Citations

This international multicenter study seeks to determine the frequency and characteristics of meningitis in myelin oligodendrocyte glycoprotein antibody (MOGAD)–associated disease and highlight its pathology.

ABSTRACT Background Transvenous lead removal (TLR) is a Class I indication for patients with cardiac implantable electronic device (CIED) infections. However, disparities in the utilization of TLR have not been fully explored, particularly concerning demographic and socioeconomic factors. Objectives This study aims to examine whether disparities exist among patients hospitalized for CIED infections with respect to the utilization of TLR, focusing on sex, race, and income characteristics. Methods We utilized the 2019 National Inpatient Sample (NIS) to assess patients hospitalized with CIED infections and identify those who underwent TLR. Multiple logistic regression was used to examine risk factors for TLR utilization, including age, sex, race/ethnicity, and socioeconomic characteristics. Results A total of 56 709 patients were hospitalized for CIED infection in the United States in 2019, of which 9867 (17.4%) underwent TLR. On an adjusted analysis, females and Black patients were found to have lower odds of undergoing TLR compared to males and White patients (OR: 0.62; 95% CI: 0.59–0.78; p < 0.01; and OR: 0.47; 95% CI: 0.39–0.57; p < 0.01, respectively). Hispanic patients also had reduced odds of TLR (OR: 0.73; 95% CI: 0.58–0.93; p = 0.01). No significant associations were observed between income or insurance status and the likelihood of receiving TLR after adjustment. Conclusions This study identified significant disparities in the utilization of TLR among patients hospitalized for CIED infections. Female, Black, and Hispanic patients were significantly less likely to receive TLR.

Background and purpose New Zealand White Rabbits are a useful preclinical model for neurovascular research. Inducing right common carotid artery aneurysms in New Zealand White Rabbits gives researchers the ability to test neurovascular devices in vivo. This study takes advantage of archived angiograms to obtain vascular measurements of interest for future research in rabbit models. Methods Rabbit angiograms from endovascular studies conducted in-house between 2005 and 2024 were analyzed using ImageJ at points of interest along the thoracic and abdominal aorta. Using scale references, the diameters of various New Zealand White Rabbit (2.5–3.5 kg) arteries were measured for aneurysm models and controls. Anatomic vascular variations were categorized and recorded. Results Measurable artery diameters at 39 points of interest were recorded for 170 female New Zealand White Rabbits. Type 1 vascular anatomy was the most common rabbit aortic arch, characterizing 85% of identifiable rabbit anatomies in this study. Conclusion By making these measurements available, this study simplifies future neurovascular studies, allowing for vasculature to be selected by size depending on the application. Additionally, the study offers insight into the relationship between elastase-induced aneurysms and surrounding vasculature size and draws size comparisons between some key arteries of interest.

Intracerebral hemorrhage (ICH), caused by the rupture of small blood vessels, remains the least treatable subtype of stroke. The pathophysiology of ICH involves immediate mechanical compression from the hematoma, followed by secondary injuries such as cerebral edema, inflammation, and neuronal damage. Management aims to prevent hematoma expansion, enable safe and effective hematoma evacuation, and mitigate secondary injuries. Recent advancements in clinical management, including blood pressure control, hemostatic therapy, surgical and minimally invasive hematoma removal, and complication management, offer new hope. This review synthesizes these advancements, integrating insights from recent research and clinical trials, and highlights significant progress in evidence-based approaches that pave the way for precise and personalized treatment strategies. Nonetheless, further research is necessary to enhance our understanding of ICH mechanisms and develop more effective clinical interventions.

