Citations

Background Despite significant cardiac involvement in sarcoidosis, real‐world data on death due to cardiovascular disease among patients with sarcoidosis is not well established. Methods and Results We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database for data on patients with sarcoidosis aged ≥25 years from 1999 to 2020. Diseases of the circulatory system except ischemic heart disease were listed as the underlying cause of death, and sarcoidosis was stated as a contributing cause of death. We calculated age‐adjusted mortality rate (AAMR) per 1 million individuals and determined the trends over time by estimating the annual percentage change using the Joinpoint Regression Program. Subgroup analyses were performed on the basis of demographic and geographic factors. In the 22‐year study period, 3301 cardiovascular deaths with comorbid sarcoidosis were identified. The AAMR from cardiovascular deaths with comorbid sarcoidosis increased from 0.53 (95% CI, 0.43–0.65) per 1 million individuals in 1999 to 0.87 (95% CI, 0.75–0.98) per 1 million individuals in 2020. Overall, women recorded a higher AAMR compared with men (0.77 [95% CI, 0.74–0.81] versus 0.58 [95% CI, 0.55–0.62]). People with Black ancestry had higher AAMR than people with White ancestry (3.23 [95% CI, 3.07–3.39] versus 0.39 [95% CI, 0.37–0.41]). A higher percentage of death was seen in the age groups of 55 to 64 years in men (23.11%) and women (21.81%), respectively. In terms of US census regions, the South region has the highest AAMR from cardiovascular deaths with comorbid sarcoidosis compared with other regions (0.78 [95% CI, 0.74–0.82]). Conclusions The increase of AAMR from cardiovascular deaths with comorbid sarcoidosis and higher cardiovascular mortality rates among adults aged 55 to 64 years highlight the importance of early screening for cardiovascular diseases among patients with sarcoidosis.

Abstract Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults. Within the tumor, there is a subtype of cells deemed brain tumor initiating cells (BTICs), which contribute to tumor progression, therapy resistance, and tumoral heterogeneity. The tumor microenvironment, surrounding tumors, contains an ecosystem of cells in which BTICs can interact with and further promote tumor progression. In the lateral wall of the lateral ventricles, the neurogenic niche of the subventricular zone (SVZ), contains neural progenitor cells (NPCs) that self-renew and generate highly migratory neuroblasts. Interestingly, GBM tumors proximal to the SVZ are more proliferative, migratory, and negatively impact the survival of patients. We have previously observed that the presence of GBM induces reciprocal changes to the SVZ altering its neurogenic capacity and resulting in a more proliferative tumor. BTICs share similar self-renewal capacity to NPCs and may exert intercellular communication resulting in increased malignancy features. The mechanisms of intercellular communication, present in the SVZ include paracrine, autocrine, direct cell contact, gap junctions, nanotubes, and more recently extracellular vesicles (EVs). However, the exact mechanisms of how BTICs communicate with NPCs is not well understood. EVs are a heterogenous group of cell-derived membranous structures that serve as means of intercellular communication, allowing for cells to exchange proteins, lipids, RNA, and other genetic material. Cancer cells release higher amounts of EVs than non-malignant cells, and these EVs help communicate with other nearby cells, leading to promotion of tumorigenesis. We have observed that BTICs-derived EVs increase the proliferation of human NPCs, while altering their morphology and expression of stem cell markers. These effects are not observed when NPCs are treated with vesicle-free BTIC-derived secreted factors. To investigate the distinctions between BTIC secreted factors and protein cargo contained in BTIC-EVs, we employ the proximity protein labelling system, TurboID, and express this system in BTIC-EVs. The overarching goal of this project is to characterize BTIC-derived EV cargo to identify proteins that modify the GBM tumor microenvironment. We hypothesize that the phenotype of non-cancer NPCs is altered by distinct protein cargo contained in BTIC-derived EVs. The results of these experiments will help us to elucidate what BTIC-specific EV cargo impacts the tumor microenvironment, with the potential of revealing therapeutic targets for GBM. Citation Format: Marissa Russo, Maria Jose Ulloa Navas, Emily Norton-Ramos, Alfredo Quiñones Hinojosa, Hugo Guerrero Cazares. Exploring the differences between brain tumor initiating cell extracellular vesicles and secreted factors that influence the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2776.

