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  1. Article ; Online: R-tPA Resistance Is Specific for Platelet-Rich Stroke Thrombi and Can Be Overcome by Targeting Nonfibrin Components.

    Vandelanotte, Sarah / François, Olivier / Desender, Linda / Staessens, Senna / Vanhoorne, Alexander / Van Gool, Fréderick / Tersteeg, Claudia / Vanhoorelbeke, Karen / Vanacker, Peter / Andersson, Tommy / De Meyer, Simon F

    Stroke

    2024  Volume 55, Issue 5, Page(s) 1181–1190

    Abstract: Background: Resistance to r-tPA (recombinant tissue-type plasminogen activator) is a well-known but poorly understood phenomenon that hampers successful recanalization in patients with acute ischemic stroke. Using clinically relevant thrombi from ... ...

    Abstract Background: Resistance to r-tPA (recombinant tissue-type plasminogen activator) is a well-known but poorly understood phenomenon that hampers successful recanalization in patients with acute ischemic stroke. Using clinically relevant thrombi from patients with acute ischemic stroke, we investigated if and how thrombus composition impacts r-tPA-mediated lysis. In addition, we explored strategies to overcome r-tPA resistance.
    Methods: Thrombi were split into 2 parts, 1 of which was used for thrombolysis and the other for detailed histological analysis. Thrombolysis was performed in normal human plasma using r-tPA alone, using r-tPA in combination with DNase-1 or using r-tPA in combination with N,N'-diacetyl-l-cystine. Thrombus lysis was calculated as the percentage of residual thrombus weight compared with its initial weight and the degree of lysis was linked to thrombus composition determined via histology.
    Results: Interestingly, we found that the efficacy of r-tPA-mediated thrombolysis was strongly correlated with the composition of the thrombi. Thrombi containing high amounts of red blood cells and low amounts of DNA and von Willebrand Factor were efficiently degraded by r-tPA, whereas thrombi containing low amounts of red blood cells and higher amounts of DNA and von Willebrand Factor were resistant to r-tPA. Importantly, combination of r-tPA with DNase-1 or N,N'-diacetyl-l-cystine significantly and specifically improved the lysis of these r-tPA-resistant thrombi.
    Conclusions: Using patient thrombus material, our results for the first time show that the composition of stroke thrombi largely determines their susceptibility to r-tPA-mediated thrombolysis. Red blood cell-poor thrombi have a specific resistance to r-tPA, which can be overcome by targeting nonfibrin components using DNase-1 or N,N'-diacetyl-l-cystine.
    Language English
    Publishing date 2024-03-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.123.045880
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Long-term outcome results after endovascular aortoiliac aneurysm repair with the bifurcated EXCLUDER Endoprosthesis.

    Van Gool, Fréderick / Houthoofd, Sabrina / Mufty, Hozan / Bonne, Lawrence / Fourneau, Inge / Maleux, Geert

    Journal of vascular surgery

    2021  Volume 75, Issue 6, Page(s) 1882–1889.e2

    Abstract: Objective: To report the long-term outcome of patients presenting with an aortic, aortoiliac, or isolated common iliac aneurysm treated with the bifurcated EXCLUDER Endoprosthesis. Furthermore, potential differences in late outcome results between the ... ...

    Abstract Objective: To report the long-term outcome of patients presenting with an aortic, aortoiliac, or isolated common iliac aneurysm treated with the bifurcated EXCLUDER Endoprosthesis. Furthermore, potential differences in late outcome results between the original- and low-permeability endoprosthesis were analyzed.
    Methods: A retrospective analysis of prospectively collected data of 182 patients who underwent endovascular aneurysm repair with the EXCLUDER Endoprosthesis between June 1998 and October 2015 in an academic, tertiary care center for aortic disease was performed. Patient follow-up was from 3 to 20 years (mean follow-up of 6.9 years). Primary end points were overall survival and reintervention-free survival. Secondary end points were device-related complications, endoleaks, and reinterventions.
    Results: Overall survival at 5, 10, and 15 years was 72.8%, 42.1%, and 12.2%, respectively, with no aneurysm-related mortality and no difference in overall survival between the original- vs low-permeability endoprosthesis group (P = .617). Freedom from type I endoleak at 5 years was 94.8%. No new type I endoleak was detected beyond the 5-year follow-up mark. No type III endoleak was identified. Reintervention-free survival was 83.6%, 66.7%, and 66.7% at 5-, 10-, and 15-year follow-up, respectively. There was a significant difference in intervention-free survival between the original- vs low-permeability endoprosthesis group (P = .029) and after the 5-year follow-up mark. In addition, patients with the low-permeability endoprosthesis showed significantly fewer device-related complications (P = .002) and endoleaks (P = .005).
    Conclusions: Endovascular aneurysm repair using the EXCLUDER Endoprosthesis is effective and durable on long-term follow-up, with acceptably low device-related complications and reinterventions. The low-permeability endoprosthesis was associated with significantly fewer new device-related complications and endoleaks after 5 years of follow-up.
    MeSH term(s) Aortic Aneurysm, Abdominal/complications ; Aortic Aneurysm, Abdominal/diagnostic imaging ; Aortic Aneurysm, Abdominal/surgery ; Blood Vessel Prosthesis/adverse effects ; Blood Vessel Prosthesis Implantation/adverse effects ; Endoleak/etiology ; Endoleak/surgery ; Endovascular Procedures/adverse effects ; Humans ; Prosthesis Design ; Retrospective Studies ; Stents/adverse effects ; Time Factors ; Treatment Outcome
    Language English
    Publishing date 2021-10-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605700-7
    ISSN 1097-6809 ; 0741-5214
    ISSN (online) 1097-6809
    ISSN 0741-5214
    DOI 10.1016/j.jvs.2021.09.042
    Database MEDical Literature Analysis and Retrieval System OnLINE

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