To evaluate the incidence, baseline characteristics, and clinical prognosis of blood-brain barrier (BBB) disruption after endovascular therapy in acute ischemic stroke patients.
A total of 220 ...patients treated with endovascular therapy between April 2007 and October 2011 were identified from a prospective, clinical, thrombolysis registry. All patients underwent a nonenhanced CT scan immediately after treatment. CT scan or MRI was systematically realized at 24 hours to assess intracranial hemorrhage complications. BBB disruption was defined as a hyperdense lesion on the posttreatment CT scan.
BBB disruption was found in 128 patients (58.2%; 95% confidence interval CI, 51.4%-64.9%). Cardioembolic etiology, high admission NIH Stroke Scale score, high blood glucose level, internal carotid artery occlusion, and use of combined endovascular therapy (chemical and mechanical revascularization) were independently associated with BBB disruption. Patients with BBB disruption had lower rates of early major neurologic improvement (8.6% vs 31.5%, p < 0.001), favorable outcome (39.8% vs 61.8%, p = 0.002), and higher rates of 90-day mortality (34.4% vs 14.6%, p = 0.001) and hemorrhagic complications (42.2% vs 8.7%, p < 0.001) than those without BBB disruption. By multivariable analysis, patients with BBB disruption remained with a lower rate of early neurologic improvement (adjusted odds ratio OR, 0.28; 95% CI, 0.11-0.70) and with a higher rate of mortality (adjusted OR, 2.37; 95% CI, 1.06-5.32) and hemorrhagic complications (adjusted OR, 6.38; 95% CI, 2.66-15.28).
BBB disruption has a detrimental effect on outcome and is independently associated with mortality after endovascular therapy. BBB disruption assessment may have a role in prognosis staging in these patients.
MR imaging quantitative T2* mapping, which provides information about thrombus composition and specifically the red blood cell content, may be obtained in the setting of acute ischemic stroke before ...treatment. This could be useful to adapt the endovascular strategy. We aimed to analyze the red blood cell content of in vitro thrombi in relation to the thrombus-T2* relaxation time.
Thirty-five thrombus analogs of different compositions were scanned with an MR imaging quantitative T2* mapping sequence. Two radiologists, blinded to thrombus composition, measured the thrombus-T2* relaxation time twice at an interval of 2 weeks. Quantitative histologic evaluations of red blood cell content were performed. Inter- and intraobserver reproducibility of the thrombus-T2* relaxation time was assessed by calculating intraclass correlation coefficients. Finally, a Spearman product moment correlation between the thrombus-T2* relaxation time and red blood cell content was performed.
The median thrombus-T2* relaxation time was 78.5 ms (range, 16-268 ms; interquartile range, 60.5 ms). The median red blood cell content was 55% (range, 0%-100%; interquartile range, 75%). Inter- and intraobserver reproducibility of the thrombus-T2* relaxation time was excellent (>0.9). The Spearman rank correlation test found a significant inverse correlation between thrombus-T2* relaxation time and red blood cell content (ρ = -0.834,
< .001).
MR imaging quantitative T2* mapping can reliably identify the thrombus red blood cell content in vitro. This fast, easy-to-use sequence could be implemented in routine practice to predict stroke etiology and adapt devices or techniques for endovascular treatment of acute ischemic stroke.
Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We ...hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-αGal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-αGal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack αGal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in αGal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability.
The susceptibility vessel sign on MR imaging has been reported to indicate acute occlusion from erythrocyte-rich thrombus. The purpose of this study was to evaluate the influence of the ...susceptibility vessel sign seen on MR imaging before treatment on the clinical outcome after mechanical thrombectomy for anterior circulation acute stroke.
We retrospectively included 73 consecutive patients who were treated for anterior circulation acute stroke by mechanical thrombectomy from December 2009 to September 2013. Each patient underwent MR imaging before mechanical thrombectomy. The presence (susceptibility vessel sign+) or absence of the susceptibility vessel sign (susceptibility vessel sign-) was recorded. Mechanical thrombectomy was performed either alone or in association with IV tPA according to the site and time after occlusion. Good functional outcome was defined by an mRS ≤ 2 at 3 months in susceptibility vessel sign+ and susceptibility vessel sign- groups. Patient clinical characteristics, initial NIHSS score and ASPECTS, site of occlusion, time between onset to groin puncture, TICI after mechanical thrombectomy, NIHSS score at day 1, and spontaneous hyperattenuation on CT at day 1 were also analyzed.
Fifty-three patients with susceptibility vessel sign+ and 20 with susceptibility vessel sign- were included in our study. mRS ≤ 2 at 3 months occurred in 65% patients in the susceptibility vessel sign+ group and 26% in the susceptibility vessel sign- group (P = .004). On multivariate analysis, the susceptibility vessel sign was the only parameter before treatment that could predict mRS ≤ 2 at 3 months (OR, 8.7; 95% CI, 1.1-69.4; P = .04).
Our study strongly suggests that the susceptibility vessel sign on MR imaging before treatment is predictive of favorable clinical outcome for patients presenting with anterior circulation acute stroke and treated with mechanical thrombectomy.
