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Patient-prosthesis mismatch (PPM) is the situation in which the area of an artificial valve is smaller than that of a healthy native valve it replaces. By this definition, all artificial valves demonstrate PPM, but large observational studies and several meta-analyses suggest that it is present in 30-50% of patients after surgical aortic valve replacement (SAVR). PPM has an impact on outcomes only when the indexed aortic valve area (AVAi) is ≤0.85cm2/m2 (moderate PPM) or 0.65cm2/m2 (severe PPM), particularly in patients with reduced LVEF. In transcatheter aortic valve replacement, the prevalence of PPM may be as low as 0.1%, and its impact on hard outcomes is not clear. We present a review of the relevant literature together with a framework for the differential diagnosis of increased pressure gradient and reduced area in prosthetic aortic valves and different strategies to reduce the risk of PPM with SAVR.

This study employs a bibliometric approach to analyze the landscape of artificial intelligence (AI) components used in performance measurement. As organizations increasingly leverage AI for optimizing processes and decisionmaking, understanding the trends in AI components becomes imperative. The identified AI components are classified based on their roles in enhancing performance measurement, offering insights into the prevalent methodologies and emerging technologies. The bibliometric analysis encompasses a comprehensive review of scholarly articles, conference papers, and patents, systematically exploring the evolving field. In this research, the methodology involves data extraction from reputable academic databases and patent repositories, followed by applying bibliometric techniques to quantify and visualize key aspects. The findings of this study contribute to the existing knowledge by mapping the intellectual structure of AI components for performance measurement.

Background: There is strong interest in the evaluation of longer-term outcome metrics for congenital heart diseases (CHDs); however, registries focus on postoperative metrics., Methods and Results: Informed by user online discussion forums and scoping of national data, we selected sentinel CHDs and long-term outcome metrics suitable for routine monitoring. We then developed sentinel CHD phenotypes and algorithms for identifying treatment pathway procedures using clinical codes. Finally, we calculated the metrics within a retrospective national cohort analysis. The 9 selected sentinel CHDs had a higher-than-average prevalence, typically involved surgery in infancy, and were associated with an increased risk of late mortality. The selected metrics of survival and reinterventions at 1, 5, and 10 years were both important and feasible. The cohort included 29 319 (41.3% of all operated CHD births) English and Welsh children born with sentinel CHDs in 2000 to 2022. Example metrics at age 10 years included: survival-hypoplastic left heart syndrome: 57.6% (95% CI, 54.9%-60.4%), functionally univentricular heart: 86.7% (95% CI, 84.6%-88.9%), transposition of the great arteries: 93.1% (95% CI, 92.2%-93.9%), pulmonary atresia: 81.0% (95% CI, 79.1%-82.9%), atrioventricular septal defect: 88.5% (95% CI, 87.5%-89.5%), tetralogy of Fallot: 95.1% (95% CI, 94.4%-95.8%), aortic stenosis: 94.4% (95% CI, 93.3%-95.6%), coarctation: 96.7% (95% CI, 96.2%-97.3%), and ventricular septal defect: 96.9% 95% CI, (96.4%-97.3%); and (2) cumulative incidence of reintervention-hypoplastic left heart syndrome : 54.5% (95% CI, 51.5%-57.3%), functionally univentricular heart: 57.3% (95% CI, 53.9%-60.5%), transposition of the great arteries: 20.9% (95% CI, 19.5%-22.3%), pulmonary atresia: 66.8% (95% CI, 64.2%-69.1%), atrioventricular septal defect: 21.6% (20.3%-23.0%), tetralogy of Fallot: 26.6% (95% CI, 25.2%-28.0%), aortic stenosis: 31.2% (95% CI, 28.8%-33.6%), coarctation: 19.8% (95% CI, 18.6%-21.1%), and ventricular septal defect: 6.1% (95% CI, 5.5%-6.8%)., Conclusions: It is feasible to report important long-term outcomes of survival and reintervention for sentinel CHDs using routinely collected procedure records, adding value to national audit.

