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Background: Mechanical thrombectomy (MT) has significantly improved clinical outcomes in acute ischemic stroke. We used single-cell RNA sequencing (scRNA-seq) to describe the landscape of human clots at single cell resolution seeking to provide greater mechanistic insight into stroke pathophysiology and to uncover an association with stroke origin. Methods: scRNA-seq was performed on 14 clots retrieved from 14 patients undergoing MT between October 2020-July 2022. We followed standard molecular biology and bioinformatics workflows for sample processing and data to characterize differences in cellular composition between clots of different stroke origin (atrial fibrillation (AF) and carotid atherosclerosis (CA)). Results: Clots revealed a significant heterogeneity of immune cells with major constituents including cells of the mononuclear phagocyte system (MPS) and neutrophils. The cellular populations most enriched in CA clots were B-cells and CD4+ T-cells. The cellular population most enriched in AF clots was red blood cells. When looking at cellular subpopulations of the MPS component, we found that CD16+ monocytes (intermediate and non-classical) were significantly more abundant than CD14+CD16- (classical) monocytes in all clots. Moreover, the proportions of CD16+ monocytes varied with stroke origin: the proportion of non-classical (CD14-CD16+) monocytes was higher in CA clots (p=0.05) whereas the proportion of intermediate monocytes (CD14+CD16+) was higher in FA clots (p=0.03). AF clots had upregulated biomarkers and pathways involved with AF or contractile dysfunction (IFI30, FABP4, PPAR, HOTAIR, ILK, Integrin). CA clots had upregulated biomarkers and pathways associated with cardiovascular diseases and atherogenesis (RNSE1, POLR2J3.1, PLTP, Sirtuin, FAK). (Figure) Conclusions: These results reveal a significant heterogeneity of immune cells and point to important differences in cellular composition associated with stroke etiology.

Introduction: Conventional MRI (cMRI) is not routinely available post-mechanical thrombectomy (MT), which can preclude accurate infarction assessment. Our objective was to evaluate the use of low-field portable MRI (pMRI) for bedside evaluation post-MT, including its use as a post-procedural baseline monitor. Methods: Low-field pMRI was used to obtain bedside imaging in post-MT patients between December 2021 to August 2022 at Yale-New Haven Hospital. All pMRI exams were conducted in the standard ferromagnetic environment of the IR suite. Volumetric analyses were performed by a neuroradiologist using 3D Slicer software. If cMRI was not available for comparison, a CT was used. Patients’ charts were reviewed for pre-revascularization MAP and occurrences of MAP dropping by 10% and 20% from individual baselines between the time of pMRI and delayed imaging. Results: A total of 25 patients (64% females, median age 77 years-old [IQR 69.5-84.5]) underwent bedside pMRIs in the IR suite post-MT. The median time from last known normal to access was 6 hours [IQR 4-17]. The median pMRI examination time was 30 minutes [IQR 17-32]. Of the 24 patients with available delayed imaging, 7 (29.2%) had infarct progression compared to immediate post-MT pMRI, while 15 patients (62.5%) had stable/decreased stroke volume. Two patients (8.3%) had parenchymal hemorrhage type 2 and were excluded from further analysis. There was no statistically significant difference between the proportions of favorable TICI scores (85.7% in the infarct progression group vs. 92.3% in the stable/decreased infarct group, p=1.00). Patients with infarct progression had comparable pre-revascularization MAP compared to those with stable/decreased delayed infarct volume (mean of 100.3±4.6 vs. 101.9±15.9 respectively, p=0.727) but had more occurrences of MAP dropping by 10% and 20% of their baseline between the time of pMRI and delayed imaging (mean of 35.0±23.3 vs. 14.7±11.3 occurrences, p=0.011; and mean of 21.7±16.5 vs. 8.5±9.5 occurrences, p=0.026, respectively). Conclusions: The use of low-field MRI in the post-MT setting can facilitate benchmark brain monitoring and serial examinations to evaluate the impact of potential physiological perturbations that may impact ongoing brain injury.

The future of cancer treatment is promising. Although marred by years of plateau in outcomes, new avenues have been identified that are poised to change how we treat cancer. Molecular targeted therapy or targeted therapy is one of these methods. Molecular targeted therapy involves identifying specific pathways or markers that allow cancer cells to flourish. Once identified, specific molecules can be used to block proliferative pathways, thereby negatively impacting tumor growth. Targeting specific pathways that prolong the survival of the cancer cell can lead to a decreased cancer burden, and improved patient outcomes. This article reviews the tenets of molecular targeted therapy, common pathways, target acquisition for drug development, and the pathways that have been elucidated in musculoskeletal tumors.