Background Acute ischemic stroke complicates 2% to 3% of transcatheter aortic valve replacements (TAVRs). This study aimed to identify the aortic anatomic correlates in patients after TAVR stroke. Methods and Results This is a single‐center, retrospective study of patients who underwent TAVR at the Mayo Clinic between 2012 and 2022. The aortic arch morphology was determined via a manual review of the pre‐TAVR computed tomography images. An “a priori” approach was used to select the covariates for the following: (1) the logistic regression model assessing the association between a bovine arch and periprocedural stroke (defined as stroke within 7 days after TAVR); and (2) the Cox proportional hazards regression model assessing the association between a bovine arch and long‐term stroke after TAVR. A total of 2775 patients were included (59.6% men; 97.8% White race; mean±SD age, 79.3±8.4 years), of whom 495 (17.8%) had a bovine arch morphology. Fifty‐seven patients (1.7%) experienced a periprocedural stroke. The incidence of acute stroke was significantly higher among patients with a bovine arch compared with those with a nonbovine arch (3.6% versus 1.7%; P =0.01). After adjustment, a bovine arch was independently associated with increased periprocedural strokes (adjusted odds ratio, 2.16 [95% CI, 1.22–3.83]). At a median follow‐up of 2.7 years, the overall incidence of post‐TAVR stroke was 6.0% and was significantly higher in patients with a bovine arch even after adjusting for potential confounders (10.5% versus 5.0%; adjusted hazard ratio, 2.11 [95% CI, 1.51–2.93]; P <0.001). Conclusions A bovine arch anatomy is associated with a significantly higher risk of periprocedural and long‐term stroke after TAVR.

Background Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. Methods Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2–5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. Results M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. Conclusions Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

Abstract Background and Aims Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. Methods This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (&lt;10%/5 years), intermediate- (10%–25%/5 years), and high-risk (&gt;25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. Results One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. Conclusions North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Abstract Multisource feedback has long been a recommended tool to assess clinical competencies within graduate medical education. Additionally, incorporating feedback supplied by patients and other members of the healthcare team can provide the framework to bridge perspectives and viewpoints that may be different from their own. This, in effect, can aid in fortifying values in diversity, equity, and inclusivity by developing more knowledgeable, empathetic, and respectful future healthcare providers.

For patients with locoregionally confined pancreatic ductal adenocarcinoma (PDAC), margin-negative surgical resection is the only known curative treatment; however, the majority of patients are not operable candidates at initial diagnosis. Among patients with resectable disease who undergo surgery alone, the 5-year survival remains poor. Adjuvant therapies, including systemic therapy or chemoradiation, are utilized as they improve locoregional control and overall survival. There has been increasing interest in the use of neoadjuvant therapy to obtain early control of occult metastatic disease, allow local tumor response to facilitate margin-negative resection, and provide a test of time and biology to assist with the selection of candidates most likely to benefit from radical surgical resection. However, limited guidance exists regarding the relative effectiveness of treatment options. In this systematic review, the American Radium Society multidisciplinary gastrointestinal expert panel convened to develop Appropriate Use Criteria evaluating the evidence regarding neoadjuvant treatment for patients with PDAC, including surgery, systemic therapy, and radiotherapy, in terms of oncologic outcomes and quality of life. The evidence was assessed using the Population, Intervention, Comparator, Outcome, and Study (PICOS) design framework and “Preferred Reporting Items for Systematic Reviews and Meta-analyses” 2020 methodology. Eligible studies included phases 2 to 3 trials, meta-analyses, and retrospective analyses published between January 1, 2012 and December 30, 2022 in the Ovid Medline database. A summary of recommendations based on the available literature is outlined to guide practitioners in the management of patients with PDAC.

