ABSTRACT
Objective To establish a quantitative and visual prediction model for spontaneous hemorrhagic transformation(sHT)after acute ischemic stroke(AIS)and validate the efficacy by nomogram.Methods A total of 240 patients with AIS were selected,and the general data,serological tests and imaging findings were collected.The patients were randomly divided into modeling group(175 cases)and validation group(65 cases).The patients were also divided into non-HT group and HT group according to the imaging results.The R 4.1.1 software and the rms package were used to build the column line graph model,while Bootstrap method was applied to repeat sampling 1000 times for internal and external validation,and the H-L goodness-of-fit test,clinical decision curve and ROC curve were used to assess the calibration and discrimination of the column line graph model,respectively.Results Among 240 patients with AIS,bleeding conversion occurred in 60 cases(25.0%).In the modeling group,the results of multifactorial Logistic regression showed that the presence or absence of previous history of atrial fibrillation,NIHSS score at the onset,Hb,high-density lipoprotein(HDL)and infarct area were significant influencing factors for sHT after AIS.The x2 values of the H-L goodness-of-fit test for the modeling and validation groups were 5.61 and 0.74,respectively,corresponding to P values of 0.13 and 0.69,indicating that the established column line graph model had good prediction accuracy;the area under the ROC curve for the column line graph prediction modeling group and validation group were 0.963(95%CI:0.926-1.000)and 0.977(95%CI:0.950-1.000),and the results suggested that the model had good discrimination.Conclusions Previous history of atrial fibrillation,NIHSS score size at onset,Hb,HDL and the size of infarct area are independent influencing factors of sHT after AIS.Establishing the visual nomogram model based on the above factors can effectively predict the risk of sHT after AIS.
ABSTRACT
OBJECTIVE Tissue plasminogen activator (tPA) is the only approved pharmaco-logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans-formation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation. METHODS Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion, tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg-1).Mice were killed at 24 h post ischaemia, and their brains were evaluated for brain infarction, oedema, haemoglobin content, apoptosis, neuroinflammation, blood-brain barrier (BBB) permeability, the expression of tight junction proteins(TJPs)and the activity/expression of MMPs. RESULTS In the mice infused with tPA at 5 h post ischaemia, there were significant increases in mortality, brain infarction, brain oedema, brain haemoglobin level, neural apoptosis, Iba-1 staining (microglia activation) and myeloperoxidase staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented by NMN administration. Mechanistically, the delayed tPA treatment increased BBB permeability by down-regulating TJPs, including claudin-1, occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes. CONCLUSION Our results demonstrate that NMN ameliorates tPA-induced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.
ABSTRACT
BACKGROUND AND PURPOSE: To evaluate the frequency and outcome of haemorrhagic transformation (HT) after ischaemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). METHODS: Patients with stroke on treatment with a NOAC were prospectively enrolled in this multicentre observational study between February 2012 and 2015. Brain imaging at admission and follow-up imaging until day 7 were reviewed for HT. Functional outcome was assessed by the modified Rankin scale (mRS) before the index event, at discharge, and at 3-months. RESULTS: 231 patients without recanalisation therapy (no-RT), and 32 patients with RT were eligible for analysis. Any HT was present at admission in 9/231 no-RT patients (3.9%, 95% CI 2.0 to 7.3) and in none of the patients with RT. In patients with follow-up imaging (no-RT, n=129, and RT, n=32), HT was present in 14.0% (no-RT; 95% CI, 8.9 to 21.1), and 40.6% (RT, 95% CI, 25.5 to 57.8), respectively. After adjustment for stroke severity, this difference between the no-RT and RT groups became non-significant. Symptomatic ICH was observed in 1 patient per group. HT was not associated with unfavourable outcome (mRS 3-6) at 3-months in multivariable analysis. Resumption of OAC after stroke was delayed in patients with HT compared to those without (15 d [IQR, 5–26] vs. 1 d [0–4], P<0.001). CONCLUSIONS: The frequency and severity of HT after stroke on NOAC appears similar to previous reports for vitamin K antagonists and no anticoagulation. Whether asymptomatic HT should delay resumption of preventive anticoagulation requires further investigation.