Citations

Purpose: Transradial intracranial aneurysm embolization is well established, but experience with large-bore 7F sheath-based guide platforms remains comparatively limited. We evaluated the technical feasibility and periprocedural outcomes of a 7F sheath-compatible 0.087inch guide catheter for transradial intracranial aneurysm embolization.Materials and Methods: In this single-arm, noncomparative retrospective study, we reviewed consecutive patients who underwent attempted transradial intracranial aneurysm embolization using the NeuGlide as the primary guide catheter at a single center between January 2025 and May 2026. Preaccess radial ultrasonography was performed in all patients, and radial diameter ≥1.7 mm was required for 7F access. The primary outcome was completion of the intended treatment through radial access without femoral conversion.Results: Target-vessel catheterization was achieved in 71/74 procedures (95.9%), and radial procedural completion in 69/74 (93.2%; 95% confidence interval, 85.1–97.1%). Three procedures required femoral conversion, and 2 were terminated without aneurysm treatment; overall treatment completion was 72/74 (97.3%). Guide instability occurred in 2 procedures: 1 repositioning-only event and 1 event resulting in femoral conversion; no guide exchanges occurred. Seven patients had 9 access-site component events, all managed conservatively; all 6 hematomas were low-grade (EASY I–II). Radial artery occlusion was identified in 1/15 patients formally assessed.Conclusion: In this radial-first cohort, the 7F sheath-compatible 0.087-inch NeuGlide guide catheter achieved a 93.2% radial procedural completion rate across multiple intracranial aneurysm treatment strategies. These findings support the NeuGlide as a technically feasible and versatile large-bore transradial platform in appropriately selected patients.

Abstract Objectives This study aimed to characterize susceptibility profiles of both currently approved and investigational β-lactam agents against difficult-to-treat resistant Pseudomonas aeruginosa (DTR P. aeruginosa) clinical isolates, including carbapenemase-producing strains. Patients and methods A total of 502 consecutive DTR P. aeruginosa clinical isolates were collected from unique hospitalized patients between 2022 and 2024 across three tertiary care centres. Isolates originated from bloodstream, respiratory, urinary and intra-abdominal infections. Minimum inhibitory concentrations (MICs) for seven β-lactam agents were determined using triplicate reference broth microdilution. Susceptibility interpretations were based on CLSI criteria or, where applicable, investigational breakpoints. Whole-genome sequencing was performed to detect β-lactamase genes. Results Among the 502 isolates, cefepime-zidebactam exhibited the highest in vitro activity (100% susceptibility), followed by cefiderocol-xeruborbactam (98%), cefiderocol (95%), ceftolozane-tazobactam (90%), cefepime-taniborbactam (86%), ceftazidime-avibactam (85%), and imipenem-relebactam (41%). Notably, only 35% of isolates were susceptible to all seven agents. Carbapenemase genes were identified in 4% of isolates, including blaGES (n = 13), blaVIM (n = 7), blaKPC (n = 1) and blaIMP (n = 1). Among carbapenemase-producing isolates, cefepime-zidebactam retained activity against all isolates (100%), exceeding that of other approved β-lactam/β-lactamase inhibitor combinations (0%–24% susceptible), cefiderocol (76%), cefiderocol-xeruborbactam (86%) and cefepime-taniborbactam (81%). Conclusions While currently approved β-lactam agents retained activity against many DTR P. aeruginosa isolates, their performance was markedly compromised in the presence of carbapenemases, with the notable exceptions of cefepime-zidebactam and cefiderocol. Investigational β-lactam/β-lactamase inhibitor combinations exhibited consistently robust activity across resistance phenotypes, including carbapenemase-producing isolates, representing promising options for DTR P. aeruginosa infections.

Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by lifelong immune dysregulation leading to high rates of autoimmune disorders, elevated risk of complications from infections, immune hypersensitivity, and a unique form of immunodeficiency. It is now appreciated that DS shares key hallmarks with interferonopathies, with vast remodeling of all branches of the immune system, hypercytokinemia, and widespread autoantibody production. Here within, we review the existing literature with an emphasis on clinical considerations toward monitoring, management, and therapeutic opportunities. We highlight recent research advances that illuminate diagnostic approaches to evaluate immune dysregulation in DS. We also discuss the evidence supporting specific immunomodulatory strategies that could have multidimensional benefits in this population, including JAK inhibitors, intravenous immunoglobulin, and B cell–depleting agents.

