Citations

Abstract Background and Aims Stroke and systemic embolism are recognized but poorly characterized complications of atrial fibrillation (AF) and left atrial flutter (AFL) catheter ablation. Their incidence, outcomes, and procedural associations remain insufficiently defined. Methods Retrospective global registry was initiated by the European Heart Rhythm Association Scientific Committee. A secure database captured data from ablation centres worldwide on general AF and left AFL ablation activity, as well as detailed information on patients with symptomatic embolic events between 2017 and 2024. Results Overall, 204 centres reported 335 743 ablation procedures and 550 embolic events (incidence 0.16%). Centre-level rate ranged from 0% to 3.1%. Most events were cerebral (94%), followed by peripheral (5%), and combined (1%). Coronary air embolism accounted for 62% of all peripheral events. Intraprocedural events occurred in 93 patients (17%), within 72 h in 357 (78%) and beyond 72 h in 100 (22%); 128 cases (23%) were diagnosed after hospital discharge. Nonparoxysmal AF (0.23% vs 0.15%; P < .001), centre experience, and ablation energy source (radiofrequency, 0.16%; cryoballoon, 0.16%; pulsed field ablation, 0.25%; laserballoon, 0.88%; P < .001) were associated with embolic risk. Median NIHSS score after stroke was 4 (interquartile range, 2–9). Three-month follow-up was available for 518 patients with embolism (95%): 181 (35%) had sequelae and 16 (3%) died. Conclusions Symptomatic embolic events are infrequent but associated with significant morbidity and mortality. Most events occur early, though a substantial proportion arise later. Higher event rates were observed with laser and possibly with pulsed field ablation. A greater centre experience was associated with a lower embolism incidence.

Abstract INTRODUCTION Visual perceptual difficulties occur in dementia with Lewy bodies (DLB). Normative data and cut scores for DLB and mild cognitive impairment with Lewy bodies (MCI‐LB) are needed for the 20‐item Noise Pareidolia Task. METHODS Participants included 344 cognitively unimpaired (CU), 112 DLB, and 105 MCI‐LB. Cumulative percentile ranking was used for normative classification. Receiver operating characteristic analyses, convergent validity, and associations with visual hallucinations (VH) were assessed. RESULTS In CU participants, a perfect score was average, one error was low average, and two or more errors fell below average. A cut score of one or more errors optimally distinguished CU participants from DLB (Total score area under the curve [AUC]: 0.82, Noise score AUC: 0.77) and MCI‐LB (Total score AUC: 0.75, Noise score AUC: 0.74). A cut score of two or more errors lowered sensitivity but increased specificity to 94%. Performance was associated with VH in DLB, but not MCI‐LB. DISCUSSION Results establish normative data for the 20‐item Noise Pareidolia Task and support its use in DLB and MCI‐LB.

Importance Adjuvant chemotherapy regimens may be administered after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMNs), although the evidence supporting their use is limited. Objective To evaluate the survival benefit associated with contemporary adjuvant chemotherapy regimens after resection in A-IPMNs between 2017 and 2023. Design, Setting, and Participants This retrospective cohort study was an international, multicenter study with 69 participating centers across Europe, North America, South America, and the Asia-Pacific region. Patients undergoing resection for A-IPMNs were included. Data were analyzed from May to August 2025. Intervention Contemporary adjuvant chemotherapy regimens, such as gemcitabine-capecitabine (GemCap); 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX), modified FOLFIRINOX (mFOLFIRINOX), and S-1. Main Outcome and Measure Overall survival (months). Results Among 1321 patients (median [IQR] age 70 [63 to 76] years; 713 males [54.0%] and 608 females [46.0%]), 781 patients (59.1%) received adjuvant chemotherapy, while in 181 patients (13.7%) it was omitted due to poor patient fitness. Of patients who received adjuvant chemotherapy, 568 patients (72.6%) received contemporary regimens, including GemCap (232 patients [29.7%]), FOLFIRINOX (176 patients [22.5%]), mFOLFIRINOX (71 patients [9.1%]), and S-1 (70 patients [9.0%]). The median (IQR) follow-up for the cohort was 64.2 (40.4 to 85.0) months, and the median overall survival was 73.8 months (95% CI, 66.4 to 81.9 months). After 90-day landmark analysis and exclusion of patients ineligible for chemotherapy, adjuvant chemotherapy vs no adjuvant chemotherapy (propensity score–matched populations, 243:243 patients) was not associated with improved overall survival (median, 82.3 months; 95% CI, 78.2 months to not applicable [NA] vs not reached; 95% CI, 75.3 months to NA; P = .58). Contemporary regimens vs no adjuvant chemotherapy (propensity score–matched populations, 309:309 patients) was not associated with longer survival, and a mean survival benefit greater than 4.2 months over 5 years was excluded (difference in restricted mean survival, 1.26 months; 95%, −1.72 to 4.24 months). Treatment outcomes did not vary by chemotherapy regimen or disease characteristic (eg, N stage or carbohydrate antigen 19-9 level). Conclusions and Relevance In this study, contemporary adjuvant chemotherapy was not associated with improved overall survival in A-IPMNs, and a randomized clinical trial is indicated.