Abstract Background In anterior acute ischemic stroke (AAIS) treated with endovascular treatment (EVT), the susceptibility vessel sign (SVS+ or SVS−) is related to recanalization results (TICI 2b/3) ...and clinical outcome. However, a binary qualitative assessment of thrombus using SVS does not reflect its complex composition. Our aim was to assess whether a quantitative MRI marker, Thrombus-T2* relaxation time, may be assessable in clinical routine and may to predict early successful recanalization after EVT, defined as a TICI 2b/3 recanalization obtained in 2 attempts or less. Material and methods Thrombus-T2* relaxation time was prospectively obtained from consecutive AAIS patients treated by EVT (concomitant aspiration and stent retriever). Quantitative values were compared between early recanalization and late or unsuccessful recanalization. Results Thirty patients with AAIS were included and Thrombus-T2* relaxation time was obtained in all patients. Earlier TICI 2b/3 recanalization were obtained in 22 patients (73%) and was significantly associated with SVS+ (1/8 vs. 16/22, P = 0.01) and a shorter Thombus-T2* relaxation time (mean SD, range: 257, 18–50 ms vs. 45 9, 35–60 ms, P < 0.001). Conclusion A new quantitative MRI biomarker, the Thrombus-T2* relaxation time is assessable in clinical routine. In a preliminary study of 30 patients, a shorter Thombus-T2* relaxation time is related to earlier recanalization after EVT using combination of stent retriever and aspiration.
Measurement of the degree of aortic valve calcification (AVC) using electron beam computed tomography (EBCT) is an accurate and complementary method to transthoracic echocardiography (TTE) for ...assessment of the severity of aortic stenosis (AS). Whether threshold values of AVC obtained with EBCT could be extrapolated to multislice computed tomography (MSCT) was unclear and AVC diagnostic value in patients with low ejection fraction (EF) has never been specifically evaluated.
Patients with mild to severe AS underwent prospectively within 1 week MSCT and TTE. Severe AS was defined as an aortic valve area (AVA) of less than 1 cm(2). In 179 patients with EF greater than 40% (validation set), the relationship between AVC and AVA was evaluated. The best threshold of AVC for the diagnosis of severe AS was then evaluated in a second subset (testing set) of 49 patients with low EF (≤40%). In this subgroup, AS severity was defined based on mean gradient, natural history or dobutamine stress echocardiography.
Correlation between AVC and AVA was good (r=-0.63, p<0.0001). A threshold of 1651 arbitrary units (AU) provided 82% sensitivity, 80% specificity, 88% negative-predictive value and 70% positive-predictive value. In the testing set (patients with low EF), this threshold correctly differentiated patients with severe AS from non-severe AS in all but three cases. These three patients had an AVC score close to the threshold (1206, 1436 and 1797 AU).
In this large series of patients with a wide range of AS, AVC was shown to be well correlated to AVA and may be a useful adjunct for the evaluation of AS severity especially in difficult cases such as patients with low EF.
To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin.
In this Phase 2b double-blind, ...placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA<lower limit of quantitation at Week 4 and undetectable at Week 10) were rerandomised at Week 12 to continue daclatasvir/peginterferon-alfa-2a/ribavirin for 24 weeks total duration or to placebo/peginterferon-alfa-2a/ribavirin for another 12 weeks. Patients without PDR and placebo patients continued peginterferon-alfa/ribavirin through Week 48. Primary efficacy endpoints were undetectable HCV-RNA at Weeks 4 and 12 (extended rapid virologic response, eRVR) and at 24 weeks post-treatment (sustained virologic response, SVR24) among genotype 1-infected patients.
Overall, eRVR was achieved by 54.4% (80/147) of genotype 1-infected patients receiving daclatasvir 20 mg, 54.1% (79/146) receiving 60 mg versus 13.9% (10/72) receiving placebo. SVR24 was achieved among 87 (59.2%), 87 (59.6%), and 27 (37.5%) patients in these groups, respectively. Higher proportions of genotype 4-infected patients receiving daclatasvir 20 mg (66.7%; 8/12) or 60 mg (100.0%; 12/12) achieved SVR24 versus placebo (50.0%; 3/6). A majority of daclatasvir-treated patients achieved PDR and experienced less virologic failure and higher SVR24 rates with a shortened 24-week treatment duration. Adverse events occurred with similar frequency across all treatment groups.
The combination of daclatasvir/peginterferon-alfa/ribavirin was generally well tolerated and achieved higher SVR24 rates compared with placebo/peginterferon-alfa/ribavirin among patients infected with HCV genotype 1 or 4.
NCT01125189.
Summary Purpose To evaluate the agreement and diagnostic accuracy of Contrast enhanced magnetic resonance angiography (CE-MRA), Doppler ultrasound (DUS) and Digital subtraction angiography (DSA) in ...the assessment of carotid stenosis. Methods DUS, CE-MRA and DSA were performed in 56 patients included in the Carotide-angiographie par résonance magnétique-échographie-doppler-angioscanner (CARMEDAS) multicenter study with a carotid stenosis ≥ 50%. Three readers evaluated stenoses on CE-MRA and DSA (NASCET criteria). Velocities criteria were used for stenosis estimation on DUS. Results CE-MRA had a sensitivity and specificity of 96–98% and 66–83% respectively for carotid stenoses ≥ 50% and a sensitivity and specificity of 94% and 76–84% respectively for carotid stenoses ≥ 70%. The interobserver agreement of CE-MRA was excellent, except for moderate stenoses (50–69%). DUS had a sensitivity and specificity of 88 and 75% respectively for carotid stenoses ≥ 50% and a sensitivity and specificity of 83 and 86% respectively for carotid stenoses ≥ 70%. Combined concordant CE-MRA and DUS had a sensitivity and specificity of 100 and 85–90% respectively for carotid stenoses ≥ 50% and a sensitivity and specificity of 96–100% and 80–87% respectively for carotid stenoses ≥ 70%. The positive predictive value of the association CE-MRA and DUS for carotid stenoses ≥ 70% is calculated between 77 and 82% while the negative predictive value is calculated between 97 and 100%. CE-MRA and DUS have concordant findings in 63–72%, and the overestimations cases were recorded only for carotid stenosis ≤ 69%. Conclusion Combined DUS–CE-MRA is excellent for evaluation of severe stenosis but remains debatable in moderate stenosis (50–69%) due to the risk of overestimations.
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