Infections, particularly those involving the respiratory tract, are associated with an increased incidence of cardiovascular events, both de novo and as exacerbations of pre-existing cardiovascular diseases. Influenza vaccination has consistently been shown to reduce the incidence of cardiovascular events. Nonetheless, vaccination rates among adults remain suboptimal, both in the general population and among high-risk individuals. Multiple barriers hinder achieving adequate vaccination rates, with physicians' beliefs and attitudes towards these interventions being crucial. The FLUence project was developed within the framework of the World Heart Federation's Emerging Leaders program, to address this issue. This project has two phases: a global quantitative survey to assess the perceptions, opinions, and attitudes and challenges of physicians worldwide regarding the safety and efficacy of the influenza vaccination use, and a qualitative survey to further investigate the barriers and facilitators of recommending and using this vaccination. The quantitative survey was created and disseminated in five languages (English, Spanish, French, Italian, and Portuguese) to physicians of all specialties who care for adults, with a particular focus on patients with cardiovascular disease. The survey included eight domains with a total of 36 questions with closed options; a Likert scale with five possible answers was used to gauge participants' opinions. To gain deeper insights into the complexities behind the low vaccination rates in adults, the second part of the project comprises a qualitative survey, conducted in the two lower-middle- and upper-middle-income countries: India and Argentina, respectively. These countries were selected because patients with cardiovascular diseases have access to free influenza vaccination in Argentina, whereas patients must pay for the vaccine out of pocket in India. Thus, the FLUence study will provide valuable information to better understand the perceptions and barriers to improving influenza vaccination rates from the perspective of physicians. It is imperative to actively engage all healthcare providers to improve influenza vaccination rates., Competing Interests: SGZ has conducted academic activities with Bayer, Sanofi Pasteur, Seqirus, and GlaxoSmith Kline; no external financial support has been related to this project. The other authors have nothing to declare., (Copyright: © 2024 The Author(s).)

Background/objectives: Today's high school students often engage in sedentary behavior by choosing passive activities during leisure time. Increasing research shows that regular physical activity (PA) provides benefits beyond physical health, especially important during childhood and adolescence. Our study investigated the association between physical activity levels and academic performance (AP) in Serbian adolescents., Methods: We selected a sample of 836 fourth-grade high school students (avg. 17.9 ± 0.7 years old) who completed the IPAQ (short-version) and the Academic Performance Scale. Data analysis was conducted using IBM SPSS 21.0. Due to non-normal data distribution, Spearman's correlation was used and hierarchical regression analysis to assess the association between PA and AP., Results: The findings revealed significant correlations between vigorous, moderate and light PA, as well as overall units of metabolic equivalent of task (METs), with AP ( p -values: 0.000, 0.005, 0.021, 0.004, respectively), although with weak correlation coefficients (0.127, 0.098, 0.080, 0.181, respectively). Vigorous PA influenced AP by 10.1%, moderate PA by 8.2%, and light PA by 11.4%., Conclusions: These results suggest that adolescents engaging in higher PA levels tend to have better AP. This finding indicates a substantial association between PA levels and AP, with both moderate and vigorous PA showing a positive correlation and influence. Further investigation is necessary to comprehensively grasp the link between light PA and AP.

Critical ostial stenosis following reimplantation of an anomalous left main coronary artery is extremely rare. Currently, there is no consensus on management following diagnosis. This report demonstrates the feasibility of percutaneous coronary intervention in an adolescent with such a condition and emphasizes the importance of periprocedural multimodality imaging., Competing Interests: Dr Johnson has received consultancy and speaker fees from Abbott Vascular, Boston Scientific, and Terumo and research grants from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background and Objectives : Cardiovascular disease (CVD) remains a major public health issue worldwide, disproportionately affecting socioeconomically disadvantaged populations due to the social determinants of health (SDOHs). In Western Romania, these populations are particularly vulnerable to CVD. This study aims to investigate the prevalence and impact of cardiovascular risk factors (CVRFs) among socioeconomically disadvantaged individuals in Western Romania and identify the primary CVRFs contributing to the high incidence of CVD within this population. Materials and Methods : A retrospective observational design was employed, utilizing data from the medical records of 1433 eligible individuals. The inclusion criteria were based on Eurostat's EU-SILC benchmarks, focusing on severe material deprivation, at-risk-of-poverty rates, and low work intensity. Data on demographics, familial and personal medical history, smoking status, blood pressure, glucose, cholesterol, triglycerides, and HbA1c levels were collected. Results : Of the 1433 subjects, 34.75% were male, with a median age of 52 years. Significant conditions included diabetes (7.39%), coronary disease (3.83%), arterial hypertension (35.58%), and dyslipidemia (21.28%). Median ages were higher for those with diabetes (65 vs. 51 years, p < 0.0001), coronary disease (64 vs. 51 years, p < 0.0001), arterial hypertension (65 vs. 43 years, p < 0.0001), and dyslipidemia (66 vs. 47 years, p < 0.0001). BMI (Body Mass Index) classifications showed 33.77% were overweight, 21.21% obese, and 15.07% morbidly obese. Smokers were younger than non-smokers (48 vs. 54 years, p < 0.0001). Conclusions : The findings highlight the significant prevalence of CVRFs among socioeconomically disadvantaged populations in Western Romania. Socioeconomically disadvantaged populations exhibit a significantly higher prevalence of cardiovascular risk factors such as diabetes, impaired glucose regulation, hypertension, and dyslipidemia compared to their before known status.