ABSTRACT Background A novel individualized antitachycardia pacing (IATP) algorithm using the post‐pacing interval for real‐time control has been introduced. Performance information is limited to a small safety and feasibility study with additional single‐center and case studies. A larger‐scale analysis is needed to better understand algorithm performance. Methods Deidentified remote monitoring transmissions from devices with the IATP therapy applied were randomly selected. Rhythms were classified and effects of the novel algorithm were assessed. For monomorphic ventricular tachycardias (MVTs) proportions of successful therapy, shock‐free episodes, and acceleration were calculated using generalized estimating equations to correct for multiple episodes and compute statistics of the algorithm's performance. Results There were 2259 MVT episodes in 336 patients. IATP succeeded in 87.1% of MVT episodes with 89.9% of MVT episodes ultimately free of shock therapy. Based on multivariate analysis, significant factors in therapy success were programming of at least the recommended number of sequences (90% at least recommended vs 73%, p = 0.00088) and female sex (95% for females vs 86%, p = 0.002). A trend to higher success was found for MVT with a cycle length of 320 ms or greater (90% vs. 83%, p = 0.10). The IATP accelerated 3.6% of MVT episodes. None of the available factors was significantly associated with acceleration in the multivariate analysis. Conclusions The IATP algorithm succeeded in a large proportion of MVT episodes and with low acceleration in patients randomly selected from remote monitoring transmissions. Using at least the recommended number of sequences had the strongest association with successful therapy.

Abstract Accurate prediction of risk of progression from smoldering (SMM) to active multiple myeloma (MM) is paramount to individualized early therapeutic strategies with minimum risk of overtreatment. Current risk stratification models do not account for evolving biomarker trajectories. We assembled the largest cohort to date of 2,270 SMM patients from six international centers with longitudinal clinical and biological data to train and validate the PANGEA 2.0 risk models. Four evolving biomarkers were significantly associated with shorter time-to-progression: M-protein increase ≥0.2g/dL, involved:uninvolved serum free light chain ratio increase ≥20, creatinine increase >25%, and hemoglobin decrease ≥1.5g/dL. PANGEA 2.0 outperforms established models including the 20/2/20 and IMWG models by more accurately predicting progression (C-statistics=0.69–0.84), even without biomarker history (C-statistics=0.69–0.83) or recent bone marrow biopsy. PANGEA 2.0 is an easy-to-use, open-access tool (https://ghobrial.shinyapps.io/pangea_2_calculator) to improve and individualize SMM risk stratification. Validation tools are available to compare PANGEA 2.0 to established models (https://ghobrial.shinyapps.io/pangea_validation).

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.

e19515 Background: The prevalence of diabetes mellitus (DM) is significantly higher in patients with multiple myeloma (MM) compared to the general population. DM has been associated with worse outcomes in MM, including reduced overall survival and increased mortality. The impact of diabetes in patients with MM is further compounded by cardiotoxicity from proteasome inhibitors and the increased thromboembolic risk linked to immunomodulatory agents. Given the potential benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors, we hypothesized that their use in MM patients with DM could improve clinical outcomes and mitigate adverse events in this population. Methods: We utilized the TriNetX network to identify patients (≥18 years old) with MM and DM between January 1, 2013, and January 1, 2019. We categorized the patients into SGLT2 inhibitors users and SGLT2 inhibitors users. Inclusion in the SGLT2 inhibitors group required exposure to SGLT2 inhibitors for at least 1 year. 1:1 Propensity score matching was performed to match these two groups based on comorbidities, medications, baseline hemoglobin A1c, low-density lipoprotein, and left ventricular ejection fraction to produce two comparable cohorts. The study outcomes include all-cause mortality, all-cause hospitalization, acute venous thromboembolism (VTE), acute heart failure (HF), acute myocardial infarction (MI), cardiac arrhythmia, and cardiac arrest over the 5-year follow-up duration. Results: A total of 43,078 patients were identified, including 3,640 SGLT2 inhibitors users and 39,438 non-SGLT-2 inhibitors users. After 1:1 propensity-score matching, there were 3,379 SGLT-2 inhibitor users (68.9 ± 10.3 years of age, 38.0% female, 23.9% African American [AA]) and 3,379 non-SGLT-2 inhibitor users (68.9 ± 11.0 years of age, 35.9% female, 22.2% AA). SGLT-2 inhibitors users were associated with lower rates of all-cause mortality (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.30-0.39) and all-cause hospitalization (OR: 0.52, 95% CI: 0.47-0.58). Lower odds of acute VTE (OR: 0.59, 95% CI: 0.49-0.70), acute HF (OR: 0.89, 95% CI: 0.81-0.98), acute MI (OR: 0.81, 95% CI: 0.69-0.95), cardiac arrhythmia (OR: 0.82, 95% CI: 0.70-0.97), and cardiac arrest (OR: 0.57, 95% CI: 0.44-0.74) were reported among SGLT-2 inhibitors users compared to non-SGLT2 inhibitor users. Conclusions: Our study revealed that only 8.4% of patients with DM and MM were prescribed an SGLT-2 inhibitor. Our study also demonstrated that SGLT2 inhibitor use was associated with lower odds of all-cause mortality and hospitalization, reduced risk of VTE, and favorable cardiovascular outcomes in this patient population.