TPS160 Background: Up to 50% of patients with gastric cancer (GC) may develop peritoneal metastasis (PM) that is associated with resistance to systemic therapy and poor prognosis. Although cytoreductive surgery and intraperitoneal (IP) chemotherapy were shown to modestly improve the survival of patients with PM from gastric GC (PM-G), these clinical trials were performed in the pre-immunotherapy era. The significant heterogeneity in trial design and patient selection criteria further limit the applicability of these trial results to current clinical practice where anti-PD-1/L1 immunotherapy and/or targeted therapy in combination with chemotherapy have become a common, standard first-line therapy for the majority of patients with metastatic GC, raising the question of whether chemotherapy such as paclitaxel remains the most effective IP therapy. IP therapy using novel immunotherapy such as bispecific antibodies and chimeric antigen receptor T-cell therapy have demonstrated safety and promising antitumor activities in PM-G. We are conducting a phase 1b clinical trial that evaluates the efficacy of IP interleukin-2 (IL-2) in patients with PM-G with stable disease on first-line chemo-immunotherapy based on the hypothesis that IP IL-2 may synergize with intravenous (IV) chemo-immunotherapy to improve the treatment of PM-G. Multi-omics studies using patient blood, peritoneal fluid, and tissue specimens serially collected from this trial will be performed to characterize the changes in the tumor immune microenvironment of PM-G and identify new therapeutic targets. Methods: Patients with PM only from gastric adenocarcinoma are eligible for this phase 1b trial. All participants will continue IV fluorouracil-containing chemotherapy with nivolumab every 2 weeks and concurrently receive up to 16 doses of IP IL-2 (aldesleukin 6 × 10 5 IU/m2) weekly through an indwelling peritoneal catheter (Bard). Diagnostic laparoscopy (DL) will be performed before initiation of IP IL-2 and after 8 doses of IP therapy to assess treatment response based on the peritoneal cancer index (PCI), which is the primary endpoint of the trial. Patients with at least stable radiographic disease will continue to receive another 8 doses of IP IL-2 and undergo a third DL. Secondary endpoints include safety, peritoneal regression grading score, overall survival, and progression-free survival. Major inclusion criteria include mismatch repair-proficient or microsatellite-stable GC, PCI of 3-24, absence of distant metastasis other than PM, stable disease on first-line IV chemo-immunotherapy, tolerability of anti-PD-1 therapy, and adequate organ function. Enrollment began in 2024 and remains active. To date, seven of planned 15 patients have received study treatment without significant treatment-related adverse events and three of these patients underwent curative-intent cytoreductive surgery. Clinical trial information: NCT05802056 .

Post-transplant lymphoproliferative disorder (PTLD) involving the central nervous system (CNS) is a rare but serious life-threatening complication seen in recipients of solid organ transplant. Primary CNS encompasses 5–15% of all types of PTLD diagnoses, and heart transplant recipients represent 3–5% of those reported cases. Diagnosis is often delayed due to the highly variable presentation, with some cases remaining undiagnosed for years. Multidisciplinary collaboration is crucial for early diagnosis and management. A 53-year-old woman patient presented with altered mental status. MRI revealed nodular ventriculitis and bilateral periventricular hyperdense infiltrates. CSF studies demonstrated lymphocytic pleocytosis, elevated protein, and EBV-PCR-positive results. A stereotactic brain needle biopsy confirmed the presence of EBV-positive diffuse large B-cell lymphoma, consistent with primary CNS PTLD, 14 months after her heart transplant. Despite appropriate management, the patient experienced progressive neurological decline and ultimately suffered a fatal intracerebral hemorrhage. We demonstrate the importance of the early diagnosis and variable presentation of post-heart-transplant PTLD. The importance of surveillance regardless of EBV status and close monitoring of disease progression due to potential life-threatening complications, such as fatal hemorrhages. Therefore, primary CNS-PTLD remains a challenging disease and is being increasingly recognized with improved transplant recipient survival and prolonged exposure to chronic immunosuppression.

