Subcortical infarcts on admission CTP predict poor outcome despite excellent reperfusion in delayed time windows.

PURPOSE: The effect of pretreatment infarct location on clinical outcome after successful mechanical thrombectomy is not understood. Our aim was to evaluate the association between computed tomography perfusion (CTP)-based ischemic core location and clinical outcome following excellent reperfusion in late time windows. METHODS: We retrospectively reviewed patients who underwent thrombectomy for acute anterior circulation large vessel occlusion in late time windows from October 2019 to June 2021 and enrolled 65 patients with visible ischemic core on admission CTP who had received excellent reperfusion (modified thrombolysis in cerebral infarction grade 2c/3). Poor outcome was defined as a modified Rankin scale score of 3-6 at 90 days. The ischemic core infarct territories were classified into the cortical and subcortical areas. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used in this study. RESULTS: Of the 65 patients analyzed, 38 (58.5%) had a poor outcome. Multivariable logistic analysis showed that the subcortical infarcts (OR 11.75; 95% CI 1.79-77.32; P = 0.010) and their volume (OR 1.17; 95% CI 1.04-1.32; P = 0.011) were independently associated with poor outcome. The ROC curve indicated the capacity of the subcortical infarct involvement (areas under the curve (AUC) = 0.65; 95% CI, 0.53-0.77, P < 0.001) and subcortical infarct volume (AUC = 0.72; 95% CI, 0.60-0.83, P < 0.001) in predicting poor outcome accurately. CONCLUSION: Subcortical infarcts and their volume on admission CTP are associated with poor outcome after excellent reperfusion in late time windows, rather than cortical infarcts.

Alberta Stroke Program Early CT Score and collateral status predict target mismatch in large vessel occlusion with delayed time windows.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) and collateral score (CS) are two readily available imaging metrics for the evaluation of acute ischemic stroke (AIS) with large vessel occlusion (LVO). OBJECTIVE: To investigate the predictive value of the ASPECTS combined with CS in detecting patients with CT perfusion (CTP) target mismatch in delayed time windows. METHODS: One hundred and sixty-four patients with LVO-AIS were included. ASPECTS was assessed on non-contrast CT (NCCT). CS was evaluated on single-phase CT angiography (sCTA). Target mismatch was defined as a CTP core volume ≤70 mL, mismatch ratio ≥1.8, and absolute mismatch volume ≥15 mL. Spearman correlation analysis and receiver operating characteristic curve analyses were performed. RESULTS: The median NCCT ASPECTS of the 164 patients was 8 (IQR 6-9), median sCTA-CS was 2 (IQR 1-2), and median CTP core volume was 8 mL (IQR 0-29.5). There was a strong correlation between NCCT ASPECTS and CTP core volume (rs=-0.756, p<0.0001) and a moderate correlation between the sCTA-CS and CTP core volume (rs=-0.450, p<0.0001). Integrating NCCT ASPECTS and sCTA-CS provided a higher area under the curve (AUC) for predicting target mismatch (AUC=0.882; sensitivity, 89.1%; specificity, 77.8%; p<0.001). CONCLUSIONS: NCCT ASPECTS had a strong correlation with CTP core volumes in patients with LVO-AIS in delayed time windows. Combining NCCT ASPECTS with sCTA-CS resulted in a more accurate prediction of target mismatch. If a CTP scan is not available, NCCT ASPECTS combined with sCTA-CS may guide clinicians in making treatment decisions.

Balloon Angioplasty Combined with Tirofiban as a First-Line Rescue Treatment After Failed Mechanical Thrombectomy for Middle Cerebral Artery Occlusion with Underlying Atherosclerosis.

