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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.)

Background: Clonal naevi are characterized by a focal proliferation of pigmented melanocytes in an otherwise banal naevus. These subclones are often composed of aggregates of larger, epithelioid melanocytes with nuclear atypia and dusty-grey cytoplasmic pigmentation, which are referred to as 'pulverocytes', and this finding may lead to a misdiagnosis of malignant melanoma (MM)., Aim: To characterize the significance of subclones of dusty-grey pigmented epithelioid melanocytes within spitzoid neoplasms., Methods: We studied the histological and molecular features of a series of 20 spitzoid neoplasms with pulverocyte subclones encountered in our practice, including both atypical Spitz tumours (ASTs) and invasive MMs., Results: Pulverocytes were predominantly dermal, and the percentage of subclones ranged from 2% to 40%, with a median of 10% in ASTs and 25% in lesions we classified as MM. In cases with > 10% subclones, there was an increased odds of fluorescence in situ hybridization positivity (OR = 12; 95% CI 1.2-293.4; P = 0.03) and an increased odds of homozygous 9p21 deletion (OR = 3.6; 95 CI 0.28-89.82; P = 0.33), although the latter did not reach statistical significance., Conclusions: We consider spitzoid lesions with a small subclone population to be a variant of a clonal naevus with indolent behaviour, whereas lesions with larger pulverocyte populations are more likely to have chromosomal copy number aberrations and in some cases may represent malignant transformation., (© 2018 British Association of Dermatologists.)

Objectives: Current materials for closure of cardiac defects such as ventricular septal defects (VSDs) are associated with compliance mismatch and a chronic inflammatory response. Bacterial nanocellulose (BNC) is a non-degradable biomaterial with promising properties such as high mechanical strength, favourable elasticity and a negligible inflammatory reaction. The aim of this study was the evaluation of a BNC patch for VSD closure and the investigation of its in vivo biocompatibility in a chronic pig model., Methods: Young's modulus and tensile strength of BNC patches were determined before and after blood exposure. Muscular VSDs were created and closed with a BNC patch on the beating heart in an in vivo pig model. Hearts were explanted after 7, 30 or 90 days. Macropathology, histology and immunohistochemistry were performed., Results: Young's modulus and tensile strength of the BNC patch decreased after blood contact from 6.3 ± 1.9 to 3.86 ± 2.2 MPa (P < 0.01) and 0.33 ± 0.06 to 0.26 ± 0.06 MPa (P < 0.01), respectively, indicating the development of higher elasticity. Muscular VSDs were closed with a BNC patch without residual shunting. After 90 days, a mild chronic inflammatory reaction was present. Moreover, there was reduced tissue overgrowth in comparison with polyester. Proceeding cellular organization characterized by fibromuscular cells, production of extracellular matrix, neoangiogenesis and complete neoendothelialization were found. There were no signs of thrombogenicity., Conclusions: BNC patches can close VSDs with good mid-term results and its biocompatibility can be considered as satisfactory. Its elasticity increases in the presence of blood, which might be advantageous. Therefore, it has potential to be used as an alternative patch material in congenital heart disease., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

We have examined the effects of exogenously administered recombinant human insulin-like growth factor-binding protein-1 (rhIGFBP-1) alone and in combination with recombinant human insulin-like growth factor-I (rhIGF-I) or human GH on weight gain and tibial epiphysis enlargement in hypophysectomized rats. rhIGF-I, given twice daily by sc injection, increased both growth parameters in a dose-dependent manner. Coadministration of increasing amounts of rhIGFBP-1 with a constant amount of rhIGF-I (80 micrograms/injection, given twice daily) resulted in a dose-dependent inhibition of the growth-promoting effects of rhIGF-I. A rhIGFBP-1 dose of 9.8 micrograms/injection (an IGFBP-1/IGF-I molar ratio of 0.04:1) caused no significant effect on rhIGF-I-stimulated growth parameters, whereas a rhIGFBP-1 dose of 1200 micrograms/injection (IGFBP-1/IGF-I molar ratio of 5:1) resulted in 78% or greater inhibition of rhIGF-I-stimulated growth (P < 0.05). rhIGFBP-1 doses of 48 and 240 micrograms/injection (IGFBP-1/IGF-I molar ratios of 0.2:1 and 1:1, respectively) had intermediate inhibitory effects. None of the rhIGFBP-1 doses potentiated the growth-promoting effects of rhIGF-I. Rats treated with rhIGFBP-1 alone (twice daily injections of 9.8, 48, 240, or 1200 micrograms) showed no significant differences in growth parameters compared to rats treated with vehicle. Coadministration of rhIGFBP-1 (1200 micrograms/injection, given twice daily) with GH (15 mU/injection, given twice daily) inhibited weight gain and tibial epiphysis enlargement stimulated by GH by at least 50% in each of two experiments (P < 0.05). These studies demonstrate that nonphosphorylated rhIGFBP-1 can inhibit the growth-promoting effects of rhIGF-I and GH in vivo. The results suggest that in addition to its proposed role in glucose homeostasis, IGFBP-1 may play a role in inhibiting somatic growth and other physiological functions stimulated by IGF-I and GH.