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 Latin America is undergoing rapid population aging alongside a rising burden of dementia. While the region holds substantial potential for dementia risk reduction, challenges remain, such as delayed diagnoses, limited access to specialized care and biomarker testing, persistent stigma, and deep‐rooted structural inequities. To address these gaps and foster regionally informed solutions, the Alzheimer's Association convened the 2025 Alzheimer's Association International Conference (AAIC) Satellite Symposium in Lima, Peru, on May 14–15, in collaboration with the Global Brain Health Institute (GBHI) and the Atlantic Fellows for Equity in Brain Health. The meeting aimed to bring core elements of the global AAIC meeting to regional Latin American settings, recognizing that national and cultural contexts demand tailored approaches to dementia prevention, risk reduction, treatment and care all aimed at promoting brain health in the region. This manuscript synthesizes the symposium's key discussions, scientific advances, and opportunities for collaboration across the region.

Background: Large language models (LLMs) are being used by surgeons for education and reference yet concerns about hallucinations and reliability limit safe adoption. Retrieval-augmented generation (RAG) can offer a potential solution by grounding responses in a high-quality external database (e.g., medical textbooks) to enhance accuracy. However, performance tradeoffs across different RAG configurations—many of which exponentially increase computational cost—remain poorly characterized. Methods: In total, 120 lightweight, open-source RAG configurations were evaluated across 40 plastic surgery-focused question-answering tasks (20 single-hop, 20 multi-hop), spanning multiple subspecialties (4800 total evaluations). Configurations varied by base LLM (Phi-3-mini-128k-instruct vs. BioMistral-7B), embedding model, database size, chunk size, and query hop type. Performance was assessed using semantic similarity (Ragas) to physician-validated reference answers. Performance was analyzed using linear mixed-effects regression with query as a random effect and fixed and interaction effects selected via likelihood testing and AIC. Results: High performance was achievable using lightweight, open-source models. While BioMistral-7B had high mean sematic similarity under specific configurations (mean semantic similarity up to 0.786), Phi-3-mini-128k-instruct demonstrated more consistent performance across query complexity. Larger database sizes significantly improved semantic similarity, with the largest gain at intermediate sizes (e.g., size 5: +0.043, p = 0.001). Embedding choice had a strong effect, with bge-large-en-v1.5 improving performance (p = 0.0016) and Bio_ClinicalBERT markedly reducing it (p < 0.001). Multi-hop queries substantially reduced performance (p < 0.001), though this effect was attenuated for Phi-3-mini-128k-instruct via a strong model × hop-type interaction (p < 0.001). Conclusions: RAG systems for plastic surgery do not require large proprietary models, as performance depends on configuration choices and interaction effects rather than isolated components. With advancements, predictive modeling may enable resource-efficient, safe deployment of clinical RAG systems.

Abstract Background IDH-mutant astrocytomas are classified as WHO grade 4 in the presence of conventional high-grade histologic features and/or homozygous CDKN2A/B deletion in the 5th edition of the WHO Classification of Central Nervous System Tumour guidelines. However, work over the past decade has indicated a number of other molecular alterations that warrant consideration as potential prognostic markers. Methods We used univariate Kaplan-Meier and multivariate Cox proportional hazards regression analysis to evaluate the prognostic effects of homozygous CDKN2A/B deletion, CDK4 amplification, CCND2 amplification, PDGFRA amplification/mutation, PIK3R1 mutation, PIK3CA mutation, MYCN amplification, EGFR amplification/mutation, TERT promoter mutation, and grade 4 histologic features in two independent cohorts of WHO grade 2-4 IDH-mutant astrocytoma (n = 840 and n = 367). Results The presence of CDK4 amplification, CCND2 amplification, PDGFRA alteration, PIK3R1 mutation, MYCN amplification, and EGFR alteration were each associated with reduced overall survival compared to WHO grade 2/3 astrocytomas without these molecular features. 17.7% (148/837) of otherwise grade 2/3 astrocytomas had one or more of these molecular criteria, with resulting intermediate clinical outcome in terms of overall survival (median survival of 67.3-82.0 months) compared to grade 2/3 astrocytomas without these molecular features (median survival of 135.0-140.7 months) and grade 4 astrocytomas (median survival of 35.3-45.0 months). Conclusions The presence of CDK4, CCND2, PDGFRA, PIK3R1, MYCN, and EGFR alterations result in an intermediate patient survival in IDH-mutant astrocytoma. Adding these molecular alterations should be considered in future diagnostic classification systems to improve stratification of high-risk patients.

