus lodgment was dependent on SAV patency (p<0.0001). In all scenarios, embolism lodging in the anterior cerebral artery (ACA) occurred after a previous middle cerebral artery (MCA) embolism (MCA first lodge: 96%, 100/104). The rate of ipsilateral ACA embolism was 28.9% (28/97) at baseline, decreasing significantly when emboli originated from an occluded CA (16%, 14/88). There were more bihemispheric embolisations in cases of contralateral CA occlusion (37%, 45/122), with bilateral ACA embolisms preceding contralateral MCA embolism in 56% of cases (14/25 opposite MCA and ACA embolism).

Conclusions: All emboli in the ACA occurred after a previous ipsilateral MCA embolism. Bihemispheric embolisms were rare, except when there was a coexisting occlusion in either CA, particularly in cases of a contralateral CA occlusion.

Background: Subarachnoid haemorrhage (SAH) and intraventricular haemorrhage (IVH) are associated with poor patient outcomes. Intraventricular fibrinolysis is effective in clearing IVH and improving patient survival and neurological outcome. By similar rationale, cisternal irrigation has been proposed as a potential method to accelerate haematoma clearance in SAH. We aimed to provide a comprehensive review and meta-analysis evaluating the effect of intraventricular and cisternal irrigation on clinical outcomes in patients with SAH and IVH.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed preparing this systematic review and study selection was performed by multiple investigators. We extracted ORs from the individual studies and aggregated these using a random effects model. The quality of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations assessment and ROBINS-I or RoB-2.

Results: 24 articles were included. In SAH, we found that cisternal irrigation with fibrinolytic agents was associated with reduced mortality (OR: 0.68, 95% CI 0.46 to 1.00), higher probability of favourable functional outcome (OR: 1.80, 95% CI 1.30 to 2.51), and reduced risks of DCI (OR: 0.28, 95% CI 0.18 to 0.42) and cerebral vasospasm (OR: 0.28, 95% CI 0.18 to 0.42), compared with conventional therapy. Cisternal irrigation with vasodilatory agents was associated with lower mortality (OR: 0.32, 95% CI 0.13 to 0.79) and reduced risk of cerebral vasospasm (OR: 0.37, 95% CI 0.17 to 0.79). The evidence for irrigation therapy of IVH was sparse and insufficient to show any significant effect.

Conclusion: In this study, we found that cisternal irrigation could improve the prognosis in patients with SAH compared with conventional therapy. There is no evidence to support cisternal irrigation treatment of IVH.

Background and purpose: The benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions.

Methods: In this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes.

Results: 122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2-5) and 4 (2-6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54).

Conclusions: Our study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.

Background: Racism contributes to higher comorbid risk factors and barriers to preventive measures for black Americans. Advancements in systems of care, tissue plasminogen activator (tPA) availability and endovascular thrombectomy (ET) have impacted practice and outcomes while outpacing contemporary investigation into acute ischaemic stroke (AIS) care disparities. We examined whether recent data suggest ongoing disparity in AIS interventions and outcomes, and if hospital characteristics affect disparities.

Methods: We examined 2016-2019 fee-for-service Medicare inpatient data. We ran unadjusted logistic regression models to calculate ORs and 95% CI for two interventions (tPA and ET) and four outcomes (inpatient mortality, 30-day mortality, discharge home and outpatient visit within 30 days), with the main predictor black versus white race, additionally adjusting for demographics, hospital characteristics, stroke severity and comorbidities.

Results: 805 181 AIS admissions were analysed (12.4% black, 87.6% white). Compared with white patients, black patients had reduced odds of receiving tPA (OR 0.71, 95% CI 0.69 to 0.74, p<0.0001) and ET (0.69, 95% CI 0.65 to 0.72, p<0.0001). After tPA, black patients had reduced odds of 30-day mortality (0.77, 95% CI 0.72 to 0.82, p<0.0001), discharge home (0.72, 95% CI 0.68 to 0.77, p<0.0001) and outpatient visit within 30 days (0.89, 95% CI 0.84 to 0.95, p=0.0002). After ET, black patients had reduced odds of 30-day mortality (0.71, 95% CI 0.63 to 0.79, p<0.0001) and discharge home (0.75, 95% CI 0.64 to 0.88, p=0.0005). Adjusted models showed little difference in the magnitude, direction or significance of the main effects.

