Mercy St. Vincent Medical Center

Tandem lesions (TLs) are a subtype of acute ischemic stroke, which involve an extracranial carotid lesion (ie, severe carotid stenosis ≥70%) with large vessel occlusion. While large vessel occlusion has a standard approach with mechanical thrombectomy (MT), the best practice for intervention of the carotid lesion is not well-established. Utilizing data from the ASSIST registry, we investigated the differences in clinical and procedural outcomes between acute versus nonacute stenting. The ASSIST registry (an international acute ischemic stroke MT prospective study) was utilized to identify the subgroup of patients with acute ischemic stroke secondary to TL who received MT. The TLs were grouped by MT+acute carotid stenting (CAS) versus MT+acute carotid nonstenting. The demographics and clinical outcomes (90-day modified Rankin Scale score) were compared between TL and non-TL groups, and between MT+CAS and MT+acute carotid nonstenting. Multivariable analyses were performed to determine independent predictors of clinical outcomes. A total of 183 of 1270 (14.4%) TLs were identified in the ASSIST registry. MT+CAS was performed in 83 of 183 (45.4%) subjects, and 100 of 183 (54.6%) received MT+acute carotid nonstenting. There are no significant differences at baseline between the 2 groups in the National Institutes of Health Stroke Scale score, Alberta Stroke Program Early Computed Tomography Score, or target vessel. Achieving a modified Rankin Scale score of 0 to 2 at 90 days was 70.9% in the MT+CAS group versus 48.9% in the MT+acute carotid nonstenting group (P=0.001), with a modified Rankin Scale score of 0 to 2 being significantly associated with the MT+CAS group in multivariable analysis (odds ratio, 2.14 [95% CI, 1.01-4.51]). There was no significant difference in mortality or symptomatic intracerebral hemorrhage between the groups. In acute ischemic stroke, secondary to TLs treatment with thrombectomy and acute carotid stenting is associated with improved 90-day functional outcome without an increase in symptomatic intracerebral hemorrhage compared with no acute stenting approach. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03845491.

Pancreatic ductal adenocarcinoma (PDAC) arises predominantly from activating KRAS mutations, yet individual genetic variants differ markedly in signaling output and clinical impact. G12D, the most prevalent variant, strongly drives oncogenic programs, whereas G12R signals less efficiently through the AKT and ERK pathways and is associated with longer patient survival than G12D-driven PDAC. To elucidate how these differences influence early cellular transformation, we expressed a panel of KRAS mutants in non-cancerous pancreatic ductal epithelial cells as a model of early PDAC initiation and profiled transcriptional and phospho-proteomic responses. We next examined whether epigenetic differences translate into mutation-specific changes in nuclear organization using quantitative imaging of G12D- and G12R-expressing nuclei at 24 and 48 h. Each variant established a unique regulatory program enriched for chromatin remodelers, histone modifiers, and nuclear structural factors, indicating that variant-specific KRAS signaling rapidly develops divergent epigenetic states. Integrated transcriptomic and phospho-proteomic analyses identified G12D and G12R as the most divergent variants. G12D induced pronounced nuclear remodeling, including increased nuclear size, irregular morphology, and reorganization of the nucleolus and spliceosome, consistent with extensive chromatin and transcriptional reprogramming. In contrast, G12R elicited a weaker response, with minimal or delayed structural changes. Together, these findings demonstrate that KRAS mutational context in pancreatic ductal epithelial cells shapes early transcriptional reprogramming that actively remodels nuclear architecture and nuclear sub-compartments. This work establishes nuclear structural remodeling as a structural state of KRAS-driven epigenetic dysregulation during PDAC initiation.

