Citations

Background/Objectives: Radiofrequency (RF) wire energy can be used for tissue ablation across many conditions. Adjusting RF generator parameters allows RF energy to puncture tissue with minimal adjacent damage. When RF energy is applied to tissue, however, microbubbles are produced, obstructing intravascular ultrasound (IVUS). Mitigation of RF-generated microbubbles has been studied for ablation but not for puncture. Methods: This paper describes an in vitro bench study using ex vivo bovine live tissue. A model was created with bovine liver tissue and an IVUS catheter submerged in a saline bath. Tissue was punctured with an RF guidewire to recreate microbubbles. Following the puncture, various methods were applied: altering the mechanical index of the IVUS, applying a VF10-5 Linear probe (Siemens), and applying a L12-3 Linear probe (Philips). Regions of interest (ROIs) were selected to track pixel brightness as a proxy for microbubbles. Results: The control increased ROI brightness by 1.5%. Altering the mechanical index of IVUS reduced ROI brightness by 1.2%. VF10-5 probe application increased ROI brightness by 1.2%. L12-3 probe application reduced ROI brightness by 33.0% (p = 0.046, n = 3, one-sample t-test). Brightness reduction was most pronounced at the site of initial RF wire puncture, where microbubbles accumulated. Tip visualization improved, allowing for more precise wire trajectory adjustments. Conclusions: External US with an L12-3 probe was able to dissipate microbubbles effectively to improve IVUS guidance following RF wire puncture in an in vitro exploratory bench model.

Background: The medial femoral trochlea flap is used for treating recalcitrant scaphoid proximal pole nonunions. Although this requires resecting a substantial portion of the scapholunate interosseous ligament, the intercarpal angular relationships are preserved. Studies have demonstrated that lunate alignment is preserved despite loss of the scapholunate ligament because the scaphoid is reconstructed with an osteochondral flap that is larger than the resected nonunited proximal scaphoid. The technique of purposeful expansion of the scaphoid height has been termed scaphoid overstuffing . The purpose of this study is to characterize the effect of scaphoid overstuffing on force transmission across the scaphoid and lunate facets of the radius. Methods: Eleven fresh frozen cadaveric upper extremities without ligament instability were selected. The radiocarpal joint was exposed via a dorsal approach, and electronic pressure sensors were introduced. Three different states of the wrist were evaluated: native, scapholunate dissociation (SLD), and overstuffed (OS). Pressures were measured in 4 positions: 30° flexion, full wrist extension, 30° extension, and clenched fist. Pressures were measured in kPa and contact areas in mm 2 . Results: In all functional positions, the OS state had higher peak pressures across the scaphoid facet. This included 30° wrist flexion (OS 383 ± 221 kPa, P = .033), full wrist extension (OS 1068 ± 767 kPa, P = .022), 30° wrist extension (OS 880 ± 518 kPa, P < .001), and clenched fist (OS 1040 ± 736 kPa, P = .02). Conclusions: In functional wrist positions, overstuffing the scaphoid increases scaphoid facet peak contact pressures. Further study is needed to examine the long-term clinical consequences of these changes and the potential for accelerated cartilage degeneration.

Abstract Echocardiography is the most widely used cardiac imaging modality, yet artificial intelligence-enabled interpretation remains limited by the inability of existing models to integrate visual assessment, quantitative measurement, and clinical reasoning within a unified framework. Here we present EchoAtlas, the first autoregressive vision-language model developed for echocardiographic interpretation. Trained on over 12.9 million question-answer pairs derived from approximately 2 million echocardiogram videos, EchoAtlas achieves 0.966 accuracy on multiple-choice questions in our internal test set and establishes a new state-of-the-art on the public MIMIC-EchoQA benchmark (0.699 vs. 0.508 previously). EchoAtlas also provides accurate quantitative measurements, segment-level regional wall motion assessment, longitudinal comparison, and diagnostic reasoning across diverse question formats — capabilities not previously demonstrated in this domain. These results highlight the potential of autoregressive vision-language models as a foundation for interactive echocardiographic interpretation, representing an early step toward scalable, auditable artificial intelligence systems in cardiology practice.