Few pharmacologic options exist for patients with clozapine-resistant schizophrenia (CRS) or schizoaffective disorder. Xanomeline/trospium represents a new class of antipsychotic medication that has efficacy as monotherapy for schizophrenia. Despite distinct mechanistic differences from standard antipsychotics, phase III evidence suggest limited benefit of xanomeline/trospium in the augmentation of non-clozapine antipsychotics. Research on the use of xanomeline/trospium in patients with clozapine-resistant illness or with partial response to clozapine is even more limited. Two cases of this combination are described with a discussion on key considerations for the management of CRS. The first case is a 42-year-old patient whose clozapine dose was limited by supratherapeutic clozapine levels in response to minor infections. She was ultimately stabilized on a combination of clozapine and xanomeline/trospium, with yet further improvements from electroconvulsive therapy (ECT). The second case is a 31-year-old patient who elected to discontinue clozapine and ECT due to cognitive side effects, despite improvement in psychosis. The addition of xanomeline/trospium to clozapine caused sialorrhea and did not produce observable clinical benefits and was thus discontinued. These case reports describe clozapine-resistant patients who were trialed on xanomeline/trospium combined with clozapine and still required consideration of ECT for symptom control. Overall, future investigation into xanomeline/trospium effectiveness as an augmentation agent or as monotherapy for CRS is necessary to guide clinical decision-making.

ABSTRACT Purpose Malignant rhabdoid tumor of the kidney (MRTK) is a rare, aggressive tumor seen in young children. The optimal timing of resection for locally advanced tumors is not well‐defined. The purpose of this study is to evaluate modern oncologic outcomes and the impact of surgical timing. Methods A multicenter retrospective review was performed by institutions participating in the Pediatric Surgical Oncology Research Collaborative. Children younger than 21 years old with MRTK diagnosed between 2000 and 2022 were included. Results Sixty‐nine patients were identified with MRTK and met the inclusion criteria. Median age of diagnosis was 10.1 months. Overall survival (OS) at 1, 5, and 10 years was 49%, 32%, and 19%, respectively. Patients with local Stage III disease who underwent upfront resection ( n = 18) compared to those who had delayed resection after NAT ( n = 15) had a similar OS, median OS greater than 60 months versus 14.6 months, respectively; p = 0.396. The surgical timing groups were balanced in terms of the presence of metastasis, length of follow‐up, and tumor characteristics. There was one occurrence of primary intraoperative tumor spill and two occurrences of organ injury in the upfront resection group compared to none in the delayed resection group. Conclusion MRTK carries a poor prognosis despite multimodal treatment. Histologic diagnosis may not be confirmed at presentation, and MRTK cannot be reliably distinguished from Wilms tumor on imaging alone. As overall survival is similar, the decision regarding surgical timing in locally advanced tumors should be individualized based on perceived resectability, balancing the risk of intraoperative complications against the possibility of tumor progression during neoadjuvant therapy.

ABSTRACT Background Driving supports independence and quality of life in later life but is vulnerable to age‐related and/or disease‐related decline. While cognitive impairment is a well‐recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. Methods We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in‐vehicle GPS dataloggers between 2019 and 2025. Linear mixed‐effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). Results At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (−0.050 vs. −0.037 trips/month), long‐distance trips (> 20 miles; p < 0.001), and maximum trip distance ( p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self‐reported driving behaviors showed that participants with higher SMI drove fewer days per‐week and were more likely to avoid night driving ( p < 0.01). Rates of self‐reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self‐regulatory behaviors. Conclusion Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low‐cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving.