Erdheim-Chester disease (ECD) and immunoglobulin G4-related disease (IgG4-RD) are both rare, multisystem disorders with overlapping clinical, radiologic, and histopathologic features. This overlap leads to delays or misdiagnoses. Early diagnosis with proper distinction is critical for treatment and a better prognosis. A review of the literature using PubMed and Google Scholar was conducted to identify distinguishing features between ECD and IgG4-RD. The focus was on clinical presentation, diagnostic imaging, histopathologic findings, immunohistochemistry, and genetic mutations. Relevant articles were screened, and data were synthesized to create a diagnostic framework. Both disorders can be characterized by retroperitoneal fibrosis, central nervous system involvement, and IgG4-positive plasma cell infiltration. ECD is characterized by long bone osteosclerosis, "hairy kidneys," a coated aorta, and diabetes insipidus, and is associated with BRAF V600E or MAPK pathway mutations. In contrast, IgG4-RD is characterized by autoimmune pancreatitis, sialadenitis, and increased serum IgG4, as well as storiform fibrosis and obliterative phlebitis on histology. Imaging is key: FDG-PET and MRI frequently show skeletal and cerebellar uptake in ECD, which is typically absent in IgG4-RD. Therapeutically, ECD often requires targeted therapies such as BRAF or MEK inhibitors, whereas IgG4-RD responds to corticosteroids or rituximab or inebilizumab. Treatment response emerged as a new diagnostic clue. This review provides a structured, multimodal approach to distinguish ECD from IgG4-RD, which improves diagnostic accuracy by integrating genetic testing, advanced imaging, neurological features, and treatment response. This allows clinicians to avoid misdiagnoses, implement targeted treatments, and improve patient outcomes.

Background: Atrial fibrillation (AF) is a common comorbidity in the U.S. and significantly contributes to the incidence of acute ischemic strokes. This study examines the impact of household income on management and outcomes of Acute ischemic stroke in patients with AF. Research: Question: How does socioeconomic status impact the management and outcomes of Acute ischemic stroke in patients with AF? Methods: We used data from the National Inpatient Sample database (2018-2020), analyzing adult hospitalizations with primary diagnosis of acute ischemic stroke and secondary diagnosis of AF. Patients were grouped into four income quartiles: Q1 ($1 - $51,999), Q2 ($52,000 - $65,999), Q3 ($66,000 - $87,999), and Q4 ($88,000+). Outcomes included in-hospital mortality, utilization of endovascular thrombectomy (EVT), length of stay (LOS), inflation-adjusted total charge (IATC), intracranial hemorrhage (ICH) and sepsis. Multivariable logistic and linear regression analyses were performed, for demographic, clinical, and hospital factors. Results: A total of 340,835 hospitalizations with Acute ischemic stroke and AF were identified. Mean age was 77 years (11), and 52% were female. When comparing highest income quartile to lowest, admissions in the highest income quartile had significantly lower in-hospital mortality rates (6.5% vs. 7.0%; p < 0.001), lower sepsis rates (2.7% vs. 3.3%; p = 0.032), shorter mean LOS (6.2 vs. 7.7 days; p < 0.001), and higher mean IATC ($116,076 vs. $107,568; p = 0.06). Hospitalizations in highest income quartile had higher rates of ICH (9.4% vs. 9.1%; p = 0.11) and EVT (6.8% vs. 6.1%; p = 0.7), but these differences were not statistically significant. After adjusting for confounders, higher income stayed markedly associated with lower in-hospital mortality (adjusted odds ratio [aOR]: 0.78, 95% CI: 0.70–0.86; p < 0.001), lower sepsis rates (aOR: 0.85, 95% CI: 0.74–0.99; p = 0.032), shorter LOS (aOR: -0.28, 95% CI: -0.43 to -0.14; p < 0.001), and higher IATC (aOR: 2,403, 95% CI: -4,911 to 105; p = 0.06). There were no significant differences observed in ICH (aOR: 0.95, 95% CI: 0.87–1.03; p = 0.02) and EVT (aOR: 1.06, 95% CI: 0.95–1.19; p = 0.3) between highest and lowest income quartiles. Conclusion: Higher socioeconomic status is associated with lower in-hospital mortality and sepsis rates, shorter LOS, and higher IATC. These disparities suggest the need for targeted interventions to address socioeconomic inequalities and improve stroke care.

