Citations

BACKGROUND: Patients with cervical artery dissection (CeAD) may experience a recurrent dissection, but its frequency, risk factors, and clinical implications are not well defined. We aimed to determine the risk, associated factors, and clinical impact of recurrent CeAD. METHODS: The STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection) was a multicenter international retrospective observational study of patients with CeAD treated between January 2015 and June 2022. Recurrent dissection was defined as a CeAD occurring at least 7 days after the diagnosis of the index event that affects a different artery or a different segment of the same artery. Patients were followed from day 7 up to 2 years. The absolute risk of recurrent CeAD over time was calculated using Kaplan-Meier survival estimates. Multivariable logistic and Cox regression models were used to assess predictors of CeAD recurrence. RESULTS: Of the 4023 patients included in STOP-CAD, 3836 (median age 46 years, 45% women) were eligible for this analysis. During a median (interquartile range) follow-up of 295 (97–720) days, 88 (2.29%) patients had a CeAD recurrence. Median time-to-recurrent CeAD was 53 (interquartile range, 18–157) days. The estimated risk of recurrent CeAD at 2 years was 3.22% (95% CI, 2.59%–4.00%). In multivariable analyses, younger age (adjusted odds ratios, 0.98 [95% CI, 0.96–0.99]), migraine (adjusted odds ratio, 1.88 [95% CI, 1.14–3.07]), and fibromuscular dysplasia (adjusted odds ratio, 2.90 [95% CI, 1.66–5.06]) were associated with CeAD recurrence, while presenting with an ischemic stroke was associated with a lower likelihood of recurrence (adjusted odds ratio, 0.47 [95% CI, 0.29–0.75]). These associations with CeAD recurrence over time were confirmed by Cox regression analyses. Among the 88 patients with recurrent CeAD, only 5 had accompanying ischemic events (3 strokes, 2 transient ischemic attacks). CONCLUSIONS: In this retrospective study, recurrent CeAD was uncommon, approximately half of the events were diagnosed within the first 2 months of the index event, and recurrent events rarely caused new ischemic events. Younger age, migraine, absence of ischemic stroke at presentation, and signs of fibromuscular dysplasia may help identify high-risk patients.

Abstract Vaccine‐induced immune thrombotic thrombocytopenia (VITT) is a new disorder that emerged in the wake of coronavirus disease 2019 (COVID‐19) vaccination. It is a rare but life‐threatening condition that requires an aggressive course of treatment to improve patient outcomes. Currently, the diagnosis of VITT relies on a comprehensive panel of criteria, including a history of recent vaccination, platelet count, positive enzyme linked immunosorbent assays (ELISA) result for a closely related thrombotic disorder, heparin‐induced thrombocytopenia (HIT), and platelet factor 4 (PF4)‐dependent functional assays. The study describes a technically simple antigenic assay designed to detect autoimmune antibodies associated with VITT. It is first shown that cross‐linked platelet factor 4 (c‐PF4) represents an antigenic target specific for VITT/VITT‐like Abs. This antigenic target is then incorporated into a microfluidic electrochemical biosensor and specific and sensitive detection of VITT/VITT‐like antibodies is demonstrated in a fully automated manner while using microliter volumes of patient sera. Fifty‐five serum samples are tested using the microfluidic electrochemical biosensor and demonstrated high accuracy for the detection of VITT sera and VITT‐like monoclonal gammopathy of thrombotic ignificance (MGTS) antibodies compared to healthy controls and HIT patients. It is envisioned that the microfluidic electrochemical biosensor will be used in combination with other clinical criteria to enable timely, sensitive, and specific diagnosis of VITT.

BACKGROUND: Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion—specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume—were associated with recurrent ischemic stroke within 90 days. METHODS: The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%–99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at T max (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome ( P <0.1). RESULTS: Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02–1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03–3.28]). CONCLUSIONS: Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.