Introduction This case describes the application of spinal cord stimulation for the treatment of phantom limb pain in a patient with a left transhumeral amputation. Treatment of pain involving a high frequency spinal cord stimulator allowed the patient to utilize his myoelectric prosthesis and improve his overall function. Clinical findings Severe, phantom limb pain with associated involuntary muscle contractions prevented the patient from wearing a prosthesis for more than three hours per day. He also had difficulty using his myoelectric prosthesis to use his left upper extremity for functional tasks. Therapeutic intervention A high frequency spinal cord stimulator was placed at the level of the cervical spine. The patient had improvement in pain and overall function. He was also able to tolerate wearing his prosthesis longer each day. Conclusion High frequency spinal cord stimulation may be an effective treatment option for individuals with phantom limb pain. Treatment of phantom limb pain may decrease barriers to prosthesis use and improve overall function.

While most cases of human muscle-invasive bladder cancer (MIBC) are diagnosed as conventional urothelial carcinoma (UC), there is growing recognition of histologic subtypes and divergent differentiation within conventional UC. In this study, 31 dogs with UC (33 slides) were evaluated for histologic subtypes and divergent differentiation, as specified by the recent World Health Organization update on the classification of urinary bladder cancers. Slides were reviewed by a medical uropathologist and 3 board-certified veterinary pathologists and assessed for expression of uroplakin III, vimentin, and E-cadherin. All tumors were classified as UC. Fifteen cases were identified as conventional UC. Among the remainder, 8 displayed glandular differentiation, 4 were classified as sarcomatoid UC, 2 showed squamous differentiation, 1 case was classified as a large nested subtype, and 1 case was classified as a tubular/microcystic subtype. This study found a higher frequency of certain histologic subtypes and divergent differentiation in canine UC, particularly sarcomatoid UC and UC with glandular differentiation, compared to previous reports of both canine UC and human MIBC. The relatively high prevalence of the sarcomatoid UC and UC with glandular differentiation in dogs observed in this study suggests that canine UC may serve as a valuable translational model for evaluating novel therapeutic agents, particularly for these rare and aggressive subtypes in humans.

Objective This study evaluates the impact of international observerships organized by Help Ukraine Group (HUG) on professional development, knowledge transfer, and clinical practice improvement in radiation oncology in Ukraine. Methods A total of 50 observerships were facilitated for Ukrainian medical professionals at 14 institutions across the USA, Canada, Europe, and Australia from 2022 to 2024, including 31 radiation oncologists and medical physicists. A survey assessed their impact on oncology care, focusing on knowledge gained, lessons learned, and challenges in implementing new techniques. The primary outcome was the success score, defined as a composite score of implementing new procedures, initiating improvement projects, and knowledge dissemination efforts. Descriptive and comparative analyses examined satisfaction and success outcomes. Results A total of 43 respondents participated in the survey (response rate 86.0%). Twenty-eight of the responders were radiation oncology professionals (67.8% radiation oncologists, 32.1% medical physicists). The median observership duration for radiation oncology professionals was four weeks, with 96.4% also attending a professional conference. Overall satisfaction was high (mean 9.5 out of 10, median 10.0, IQR 9.0-10.0) while the success score was substantial (mean 6.1 out of 10, median 7.0, IQR 5.0-8.0). Time since certification influenced success, with ≥10 years’ experience associated with higher success scores (7.4 vs. 4.7, p=0.01). Importantly, 100% of respondents learned new procedures, 89.3% reported shifts in their clinical perspective, and 60.7% successfully implemented new techniques. Subsequent knowledge dissemination in Ukraine was substantial: 82.1% provided informal training, 60.7% delivered institutional or national presentations, 39.3% incorporated materials into lectures, and 10.7% engaged in all activities. Continued mentorship with host institutions was reported by 82.1%. Conclusions Amid the war, international observerships advanced clinical practice, education, and procedures in Ukraine, demonstrating the resilience of its medical community and providing a model that other LMICs/UMICs can follow.