Journal of Investigative Medicine最新文献

Background: The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.

Objective: We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage.

Methods: In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining.

Results: The puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5-6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration.

Conclusions: Selective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days.

Background: Intraoperative antiplatelet therapy is recommended for emergent stenting during mechanical thrombectomy (MT). Most patients undergoing MT are also given thrombolysis. Antiplatelet agents are contraindicated within 24 hours of thrombolysis. We evaluated outcomes and complications of patients stented with and without intravenous aspirin during MT.

Methods: All patients who underwent emergent extracranial stenting during MT at the Royal Stoke University Hospital, UK between 2010 and 2020, were included. Patients were thrombolysed before MT, unless contraindicated. Aspirin 500 mg intravenously was given intraoperatively at the discretion of the operator. Symptomatic intracranial haemorrhage (sICH) and the National Institutes for Health Stroke Scale score (NIHSS) were recorded at 7 days, and mortality and functional recovery (modified Rankin Scale: mRS ≤2) at 90 days.

Results: Out of 565 patients treated by MT 102 patients (median age 67 IQR 57-72 years, baseline median NIHSS 18 IQR 13-23, 76 (75%) thrombolysed) had a stent placed. Of these 49 (48%) were given aspirin and 53 (52%) were not. Patients treated with aspirin had greater NIHSS improvement (median 8 IQR 1-16 vs median 3 IQR -9-8 points, p=0.003), but there were no significant differences in sICH (2/49 (4%) vs 9/53 (17%)), mRS ≤2 (25/49 (51%) vs 19/53 (36%)) and mortality (10/49 (20%) vs 12/53 (23%)) with and without aspirin. NIHSS improvement (median 12 IQR 4-18 vs median 7 IQR -7-10, p=0.01) was greater, and mortality was lower (4/33 (12%) vs 6/15 (40%), p=0.05) when aspirin was combined with thrombolysis, than for aspirin alone, with no increase in bleeding.

Conclusion: Our findings based on registry data derived from routine clinical care suggest that intraprocedural intravenous aspirin in patients undergoing emergent stenting during MT does not increase sICH and is associated with good clinical outcomes, even when combined with intravenous thrombolysis.

Stroke is a common neurological condition and among the leading causes of death and disability worldwide. Depression is both a risk factor for and complication of stroke, and the two conditions may have a complex reciprocal relationship over time. However, the secondary effects of depression on stroke are often overlooked, resulting in increased morbidity and mortality. In the previous concept of 'poststroke depression', stroke and depression were considered as two independent diseases. It often delays the diagnosis and treatment of patients. The concept 'stroke depression' proposed in this article will emphasise more the necessity of aggressive treatment of depression in the overall management of stroke, thus to reduce the incidence of stroke and in the meantime, improve the prognosis of stroke. Hopefully, it will lead us into a new era of acute stroke intervention.

Background: Hypertension is widely acknowledged as a significant contributory factor to the heightened risk of intracranial aneurysm rupture. Nevertheless, the impact of hypertension management on the outcomes subsequent to aneurysmal subarachnoid haemorrhage (aSAH), particularly concerning the severity of aSAH, remains an underexplored area.

Methods: We conducted a retrospective analysis using data from a prospectively multicentre cohort of 4545 patients with aSAH in China. Premorbid hypertension status and the utilisation of antihypertensive medications prior to admission were set as key exposure factors. The primary outcomes encompassed unfavourable clinical grading scales observed on admission. Employing multivariable logistic regression, we explored the association between premorbid hypertension status, preadmission use of renin-angiotensin-aldosterone system (RAAS) inhibitors and unfavourable clinical grading scales.

Results: In comparison to patients with normal blood pressure, only uncontrolled hypertension demonstrated a significant and independent association with an elevated risk of poor outcomes on the Hunt-Hess scale (OR=1.799, 95% CI 1.413 to 2.291, p<0.001) and the World Federation of Neurological Surgeons (WFNS) scale (OR=1.721, 95% CI 1.425 to 2.079, p<0.001). Furthermore, the antecedent use of RAAS inhibitors before admission was markedly and independently linked to a diminished risk of adverse outcomes on the Hunt-Hess scale (OR=0.653, 95% CI 0.430 to 0.992, p=0.046) and the WFNS scale (OR=0.656, 95% CI 0.469 to 0.918, p=0.014).