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for advancements in risk assessment and management strategies. Although significant progress has been made recently, identifying and managing apparently healthy individuals at a higher risk of developing atherosclerosis and those with subclinical atherosclerosis still poses significant challenges. Traditional risk assessment tools have limitations in accurately predicting future events and fail to encompass the complexity of the atherosclerosis trajectory. In this review, we describe novel approaches in biomarkers, genetics, advanced imaging techniques, and artificial intelligence that have emerged to address this gap. Moreover, polygenic risk scores and imaging modalities such as coronary artery calcium scoring, and coronary computed tomography angiography offer promising avenues for enhancing primary cardiovascular risk stratification and personalised intervention strategies. On the other hand, interventions aiming against atherosclerosis development or promoting plaque regression have gained attention in primary ASCVD prevention. Therefore, the potential role of drugs like statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, omega-3 fatty acids, antihypertensive agents, as well as glucose-lowering and anti-inflammatory drugs are also discussed. Since findings regarding the efficacy of these interventions vary, further research is still required to elucidate their mechanisms of action, optimize treatment regimens, and determine their long-term effects on ASCVD outcomes. In conclusion, advancements in strategies addressing atherosclerosis prevention and plaque regression present promising avenues for enhancing primary ASCVD prevention through personalised approaches tailored to individual risk profiles. Nevertheless, ongoing research efforts are imperative to refine these strategies further and maximise their effectiveness in safeguarding cardiovascular health., Competing Interests: Declaration of competing interest F.B. has received honoraria and grants from Novartis, Novo Nordisk, Sanofi, and Viatris, outside the scope of the submitted work. All other authors declare to have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background : Congenital cardiac care involves multiple stakeholders including patients and their families, surgeons, cardiologists, anaesthetists, the wider multidisciplinary team, healthcare providers, and manufacturers, all of whom are involved in the decision-making process to some degree. Game theory utilises human behaviour to address the dynamics involved in a decision and what the best payoff is depending on the decision of other players. Aim : By presenting these interactions as a strategic game, this paper aims to provide a descriptive analysis on the utility and effectiveness of game theory in optimising decision-making in congenital cardiac care. Methodology : The comprehensive literature was searched to identify papers on game theory, and its application within surgery.  Results : The analysis demonstrated that by utilising game theories, decision-making can be more aligned with patient-centric approaches, potentially improving clinical outcomes. Conclusion : Game theory is a useful tool for improving decision-making and may pave the way for more efficient and improved patient-centric approaches.

Intraocular epithelial ingrowth is a rare but serious complication of eye surgery or trauma. The diagnosis is challenging but can be aided by techniques such as anterior optical coherence tomography (AS-OCT). This study aimed to compare clinical and histopathological diagnostic data to evaluate the accuracy of AS-OCT. This retrospective analysis focused on patients presenting with suspected epithelial invasion between 2017 and 2022. Clinical data and histopathological findings were analyzed for diagnostic confirmation. Immunohistochemistry using the corneal-specific marker cytokeratin 3 and the conjunctival-specific marker cytokeratin 13 helped to identify the type of invading epithelial cells. Statistical analysis was used to evaluate the effectiveness of AS-OCT for diagnosis. This study included 51 patients who underwent keratoplasty or enucleation. Sixteen cases (31%) of epithelial ingrowth were histologically confirmed. The most common type was the cystic form (82%). Enucleation was required in 25% of patients, mainly due to diffuse epithelial invasion. Immunohistochemistry revealed a conjunctival origin in 82% of the infiltrated cells. AS-OCT showed a sensitivity of 78% and a specificity of 26% in detecting hyperreflective structures associated with epithelial invasion. This study highlights the diverse manifestations of epithelial ingrowth and the need for improved diagnostic techniques, with AS-OCT showing promising results but requiring further validation to avoid misdiagnosis.

Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoband 6q27 is an independent poor prognostic marker in multiple data sets. We then combined CRISPR-Cas9 data, human spatial transcriptomic data, and human and mouse RNA sequencing data to nominate PDE10A as a potential haploinsufficient tumor suppressor in the 6q27 region. Mouse glioblastoma modeling using the RCAS/tv-a system confirmed that Pde10a suppression induced an aggressive glioma phenotype in vivo and resistance to temozolomide and radiation therapy in vitro. Cell culture analysis showed that decreased Pde10a expression led to increased PI3K/AKT signaling in a Pten-independent manner, a response blocked by selective PI3K inhibitors. Single-nucleus RNA sequencing from our mouse gliomas in vivo, in combination with cell culture validation, further showed that Pde10a suppression was associated with a proneural-to-mesenchymal transition that exhibited increased cell adhesion and decreased cell migration. Our results indicate that glioblastoma patients harboring PDE10A loss have worse outcomes and potentially increased sensitivity to PI3K inhibition., (© 2024 Nuechterlein et al.; Published by Cold Spring Harbor Laboratory Press.)