Background: The outcomes of leadless pacemaker (LP) implantation after transvenous lead removal (TLR) of infected cardiac implantable electronic devices (CIED) are not well-established. Objective: This study sought to describe the outcomes of LP implantation following TLR of infected CIED. Method: We conducted a literature search using PubMed and Embase for a combination of term including leadless pacemaker implantation, transvenous lead extraction, transvenous lead removal , transvenous lead explant , infected cardiac implantable electronic device . The inclusion criterion was LP implantation after TLR of infected CIED. The exclusion criterion was TLR for non-infectious reason. Study end-points were procedural complications and LP infection. Result: Of 132 publications reviewed, 13 studies with a total of 253 patients (74 ± 14 years of age, 69% males) were included. Amongst, 56.8% had systemic CIED infection and 43.2% had isolated pocket infection. Staphylococcus Aureus was the most common causative organism in 33% of the reported patients. Of 253 patients included, 105 patients (41.5%) underwent concomitant LP implantation during TLR procedure, and 36 patients (14.2%) had transvenous pacing as a bridge from TLR to LP implantation. During the LP implantation, 1 patient (0.4%) had an intra-procedural complication requiring sternotomy. Post-LP implantation, 2 patients (0.8%) developed groin hematoma, 2 patients (0.8%) developed femoral arteriovenous fistula, and 1 patient (0.4%) developed pericardial effusion requiring pericardiocentesis. During a mean follow-up of 11.3 ±10.6 months, 3 patients (1.2%) developed pacemaker syndrome, 1 patient (0.4%) developed acute on chronic heart failure exacerbation, and only 1 patient (0.4%) developed LP-related infection requiring LP retrieval. Conclusion: This study suggests that LP implant is feasible and safe post-removal of infected CIED with cumulative adverse events at 4% and a reinfection rate of 0.4%.

Introduction: The combination of local impedance (LI), a direct measure of electrical resistance at the catheter tip, and contact force (CF) may facilitate treatment of atrial fibrillation (AF). This trial is designed to examine the safety and effectiveness of a novel RF catheter that allows measurement of both LI and CF. Hypothesis: Demonstrate the safety and effectiveness of a novel radiofrequency catheter with LI and CF for treatment of drug refractory, recurrent, symptomatic Paroxysmal AF (PAF). Methods: NEwTON AF is a multi-center, global, prospective, single arm study. Patients received index treatment for PAF with the study catheter. The present 6-month endpoint analysis was prospectively planned. Results: The study treated 299 patients at 45 sites in North America, Europe, and Asia. Patients were 39.5% female with a mean age of 62yrs (±12), and had a mean LVEF of 59% and an LA diameter of 3.9cm. Procedure time, LA dwell, and fluoroscopy times were 166, 136, and 15 minutes, respectively. High-power short-duration (HSPD, 45-50W) was exclusively used in 210 cases, which had notably shorter procedure times than the 82 cases that used conventional power, 148 vs 208 min, respectively. Acute procedural success was observed in 98.3% of cases. As of 6 months, freedom from documented recurrence of any atrial arrhythmia was 79.9% (Figure). Recurrence in relation to LI shows that pts with a 20Ω LI drop (in at least 60% of lesions) had better 6m outcomes (84.2% vs 73.3, p=0.04). The freedom from safety event rate at 30d was 96.0%; events included pericarditis (6), access complications (2), pulmonary edema (2), embolism (2), cerebrovascular accident (1), tamponade (1). Pericarditis was higher in pts with a history of COVID at enrollment, 16.3% vs 5.9%, p=0.025. Conclusions: This data suggests that patient outcomes and safety for this novel catheter are promising. Further data from this study, including 12m outcomes, and detailed analysis of local impedance data are forthcoming.