Background: Patients with acute ischemic stroke secondary to distal and medium vessel occlusion (AIS-DMVO) and minor strokes present a challenge in determining the most appropriate emergent treatment. Factors leading to early neurological deterioration (END) in this patient population are understudied, but END is known to result in poor functional outcomes. Therefore, we aimed to investigate the factors contributing to END in minor AIS-DMVO cases. Methods: We included patients with AIS-DMVO and minor strokes from 37 sites across North America, Asia, and Europe. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score of ⩽5. The primary outcome measure, END, was defined as a shift of ⩾4 points in the NIHSS score at day one after treatment compared to baseline. Univariable and multivariable logistic regression analyses were performed to identify factors associated with END. Results: Among 559 consecutive patients with DMVO and minor strokes, END was reported in 68 patients. In multivariable analysis, mechanical thrombectomy (MT) was independently associated with higher odds of END (adjusted odds ratio [aOR] 2.37, 95% CI 1.12–5.02, p = 0.02), while intravenous thrombolysis (IVT) was associated with lower odds of END (aOR 0.46, 95% CI 0.26–0.81, p = 0.008). However, the association between MT and END was no longer statistically significant in the IPTW-adjusted analysis (OR 1.65, 95% CI 0.69–3.98, p = 0.26). Hypertension and antiplatelet use at baseline were also independently associated with END. Among MT-treated patients, successful and excellent recanalization and first-pass effect were protective against END. Conclusion: MT was associated with END in patients with minor AIS-DMVO, although this association was not significant after IPTW adjustment. IVT was independently associated with reduced risk of END. These findings support careful patient selection and further study in randomized trials.

Type 1 diabetes is characterized by the autoimmune destruction of pancreatic β cells, resulting in permanent loss of glucose homeostasis. Islet transplantation is a promising potential cure that remains hindered by immune rejection. We previously showed that ST8Sia6 expression on tumors reduced immune surveillance and hypothesized that this sialyltransferase could protect β cells from autoimmune destruction. Here, we demonstrate that ectopic expression of ST8Sia6 in β cells of female nonobese diabetic mice (NOD βST) decreased the spontaneous incidence of diabetes by 90% and preserved β cell mass. NOD βST mice had comparable insulitis at 8 weeks of age that did not progress over time compared with littermate controls. β Cell–autoreactive B and T cells were present in NOD βST mice, indicating a peripheral rather than central mechanism of immune tolerance. The islets of NOD βST mice displayed a dampened type 1 immune response and reduced IL-12p35 expression in dendritic cells compared with those of littermate controls. The peripheral protection persisted even after removal of ST8Sia6 expression at 20 weeks of age, indicating that transient expression was sufficient for establishment of tolerance. These results demonstrate that ST8Sia6 protects β cells from immune-mediated attack and rejection, highlighting its therapeutic potential for autoimmune disorders.

Objective Mechanical thrombectomy (MT) is well-established for the treatment of acute ischemic stroke (AIS) from large vessel occlusion (LVO), with growing data supporting the expansion to distal and medium vessel occlusions (DMVO). Despite successful recanalization in DMVO, certain patients still experience poor long-term clinical outcomes, prompting our study to comprehensively explore pre-MT factors influencing outcome despite excellent recanalization (final modified Thrombolysis in Cerebral Infarction [mTICI] score ≥2c). Methods We retrospectively examined data from patients who consecutively underwent MT for a primary middle cerebral artery (MCA) DMVO across 37 centers in North America, Asia, and Europe. We identified baseline clinical and imaging factors associated with poor clinical outcome (defined as a modified Rankin Scale [mRS] score of 3–6) at 3 months, despite excellent recanalization using a multivariable model. Results Between September 2017 and July 2021, 623 patients achieved mTICI > 2b and they were included in our study. Among them, 198 (32%) experienced a poor clinical outcome (mRS 3–6). Predictors of poor clinical outcome included higher age (OR 1.05 [1.03–1.07], p < 0.001), higher NIHSS at admission (OR 1.12 [1.08–1.15], p < 0.001), higher baseline mRS (OR 1.77 [0.96–3.26], p = 0.067), and diabetes (OR 1.59 [1.01–2.48], p = 0.044). Higher ASPECTS was associated with a decreased risk of poor clinical outcome (OR 0.82 [0.71–0.94], p = 0.006). Conclusion Older age, diabetes, higher baseline mRS, and NIHSS were associated with poor clinical outcome in MCA DMVO despite excellent recanalization. Conversely, a higher ASPECTS decreased the probability of such an outcome.