The surgical treatment of the thalamic lesions is one of the most technically challenging interventions because of their deep-seated location and the proximity of the surrounding vital neurovascular structures: thalamic nuclei, limbic system components, visual and oculomotricity pathways, deep cerebral veins, and posterior cerebral artery branches.1 Traditional microsurgical approaches for these lesions usually require large open craniotomies and further retraction or resection of neural tissue to facilitate better visualization, associating significant postoperative morbidity or even mortality. The recent improvements in high-resolution fiber optics technology have allowed neurosurgeons to expand their surgical armamentarium for tackling these difficult-to-reach lesions. The patient consented to the procedure, and in this surgical video, we try to emphasize the advantages of an endoscopic supracerebellar infratentorial approach over the classic microsurgical approach, along with the keyhole craniotomy and the sitting positioning of the patient. The endoscope provides better visualization-dynamic in-depth view of the anatomic and pathological structures, angled-optics help the surgeon to see "around-the-corner," and the entire procedure is a more comfortable experience for the surgeon and also for the patient, using the minimally invasive techniques. Moreover, we underline the need for a strong collaboration with an experienced endoscopic surgeon (for eg, ear, nose and throat surgeon), as for other endoscopic skull base approaches. The participants and any identifiable individuals consented to publication of his/her image., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages., Objectives: The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease., Methods: Phase 2, open-label trial in children (ages, 28 days to <18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis., Primary Endpoint: a composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy., Results: From 2017 to 2021, 192 participants were randomized, 129 apixaban and 63 SOC. Diagnoses included single ventricle (74%), Kawasaki disease (14%), and other heart disease (12%). One apixaban participant (0.8%) and 3 with SOC (4.8%) had major or clinically relevant nonmajor bleeding (% difference -4.0 [95% CI: -12.8 to 0.8]). Apixaban incidence rate for all bleeding events was nearly twice the rate of SOC (100.0 vs 58.2 per 100 person-years), driven by 12 participants with ≥4 minor bleeding events. No thromboembolic events or deaths occurred in either arm. Apixaban pediatric PK steady-state exposures were consistent with adult levels., Conclusions: In this pediatric multinational, randomized trial, bleeding and thromboembolism were infrequent on apixaban and SOC. Apixaban PK data correlated well with adult trials that demonstrated efficacy. These results support the use of apixaban as an alternative to SOC for thromboprophylaxis in pediatric heart disease. (A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist [VKA] or Low Molecular Weight Heparin [LMWH] in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation; NCT02981472)., Competing Interests: Funding Support and Author Disclosures This trial was supported by the Bristol Myers Squibb/Pfizer Alliance, in collaboration with the NHLBI-funded Pediatric Heart Network (grant numbers: HL135646, HL135665, HL135666, HL135678, HL135680, HL135682, HL135683, HL135685, HL135689, HL135691). Bristol Myers Squibb provided all financing and drugs for this trial; managed the trial data, adjudication process, and clinical sites; and was involved in the design of the study. The Pediatric Heart Network (PHN) provided scientific input on the trial design and contributed organizational infrastructure including the Data and Safety Monitoring Board, Protocol Review Committee, Publications and Presentations Committee, and additional logistical support for United States–based sites. Editorial support was provided by Caudex and was funded by Bristol Myers Squibb. Any publication-related fees will be funded by Bristol Myers Squibb. In collaboration with the trial steering committee, Bristol Myers Squibb was involved in the writing of this manuscript and decision to submit the paper for publication. Dr Payne has received grants or contracts from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), Friedreich Ataxia Research Alliance, and Additional Ventures non-profit organization; has received royalties or license from inventions: Wake Forest University, Larimar Therapeutics, and Indiana University; has received consulting fees from Larimar Therapeutics Inc.; has received support for attending meetings or travel from Indiana University School of Medicine; has 2 patents pending at Indiana University School of Medicine; is chair or is on the Data and Safety Monitoring Board (DSMB) for NIH study on Friedreich Ataxia; has served on the scientific advisory board for Friedreich Ataxia Research Alliance; and has stock in Larimar Therapeutics, Inc. Dr Glatz has received grants or contracts from NIH/NHLBI. Dr Male has received payment or honoraria from Anthos, AstraZeneca, Bayer, Chiesi, Janssen, and Norgine; and has a leadership or fiduciary role in Pediatric