Background: Automated discharge instructions are increasingly used to support post-discharge communication, patient education, and nursing follow-up, yet the current state remains unidentified. This systematic review explores the types of automated discharge instructions used and their effectiveness in enhancing patient engagement and reducing readmission, emergency department visits and reoperation rates. Methods: A systematic search was conducted on 15 April 2025, using Embase, PubMed, Scopus, Web of Science, and CINAHL, following PRISMA guidelines. Inclusion criteria required peer-reviewed original research evaluating the utilization of automated patient discharge instructions following hospital admission or surgical stay. Exclusion criteria included correspondence, reviews, educational materials, not peer-reviewed, retracted reports, not retrievable, and no English translation. Risk of bias was assessed independently using NIH, JBI, ROB-2, and ROBINS-I tools. Two investigators independently conducted the screening, extraction, and synthesis of results using Endnote and Microsoft Excel. Results: Of the 1252 records identified, 13 studies were selected for analysis. There was a total of 34,386 patients across a diverse range of healthcare settings and clinical contexts. The average sample size per study was approximately 4912, with study samples ranging from 16 to 13,188 patients. The modalities of discharge instructions included automated phone calls (23.1%) and/or text messages (53.8%), as well as printed out auto-generated summaries (15.4%). Patient engagement was generally high, with automated phone calls showing the most consistent interaction, with completion rates ranging from 44% to 56%, often prompting clinical follow-up. SMS tools demonstrated strong scalability and response rates up to 87%. Two studies reported on hospital readmission outcomes and only a single study reported on emergency department revisit rates, while none assessed reoperation outcomes. Among those reporting readmission, automated phone calls and SMS were associated with lower or proxy-reduced readmission rates. Included studies had low to moderate levels of bias. Conclusions: While evidence on clinical outcomes such as readmissions, emergency department revisits, and reoperations remains limited and inconclusive, automated discharge tools—particularly phone calls and SMS—consistently demonstrated high patient engagement. Automated discharge tools show promise for supporting transitional care, discharge education, and post-discharge monitoring, highlighting the future role of automated tools in nursing workflows to support follow-up, escalation, and continuity of care.

Thalamic neuromodulation has re-emerged as a central strategy for the treatment of drug-resistant epilepsy, driven by advances in stereo-electroencephalography, network neuroscience, and signal processing. This perspective paper summarizes and integrates the key scientific, technical, and clinical insights presented during the American Epilepsy Society (AES) 2025—Epilepsy Surgery Symposium on Advances in Thalamic Neuromodulation for Epilepsy: From Mechanisms of Action to Clinical Application . Beyond a summary of the individual presentations, this manuscript reflects the collective opinions of the panel regarding current evidence, unresolved controversies, and future directions. An unifying theme emerged: effective thalamic neuromodulation requires a shift from empiric, one-size-fits-all targeting toward patient-specific, hodology-informed strategies grounded in in situ electrophysiology and network-level biomarkers.

Abstract Platelet‐rich plasma (PRP) continues to generate both excitement and skepticism within orthopaedics and sports medicine. As a biologic derived from autologous blood, PRP offers an appealing, minimally invasive option for treating musculoskeletal pathology through the delivery of concentrated growth factors and cytokines. Evidence across orthopaedic subspecialties remains mixed, however, with studies showing variable efficacy and inconsistent methodologies. Recent data on PRP use for extra‐articular hip pathology, particularly greater trochanteric pain syndrome, hamstring injuries, and piriformis syndrome show encouraging improvements in pain and function, including faster return to sport and favorable patient‐reported outcomes. Yet, significant heterogeneity in study design, PRP preparation, and control interventions limits generalizability and hinders clear clinical guidance. These inconsistencies mirror similar challenges in PRP research for a variety of other orthopaedic pathologies, underscoring the need for standardized preparation protocols and consistent reporting frameworks. Despite these limitations, a signal of efficacy persists within the data, suggesting PRP may indeed provide meaningful benefit for select extra‐articular hip conditions. As surgical alternatives for these pathologies often carry substantial morbidity, continued refinement of PRP formulations and methodology represents a promising step toward establishing biologics as reliable, evidence‐based tools in orthopaedic care.

Abstract Sarcomeres are the fundamental functional units of skeletal muscle, essential for both force generation and metabolic homeostasis. While sarcomere degradation has been extensively studied, the mechanisms that preserve its integrity remain poorly defined. Here, we identify HECTD1 as an E3 ubiquitin ligase required for sarcomere maintenance and mitochondrial integrity. We show that HECTD1 ubiquitylates and stabilizes the chaperones KLHL40/41, which protect thin-filament components from misfolding and degradation. Consequently, reducing Hectd1 expression in myotubes coordinately decreases the levels of multiple sarcomere proteins. Skeletal muscle–specific Hectd1 knockout mice ( Hectd1 mKO) show severe sarcomere and mitochondrial disorganization and dysfunction, progressive muscle weakness, exercise and glucose intolerance, and unresolved tissue remodeling. Importantly, human iPSC-derived myotubes carrying a patient-associated HECTD1 mutation, recapitulate key molecular features of the Hectd1 mKO. These findings establish HECTD1 as a central regulator linking sarcomere proteostasis to mitochondrial function and identify its dysfunction as a cause of myopathy with mitochondriopathy.