How Clot Composition Influences Fibrinolysis in the Acute Phase of Stroke: A Proteomic Study of Cerebral Thrombi.

BACKGROUND: The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA). METHODS: In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FAout) by measuring D-dimer levels at the blood-thrombus interface and inside (FAin) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FAin, and FAout were determined by intravenous thrombolysis-adjusted linear regression. RESULTS: FAout (P<0.0001) and FAin (P=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FAout was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FAout was increased with cardioembolic thrombi (72/104), which are rich in fibrin (P=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (P=0.0139), and hemoglobin level (P=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FAout (P=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FAout was significantly associated with reduced thrombus weight (P=0.0310), increased recanalization rate (P=0.0150), good clinical outcome (P=0.0480), and reduced mortality (P=0.0080). CONCLUSIONS: Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.

Clinical, imaging, and management features of symptomatic carotid web: Insight from CAROWEB registry.

BACKGROUND: Although carotid web (CaW) is increasingly diagnosed as a cause of cryptogenic stroke, data are still limited to monocentric small sample cohort. To broaden knowledge on symptomatic CaW, CAROWEB registry has been recently implemented. AIMS: In a large cohort of symptomatic CaW patients, we described epidemiologic characteristics, admission clinical and imaging features, and the current management including the secondary preventive strategy choice made in comprehensive French Stroke Units. METHODS: CAROWEB is an ongoing French observational multicenter registry enrolling consecutive CaW patients diagnosed after an ipsilateral ischemic stroke (IS) or transient ischemic attack (TIA). Submitted cases were validated by two experienced neurologist and neuroradiologist. Clinical, imaging, and management features were collected for this study. RESULTS: Between June 2019 and December 2021, 244 cases were submitted by 14 centers, 42 rejected, and 202 included (IS, 91.6%; TIA, 7.9%; retinal infarction, 0.5%; mean age, 50.8 ± 12.2 years; female, 62.9%; Caucasian, 47.5%; Afro-Caribbean, 20.3%). IS patients showed median (interquartile range (IQR)) admission National Institutes of Health Stroke Scale (NIHSS) score, 8 (2-15); intracranial artery occlusion, 71.8%; ipsilateral chronic cerebral infarction (CCI), 16.3%; and reperfusion treatment, 57.3%. CaW was not identified during the mechanical thrombectomy procedure in 30 of 85 (35.3%) patients. Secondary prevention was invasive in 55.6% (stenting, n = 80; surgery, n = 30). In multivariable analysis, the invasive therapeutic option was associated with ipsilateral CCI (odds ratio (OR): 4.24 (1.27-14.2), p = 0.019) and inversely associated with risk factors (OR: 0.47 (0.24-0.91), p = 0.025) and admission NIHSS score (OR: 0.93 (0.89-0.97), p = 0.001). CONCLUSION: CaW must be considered in all ethnic groups including Caucasians. Secondary prevention is heterogeneous in large French Stroke Centers. The absence of risk factors, milder severity strokes, and ipsilateral CCI were predictive variables of secondary invasive treatment. The high rate of invasive treatment suggests that medical treatment alone is deemed ineffective to avoid recurrence and emphasize the need of randomized trials.

Distal cerebral vasospasm treatment following aneurysmal subarachnoid hemorrhage using the Comaneci device: technical feasibility and single-center preliminary results.

BACKGROUND: Balloon-assisted mechanical angioplasty for cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) has a number of limitations, including transient occlusion of the spastic blood vessel. Comaneci is an FDA-approved device for temporary coil embolization assistance which has recently also been approved for the treatment of distal symptomatic refractory vasospasm. We aimed to report the feasibility, efficacy and safety of our experience with Comaneci angioplasty for refractory distal vasospasm (up to the second segment of the cerebral arteries) following aSAH. METHODS: This is a retrospective analysis of a prospective series of 18 patients included between April 2019 and June 2021 with aSAH and symptomatic vasospasm refractory to medical therapy, who were treated using Comaneci-17-asssisted mechanical distal angioplasty. Immediate angiographic results, procedure-related complications, and clinical outcomes were assessed. Inter-rater reliability of the scores was determined using the intraclass correlation coefficient. RESULTS: Comaneci-assisted distal angioplasty was performed in 18 patients, corresponding to 31 target arteries. All distal anterior segments were easily accessible with the Comaneci-17 device. Vasospasm improvement after Comaneci mechanical angioplasty was seen in 22 distal arteries (71%) (weighted Cohen's kappa (κw) 0.73, 95% CI 0.69 to 0.93). Vasospasm recurrence occurred in three patients (16.67%) and delayed cerebral infarction in three patients (16.67%), with a mean±SD delay between onset of symptoms and imaging follow-up (MRI/CT) of 32.61±8.93 days (κw 0.98, 95% CI 0.88 to 1). CONCLUSION: This initial experience suggests that distal mechanical angioplasty performed with the Comaneci-17 device for refractory vasospasm following aSAH seems to be safe, with good feasibility and efficacy.

Optimizing the treatment of liver metastases from uveal melanomas with transarterial chemoembolization using melphalan and calibrated microspheres.

INTRODUCTION: Patients with liver metastasis from uveal melanoma have a poor prognosis. Efficacy and safety of hepatic transarterial chemoembolization (TACE) using melphalan and microspheres was evaluated. MATERIALS AND METHODS: Monocentric retrospective study of all consecutive patients treated by TACE using melphalan and 250µm calibrated microspheres between 2004 and 2016. Radiological response was assessed according to RECIST 1.1, modified (m)-RECIST and EASL on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The primary endpoint was overall survival (OS). Liver metastasis response, hepatic, extrahepatic and global progression free survival (PFS) complications were evaluated with the common terminology criteria for adverse events version 4.0 (CTCAE 4.0) and survival factors were secondary endpoints. RESULTS: Thirty-four patients underwent 138 TACE (4; 4.1 sessions; range 1-9). Median OS was 16.5 months (mean 21.6 months). Liver metastasis response combining partial and complete response was 42.4%, 97%, 97% with RECIST 1.1, mRECIST, EASL, respectively. There were 58 severe (CTCAE≥3) but manageable complications in 28 patients, except for 1 toxic death. CONCLUSION: For patients with liver metastases from uveal melanoma ineligible for local treatments, TACE using melphalan may be performed as first line therapy in metastatic miliary disease from uveal melanomas with careful supportive care.