Introduction Preclinical animal experiments and initial feasibility studies in humans have shown encouraging outcomes using the novel Saccular Endovascular Aneurysm Lattice (SEAL™) system for the treatment of both ruptured and unruptured wide‐neck intracranial aneurysms (IAs). The SEAL™ Interventional Pivotal IDE PMA Trial (SEAL™ IT) is designed to assess the safety and efficacy of the SEAL™ in patients with saccular IAs. This ongoing, prospective, multicenter trial includes three study arms and will enroll a total of 279 participants with wide‐neck bifurcation (WNBA), sidewall (SW), or acutely ruptured IAs across 50 U.S. sites. Methods Eligibility requirements include patients aged 20‐80 years with a wide‐neck saccular intracranial aneurysm (2‐19 mm) deemed suitable for treatment with the SEAL™ Intrasaccular Device (SID). Participants receive treatment using the SEAL™ device (Galaxy Therapeutics Inc.) and are monitored at discharge, and again at 3, 6, and 12 months, followed by yearly assessments for up to 5 years. The primary efficacy outcome is defined as complete aneurysm occlusion at 12 months without evidence of parent vessel stenosis or the need for retreatment, as determined by an independent core laboratory. Key safety outcomes include neurological death within 12 months, stroke occurring within the first 30 days, and ipsilateral stroke between 30 days and 1 year. Results As of submission, 163 WNBA, 58 WNSW, and 33 ruptured for a total of 254 patients (76.3% female; mean age 61.7 ± 11.3) have been enrolled at 50 sites. Mean aneurysm width was 5.2 ± 2.1, neck size of 3.7 ± 1.4, and neck‐to‐dome ratio of 1.4 ± 0.32. SEAL Arc was used in 63.6% and SEAL Base in 36.4%. Technical device success rate is 100% for WNBA, 94.8% WNSW, and 97.0% ruptured. The interim complete occlusion rate for the primary group is 84.5% at most recent date based on available imaging. Conclusion Preliminary data for the SEAL™ intrasaccular device is promising; Safety and effectiveness updates will be presented at the SVIN Conference.

Introduction The influence of collateral circulation on outcomes in intracranial atherosclerotic stenosis‐related large vessel occlusion (ICAS‐LVO) treated with mechanical thrombectomy (MT) with or without rescue stenting is not well defined. We aimed to determine whether collateral status modifies the effect of stenting on angiographic and clinical outcomes. Methods We analyzed patients with ICAS‐LVO in the RESCUE‐ICAS registry who underwent MT alone or with rescue stenting in the anterior circulation. Collaterals were graded as good or bad based on ASITN/SIR score. Outcomes included functional independence (mRS 0‐2 at 90 days), mortality, successful recanalization, sICH, and 24‐hour DWI infarct volume. Regression models evaluated stenting and collateral status interaction, adjusted using inverse probability weighting for age, sex, race, diabetes, hypertension, atrial fibrillation, hyperlipidemia, prior stroke, smoking, pre‐stroke mRS, admission NIHSS, IV tPA, and baseline ASPECTS, with weights trimmed at ≤4. Results A total of 324 patients were included (MT alone, n=182; stent+MT, n=142). Median age was 67 years, 57% were male, and vascular comorbidities were frequent. Good collaterals were present in 27% of cases. Interaction analysis between stenting and collateral status showed no significant effect modification for functional independence (adjusted OR 0.78, 95% CI 0.33‐1.82, p =0.560), mortality (adjusted OR 1.56, 95% CI 0.52‐4.68, p =0.425), sICH (adjusted OR 0.22, 95% CI 0.04‐1.42, p =0.112), or infarct volume (β = ‐10.1 mL, 95% CI ‐32.9 to 12.7, p =0.656). A borderline interaction was observed for successful recanalization, with stenting in the setting of good collaterals associated with higher odds of reperfusion (adjusted OR 5.34, 95% CI 0.90‐31.7, p =0.065). Conclusions In patients with anterior circulation ICAS‐LVO, collateral status did not significantly modify the benefit of rescue stenting. These findings suggest that good collaterals alone do not obviate the need for stenting, and highlight the need for prospective studies to define optimal medical management strategies in this population. image image