7014 Background: Mosun is a CD20xCD3 bispecific antibody that can be administered in the outpatient setting for a fixed duration. Intravenous Mosun is approved for the treatment of relapsed/refractory FL after ≥2 prior lines of therapy. Mosun SC achieved high response rates with manageable safety in patients with 3L+ FL in a pivotal Phase II study (Bartlett et al. ASH 2024). We report the efficacy and safety of Mosun SC in patients with previously untreated high-tumor burden FL in the Phase II MorningSun study (NCT05207670). Methods: Patients with previously untreated high-tumor burden FL, per GELF criteria, were enrolled into this cohort. Mosun SC was administered with step-up dosing in Cycle (C)1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg) then 45mg on D1 for up to 17 cycles (1 year; 21-day cycles). Patients with a partial or complete metabolic response (CMR) after C17 could receive additional Mosun maintenance therapy (45mg every 8 weeks for up to 1 year). Corticosteroid prophylaxis to reduce the risk of cytokine release syndrome (CRS) was mandatory in C1–2 and optional thereafter. The primary endpoint was progression-free survival (PFS) rate at 24 months. Key secondary endpoints included objective response rate (ORR), time to response (TTR), and safety. Results: As of May 29, 2024, 102 patients were enrolled; 55 patients had completed initial treatment (17 cycles), 31 had discontinued (most commonly due to progressive disease [n=19] and adverse events [AEs; n=4]), and 16 were ongoing initial treatment. Forty-two patients received maintenance treatment, and this was ongoing in 38 patients. Median age was 65 years (range: 24–86); 52.0% of patients were female. Most patients had Ann Arbor stage III/IV (91.2%) and a FLIPI score ≥2 (78.4%). Median duration of follow-up was 13.9 months. The 12-month PFS rate was 82.8% (95% confidence interval [CI]: 73.0–89.3). ORR was 87.3%; 60.8% of patients had a CMR. Among the 89 patients with a response, the median TTR was 2.7 months (range: 1.2–5.8). The most common AEs (≥30%) were injection-site reaction (57.8%), fatigue (42.2%), CRS (34.3%), headache (31.4%), and nausea (30.4%). Grade ≥3 AEs and serious AEs (SAEs) were reported in 44.1% and 29.4% of patients, respectively. CRS events were all Grade 1/2 and SAE of CRS occurred in 10.8% of patients (Table); all events resolved. Conclusions: Mosun SC demonstrated promising efficacy in patients with previously untreated high-tumor burden FL. The manageable safety profile, including rate of CRS, supports the administration of fixed duration Mosun SC in an outpatient setting. Additional data, including cytokine profiling and T/B/NK dynamics, will be presented. Clinical trial information: NCT05207670 . CRS events, n (%) PatientsN=102 Any grade 35 (34.3) Grade12 30 (29.4)5 (4.9) SAE 11 (10.8) ManagementSteroidsTocilizumabSteroids + tocilizumabFluidsICU admission 8 (7.8)6 (5.9)3 (2.9)3 (2.9)2 (2.0)