OBJECTIVE: The standard rescue modality for patients with intracranial atherosclerotic stenosis after failed mechanical thrombectomy (MT) is not well established. We evaluated the safety and efficacy of balloon dilation in combination with tirofiban as the first-line salvage therapy when MT failed in these patients. METHODS: We retrospectively analyzed the records of 47 patients admitted between January 2018 and June 2021, with middle cerebral artery atherosclerotic occlusion, who underwent balloon angioplasty in combination with tirofiban as the first-line salvage therapy after the failure of MT. The recanalization outcome, procedure-related complications, symptomatic intracranial hemorrhage, and functional outcome at 90 days were reviewed. RESULTS: Recanalization with a modified Thrombolysis in Cerebral Infarction grade of 2b-3 was achieved in 41 (87.2%) of the 47 patients. Acute stents were deployed in another 6 patients who did not achieve successful re-perfusion after balloon angioplasty. Successful recanalization was achieved in 3 of them. One patient (2.1%, 1/47) experienced re-occlusion several days later due to the withdrawal of antiplatelet therapy for parenchymal hematoma. Seven patients (14.9%, 7/47) underwent stent angioplasty in the stable stage (range: 1-2 months) because severe residual stenosis was detected on follow-up imaging. There was only one event of periprocedural complication, namely ectopic migration of emboli. The good functional outcome rate was 55.3% (26/47), without the events of symptomatic intracranial hemorrhage and mortality. CONCLUSIONS: Balloon angioplasty in combination with tirofiban is safe and effective for middle cerebral artery atherosclerotic occlusion after the failure of MT.

Effect of a novel proteoglycan PTP1B inhibitor from Ganoderma lucidum on the amelioration of hyperglycaemia and dyslipidaemia in db/db mice.

Protein tyrosine phosphatase 1B (PTP1B) is implicated in the negative regulation of the insulin signalling pathway by dephosphorylating the insulin receptor (IR) and IR substrates. Ganoderma lucidum has traditionally been used for the treatment of diabetes in Chinese medicine; however, its anti-diabetic potency and mechanism in vivo is still unclear. Our previously published study reported a novel proteoglycan PTP1B inhibitor, named Fudan-Yueyang-Ganoderma lucidum (FYGL) from G. lucidum, with a half-maximal inhibitory concentration (IC50) value of 5·12 (sem 0·05) µg/ml, a protein:polyglycan ratio of 17:77 and 78 % glucose in polysaccharide, and dominant amino acid residues of aspartic acid, glycine, glutamic acid, alanine, serine and threonine in protein. FYGL is capable of decreasing plasma glucose in streptozotocin-induced diabetic mice with a high safety of median lethal dose (LD50) of 6 g/kg. In the present study, C57BL/6 db/db diabetic mice were trialed further using FYGL as well as metformin for comparison. Oral treatment with FYGL in db/db diabetic mice for 4 weeks significantly (P < 0·01 or 0·05) decreased the fasting plasma glucose level, serum insulin concentration and the homeostasis model assessment of insulin resistance. FYGL also controlled the biochemistry indices relative to type 2 diabetes-accompanied lipidaemic disorders. Pharmacology research suggests that FYGL decreases the plasma glucose level by the mechanism of inhibiting PTP1B expression and activity, consequently, regulating the tyrosine phosphorylation level of the IR ß-subunit and the level of hepatic glycogen, thus resulting in the improvement of insulin sensitivity. Therefore, FYGL is promising as an insulin sensitiser for the therapy of type 2 diabetes and accompanied dyslipidaemia.

A protein tyrosine phosphatase 1B activity inhibitor from the fruiting bodies of Ganoderma lucidum (Fr.) Karst and its hypoglycemic potency on streptozotocin-induced type 2 diabetic mice.

Inhibition of protein tyrosine phosphatase 1B (PTP1B) activity has been considered to be a promising therapy approach to treat type 2 diabetes. In this work, a novel PTP1B activity inhibitor, named FYGL (Fudan-Yueyang-G. lucidum), was screened from the fruiting bodies of Ganoderma lucidum and showed an efficient PTP1B inhibitory potency with IC50 = 5.12 ± 0.05 µg/mL. FYGL is a water-soluble macromolecular proteoglycan with a protein to polysaccharide ratio of 17:77 and a viscosity-average molecular weight (M(η)) of 2.6 × 105. The type 2 diabetic mice treated orally by FYGL showed an obvious decrease in plasma glucose level compared with the diabetic controls without drug treatment, comparable with that of diabetic mice treated with metformin, a clinical drug. The toxicity of FYGL is very low. The results indicate that FYGL may serve as a drug candidate or a health-care food for diabetic therapy or protection.