OBJECTIVE Mechanical thrombectomy (MT) is well established for large-vessel occlusion (LVO) strokes, but its safety in distal and medium-vessel occlusions (DMVOs) requires further investigation. This study analyzed the relationship between procedural approaches, petechial hemorrhage (PetH), and clinical outcomes in DMVO thrombectomy, with particular attention to technical considerations and the complex interplay between tissue injury and hemorrhagic complications. METHODS A retrospective cohort study was conducted on DMVO stroke patients treated with MT at 37 stroke centers worldwide from 2016 to 2024. Patients were categorized based on follow-up imaging into those with or without PetH. Four logistic regression models analyzed the association of PetH with favorable functional outcomes (modified Rankin Scale score ≤ 2) at 90 days, early neurological improvement (≥ 4-point National Institutes of Health Stroke Scale score decrease at 24 hours), all-cause mortality, and independent determinants of PetH. Adjusted odds ratios (aORs), 95% confidence intervals, and p values were reported. RESULTS Of 1428 patients, 439 (30.7%) developed PetH. Factors independently associated with PetH were multiple thrombectomy passes (aOR 1.58, 95% CI 1.21–2.06; p = 0.001), IV thrombolysis (aOR 1.31, 95% CI 1.01–1.69; p = 0.04), and the combined use of a stent retriever with aspiration as the first-line method compared with aspiration alone (aOR 1.66, 95% CI 1.15–2.38; p = 0.007). Conversely, general anesthesia (aOR 0.55, 95% CI 0.40–0.77; p < 0.001), higher Alberta Stroke Program Early CT Scores (aOR 0.76, 95% CI 0.69–0.83; p < 0.001), and successful recanalization (aOR 0.56, 95% CI 0.39–0.80; p = 0.002) were significantly associated with a lower odds of PetH. PetH was associated with a decreased odds of favorable functional outcomes (aOR 0.51, 95% CI 0.36–0.73; p < 0.001), reduced early neurological improvement (aOR 0.59, 95% CI 0.44–0.79; p < 0.001), and increased all-cause mortality (aOR 1.84, 95% CI 1.23–2.76; p < 0.001). CONCLUSIONS PetH is a frequent sequela following MT in DMVO strokes and is associated with poorer outcomes, likely reflecting underlying ischemic injury rather than direct causation. Procedural factors influence PetH risk, suggesting medical treatment as first-line therapy for DMVOs, with MT reserved for refractory cases using less aggressive approaches.

Obesity is a prevalent metabolic condition that is strongly associated with the development of cardiovascular disease. Adipose arteries exhibit robust endothelial dysfunction in diet-induced obese mice. Obesity is also associated with elevated plasma long chain fatty acids (LCFAs), well-established contributors to endothelial dysfunction, which require a receptor to facilitate their uptake. CD36, facilitates LCFA uptake which when in excess contributes to endothelial dysfunction. Our previous work demonstrated that global CD36 ablation restores endothelium-dependent dilations to flow. Therefore, to determine if an upregulation in CD36 expression was driving these differences, we first assessed if obesity alters endothelial CD36 expression using flow cytometry and immunofluorescence imaging. For flow cytometry experiments mesenteric arteries were digested and sorted to identify the endothelial cell population (i.e., CD45-CD31+ cells). En face preparations were stained for VE-cadherin to locate the endothelial cell layer using confocal microscopy. In both experiments, an antibody that detects an extracellular epitope of CD36 was used to detect membrane expression. Obesity did not alter the expression of CD36 in endothelium of mesenteric arteries relative to lean counterpart controls in WT mice. We next aimed to determine if obesity influences the functional capacity of endothelial CD36. First, we measured LCFA uptake in mesenteric arteries from lean and obese WT mice. Arteries were exposed to a fluorescent palmitic acid analogue, BODIPYC-16, and internalized endothelial LCFA uptake was assessed at different time points using confocal microscopy. Arteries from obese mice had elevated endothelial LCFA uptake and lipid accumulation relative to lean controls. To determine if the effects of obesity on LCFA uptake were mediated by endothelial CD36, we repeated the fluorescent LCFA uptake experiments using the Tie2eCreCD36 fl/fl model. First, to determine if endothelial cell CD36 was driving obesity induced endothelial dysfunction, mesenteric arteries were isolated from lean and diet-induced obese Tie2eCreCD36 fl/fl mice. Arteries from Tie2eCreCD36 fl/fl diet induced obese mice exhibited attenuated fatty acid uptake, compared to their lean and obese genotype controls. Next, we measured endothelial function ex vivo via pressure myography. Mesenteric arteries from obese Tie2eCreCD36 fl/fl mice exhibited a restored response to flow induced vasodilation relative to respective controls suggesting a role for endothelial cell CD36 in mediating endothelial dysfunction perhaps through promoting lipid accumulation in obesity. Ongoing work within our lab is aimed at determining the mechanism underlying obesity-induced alterations to endothelial CD36 and how the observed increase in LCFAs may be contributing to reduced endothelial function. Center of Biomedical Research Excellence in Cardiovascular Health (COBRE): 5P20GM113125-08, University of Delaware Research Fund (UDRF) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.