Introduction/Purpose Balloon guide catheters (BGCs) may improve recanalization outcomes in mechanical thrombectomy by providing proximal flow control and reducing distal embolization. We evaluated the safety and efficacy of EMBOGUARD ™ compared to conventional guide catheters in acute ischemic stroke thrombectomy. Materials/Methods Consecutive patients undergoing mechanical thrombectomy for stroke at four thrombectomy‐capable centers from January 2022 to December 2024 were retrospectively analyzed and stratified by use of EMBOGUARD ™ versus conventional guide catheters. Patients were eligible for inclusion if they were aged 18‐85 years with an initial NIHSS score >5, had a last known well time to procedure start <24 hours, demonstrated baseline functional independence (mRS 0‐1), and presented with involvement of intracranial vessels including the internal carotid artery beyond the petrous segment and/or middle cerebral artery. Patients were excluded if they had tandem ipsilateral proximal extracranial stenosis, previous stent placement in the target lesion, steno‐occlusive disease related to intracranial atherosclerotic disease with ≥50% stenosis/occlusion, pre‐treatment CT ASPECTS <5, any intracranial hemorrhage within the prior 30 days, or untreated chronic subdural hematoma >5 mm thickness. The primary outcome was first‐pass effect (modified TICI [mTICI] ≥2c in a single pass without adjunctive treatment). Secondary outcomes included successful recanalization (mTICI ≥2b), favorable functional outcome (mRS 0‐2 at 90 days), procedural metrics, and safety endpoints. Univariate comparisons, propensity score matching (PSM), sensitivity analyses (by site and vessel), and missing data analysis were performed. Results Among 178 patients (EMBOGUARD ™ n=135; conventional n=43), baseline characteristics were balanced except for higher atrial fibrillation (33.3% vs 20.9%, p=0.044) and intracranial ICA occlusions (17.8% vs 9.3%, p=0.012) with EMBOGUARD ™ . First‐pass effect occurred in 33.3% (45/135) with EMBOGUARD ™ vs 37.2% (16/43) with conventional catheters (p=0.678). Successful recanalization rates were similar (86.7% vs 86.0%, p=0.924). A higher proportion of EMBOGUARD ™ patients achieved favorable 90‐day outcomes (45.7% vs 22.5%, p=0.012). Procedural time was numerically shorter with EMBOGUARD ™ (43.3±35.3 vs 54.2±30.3 min, p=0.089). Symptomatic intracerebral hemorrhage (2.0% vs 0.0%, p=0.373) and 90‐day mortality (13.7% vs 16.7%, p=0.656) were comparable. PSM validated these findings, confirming no difference in first‐pass effect and a persistent benefit in functional outcome (43.2% vs 22.5%, p=0.047). Sensitivity analyses by vessel occlusion revealed first‐pass effect rates for ICA: 50.0% vs 25.0%; M1: 44.8% vs 45.0%; beyond M1: 6.8% vs 31.6% (EMBOGUARD ™ vs conventional, respectively). Two centers adopted only EMBOGUARD ™ . Conclusion In this multicenter retrospective study, EMBOGUARD ™ balloon guide catheter was not superior to conventional guide catheters for first‐pass effect but was associated with significantly better 90‐day functional outcomes. Operator experience, case selection, and site‐level adoption may influence effectiveness; prospective trials are needed.

Graves’ orbitopathy (GO) is a clinically significant extrathyroidal manifestation of Graves’ disease (GD), often resulting in functional and cosmetic morbidity. Preventive strategies remain limited. Statins, widely prescribed for cardiovascular disease, possess anti-inflammatory and immunomodulatory properties that may also mitigate the risk of GO. This systematic review and meta-analysis aimed to evaluate the association between statin use and GO risk in GD, with subgroup analyses by geographic region and sex to capture potential differential effects. This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, the Excerpta Medica database (Embase), and the Cochrane Library were systematically searched from database inception through May 2025 using a predetermined strategy. Eligible observational studies (cohort or case-control) assessing the effect of statin use on incident GO were included. Where feasible, pooled hazard ratios (HRs) or odds ratios (ORs) were estimated using random-effects models (Western cohorts). For Asian populations, effect estimates were synthesized narratively due to heterogeneity in effect measures. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the ROBINS-I tool. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD420251032246). Five studies (n = 156,926) met the inclusion criteria. In Asian populations (n = 113,628), statin use was associated with a significantly reduced risk of GO (HR = 0.56; 95% CI: 0.46-0.68; p < 0.001). In Western populations (n = 43,298), pooled analysis suggested a non-significant trend toward risk reduction (HR = 0.76; 95% CI: 0.53-1.10; p = 0.14), with substantial heterogeneity (I² = 60.8%). Among Asian females (n = 83,997), statin use consistently demonstrated protective associations (HRs 0.37-0.66), while male subgroup estimates, derived from a single study, were not statistically significant. Across all studies, risk of bias was rated as moderate, primarily due to confounding and variability in outcome measurement. Statin use appears to reduce the risk of GO among patients with GD, with the strongest protective effect observed in Asian women. Although Western data suggested a protective trend, findings did not reach statistical significance and were limited by heterogeneity. These results highlight the importance of region- and sex-specific investigations. Large-scale prospective cohort studies and randomized controlled trials (RCTs) are warranted to confirm the potential preventive role of statins in GO and to clarify dose-response relationships.