Anti-thrombotic Trials Leadership & Steering (Pedi-ATLAS) Group. Dr Brandão has received participation in an advisory committee for AstraZeneca (Andexxa in pediatrics) and Boehringer Ingelheim (dabigatran in children). Dr VanderPluym has received grants or contracts from the Georgia Claire Bowen Foundation; has received consulting fees from AstraZeneca and Merck; and participates in an advisory committee for the Valor Trial (Veriguciat in pediatric heart failure), and Andexxa in pediatrics in Europe. Dr Kochilas has received grants or contracts from NIH/NHLBI, Department of Defense, and Novartis Pharma; and participates in the Mitochondrial transplant study: Boston Children’s Hospital. Dr Stiller has received consulting fees from Janssen and Novartis; and has received payment or honoraria from Bristol Myers Squibb. Dr Cnota has received grants or contracts from NIH/NHLBI and Additional Ventures nonprofit organization; has received support for attending meetings or travel from the American Heart Association CSSP committee; and has participated on the NIH-NHLBI DSMB, Advisory Board for Inozyme Pharma. Dr Rahkonen has received payment or honoraria from Bristol Myers Squibb. Dr Adorisio has received grants or contracts from HORIZON 2022, Ministry of Italian Public Health; and has received consulting fees and payment or honoraria from PTC Therapeutics. Dr Stoica has been a co-applicant on research grants from local charities, National Institute of Health Research, the Health Foundation, and industry (Livanova, Admedus); has received payment or honoraria from LeMaitre Vascular; has received payment for expert testimony; and was audit co-lead in the Society of Cardiothoracic Surgeons of Great Britain and Ireland and at the National Institute of Cardiovascular Outcomes and Research. Dr May has received institutional support for conference fees. Dr Saraiva has a conflict of interest with AstraZeneca, Novartis, Merck, Novo Nordisk, Boehringer, Janssen, and Bayer; has received consulting fees from AstraZeneca, Novartis, Merck, Novo Nordisk, Boehringer, Janssen, and Bayer; has received payment or honoraria from AstraZeneca, Novartis, Merck, Novo Nordisk, Boehringer, Janssen, and Bayer; has received payment for expert testimony from AstraZeneca; has received support for attending meetings or travel from Novo Nordisk, AstraZeneca, and Boehringer; and has participated in the Allbert Einstein Academic Research Organization, Brazil. Dr Rubio has stock in BMS (obtained in 2001). Dr Meador has Concurrent employment with AtriCure effective September 2022. Ms Wheaton has a contract between HealthCore (now known as Carelon Research) and BMS to conduct the SAXOPHONE study. Dr Ajavon-Hartmann and Ms Mills are employees of and have stock options in Bristol Myers Squibb. Drs Jarugula, Reedy, and Dyme and Ms Carlson-Taneja are employees of Bristol Myers Squibb. Dr Monagle has received patents planned, issued, or pending from University of Melbourne and McMaster University: No commercial interests or connections since 2011. No current licensing agreements and no ongoing negotiations to license. Expect patents to expire in the next couple of years - Thrombin generation assay. Inventors: Berry LR, Ignjatovic V, Monagle PT, Chan AKC. U.S. patent, patent no. 8138308, “Modified Peptide Substrate”, issued 20 March 2012 “Enzyme Measurement Assay Using a Modified Substrate Comprising a Substrate Attached to a Macromolecule via a Spacer”: India patent no. 244241, issued November 25, 2010; Europe patent application, serial no. 06840527.3, issued October 2019; China patent application, serial no. 200680053447, filed December 21, 2006; and Japan patent application, serial no. 2008-547812, filed December 21, 2006. Dr Monagle has participated in Bayer Einstein junior suite of studies (Rivaroxaban in children): steering committee and writing committee; is an unpaid site investigator for the Bristol Myers Squibb SAXOPHONE study (apixaban in children): steering committee and writing committee; has been a site investigator (Unpaid, Ongoing) for Janssen; is an unpaid advisory board member for Milvexian; is an unpaid advisory board member for Takeda; is an unpaid advisory board member for Ceprotinin; and is an Associate Investigator for AstraZeneca, Takeda, Stago, Bayer, Janssen, and Pfizer. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, the U.S. Department of Health and Human Services, or Bristol Myers Squibb/Pfizer Alliance. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Epilepsy surgery in genetic drug-resistant epilepsy is a debated subject as more histological and molecular data are available. We retrospectively collected data from focal drug-resistant epilepsy patients that underwent stereoelectroencephalography (SEEG) invasive recordings. Patients with nonlesional brain imaging or in whom a first epilepsy surgery failed to control seizures were selected. We computed and displayed the intracranial ictal onset activity pattern on structural imaging. Patients underwent epilepsy gene panel testing, next generation sequencing-NGS. Of 113 patients, 13 underwent genetic testing, and in 6 patients, a mechanistic target of rapamycin pathway gene germline mutation (mTOR) was identified. Brain imaging