Bon Secours Mercy Health

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.

Introduction: Intracranial stenting during endovascular thrombectomy (EVT) is a common practice in the setting of failed reperfusion or severe stenosis. Immediate stent patency requires periprocedural antiplatelet therapy (APT). How APT intensity interacts with prior intravenous thrombolysis (IVT) to influence hemorrhagic risk remains uncertain. We aimed to assess whether the APT regimen modifies the association of IVT with early intracranial hemorrhage after intracranial stenting during EVT. Methods: This was a subanalysis of the RESISTANT registry, a multicenter, international, retrospective cohort (2016 to 2023) of adults with acute ischemic stroke who underwent intracranial stenting during EVT. APT regimens were categorized as conservative (intravenous or oral aspirin alone, or aspirin plus an oral P2Y12 inhibitor) and aggressive (any regimen including intravenous GPIIb/IIIa inhibitor or intravenous cangrelor). Four main groups were compared according to the APT regimen (conservative/aggressive) and the use of IVT (+/-). The primary outcome was a composite of sICH and parenchymal hematoma types 1 and 2 (sICH-PH2-PH1). Multivariable logistic regression models were used to evaluate the interaction between IVT and APT, adjusting for clinically relevant covariates. Results: Among the 823 included patients, 44 (5.3%) received conservative APT with IVT, 130 (15.8%) received conservative APT without IVT, 145 (17.6%) received aggressive APT with IVT, and 504 (61.2%) received aggressive APT without IVT. Among patients who received IVT, sICH-PH2-PH1 rates were 9.3% with conservative APT and 10.7% with aggressive APT; among those without IVT, rates were 3.2% and 9.9%, respectively. Administration of IVT (adjusted odds ratio [aOR] 5.84, 95%CI 1.07 to 43.92; p=0.05) and aggressive APT (aOR 4.81, 95% CI 1.41 to 30.22; p=0.03) were each associated with higher odds of hemorrhagic complications, with a significant IVT by APT interaction (P interaction =0.05; Figures 1 and 2 ). Within the aggressive APT plus IVT subgroup, sICH-PH2-PH1 occurred in 20% of patients treated with cangrelor and 6.1% treated with a glycoprotein IIb/IIIa inhibitor ( Figure 3 ). Conclusion: Among patients requiring intracranial stenting, aggressive periprocedural APT and prior IVT are each associated with higher hemorrhagic risk, with the combination showing the worst observed crude outcome. Prospective evaluation of protocolized APT pathways in the IVT setting is warranted.

It remains unclear whether outcomes of patients treated with endovascular thrombectomy with large-vessel occlusion and unwitnessed onset of stroke differ from those with witnessed onset in the extended time window. We enrolled patients with anterior circulation large-vessel occlusion (internal carotid artery, M1, or M2 segment of the middle cerebral artery) undergoing endovascular thrombectomy within 6 to 24 hours from the time last seen well, from 2014 to 2022, at 66 sites in Europe, North America, and Asia. Patients with a prestroke modified Rankin Scale score of >3 or age <18 were excluded. We categorized patients by onset mode as witnessed or unwitnessed. The primary outcome was the modified Rankin Scale shift at 90 days. Secondary outcomes were functional independence, a composite of functional independence or return of Rankin to prestroke level, symptomatic intracranial hemorrhage, mortality, and a composite of severe disability or mortality at 90 days. We applied inverse probability of treatment weighting to compare outcomes between the groups. Of 5098 patients assessed for eligibility, we included 2073, of whom 1760 (84.9%) had unwitnessed onset, and 313 (15.1%) were witnessed. In the univariate comparison (before inverse probability of treatment weighting), 38.8% of the unwitnessed and 45.7% of the witnessed patients achieved functional independence (P=0.022). Mortality was 21.6% among unwitnessed and 22.0% among witnessed (P=0.847), and symptomatic intracranial hemorrhage rates were 6.6% and 5.8%, respectively (P=0.623). The primary outcome (modified Rankin Scale shift) showed no difference comparing unwitnessed to witnessed patients (odds ratio, 1.35 [95% CI, 0.82-2.20]; P=0.235) in the inverse probability of treatment weighting. Unwitnessed patients were more likely to achieve functional independence or return of Rankin (1.53 [1.01-2.33]; P=0.045). Other secondary outcomes did not differ between the witnessed and unwitnessed patients. In the extended time window, unwitnessed patients with large-vessel occlusion undergoing endovascular thrombectomy have at least the same likelihood of favorable outcomes as witnessed patients. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Long-term survivors of childhood, adolescent, and young adult cancer are at risk for treatment-related late effects; therefore, survivorship care is essential. We explored the survivorship experience among young adult survivors of hematologic malignancies participating in a multi-institutional financial navigation trial. We conducted a secondary analysis using a mixed-methods, qualitative-dominant approach. Analysis was restricted to participants who completed an end-of-study interview. Baseline quantitative survey data related to survivorship care and engagement were included. Interview transcripts were analyzed using directed content analysis and inductive reasoning. Themes related to survivorship care were reviewed and further examined as factors influencing survivorship care engagement. The 45 participants' median age was 31.5years (Q1 = 28, Q3 = 35), with more than half (57.2%) identifying as Asian, Hispanic, or other non-Hispanic non-White. Median time since their blood cancer diagnosis was 9years (interquartile range 6-18). During baseline assessment, 45.2% of participants reported having a treatment summary and 50.0% were currently receiving survivorship care. Most (83.3%) felt they had received all recommended care within the previous year; however, 50.0% reported delaying or foregoing care due to cost. Nearly half referenced engagement in survivorship care during their interview. Factors serving as catalysts or barriers that influenced care engagement included late effects, mental health concerns, cost of care, and travel logistics for continued care at specialty centers. Young adults' survivorship engagement is influenced by varied factors long after diagnosis. These findings emphasize the importance of tailoring information delivery and interventions to meet the needs of this growing population. NCT05620979, registered/posted on 11/17/2022.

