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Summary Rosai–Dorfman disease (RDD) is a rare histiocytic neoplasm with diverse clinical behaviour and immune abnormalities with unknown clinical significance. We performed a retrospective cohort study of 162 patients with RDD from 2003 to 2025 at five international referral centres. Median age was 48 years and 64.8% were female. Multisystem disease occurred in 87 patients (53.7%), commonly involving skin/subcutaneous tissue (49.4%), lymph nodes (39.5%) and bones (34%). Molecular testing was available for 102 patients; 40 (39.2%) were mitogen‐activated protein kinase/rat sarcoma virus oncogene homolog signaling pathway (MAPK/RAS)‐altered, commonly with kirsten rat sarcoma viral oncogene homolog ( KRAS ) or mitogen‐activated protein kinase 1 ( MAP2K/MEK ) alterations. MAPK/RAS alterations were associated with multisystem disease ( p = 0.0034). Autoimmune disease (AID) was documented in 29 patients (17.9%), usually preceding RDD, and 45/95 patients (47.4%) with available autoantibody status had at least one positive autoantibody. Among 153 patients with response data, objective response occurred in 94 (61.4%). Response distribution differed by disease extent; single‐system disease was associated with more complete responses and less progression than multisystem disease. At a median follow‐up of 2.49 years, eight deaths occurred; 5‐year overall survival was 93.4%. AID and autoantibody positivity were not associated with response or overall survival. These findings support disease extent and molecular status as clinically relevant dimensions of RDD assessment, while autoimmune and serological abnormalities should be interpreted in clinical context.

Abstract Background and Aims The aim of the study was to assess the effect of guideline-directed medical therapy (GDMT) on cardiac function, neurohormonal activation, and mortality in adults with congenitally corrected transposition of the great arteries (cc-TGA) presenting with systemic right ventricular (RV) systolic dysfunction. The study hypothesis was that GDMT use (assessed using the GDMT score) was associated with improved cardiac function (higher RV free wall strain [RVFWS]), less neurohormonal activation (lower N-terminal pro-B-type natriuretic peptide [NT-proBNP] levels), and lower mortality. Methods GDMT score, RVFWS, and NT-proBNP levels were assessed at baseline and 1-year follow-up. GDMT uptitration was assessed using ΔGDMT (GDMT at 1-year minus GDMT at baseline). Improvements in RV systolic function and neurohormonal activation were defined as a relative increase in RVFWS of >20% and a relative decrease in NT-proBNP levels of >20%, respectively. Results Of 213 patients (age 43 ± 15 years; 54% male), baseline GDMT score was 1.97 ± 1.27, and ΔGDMT score was 0.74 ± 0.39. Baseline RVFWS was −18 ± 5%; 25% had improved RV systolic function. Baseline NT-proBNP was 369 (142, 1004) pg/mL; 56% had improved neurohormonal activation. Higher baseline GDMT score and ΔGDMT score were associated with improvement in RV systolic function and neurohormonal activation. Overall, 34 (16%) patients died, and higher baseline GDMT score and ΔGDMT score were associated with a lower risk of mortality and of the composite adverse event endpoint (heart failure hospitalization, death, and heart transplantation). Clinical benefits of GDMT use were observed only in patients with moderate/severe RV systolic dysfunction, and not in patients with mild RV systolic dysfunction. Conclusions GDMT use was associated with improved outcomes in patients with moderate/severe RV systolic dysfunction.