was nonlesional except for one patient in whom two abnormalities suggestive of focal cortical dysplasia (FCD) were found. Patients underwent tailored brain surgery based on SEEG data, tissue analysis revealed FCD and postsurgical outcome was favorable. Our findings are similar to previous case series suggesting that epilepsy surgery can be a treatment option in patients with mTOR pathway mutation. In patients with mTOR pathway mutation, the postsurgical outcome is favorable if complete resection of the epileptogenic zone is performed. Electrophysiological seizure onset patterns in FCDs associated with mTOR pathway mutations display low-voltage fast activity as previously described., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Introduction: Congenital heart disease (CHD) represents the most common birth defect, affecting from 0.4% to 1.2% of children born in developed countries. The survival of these patients has increased significantly, but CHD remains one of the major causes of neonatal and childhood death. The aetiology of CHD is complex, with some evidence of both genetic and environmental causes. However, there is still lack of knowledge regarding modifiable risk factors and molecular and genetic mechanisms underlying the development of CHD. This study aims to develop a prospective cohort of patients undergoing cardiac procedures that will bring together routinely collected clinical data and biological samples from patients and their biological mothers, in order to investigate risk factors and predictors of postoperative-outcomes, as well as better understanding the effect of the surgical intervention on the early and long-term outcomes., Methods and Analysis: Children OMACp (OMACp, outcome monitoring after cardiac procedure in congenital heart disease) is a multicentre, prospective cohort study recruiting children with CHD undergoing a cardiac procedure. The study aims to recruit 3000 participants over 5 years (2019-2024) across multiple UK sites. Routine clinical data will be collected, as well as participant questionnaires collecting sociodemographic, NHS resource use and quality of life data. Biological samples (blood, urine and surgical waste tissue from patients, and blood and urine samples from biological mothers) will be collected where consent has been obtained. Follow-up outcome and questionnaire data will be collected for 5 years., Ethics and Dissemination: The study was approved by the London-Brent Research Ethics Committee on 30 July 2019 (19/SW/0113). Participants (or their parent/guardian if under 16 years of age) must provide informed consent prior to being recruited into the study. Mothers who wish to take part must also provide informed consent prior to being recruited. The study is sponsored by University Hospitals Bristol and Weston Foundation Trust and is managed by the University of Bristol. Children OMACp is adopted onto the National Institute for Health Research Clinical Research Network portfolio. Findings will be disseminated through peer-reviewed publications, presentation at conference, meetings and through patient organisations and newsletters., Trial Registration Number: ISRCTN17650644., Competing Interests: Competing interests: DL has received support from Medtronic and Roche Diagnostics for research unrelated to this publication., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Missense mutated von Hippel Lindau (VHL) protein (pVHL) maintains intrinsic function but undergoes proteasomal degradation and tumor initiation and/or progression in VHL disease. Vorinostat can rescue missense mutated pVHL and arrest tumor growth in preclinical models. We asked whether short-term oral vorinostat could rescue pVHL in central nervous system hemangioblastomas in patients with germline missense VHL., Patients and Methods: We administered oral vorinostat to 7 subjects (ages 46.0 ± 14.5 years) and then removed symptomatic hemangioblastomas surgically (ClinicalTrials.gov identifier NCT02108002)., Results: Vorinostat was tolerated without serious adverse events by all patients. pVHL expression was elevated in neoplastic stromal cells compared with untreated hemangioblastomas from same patients. We found transcriptional suppression of downstream hypoxia-inducible factor (HIF) effectors. Mechanistically, vorinostat prevented Hsp90 recruitment to mutated pVHL in vitro. The effects of vorinostat on the Hsp90-pVHL interaction, pVHL rescue, and transcriptional repression of downstream HIF effectors was independent of the location of the missense mutation on the VHL locus. We confirmed a neoplastic stromal cell-specific effect in suppression of protumorigenic pathways with single-nucleus transcriptomic profiling., Conclusions: We found that oral vorinostat treatment in patients with germline missense VHL mutations has a potent biologic effect that warrants further clinical study. These results provide biologic evidence to support the use of proteostasis modulation for the treatment of syndromic solid tumors involving protein misfolding. Proteostasis modulation with vorinostat rescues missense mutated VHL protein. Further clinical trials are needed to demonstrate tumor growth arrest., (©2023 American Association for Cancer Research.)