Introduction Psychological comorbidities can negatively impact outcomes of spinal cord stimulation (SCS) for chronic pain. While psychological assessment is commonly required before SCS implantation, evidence supporting its impact on outcomes is limited, and such assessments may be unnecessary for many patients and contribute to delays in care. Our center implemented a screening tool incorporating validated questionnaires and a mental health checklist to triage the need for formal psychological evaluation. This prospective, observational cohort study compared outcomes of SCS trials and implants between patients who bypassed (fast track: FT) versus those who underwent a formal assessment by a psychologist (AP). Methods Data were collected from patients undergoing SCS trials between July 2017 and December 2021. The screening tool used thresholds on validated questionnaires assessing anxiety, depression, catastrophizing, and opioid misuse risk, along with a checklist capturing significant anxiety or depression, self-harm, substance abuse, or mental-health-related hospitalization. Patients screening positive underwent an AP; others proceeded directly to trial (FT). 1 year post implantation outcomes were collected, with successful implantation defined as ≥30% pain reduction from baseline. Results Of 171 patients (114 AP, 57 FT), trial-to-implant rates were similar (72% AP vs 70% FT, p=0.811). The proportion of responders at 1 year post implant was also comparable (53% AP vs 60% FT, p=0.927). Multivariate logistic regression identified that higher baseline pain intensity (adjusted OR (aOR) 0.70, 95% CI 0.53 to 0.92, p=0.011) and use of tricyclic antidepressants (aOR 0.15, 95% CI 0.04 to 0.56, p=0.005) were associated with implant failure, whereas pain duration >10 years was associated with implant success (aOR 3.09, 95% CI 1.06 to 9.02, p=0.039). Conclusions This screening tool effectively identifies patients who can bypass routine psychological assessment without compromising 1 year SCS outcomes. Implementation can streamline patient flow, reduce wait times, and reserve psychological resources for those who need formal evaluation.

We searched for oncogenes activated by copy number increases using whole-genome sequencing data of 535 pancreatic ductal adenocarcinomas (PDACs). We found that gains of 1q were the second most common gain, occurring in 213 (39.8%) of PDACs. Single-cell analysis via fluorescence in situ hybridization on 33 cancers confirmed these results. A portion of 1q, rather than the entire 1q arm, was gained in 75 (14.0%) PDACs, allowing us to pinpoint two ~3-megabase regions of 1q that were nearly always gained. These two regions contained NCSTN and PSEN2 , genes that code two subunits of the γ-secretase complex. Evaluation of 267 precancerous lesions revealed that extra copies of NCSTN and PSEN2 were common (49%) in noninvasive neoplasms (high-grade pancreatic intraepithelial neoplasms), which are at relatively high risk for progression to PDACs, but uncommon (6%) in low-grade pancreatic intraepithelial neoplasia lesions, which have low malignant potential. We hypothesize that γ-secretase genes are genetically activated oncogenes in the early phases of pancreatic neoplasia.

Abstract Background PALLAS trial compared palbociclib plus endocrine therapy (ET) vs. ET alone in stage II-III HR+/HER2- breast cancer. SETER/PR index quantifies transcriptional activity related to estrogen and progesterone receptors and serves as a measure of endocrine sensitivity. In CALGB 9741, low SETER/PR (&lt; 0.75) - reflecting endocrine resistance - predicted survival benefit from adjuvant anthracycline/taxane-based treatment. In PALLAS low SETER/PR was associated with worse prognosis and early recurrence. Early recurrences driven by endocrine-resistant tumors may obscure the benefit of palbociclib by disproportionately contributing events from a more resistant population. We hypothesized that palbociclib efficacy might vary by endocrine sensitivity and prior chemotherapy regimen, with greatest benefit in patients with intermediate SETER/PR index. Methods Invasive disease-free survival (iDFS) was summarized with Kaplan-Meier plots and the treatment arms were compared with a log-rank test. Cox models estimated the hazard ratio (HR) with 95% confidence interval (95%CI) (significance level used was a two-sided 0.05). SETER/PR index was successfully obtained for 3,090 PALLAS patients (TransPALLAS ITT cohort, Metzger et al. ASCO 2024). SETER/PR index cut points (0.75 and 1.50) were proposed from previous studies comparing different adjuvant chemotherapy regimens. Results Table 1 summarizes the efficacy of adjuvant palbociclib by prior (neo)adjuvant chemotherapy regimen. Palbociclib was associated with longer iDFS in the group who received prior anthracycline-paclitaxel chemotherapy (AC-P), though the chemo regimen x palbociclib interaction term was not significant (Table 1). In the 1,132 patients from the TransPALLAS cohort who received AC-P chemotherapy, the 518 (46%) patients with intermediate SETER/PR (0.75≤ SETER/PR &lt;1.50) had longer iDFS with palbociclib (HR 0.58; 95% CI: 0.40-0.84; p=0.004; 7-yr iDFS 80.2% vs. 68.4%), but this subset did not predict palbociclib benefit relative to all others, i.e., 206 (18%) patients with low SETER/PR (&lt;0.75) and 408 (36%) high SETER/PR (≥1.50); P interaction=0.11. Exploratory analysis of SETER/PR index as a continuous variable in patients who received prior AC-P chemotherapy revealed a non-linear relationship with the hazard ratio favoring palbociclib observed in the subset with SETER/PR values between 1.1 and 1.8, compared to all others (P interaction=0.01). Conclusions In PALLAS, we observed a numerical benefit favoring palbociclib among pts treated with adjuvant AC-P; in this subset a moderate level of endocrine transcriptional activity (SETER/PR index between 1.1 and 1.8) predicted palbociclib benefit. These results are hypothesis-generating. Citation Format: O. Metzger, P. O'Brien, K. Ballman, M. Gnant, M. Watson, E. Chen, K. Tran, D. Hlauschek, M. Martin, J. Balko, Z. Nowecki, O. Hahn, C. Denkert, C. Curtis, F. Liu, A. Dueck, C. Fesl, E. Mayer, A. De Michele, W. Symmans. Exploratory analysis of palbociclib benefit in the PALLAS trial by SETERPR index and prior chemotherapy regimens (ABCSG-42/AFT-05/BIG-14-13) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-08-13.