Background: Assessing craniocervical fibromuscular dysplasia (cc-FMD) can be challenging using cross-sectional imaging. We hypothesize that photon-counting detector CT (PCD-CT), owing to its superior spatial resolution over conventional energy-integrating detector CT (EID-CT), may better help appreciate changes in cc-FMD. Materials and Methods: In this retrospective cohort, 24 patients with radiologically reported cc-FMD (mean age: 54 y; 75% women) underwent both PCD-CT and EID-CT within 180 days (median: 52 d). Bilateral internal carotid (ICA) and vertebral artery (VA) segments without dissection/occlusion were graded on a 3-point scale (absent/likely present/present). Intermodality agreement was evaluated with weighted Cohen κ, and radiation dose metrics (CTDIvol) were compared using the paired Wilcoxon signed-rank tests. Results: Eighty-seven paired segments were analyzed. PCD-CT detected FMD in 48 segments (55.1%) versus 30 (34.5%) on EID-CT. The mean reader confidence scores were consistently higher with PCD-CT compared with EID-CT, for both ICAs (2.16±0.95 vs. 1.93±0.99) and VAs (1.86±0.95 vs. 1.36±0.75). Intermodality agreement was almost perfect for ICAs (κ=0.807) and substantial for VAs (κ=0.662). Under our institutional protocols, median CTDIvol was lower with PCD-CT (16.6 mGy) than EID-CT (21.5 mGy; P =0.0112). Conclusion: PCD-CT demonstrated more frequent reader categorization of cc-FMD features than EID-CT, particularly in the VAs, and had a lower median CTDIvol under our institutional protocols. These preliminary findings suggest improved cc-FMD detection with PCD-CT as compared with EID-CT and require prospective, reference-standard validation to establish accuracy and clinical impact.

Chimeric antigen receptor T-cell (CAR-T) and CD20xCD3 bispecific antibody (BsAb) therapies are both effective for relapsed/refractory (R/R) follicular lymphoma (FL), but comparative real-world survival outcomes and time toxicity have not been characterized. We performed a multicenter retrospective study of 228 patients with R/R FL treated with standard-of-care CAR-T (n = 141) or BsAb (n = 87) across 17 U.S. academic centers in the third-line or later setting. Progression-free survival (PFS) and overall survival (OS) were stratified by 2 or ≥3 prior lines of therapy (LOT2 or LOT3+), including propensity matching. Time toxicity was measured by physical health care contact days. Median PFS was not reached (NR) with CAR-T and 581 days with BsAb in the LOT2 cohort (p < .0001), and was NR with CAR-T and 584 days with BsAb in the LOT3+ cohort (p = .0064). CAR-T recipients were younger (p < .0001) and had better performance status (p = .007) but were more refractory to prior LOT (p = .017). PFS advantages of CAR-T were independent of these differences. OS did not differ between treatment groups. CAR-T had significantly greater time toxicity over the first year, with higher mean contact days than BsAb in both the LOT2 (58 vs 44) and LOT3+ (69 vs 49) cohorts. In this large multicenter cohort of patients with R/R FL, CAR-T was associated with superior PFS but greater time toxicity compared with BsAb therapy. These findings provide real-world outcomes data and time toxicity benchmarks to support treatment sequencing decision-making in R/R FL.

Study Design: Case presentation. Objective: The interlaminar endoscopic lateral recess decompression (IE-LRD) represents a novel surgical alternative to consider in carefully selected cases, particularly when patients do not respond to conservative treatment. Background: Lumbar spinal stenosis (LSS) constitutes one of the most prevalent spinal conditions in the elderly population around the world. A myriad of causes have been elucidated, and although infrequent, vertebral compression fractures (VCF) may also cause LSS. Conservative treatment might be the first option; however, patients often require surgery. Methods: A 76-year-old woman with a medical history of dementia consulted for radicular pain in her left leg during the past 6 months, without any favorable response to conservative treatment. Neurological examination revealed a positive straight leg raising test on the left. A spine MRI revealed a VCF in L5, linked with spondylolisthesis (grade I) at L5–S1. An IE-LRD was planned, as the patient did not consent to a classical open surgery. The incision was placed over the inferior medial edge of the left L4 lamina. Following sequential dilatators, the working channel was located on the inferomedial edge of the left L4 lamina. Lateral fluoroscopy (LF) guided the entire procedure. During the procedure, laminotomy was extended cranially and caudally to ensure sufficient vertebral decompression. Results: After surgery, the patient was mobilized in the first 6 hours and discharged in the next 24 hours. Her lower back pain score improved significantly to 2–3, while her leg VAS pain improved to 0–1. After a follow-up for 18 months, the patient did not manifest complications or recurrences, and no additional treatment was carried out. Conclusion: (1) IE-LRD might be a useful and safe surgical procedure for the surgical management of LSS caused by VCF. (2) Consider this surgical alternative for elderly patients without a previous response to conservative medical treatment.

