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Aims: Recommendations on cardiac resynchronization therapy (CRT) in patients with atrial fibrillation or flutter (AF) are based on less robust evidence than those in sinus rhythm (SR). We aimed to assess the efficacy of CRT upgrade in the BUDAPEST-CRT Upgrade trial population by their baseline rhythm., Methods and Results: Heart failure patients with reduced ejection fraction (HFrEF) and previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and ≥20% right ventricular (RV) pacing burden were randomized to CRT with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145). Primary [HF hospitalization (HFH), all-cause mortality, or <15% reduction of left ventricular end-systolic volume] and secondary outcomes were investigated. At enrolment, 131 (36%) patients had AF, who had an increased risk for HFH as compared with those with SR [adjusted hazard ratio (aHR) 2.99; 95% confidence interval (CI) 1.26-7.13; P = 0.013]. The effect of CRT-D upgrade was similar in patients with AF as in those with SR [AF adjusted odds ratio (aOR) 0.06; 95% CI 0.02-0.17; P < 0.001; SR aOR 0.13; 95% CI 0.07-0.27; P < 0.001; interaction P = 0.29] during the mean follow-up time of 12.4 months. Also, it decreased the risk of HFH or all-cause mortality (aHR 0.33; 95% CI 0.16-0.70; P = 0.003; interaction P = 0.17) and improved the echocardiographic response (left ventricular end-diastolic volume difference -49.21 mL; 95% CI -69.10 to -29.32; P < 0.001; interaction P = 0.21)., Conclusion: In HFrEF patients with AF and PM/ICD with high RV pacing burden, CRT-D upgrade decreased the risk of HFH and improved reverse remodelling when compared with ICD, similar to that seen in patients in SR., Competing Interests: Conflict of interest: B.M. reports grants from Boston Scientific, NRDIF Hungary, and National Heart Program during the conduct of the study; personal fees from Biotronik, Abbott, AstraZeneca, Novartis, and Boehringer Ingelheim; and grants from Medtronic outside the submitted work. I.O. reports lecture and advisory fees from Abbott, Biotronik, Boston Scientific, Medtronic, and Vitatron and travel grants from Abbott, Biotronik, Boston Scientific, and Medtronic. Attila K. reports grants from Bolyai Research Scholarship and FK ‘OTKA’ Research Grant from NKFIH outside the submitted work, stock from CardioSight, Inc. and stock option from Argus Cognitive, Inc. outside the submitted work, and personal fees from Argus Cognitive, Inc. and CardioSight Hungary LLC outside the submitted work. G.D. reports research grants to institution from Medtronic and Biotronik and lecture and advisory fees from Medtronic, Biotronik, and Abbott. C.F. reports support from the Semmelweis University, grants from Medtronic, consulting fees from Medtronic and Biotronik Hungary, and payment or honoraria for lectureures from Johnson and Johnson Co., Abbott Laboratories and Boehringer Ingelheim RCV GmbH and Co. L.G. reports support for the present manuscript from Vitatron Medical, Boston Scientific, Abbott Laboratories, Medtronic Hungary, and Biotronik Hungary; consulting fees from Medtronic Hungary and Abbott Hungary; honoraria; travel grants; participation on a data safety monitoring board or advisory board; and role in other board and committee (FESC, FEHRA, President of the Scientific Committee of the Hungarian Society of Cardiology, Past President of the Working Group on Cardiac Arrhythmias and Pacing, and EHRA Scientific Programme Board). Annamária K. reports grants from Bolyai Research Scholarship outside the submitted work; consulting fees from Medtronic; honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Biotronik, and Novartis; payment for expert testimony from Boehringer Ingelheim and Boston Scientific; travel grants from AstraZeneca and Novartis; participation on a data safety monitoring board or advisory board for Boehringer Ingelheim and Boston Scientific; and role in other board and committee (committee member of Hungarian Society of Cardiology and secretary of the Working Group on Cardiac Arrhythmias and Pacing, Hungarian Society of Cardiology). S.D.S. reports grants to institution from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, NeuroTronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI and consulting fees outside the scope of the current work from Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GSK, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProthera, Moderna, American Regent, Sarepta, Lexicon, AnaCardio, Akros, and Valo. R.H. reports institutional grants from Abbott, Biotronik, and Slovak Research and Development Agency; honoraria from Abbott and Medtronic; and travel grants from the European Society of Cardiology and Pfizer. He is also the president of the Slovak Heart Rhythm Association. E.M. reports grants from Novartis, Boehringer Ingelheim, and Biotronik Hungary. V.K. reports grants from Boston Scientific, ZOLL, Biotronik, Spire Inc., and NIH, consulting fees from Biotronik and Zoll, and payment or honoraria for lectures from Abbott Medical and Medtronic. The other authors declare no conflict of interest for this contribution., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflicts of interest None disclosed.

