BACKGROUND: The Tigertriever device offers a unique feature that enables gradual control of the radial expansion. We sought to evaluate the safety and efficacy of the Tigertriever device in patients with large vessel occlusion (LVO) and underlying intracranial atherosclerotic disease (ICAD). The patients were part of the TIGER trial. METHODS: The presence of underlying ICAD was determined by a core imaging laboratory using CT angiography and digital subtraction angiography. The primary outcomes included successful reperfusion, puncture to reperfusion time, and complications associated with the use of the Tigertriever device. Patients underwent mechanical thrombectomy with the Tigertriever device for up to three passes, and alternative devices were employed for subsequent passes. RESULTS: A total of 160 patients were enrolled in the TIGER trial, and 32 patients had ICAD. Among the patients with ICAD, 78% achieved successful reperfusion within three passes of the Tigertriever device, without requiring rescue therapy. Additionally, a first pass effect was observed in 46.8%. The median time from puncture to reperfusion was 22 minutes. There were no device-related complications. The National Institutes of Health Stroke Scale (NIHSS) score at 24 hours was significantly reduced, from an average of 17 at baseline to 8. At the 3 month follow-up, 50% of patients achieved a modified Rankin Scale score of ≤2. CONCLUSION: Endovascular therapy (EVT) with the Tigertriever device for LVO in patients with underlying ICAD is effective and safe. When compared with historical data from other devices employed in similar cases, we observed a high rate of successful reperfusion, along with a shorter puncture to reperfusion time.

Dengue virus (DENV) is the most important human virus transmitted by mosquitos. Dengue pathogenesis is characterized by a large induction of proinflammatory cytokines. This cytokine induction varies among the four DENV serotypes (DENV1 to 4) and poses a challenge for live DENV vaccine design. Here, we identify a viral mechanism to limit NF-κB activation and cytokine secretion by the DENV protein NS5. Using proteomics, we found that NS5 binds and degrades the host protein ERC1 to antagonize NF-κB activation, limit proinflammatory cytokine secretion, and reduce cell migration. We found that ERC1 degradation involves unique properties of the methyltransferase domain of NS5 that are not conserved among the four DENV serotypes. By obtaining chimeric DENV2 and DENV4 viruses, we map the residues in NS5 for ERC1 degradation, and generate recombinant DENVs exchanging serotype properties by single amino acid substitutions. This work uncovers a function of the viral protein NS5 to limit cytokine production, critical to dengue pathogenesis. Importantly, the information provided about the serotype-specific mechanism for counteracting the antiviral response can be applied to improve live attenuated vaccines.