Ziftomenib - a potent, selective, oral menin inhibitor - is approved as monotherapy for adults with relapsed/refractory (R/R) NPM1-mutated acute myeloid leukemia (NPM1-m AML). The KOMET-007 phase 1 trial investigated clinical activity and tolerability of ziftomenib in combination with standard therapies for R/R and newly diagnosed AML. Here, we report outcomes of adults with R/R NPM1-m AML treated with ziftomenib plus venetoclax/azacitidine. In phase 1a, patients received ziftomenib 200, 400, or 600 mg once daily with standard doses of venetoclax/azacitidine. In phase 1b, ziftomenib 600 mg was selected for expansion. Sixty-seven patients were treated (27 phase 1a; 40 phase 1b). Median age was 66 years, and 55% were men. Median number of prior therapies was 1 (range 1-8); 55% received prior venetoclax and 22% had prior transplantation. Most common (≥20%) grade ≥3 treatment-emergent adverse events were leukopenia (34%), thrombocytopenia (28%), febrile neutropenia and neutropenia (25% each). Six patients developed QTc prolongation (1 ziftomenib-related; grade 1), and 2 experienced differentiation syndrome (grade 3); all events were successfully managed. In patients receiving ziftomenib 600 mg, composite complete remission (CRc) rate was 46% (22/48), with 67% (12/18) achieving central measurable residual disease (MRD) negativity (<0.01% threshold). In venetoclax-naïve and -exposed patients, CRc rates were 70% (16/23) and 24% (6/25), with MRD-negativity rates of 75% (9/12) and 50% (3/6), respectively. Median duration of response was 8.6 months, and median overall survival was not reached. The combination of ziftomenib 600 mg with venetoclax/azacitidine was well tolerated with deep and durable clinical activity in R/R NPM1-m AML. This trial was registered at www.ClinicalTrials.gov as #NCT05735184.

Abstract Background Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma. While localized disease has an excellent prognosis, metastatic EMPD is aggressive with no standardized systemic therapy. This study characterizes the clinicopathologic and molecular landscape of metastatic/recurrent EMPD to identify therapeutic vulnerabilities. Patients and methods We conducted a retrospective cohort study of 26 patients with metastatic or distantly recurrent EMPD treated at Mayo Clinic (2000-2025). Descriptive statistics were used to summarize baseline characteristics. Survival outcomes were estimated using Kaplan–Meier methods, with group comparisons performed using log-rank testing. Continuous variables were compared using nonparametric tests, and categorical variables were analyzed using appropriate comparative tests. Pathway-level genomic correlations with TCGA reference cohorts were assessed using Spearman rank correlation. Treatment responses were retrospectively evaluated from radiologic reports. Results The cohort was predominantly male (73.1%) and White (92.3%), with a median age of 68 (IQR, 53-79). Lymph nodes were the most common metastatic site (61.5%). The median overall survival (OS) was 20.0 months (95% CI, 0-40.4). IHC showed universal CK7 and GATA3 positivity, with 80% androgen receptor (AR) expression. HER2 was positive (3+) or amplified in approximately one-third of cases. NGS revealed frequent mutations in TP53 (68.8%), ERBB2 (50%), and CDKN2A/B (50%). A “triple-hit” deletion at the 9p21 locus (CDKN2A/B/MTAP) was identified in 25% of cases. Genomic profiling showed strong similarity to HER2+ breast and urothelial carcinomas. HER2-directed therapy was associated with longer overall survival (median OS 73.0 months [95% CI, 0-177.9] vs 19.0 months [95% CI, 0-41.4]; HR 0.50 [95% CI, 0.0-177.9], P = .3), although this difference did not reach statistical significance. Conclusion Metastatic EMPD exhibits distinct clinicopathologic and molecular features, including high AR and HER2 expression, TP53 and CDKN2A/B alterations, and similarity to systemic HER2+ malignancies. The observed activity of HER2-directed therapies in this cohort suggests the potential value of further investigating biomarker-guided treatment strategies in metastatic EMPD. NGS-guided profiling may inform precision treatment strategies, including AR-targeted therapy and emerging MTAP-directed approaches.

Recent advances in gastroesophageal cancer highlight the continued evolution of systemic therapy across disease stages, including refinements in perioperative strategies and expansion of biomarker‐directed treatment in advanced disease. Emerging therapeutic approaches, including next‐generation antibodies and combination strategies, are expected to further shape treatment selection and improve outcomes.