Problem: Palliative care (PC) is high-value, holistic care for a child and their family across the entire arc of an illness. All physicians should be competent in symptom management and providing goal-concordant care that acknowledges the quality of life; however, there is insufficient education in pediatric residency to develop competence in basic or ..úPrimary..Ñ PC., Approach: We completed a needs assessment and developed a longitudinal, comprehensive, and integrated primary PC curriculum for pediatric residents with the goal of developing foundational primary PC skills regardless of eventual career trajectory. After 1 year of implementation, we assessed resident comfort with primary PC skills via a retrospective pre-post survey., Outcomes: We found a statistically significant (P.ß<.ß.05) increase in residents... comfort with pain management, delivering serious news, and discussing goals of care. An increase in comfort with the management of other symptoms was not statistically significant., Next Steps: After 1 year of implementation, residents describe an increase in comfort with primary PC skills. The next steps include more rigorous evaluation and expansion to include more education in medical ethics. While the educational need is universal, resident needs are constantly evolving and each institution should tailor this curriculum to fit their specific trainee needs and institutional expertise., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Gene therapy is emerging as a modality in 21st-century medicine. Adeno-associated viral (AAV) gene transfer is a leading technology to achieve efficient and durable expression of a therapeutic transgene. However, the structural complexity of the capsid has constrained efforts to engineer the particle toward improved clinical safety and efficacy. Here, we generate a curated library of barcoded AAVs with mutations across a variety of functionally relevant motifs. We then screen this library in vitro and in vivo in mice and nonhuman primates, enabling a broad, multiparametric assessment of every vector within the library. Among the results, we note a single residue that modulates liver transduction across all interrogated models while preserving transduction in heart and skeletal muscles. Moreover, we find that this mutation can be grafted into AAV9 and leads to profound liver detargeting while retaining muscle transduction-a finding potentially relevant to preventing hepatoxicities seen in clinical studies., Competing Interests: Declaration of interests L.H.V. holds equity in Affinia Therapeutics, Akouos, and ciendias bio. He serves on the Board of Directors of Affinia Therapeutics, Addgene, ciendias bio, and Odylia. L.H.V. is an employee of ciendias bio. L.H.V. and E.Z. are inventors of AncAAV technology licensed to Affinia, Akouos, and/or other biopharmaceutical companies from which they may receive royalties. L.H.V. is compensated for his scientific advisory position with Affinia and Akouos. L.H.V. is a SAB member to Akouos, consultant to Affinia and Novartis, and receives research support from Novartis. L.H.V.’s interests were reviewed and are managed by Mass Eye and Ear and Mass General Brigham in accordance with their conflict-of-interest policies. L.H.V., E.Z., C.U., P.F.S., C.T., and H.T.T. are inventors on patent applications relating to AAVSeq, CombiAAV, or the liver toggle technology contained in this publication. A.J.W. and L.H.V. are inventors on patents related to use of AAVs for therapeutic gene delivery in the muscle and other tissues., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence 1 . High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition 1 , and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes 2 . Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)