e16068 Background: Esophageal cancer (EC) originates in the lining of the esophagus and often necessitates hospitalization in advanced stages. Sepsis, a severe and potentially fatal complication, poses significant challenges for hospitalized patients with EC. This study investigates and compares the outcomes of EC hospitalizations complicated by sepsis to enhance understanding and improve patient care strategies. Methods: Hospitalizations with a diagnosis of esophageal cancer were identified from the 2019 National Inpatient Sample (NIS) using ICD-10 codes. Patients were categorized based on the presence or absence of sepsis. Sociodemographic characteristics and comorbidities were analyzed. The primary outcome was in-hospital all-cause mortality, while secondary outcomes included complication rates. Multivariable regression analyses were performed to assess associations, with statistical significance defined as p &lt; 0.05. Results: Among the 34,030 hospitalizations for esophageal cancer, 4,190 (12.3%) involved sepsis. Patients in the sepsis group were older, with a mean age of 68.1 years compared to 67.3 years in those without sepsis (p &lt; 0.05). Sepsis was also associated with a significantly higher risk of in-hospital mortality (adjusted odds ratio [aOR] 2.74; 95% CI: 2.22–3.38, p &lt; 0.001). Additionally, patients with sepsis had significantly higher odds of developing respiratory failure ([aOR] 4.21; 95% CI: 3.57–4.97, p &lt; 0.001), requiring mechanical ventilation (aOR 2.64; 95% CI: 1.95–3.58, p &lt; 0.001), and experiencing pulmonary embolism (aOR 1.59; 95% CI: 1.06–2.38, p &lt; 0.001). Patients with sepsis also exhibited significantly higher odds of acute kidney injury (aOR 2.80; 95% CI: 2.35–3.33, p &lt; 0.001) and deep venous thrombosis (aOR 2.94; 95% CI: 1.74–4.98). However, there were no statistically significant differences in the odds of gastrointestinal hemorrhage. Conclusions: Hospitalizations for esophageal cancer complicated by sepsis are strongly linked to increased in-hospital mortality and severe complications. These findings highlight the urgent need for tailored interventions to reduce the morbidity and mortality associated with sepsis in this high-risk population. Future research should prioritize refining preventive measures and therapeutic strategies to enhance clinical outcomes for oncology patients facing these challenges.