ABSTRACT Background Left atrial appendage occlusion (LAAO) has emerged as a non‐pharmacological alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). Following the publication of recent CHAMPION‐AF and CLOSURE‐AF trials, an updated synthesis of evidence is warranted to clarify the long‐term comparative efficacy and safety of LAAO versus OAC in patients with AF. Methods We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing LAAO with OAC in adults with AF. A comprehensive search of major databases was performed from inception to April 2026. The primary efficacy outcomes were major adverse cardiovascular events (MACE) and stroke. The primary safety outcome was non–procedure‐related bleeding. Random‐effects models were used to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Results Six RCTs including 7,004 patients (3,681 LAAO; 3,323 OAC) were analyzed. No statistically significant difference was observed for MACE (7.5% vs 6.9%; RR 1.03, 95% CI 0.79‐1.34) or stroke (3.7% vs 3.2%; RR 1.07, 95% CI 0.80‐1.43). LAAO was associated with a significantly lower risk of non‐procedure‐related bleeding (9.8% vs 16.7%; RR 0.63, 95% CI 0.52‐0.77), corresponding to an absolute risk reduction of 6.9% and an approximate number needed to treat of 15 based on crude pooled event rates over the observed trial follow‐up. Trial sequential analysis indicated that the accumulated evidence for MACE and stroke remained inconclusive. Comparator‐type subgroup analyses showed no significant interaction for MACE ( p = 0.67) or stroke ( p = 0.81) between contemporary predominantly‐DOAC and VKA comparator trials. Conclusions LAAO was associated with lower non‐procedure‐related bleeding, while no statistically significant differences were observed for MACE or stroke. The available efficacy evidence remains inconclusive regarding equivalence or non‐inferiority, and larger trials are needed. These findings support individualized consideration of LAAO when the long‐term bleeding burden of anticoagulation is clinically important.

Cardiovascular responses exhibited both sex-dependent and sex-independent alterations in acute pancreatitis models of differing severity. In cerulein-induced mild acute pancreatitis, both sexes showed enhanced cardiac systolic function with only modest differences in vascular permeability. In severe acute pancreatitis, vascular permeability was similar between sexes, but compensatory cardiac systolic augmentation was preserved only in females. Angiopoietin-2 was identified as a compensatory cardiac mediator in severe disease.

Abstract Pancreatic ductal adenocarcinoma (PDAC), the most common subtype of pancreatic cancer, is a deadly disease with a complex tumor microenvironment (TME). Cytotoxic combination chemotherapy treatments are the mainstay of PDAC therapy, but patients rapidly develop chemoresistance, highlighting the need to elucidate how chemotherapy alters the TME and whether these changes drive chemoresistance. Here, we examined matched pre- and post-treatment tissue specimens using single-cell RNA-sequencing and found near-universal enrichment after treatment of axonal guidance genes in cancer-associated fibroblasts (CAFs). These neural CAFs were enriched near sites of perineural invasion, coinciding with regions of increased tumor cell proliferation, and were enriched in tumor areas distant from nerves after chemotherapy. Metastatic recurrent lesions had the highest prevalence of neural CAFs versus primary tumors and untreated metastases. Neural CAFs showed elevated non-canonical WNT mediators and axonal guidance genes, which complemented matching cognate binding partners in tumor epithelial cells, suggesting a role in tumor-stroma crosstalk. Additionally, in vitro studies revealed enrichment of axonal guidance genes in patient-derived CAF lines upon exposure to chemotherapy or tumor cells. Altogether, these findings implicate fibroblast-derived axonal-guidance genes in promoting PDAC invasion and point to a promising therapeutic target for this disease.