Abstract Background Recurrent pericarditis (RP) predominantly shows features consistent with IL-1-mediated chronic autoinflammatory disease (1-4). A recent analysis suggested that supplementing anakinra with colchicine incrementally reduced pericarditis recurrence vs. anakinra alone (5). Rilonacept (a weekly IL-1α and IL-1β cytokine trap with 6-week washout) prevents engagement with IL-1 receptor, inhibiting both IL-1α and IL-1β activity (6). The Phase 3 trial RHAPSODY demonstrated rilonacept efficacy in two independent analyses: Randomized Withdrawal (RW) and Long-Term Extension (LTE) periods (7,8). Purpose Assess long-term recurrence-free persistence with rilonacept as monotherapy in pts with RP during the combined RW and LTE periods of RHAPSODY. Methods Post-hoc analysis. Freedom from recurrence on rilonacept monotherapy was quantified using the Kaplan-Meier (KM) method from RW start (if randomized to rilonacept) or from initiation of bailout rilonacept (if randomized to placebo) until the end of treatment. Prespecified recurrence adjudication criteria were pericarditis pain (numerical rating scale [NRS]) ≥4 plus C-reactive protein (CRP) ≥1 mg/dL. Per RHAPSODY protocol, background therapies were discontinued during the Run-In Period before randomization. In pts treated with rilonacept, concomitant colchicine was not added during the RW period. In the LTE, 6.8% (5/74) of pts added colchicine: one for 2 days of chest pain without CRP elevation, 4 in the absence of chest pain, CRP elevation, or recurrence; these 5 pts were censored in the KM curve at 6 days after last rilonacept dose or at colchicine initiation (whichever was first). One additional pt added colchicine prophylactically before an intentional rilonacept treatment interruption for elective cardiac surgery and experienced a recurrence after this interruption; this pt was not censored from the recurrence-free persistence analysis at colchicine initiation in order to capture this event. Results 74 pts (mean [SD] age 43.9 [15.7] years, 83.8% idiopathic pericarditis, mean [SD] disease duration 2.5 [3.2] years) were analyzed over three years. Rilonacept was well tolerated. Recurrence-free persistence was 95.9% (n=71/74) while receiving rilonacept as monotherapy (Figure 1). The three observed adjudicated recurrences were each associated with temporary interruptions of 1-3 doses of rilonacept. Conclusions Rilonacept as monotherapy provided recurrence-free persistence over the three-year trial duration when used continuously without interruption; pericarditis recurrences occurred only after interruptions. These findings support evidence-based use of rilonacept as monotherapy, minimizing the need for adjunctive treatments and reducing polypharmacy in long-term RP management. Further investigations are warranted to address how to assess pts as candidates for long-term treatment with rilonacept and when to cease rilonacept treatment.

