5 research outputs found

    Subcapsular sinus macrophages promote melanoma metastasis to the sentinel lymph nodes via an IL-1α-STAT3 axis.

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    During melanoma metastasis, tumor cells originating in the skin migrate via lymphatic vessels to the sentinel lymph nodes (sLNs). This process facilitates tumor cell spread across the body. Here, we characterized the innate inflammatory response to melanoma in the metastatic microenvironment of the sLNs. We found that macrophages located in the subcapsular sinus (SS) produced pro-tumoral IL-1α after recognition of tumoral antigens. Moreover, we confirmed that the elimination of LN macrophages or the administration of an IL-1α-specific blocking antibody reduced metastatic spread. To understand the mechanism of action of IL-1α in the context of the sLN microenvironment, we applied single-cell RNA sequencing to microdissected metastases obtained from animals treated with the IL-1α-specific blocking antibody. Amongst the different pathways affected, we identified STAT3 as one of the main targets of IL-1α signaling in metastatic tumor cells. Moreover, we found that the antitumoral effect of the anti-IL-1α was not mediated by lymphocytes because Il1r1 knockout mice did not show significant differences in metastasis growth. Finally, we found a synergistic anti-metastatic effect of the combination of IL-1α blockade and STAT3 inhibition with stattic, highlighting a new immunotherapy approach to preventing melanoma metastasis

    The Society of Vascular and Interventional Neurology (SVIN) Mechanical Thrombectomy Registry: Methods and Primary Results

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    Background A better understanding of real‐world practice patterns in the endovascular treatment for large vessel occlusion acute ischemic stroke is needed. Here, we report the methods and initial results of the Society of Vascular and Interventional Neurology (SVIN) Registry. Methods The SVIN Registry is an ongoing prospective, multicenter, observational registry capturing patients with large vessel occlusion acute ischemic stroke undergoing endovascular treatment since November 2018. Participating sites also contributed pre‐SVIN Registry data collected per institutional prospective registries, and these data were combined with the SVIN Registry in the SVIN Registry+ cohort. Results There were 2088 patients treated across 11 US centers included in the prospective SVIN Registry and 5372 in SVIN Registry+. In the SVIN Registry cohort, the median number of enrollments per institution was 160 [interquartile range 53–243]. Median age was 67 [58–79] years, 49% were women, median National Institutes of Health Stroke Scale 16 [10–21], Alberta stroke program early CT score 9 [7–10], and 20% had baseline modified Rankin scale (mRS)≄2. The median last‐known normal to puncture time was 7.7 [3.1–11.5] hours, and puncture‐to‐reperfusion was 33 [23–52] minutes. The predominant occlusion site was the middle cerebral artery‐M1 (45%); medium vessel occlusions occurred in 97(4.6%) patients. The median number of passes was 1 [1–3] with 93% achieving expanded Treatment In Cerebral Ischemia2b50–3 reperfusion and 51% expanded Treatment In Cerebral Ischemia3/complete reperfusion. Symptomatic intracranial hemorrhage occurred in 5.3% of patients, with 37.3% functional independence (mRS0–2) and 26.4% mortality rates at 90‐days. Multivariable regression indicated older age, longer last‐normal to reperfusion, higher baseline National Institutes of Health Stroke Scale and glucose, lower Alberta stroke program early CT score, heart failure, and general anesthesia associated with lower 90‐day chances of mRS0–2 at 90‐days. Demographic, imaging, procedural, and clinical outcomes were similar in the SVIN Registry+. A comparison between AHA Guidelines‐eligible patients from the SVIN Registry against the Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke Trials study population demonstrated comparable clinical outcomes. Conclusions The prospective SVIN Registry demonstrates that satisfactory procedural and clinical outcomes can be achieved in real‐world practice, serving as a platform for local quality improvement and the investigation of unexplored frontiers in the endovascular treatment of acute stroke

    Regulation of Endothelial Barrier Function

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