Conclusions: Uncontrolled hypertension markedly elevates the risk of adverse clinical outcomes following an aSAH. Conversely, the preadmission utilisation of RAAS inhibitors demonstrates a noteworthy association with a favourable clinical outcome after aSAH.

Background: The incidence of vascular cognitive impairment (VCI) is high in patients suffering from ischaemic stroke or transient ischaemic attack (TIA) or with vascular risk factors. Effective prevention strategies for VCI remain limited. Anaemia or low haemoglobin was found as an independent risk factor for adverse outcomes after acute stroke. Anaemia or low haemoglobin was possibly associated with an increased risk of poststroke cognitive impairment. Whether supplement of ferrous iron to correct anaemia reduces the risk of VCI and improves adverse outcomes in patients with ischaemic cerebrovascular disease remains uncertain.

Aim: We aim to introduce the design and rationale of the safety and efficacy of Ferrous iron on the prevention of Vascular cOgnitive impaiRment in patients with cerebral Infarction or TIA (FAVORITE) trial.

Design: FAVORITE is a randomised, placebo-controlled, double-blind, multicentre trial that compares supplement of ferrous iron with placebo for recent minor stroke/TIA patients complicated with mild anaemia or iron deficiency: Ferrous succinate sustained-release tablet 0.2 g (corresponding to 70 mg of elemental iron) once daily after or during breakfast for 12 weeks or placebo with much the same colour, smell and size as ferrous iron once daily during or after breakfast for 12 weeks. All paticipants will be followed within the next year.

Study outcomes: The primary effective outcome is the incidence of VCI at 3 months after randomisation and the primary safety outcome includes any gastrointestinal adverse event during 3 months.

Discussion: The FAVORITE trial will clarify whether supplement of ferrous iron to correct low haemoglobin reduces the risk of VCI in patients with recent ischaemic stroke or TIA complicated with mild anaemia or iron deficiency compared with placebo.

Trial registration number: NCT03891277.

Background: Statins are essential for secondary prevention after ischaemic stroke (IS). However, statin intensity recommendations differ, and there is a concern about intracerebral haemorrhage (ICH). We studied the long-term impacts of initial statin intensity following IS.

Methods: Consecutive patients using high-intensity, moderate-intensity or low-intensity statin early after IS (n=45 512) were retrospectively studied using national registries in Finland. Differences were adjusted using multivariable regression. The primary outcome was all-cause death within 12-year follow-up (median 5.9 years). Secondary outcomes were recurrent IS, cardiovascular death and ICH studied using competing risk analyses.

Results: High-intensity therapy was initially used by 16.0%, moderate-intensity by 73.8% and low-intensity by 10.2%. Risk of death was lower with high-intensity versus moderate-intensity (adjusted HR (adj.HR) 0.92; 95% CI 0.87 to 0.97; number needed to treat (NNT) 32.0), with moderate-intensity versus low-intensity (adj.HR 0.91; 95% CI 0.87 to 0.95; NNT 27.5) and with high-intensity versus low-intensity (adj.HR 0.83; 95% CI 0.78 to 0.89; NNT 14.6) statin. There was a dose-dependent association of initial statin intensity with a lower probability of recurrent IS (p<0.0001) and cardiovascular death (p<0.0001). The occurrence of ICH was not associated with initial statin intensity (p=0.646).

Conclusions: Following IS, more intense initial statin treatment is associated with improved long-term outcomes but not with the risk of ICH. These findings emphasise the importance of high statin intensity shortly after IS.

Background: The occurrence of acute ischaemic stroke (AIS) while using oral anticoagulants (OAC) is an increasingly recognised problem among nonvalvular atrial fibrillation (NVAF) patients. We aimed to elucidate the potential role of left atrial appendage closure (LAAC) for stroke prevention in patients with AIS despite OAC use (AIS-despite-OAC).