Objectives: To assess the effectiveness of injectable tissue pulmonary valve compared with standard pulmonary valve in patients requiring pulmonary valve replacement surgery., Design: A multicentre, single-blind, parallel two-group randomised controlled trial. Participants were blind to their allocation. Follow-up continued for 6 months. Randomised allocations were generated by a computer using block randomisation, stratified by centre., Setting: Two National Health Service secondary care centres in the UK., Participants: People aged 12-80 years requiring pulmonary valve replacement., Interventions: Participants were randomly allocated (1:1 ratio) to injectable pulmonary valve replacement (IPVR) without cardiopulmonary bypass (CPB) or standard pulmonary valve replacement (SPVR) with CPB., Primary and Secondary Outcome Measures: The primary outcome was chest drainage volume over the first 24 hours after surgery. Secondary outcomes included in-hospital clinical outcomes; valve and heart function 6 months postsurgery and health-related quality of life 6 weeks and 6 months postsurgery., Results: Nineteen participants agreed to take part. Eleven were allocated to IPVR and eight to SPVR. The trial was stopped before the target sample size of 60 participants was reached due to challenges in recruitment. The primary analysis includes all randomised participants; there were no withdrawals. Chest drain volume 24 hours after surgery was on average 277.6 mL lower with IPVR (IPVR mean 340.0 mL; SPVR mean 633.8 mL; mean difference, -277.6; 95% CI, -484.0 to -71.2; p=0.005). There were no statistically significant differences in time to readiness for extubation (p=0.476), time to fitness for discharge (p=0.577) and time to first discharge from the intensive care unit (p=0.209). Six participants with IPVR required CPB. Safety profiles and quality of life scores were similar., Conclusions: IPVR reduced chest drain volume despite >50% of participants requiring CPB. There was no evidence of any other benefit of IPVR., Trial Registration Number: ISRCTN23538073., Competing Interests: Competing interests: Pierson Ltd agreed to provide the injectable tissue valves (BioPulmonic, Biointegral Surgical) used in the trial at a discounted rate. Pierson Ltd paid for travel-related expenses for Stefano Marianeschi to visit the trial centres and provide injectable pulmonary valve replacement training., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: There is uncertainty about surgical procedures for adult patients aged 18-60 years undergoing aortic valve replacement (AVR). Options include conventional AVR (mechanical, mAVR; tissue, tAVR), the pulmonary autograft (Ross) and aortic valve neocuspidisation (Ozaki). Transcatheter treatment may be an option for selected patients. We used formal consensus methodology to make recommendations about the suitability of each procedure., Methods: A working group, supported by a patient advisory group, developed a list of clinical scenarios across seven domains (anatomy, presentation, cardiac/non-cardiac comorbidities, concurrent treatments, lifestyle, preferences). A consensus group of 12 clinicians rated the appropriateness of each surgical procedure for each scenario on a 9-point Likert scale on two separate occasions (before and after a 1-day meeting)., Results: There was a consensus that each procedure was appropriate (A) or inappropriate (I) for all clinical scenarios as follows: mAVR: total 76% (57% A, 19% I); tAVR: total 68% (68% A, 0% I); Ross: total 66% (39% A, 27% I); Ozaki: total 31% (3% A, 28% I). The remainder of percentages to 100% reflects the degree of uncertainty. There was a consensus that transcatheter aortic valve implantation is appropriate for 5 of 68 (7%) of all clinical scenarios (including frailty, prohibitive surgical risk and very limited life span)., Conclusions: Evidence-based expert opinion emerging from a formal consensus process indicates that besides conventional AVR options, there is a high degree of certainty about the suitability of the Ross procedure in patients aged 18-60 years. Future clinical guidelines should include the option of the Ross procedure in aortic prosthetic valve selection., Competing Interests: Competing interests: SS received speaker honoraria from Admedus. VD is a member of Heart’s editorial board., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Intermittent cold blood cardioplegia is commonly used in children, whereas intermittent warm blood cardioplegia is widely used in adults. We aimed to compare clinical and biochemical outcomes with these 2 methods., Methods: A single-centre, randomized controlled trial was conducted to compare the effectiveness of warm (≥34°C) versus cold (4-6°C) antegrade cardioplegia in children. The primary outcome was cardiac troponin T over the 1st 48 postoperative hours. Intensive care teams were blinded to group allocation. Outcomes were compared by intention-to-treat using linear mixed-effects, logistic or Cox regression., Results: 97 participants with median age of 1.2 years were randomized (49 to warm, 48 to cold cardioplegia); 59 participants (61%) had a risk-adjusted congenital heart surgery score of 3 or above. There were no deaths and 92 participants were followed to 3-months. Troponin release was similar in both groups [geometric mean ratio 1.07; 95% confidence interval (CI) 0.79-1.44; P = 0.66], as were other cardiac function measures (echocardiography, arterial and venous blood gases, vasoactive-inotrope score, arrhythmias). Intensive care stay was on average 14.6 h longer in the warm group (hazard ratio 0.52; 95% CI 0.34-0.79; P = 0.003), with a trend towards longer overall hospital stays (hazard ratio 0.66; 95% CI 0.43-1.02; P = 0.060) compared with the cold group. This could be related to more unplanned reoperations on bypass in the warm group compared to cold group (3 vs 1)., Conclusions: Warm blood cardioplegia is a safe and reproducible technique but does not provide superior myocardial protection in paediatric heart surgery., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Patient-reported outcome measures are commonly used to evaluate the effectiveness of treatments. CHD remains the most common congenital malformation. There has been a gradual shift in evaluating the outcome of surgery for CHD from mortality to morbidity and now to self-reported outcomes., Aims: We aimed to review studies assessing patient-reported outcome measures as a useful marker of outcome for patients, both children and adults, who underwent surgery for CHD., Methods: A systematic database search was conducted of original articles that explored the application of patient-reported outcome measures in the CHD surgical setting in PubMed and SCOPUS from inception to February 2022., Results: Our search yielded 1511 papers, of which six studies were included in this review after screening abstract and full-text, with a total sample size of 5734 patients. The main areas of discussion were the utility of patient-reported outcome measures, determinants of patient-reported outcome measures, and the need for a congenital cardiac surgery-specific patient-reported outcome measure for paediatric patients and their parents/guardians and adult patients., Conclusion: This systematic review reports the use of patient-reported outcome measures to be a useful indicator to gain insight into the patients' perspective to provide holistic and patient-centred management. However, further studies are required to assess the utility of patient-reported outcome measures in a congenital cardiac surgical setting.