Conclusions: Black patients were less likely to receive AIS treatments, and if treated had lower likelihood of 30-day mortality, discharge home and outpatient visits. Despite advancements in practice and therapies, racial disparities remain in the modern era of AIS care and are consistent with inequalities previously identified over the last 20 years. The impact of hospital attributes on AIS care disparities warrants further investigation.

Background: Remnant cholesterol (RC) is considered to be one of the most significant and important risk factors for atherosclerotic cardiovascular disease (ASCVD). Nonetheless, the association between RC and unstable carotid plaque remains unclear. Our primary objective is to ascertain whether RC exhibits an independent and significant association with unstable carotid plaque in a neurologically healthy population.

Methods: In the cross-sectional study, we enrolled neurologically healthy participants who visited our centre for health checkups between 2021 and 2022. All eligible participants underwent a standardised questionnaire, physical examinations and laboratory testing. The carotid plaque was evaluated with a standard carotid ultrasound and an advanced ultrasound imaging technique called superb microvascular imaging. The correlation between lipids and unstable carotid plaque was primarily assessed utilising univariate and multivariate logistic regression.

Results: The study totally enrolled 1100 participants who had an average age of 57.00 years (IQR: 49.00-63.00), with 67.55% being men. Among the participants, 321 (29.18%) had unstable carotid plaque. In the multivariate logistic regression analysis, higher RC had an independent association with an elevated incidence of unstable carotid plaque compared with the lowest concentrations of RC (OR=1.673, 95% CI 1.113 to 2.515, p=0.0134), but not other lipids. In addition, apolipoprotein A1 was negatively related to unstable carotid plaque (OR=0.549, 95% CI 0.364 to 0.830, p=0.0045).

Conclusions: Elevated concentrations of RC are independently and excellently correlated with unstable carotid plaque within a neurologically healthy population.

Objective: This study aims to investigate the prevalence of familial cerebral cavernous malformations (FCCMs) in first-degree relatives (FDRs) using familial screening, to describe the distribution of initial symptoms, lesion count on cranial MRI and pathogenic gene in patients.

Methods: Patients with multiple CCMs who enrolled from the Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in China database were considered as probands and FDRs were recruited. Cranial MRI was performed to screen the CCMs lesions, and whole-exome sequencing was performed to identify CCM mutations. MRI and genetic screening were combined to diagnose FCCM in FDRs, and the results were presented as prevalence and 95% CIs. The Kaplan-Meier (KM) method was used to calculate the cumulative incidence of FCCM.

Results: 33 (76.74%) of the 43 families (110 FDRs) were identified as FCCM (85 FDRs). Receiver operating characteristic analysis revealed three lesions on T2-weighted imaging (T2WI) were the strong indicator for distinguishing probands with FCCM (sensitivity, 87.10%; specificity, 87.50%). Of the 85 FDRs, 31 were diagnosed with FCCM, resulting in a prevalence of 36.5% (26.2%-46.7%). In families with FCCMs, the mutation rates for CCM1, CCM2 and CCM3 were 45.45%, 21.21% and 9.09%, respectively. Furthermore, 53.13% of patients were asymptomatic, 17.19% were intracranial haemorrhage and 9.38% were epilepsy. The mean age of symptom onset analysed by KM was 46.67 (40.56-52.78) years.

Conclusion: Based on MRI and genetic analysis, the prevalence of CCMs in the FDRs of families with FCCMs in China was 36.5%. Genetic counselling and MRI screening are recommended for FDRs in patients with more than three CCM lesions on T2WI.