Methods: We retrospectively collected baseline and follow-up data from consecutive NVAF patients who had AIS-despite-OAC and subsequently underwent endovascular LAAC, between January 2015 and October 2021. The primary outcome measure was the occurrence of AIS after LAAC, and the safety outcome was symptomatic intracerebral haemorrhage (ICH).

Results: 29 patients had LAAC specifically because of AIS-despite-OAC. The mean age at the time of the procedure was 73.4±8.7, 13 were female (44.82%). The mean CHA₂DS₂-VASc score was 5.96±1.32, with an expected AIS risk of 8.44 per 100 patient-years. 14 patients (48%) had two or more past AIS-despite-OAC. After LAAC, 27 patients (93.10%) were discharged on OAC which was discontinued in 17 (58.62%) after transoesophageal echocardiogram at 6 weeks. Over a mean of 1.75±1.0 years follow-up after LAAC, one patient had an AIS (incidence rate (IR) 1.97 per 100 patient-years). One patient with severe cerebral microangiopathy had a small ICH while on direct OAC and antiplatelet 647 days after LAAC.

Conclusions: LAAC in AIS-despite-OAC patients demonstrated a low annual AIS recurrence rate in our cohort (1.97%) compared with the expected IR based on their CHA₂DS₂-VASc scores (8.44%) and to recent large series of AIS-despite-OAC patients treated with OAC/aspirin only (5.3%-8.9%). These hypothesis-generating findings support randomised trials of LAAC in AIS-despite-OAC patients.

Background: The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke (AIS) is uncertain. We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged ≥80 years.

Methods: We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial, a randomised, phase 3, non-inferiority clinical trial. Disabling AIS patients aged ≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale (mRS) score of 0-1 at 90 days. Symptomatic intracranial haemorrhage (sICH) within 36 hours was the safety outcome.

Results: Of 137 participants, mRS 0-1 at 90 days occurred in 37 (49.3%) of 75 in the tenecteplase group vs 20 (33.9%) of 59 in the alteplase group (risk ratio (RR) 1.47, 95% CI 0.96 to 2.23). sICH within 36 hours was observed in 3 (4.0%) of 76 in the tenecteplase group and two (3.3%) of 61 in the alteplase group (RR 1.30, 95% CI 0.20 to 8.41).

Conclusions: The risk-benefit profile of tenecteplase thrombolysis was preserved in the elderly patients, which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.

Background: Compared with dural arteriovenous fistulas (DAVFs) in adult, paediatric DAVFs are notable for distinct clinical manifestations, low cure rate and poor prognosis. However, due to the limitations of small sample sizes, the long-term prognosis and follow-up data have not been described.

Methods: Clinical data from 43 consecutive paediatric DAVFs were documented and analysed between 2002 and 2022 at the author's institution. They were divided into infantile (Lasjaunias classification) and non-infantile (adult type and dural sinus malformation (DSM)) type DAVFs based on prognosis differences.

Results: Their mean age at first symptoms was 8.4±6.0 years. 29 boys and 14 girls presented between at birth and 18 years of age. 5 of 10 patients ≤1 year of age presented with asymptomatic cardiomegaly compared with 5/33 patients >1 year of age (p=0.022). 42 (88.4%) patients received endovascular treatment alone, while 9.3% underwent radiosurgery, burr hole embolisation or surgery. 28 (65.1%) patients experienced DAVF obliteration by the end of treatment. Among them, 26 cases underwent embolisation alone, one case had embolisation in conjunction with surgery, and one case underwent burr hole embolisation. The overall complication rate among patients was 9.3%, all resulting from endovascular treatment. According to the Lasjaunias Classification, there were 18 cases of adult type, 17 cases of infantile type and 8 cases of DSM. Compared with non-infantile-type DAVFs, infantile-type DAVFs showed more times of treatment, lower cure rate and worse prognosis (p<0.001, 0.003 and 0.021, respectively). The average follow-up duration was 41.4±36.2 months (3-228 months). 8 (22.9%) patients died.

Conclusions: Most adult-type DAVFs and DSMs can now be effectively treated with embolisation, resulting in good outcomes and prognosis. However, there are still challenges in treating infantile-type DAVFs, and the prognosis is frequently poor.