Abstract Background Recurrent pericarditis (RP) is an IL-1-mediated chronic autoinflammatory disease (1,2). The phase 3 trial RHAPSODY demonstrated that rilonacept (IL-1α and IL-1β cytokine trap), the first and only FDA-approved treatment for RP, was effective in treating RP not only as a third-line agent (3L; after corticosteroids) but also as a second-line agent (2L; instead of corticosteroids) and reduced recurrence risk as monotherapy (3). The REgiStry Of the NAtural history of recurreNt periCarditis in pEdiatric and adult patients (RESONANCE) has been collecting long-term combined prospective and retrospective data from US-based pericardial-disease-dedicated programs since 2020 (4). Purpose To assess the efficacy of rilonacept in RP in a real-world setting, extending the clinical trial findings of RHAPSODY. Methods Database cut-off (DCO) was 05 February 2025. Data on RP management were collected and analyzed from pts with ≥2 years of observation in RESONANCE. Disease duration at DCO was defined as time from RP diagnosis to either disease resolution (no disease flares while off all RP treatments for ≥6 months before DCO) or last follow-up (for pts with ongoing treatment at DCO). Pericarditis recurrences (investigator-assessed) were confirmed based on RP symptom data and/or objective findings. Annualized recurrence rates were calculated per RP treatment regimen as total pericarditis recurrences divided by total patient-years (PY) while receiving that treatment. Wilcoxon signed-rank test was utilized to analyze the significance in change of annualized recurrence rates before and after rilonacept initiation. Results At DCO, 81 pts had ≥2 years of follow-up data in RESONANCE; mean (SD) age was 51.0 (16.8) years; most (66.7%) were female; 84% had idiopathic etiology; median (Q1-Q3) disease duration was 3.1 (2.6-3.7) years; and median observation was 2.93 (2.54-3.38) years. Patient-year treatment exposures per treatment were: NSAIDS ± colchicine (n=79; 187.8 PY), corticosteroids (n=30; 61.1 PY), anakinra (n=1; 1.2 PY) and rilonacept (n=35; 72.8 PY). Of the 35 pts treated with rilonacept for any duration (median observation: 3.2 years; median time on rilonacept: 2.08 years), the most common reason for rilonacept initiation was chest pain/recurrence on prior treatment (n=28). The annualized recurrence rate while receiving rilonacept was significantly lower versus all combined prior lines of treatment (4.00 vs. 0.02 events per PY; p=0.002); this outcome was consistent across line of treatment for rilonacept use (2L: 3.73 vs. 0.06 events per PY, p=0.02; 3L: 4.14 vs. 0 events per PY, p&lt;0.001; Table 1). Conclusions This first report of real-world outcomes from RESONANCE shows that rilonacept-containing regimens for RP as 1st, 2nd, or 3rd line therapy reduced recurrence risk over long- term (&gt;2 year) treatment, supporting prolonged management during RP natural history.

Background: The optimal role of advanced cardiac imaging in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that advanced imaging would provide greater diagnostic utility than transthoracic echocardiography with bubble study (bTTE). Methods: We retrospectively analyzed adults ≥18 years admitted with ESUS/cryptogenic stroke or recurrent embolic stroke with known atrial fibrillation (Aug 2024–Aug 2025). Patients with incomplete workup or known stroke mechanism prior to advanced imaging were excluded. Transesophageal echocardiography (TEE), cardiac MRI (CMRI), or CT heart morphology (CTH) were considered diagnostic if thrombus, patent foramen ovale (PFO), aortic plaque, or valvular pathology was detected. Outcomes included (1) etiology determination, (2) management change, and (3) diagnostic yield comparison between bTTE and advanced imaging. Results: Of 588 ischemic strokes, 178 met inclusion criteria; 48 were excluded for incomplete workup. Among 130 eligible patients, 65 (50%) underwent advanced imaging (40 TEE, 19 CTH, 6 CMRI). Etiology was identified in 41.5% (95% CI 30–54%), and management was changed in 40.0% (95% CI 29–52%). Compared with bTTE alone (14.6% yield), advanced imaging identified additional etiologies in 42.9% (McNemar p<0.001). Advanced imaging was more frequently performed in younger patients (mean 59.6 vs 69.2 years, p<0.001), while posterior circulation strokes were associated with higher odds of positive findings (OR 5.25, 95% CI 1.01–27.2). Conclusions: Advanced cardiac imaging identified a potential etiology and changed management in ~40% of ESUS/cryptogenic strokes, significantly outperforming bTTE. Although younger patients more often underwent advanced imaging in this cohort, only posterior circulation strokes predicted clinically actionable findings. Routine incorporation of advanced cardiac imaging into ESUS evaluation may improve diagnostic accuracy and treatment decisions.