e16411 Background: Ascites is a frequent complication in cancer patients, significantly contributing to morbidity. Pancreatic cancer patients, particularly those with metastatic disease, are at an increased risk of developing ascites. Despite its clinical importance, the impact of ascites on hospitalization outcomes in pancreatic cancer patients remains inadequately studied. This research aims to investigate the effects of ascites on inpatient outcomes in this population, addressing a notable gap in the current body of knowledge. Methods: The 2019 National Inpatient Sample was analyzed to identify patients with a diagnosis of pancreatic cancer using International Classification of Diseases, 10th Revision (ICD-10) codes. The study cohort was divided into two groups: patients admitted with ascites and those without ascites. Sociodemographic characteristics and comorbidities were systematically compared between the groups. The primary outcome was all-cause in-hospital mortality, while additional secondary outcomes were also evaluated. Multivariate regression models were used to examine differences in outcomes between the groups, with statistical significance defined as p &lt; 0.05. Results: Among 93,330 adult patients hospitalized with pancreatic cancer, 15,180 (16.2%) had concurrent ascites. These patients were significantly younger, with a mean age of 66.1 years compared to 69.0 years in those without ascites (p &lt; 0.005), and included a higher proportion of males (56%) compared to females (44%). Patients with pancreatic cancer and concurrent ascites exhibited significantly increased odds of all-cause mortality (adjusted odds ratio [aOR] 2.30, 95% confidence interval [CI] 2.02–2.62, p &lt; 0.001), concurrent gastrointestinal hemorrhage (aOR 1.25, 95% CI 1.04–1.51, p = 0.019), acute kidney injury (aOR 1.86, 95% CI 1.68–2.05, p &lt; 0.001), and septic shock (aOR 1.77, 95% CI 1.52–2.05, p &lt; 0.001). Additionally, these patients experienced longer hospital stays (mean length of stay: 7.4 days vs. 5.6 days; p &lt; 0.005) and higher hospitalization costs ($81,420 vs. $63,100; p &lt; 0.001). Conclusions: Pancreatic cancer patients with concurrent ascites had substantially higher odds of mortality, acute kidney injury, gastrointestinal hemorrhage, and septic shock. They also experienced longer hospital stays and incurred greater hospitalization costs compared to patients without ascites. These findings provide important insights into the prognosis of pancreatic cancer patients with ascites and highlight the need for targeted management strategies for this high-risk population.

e20032 Background: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent condition among smokers, often leading to substantial morbidity. Lung cancer patients, many of whom have a history of smoking, frequently experience concurrent COPD and are at an increased risk of COPD exacerbations. However, the impact of COPDE on clinical outcomes in patients with lung cancer remains insufficiently studied. This study aims to explore the effects of COPDE on inpatient outcomes in this population, addressing an important gap in the current body of knowledge. Methods: Data from the 2019 National Inpatient Sample were analyzed to identify patients with a diagnosis of lung cancer using International Classification of Diseases, 10th Revision (ICD-10) codes. The study population was divided into two groups: those with COPD exacerbation (COPDE) and those without. Sociodemographic variables and comorbidities were compared between the groups. The primary outcome was all-cause in-hospital mortality, with several secondary outcomes also assessed. Multivariate regression models were utilized to evaluate differences in outcomes between the groups, with statistical significance set at p &lt; 0.05. Results: Among 317,180 adult patients hospitalized with lung cancer, 10,155 (3.2%) were admitted with a diagnosis of chronic obstructive pulmonary disease exacerbation (COPDE). These patients were older on average (mean age: 70.1 years vs. 69.5 years) and included a higher proportion of females (54.6%) compared to males (45.4%). Patients with lung cancer and COPDE demonstrated significantly reduced odds of all-cause mortality (adjusted odds ratio [aOR]: 0.28; 95% confidence interval [CI]: 0.21–0.38; p &lt; 0.001), concurrent pulmonary embolism (aOR: 0.39; 95% CI: 0.26–0.59; p &gt; 0.001), acute kidney injury (aOR: 0.59; 95% CI: 0.51–0.69; p &lt; 0.001), and sudden cardiac death (aOR: 0.31; 95% CI: 0.14–0.66; p = 0.002). Additionally, patients with COPDE had shorter hospital stays (mean length of stay: 4.4 days vs. 6.1 days; p &lt; 0.001) and incurred lower hospitalization costs ($44,103 vs. $70,100; p &lt; 0.001). Conclusions: Lung cancer patients with concurrent COPDE demonstrated significantly lower odds of mortality, acute kidney injury, pulmonary embolism, and sudden cardiac death. They also experienced shorter hospital stays and reduced hospitalization costs compared to those without COPDE. These findings provide important insights into the prognosis of lung cancer patients with COPDE, highlighting potential differences in outcomes that may guide clinical management strategies.