Bicuspid aortic valve (BAV) patients develop ascending aortic (AAo) dilation. The pathogenesis of BAV aortopathy (genetic vs. haemodynamic) remains unclear. This study aims to identify regional changes around the AAo wall in BAV patients with aortopathy, integrating molecular data and clinical imaging. BAV patients with aortopathy (n = 15) were prospectively recruited to surgically collect aortic tissue and measure molecular markers across the AAo circumference. Dilated (anterior/right) vs. non-dilated (posterior/left) circumferential segments were profiled for whole-genomic microRNAs (next-generation RNA sequencing, miRCURY LNA PCR), protein content (tandem mass spectrometry), and elastin fragmentation and degeneration (histomorphometric analysis). Integrated bioinformatic analyses of RNA sequencing and proteomic datasets identified five microRNAs (miR-128-3p, miR-210-3p, miR-150-5p, miR-199b-5p, and miR-21-5p) differentially expressed across the AAo circumference. Among them, three miRNAs (miR-128-3p, miR-150-5p, and miR-199b-5p) were predicted to have an effect on eight common target genes, whose expression was dysregulated, according to proteomic analyses, and involved in the vascular-endothelial growth-factor signalling, Hippo signalling, and arachidonic acid pathways. Decreased elastic fibre levels and elastic layer thickness were observed in the dilated segments. Additionally, in a subset of patients n = 6/15, a four-dimensional cardiac magnetic resonance (CMR) scan was performed. Interestingly, an increase in wall shear stress (WSS) was observed at the anterior/right wall segments, concomitantly with the differentially expressed miRNAs and decreased elastic fibres. This study identified new miRNAs involved in the BAV aortic wall and revealed the concomitant expressional dysregulation of miRNAs, proteins, and elastic fibres on the anterior/right wall in dilated BAV patients, corresponding to regions of elevated WSS., Competing Interests: Chiara Bucciarelli-Ducci is the Chief Executive Officer (part-time) of the Society for Cardiovascular Magnetic Resonance. The remaining authors have nothing to disclose.

Objective: There are several choices for the correction of complex transposition of the great arteries and double outlet right ventricle not amenable to the Rastelli-type surgery, but outcome data are limited to small series. This study aims to report results after the aortic root translocation and en bloc rotation of the outflow tract procedures., Methods: This is a retrospective, multicentric, observational study. Clinical, anatomy, procedural, and detailed follow-up data (median, 4.43 years) were collected., Results: A total of 70 patients (62.9% male; median age, 1 year; range 4 days to 12.4 years) were included: n = 43 in the aortic root translocation group and n = 27 in the en bloc rotation group. Those in the aortic root translocation group were older (P = .01) and more likely to have had previous procedures (P < .0001), but cardiac anatomy was similar in both groups. Aortic root translocation and en bloc rotation early mortality (30 days) was similar (4.7% vs 3.7%, P = .8). Late survival and freedom from any cardiac reintervention were 92.7% and 16.9% at 15 years overall, respectively. Freedom from right ventricular outflow tract/conduit reintervention was better in the en bloc rotation group than in the aortic root translocation group (100% vs 24.5%, P = .0003), but more patients in the en bloc rotation group had moderate (or worse) aortic valve regurgitation during follow-up (16% vs 2.6%, P = .07)., Conclusions: Both aortic root translocation and en bloc rotation are valuable surgical options for the treatment of complex transposition of the great arteries and double outlet right ventricle. In the en bloc rotation group, there was better freedom from right ventricular outflow tract reinterventions, but a higher probability of aortic valve regurgitation. Identifying the main driving forces for these observed differences requires further study of these procedures., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Atrioventricular rupture is a life-threatening complication of mitral valve replacement. We present how incising the intervalvular fibrosa critically improves exposure. The aortic valve sacrifice allows access to a large atrioventricular dissociation defect and reliable repair of the anterolateral aspect of mitral valve annulus., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)