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Background: Bullying, harassment, and undermining behaviour has a profound detrimental effect on the multi-professional team, patient safety, and clinical outcomes. Bullying creates a poor working and training environment , increasing stress, damaging confidence, and impairing wellbeing. We sought to characterize the prevalence and nature of bullying, harassment and undermining within cardiothoracic surgery in the United Kingdom and Republic of Ireland., Methods: A 21-question survey was sent to all members of the Society for Cardiothoracic Surgery (SCTS) in Great Britain & Ireland. Participants were asked about baseline demographics and their experience of bullying as victim or witness., Results: The survey was sent to 1,326 SCTS members and there were 278 responses (21.0%). Most respondents were physicians (75.2%, n = 209) and most were male (58.3%, n = 162). The majority (79.1%, n = 220) had experienced or witnessed bullying in some form within the last three years (or appointment as a professional). This was experienced directly the majority of respondents (62%, n=136) and a large minority (23.6%, n = 52) had witnessed it in their workplace CONCLUSIONS: Bullying is observed or experienced by a concerning proportion of healthcare professionals working in cardiothoracic surgery. Ongoing initiatives to reduce this within British and Irish healthcare need to be strengthened to improve prevention, reporting and investigation, and support for victims and perpetrators to keep workplaces safe for teams and individuals and to facilitate the delivery of the best possible patient care., (Copyright © 2024. Published by Elsevier Inc.)

Integrating clinical knowledge into AI remains challenging despite numerous medical guidelines and vocabularies. Medical codes, central to healthcare systems, often reflect operational patterns shaped by geographic factors, national policies, insurance frameworks, and physician practices rather than the precise representation of clinical knowledge. This disconnect hampers AI in representing clinical relationships, raising concerns about bias, transparency, and generalizability. Here, we developed a resource of 67,124 clinical vocabulary embeddings derived from a clinical knowledge graph tailored to electronic health record vocabularies, spanning over 1.3 million edges. Using graph transformer neural networks, we generated clinical vocabulary embeddings that provide a new representation of clinical knowledge by unifying seven medical vocabularies. These embeddings were validated through a phenotype risk score analysis involving 4.57 million patients from Clalit Healthcare Services, effectively stratifying individuals based on survival outcomes. Inter-institutional panels of clinicians evaluated the embeddings for alignment with clinical knowledge across 90 diseases and 3,000 clinical codes, confirming their robustness and transferability. This resource addresses gaps in integrating clinical vocabularies into AI models and training datasets, paving the way for knowledge-grounded population and patient-level models., Competing Interests: Competing interests The authors declare no competing interests.

Objectives: Cardiothoracic surgery has reported poor equality, diversity, and inclusion amongst its faculty [1-3]. We explored how gender, ethnicity, and disability influence medical students' interest in cardiothoracic surgery as a career choice, as well as overall exposure to cardiothoracic surgery in the undergraduate curriculum., Methods: We distributed a 26-item Google Forms online survey to student members of a medical education group from all 37 UK medical schools via social media. Respondents were asked to rank different 'factors of interest' on a 1-5 Likert scale (1 ​= ​not important at all, 5 ​= ​very important) and were encouraged to add free-text comments. Quantitative data were analysed using SPSS., Results: There were 258 respondents, 62% identifying as female and 38% male. Respondents' ethnicities were 45% White, 44% Asian or Asian British, and 11% from other ethnic groups. 11% of respondents confirmed 'long-standing illness or disability'. Men were almost twice as likely to consider a career in cardiothoracic surgery than women (33% vs 19%; p ​< ​0.001). Women were more likely than men to feel that their gender, lack of a similarly gendered mentor, and long working hours were important factors when considering cardiothoracic surgery as a career. Ethnicity of the respondent did not appear to affect how they perceived the challenges of a career in cardiothoracic surgery. Interestingly, 'long-standing illness or disability' did not significantly affect the decision making to consider this specialty as a career. Overall, 73% of respondents reported not having adequate exposure to cardiothoracic surgery at medical school and agreed they would benefit from more time., Conclusions: Female medical students felt their gender, lack of same-sex role models, and perceived long working hours were barriers in considering cardiothoracic surgery as a career. All students felt the need for more exposure to Cardiothoracic Surgery in the undergraduate curriculum., Competing Interests: Declaration of competing interest None., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Coronary heart disease (CHD) is a prevalent cardiac disease that causes over 370,000 deaths annually in the USA. In CHD, occlusion of a coronary artery causes ischemia of the cardiac muscle, which results in myocardial infarction (MI). Junctophilin-2 (JPH2) is a membrane protein that ensures efficient calcium handling and proper excitation-contraction coupling. Studies have identified loss of JPH2 due to calpain-mediated proteolysis as a key pathogenic event in ischemia-induced heart failure (HF). Our findings show that calpain-2-mediated JPH2 cleavage yields increased levels of a C-terminal cleaved peptide (JPH2-CTP) in patients with ischemic cardiomyopathy and mice with experimental MI. We created a novel knock-in mouse model by removing residues 479-SPAGTPPQ-486 to prevent calpain-2-mediated cleavage at this site. Functional and molecular assessment of cardiac function post-MI in cleavage site deletion (CSD) mice showed preserved cardiac contractility and reduced dilation, reduced JPH2-CTP levels, attenuated adverse remodeling, improved T-tubular structure, and normalized SR Ca 2+ -handling. Adenovirus mediated calpain-2 knockdown in mice exhibited similar findings. Pulldown of CTP followed by proteomic analysis revealed valosin-containing protein (VCP) and BAG family molecular chaperone regulator 3 (BAG3) as novel binding partners of JPH2. Together, our findings suggest that blocking calpain-2-mediated JPH2 cleavage may be a promising new strategy for delaying the development of HF following MI., Competing Interests: Declaration of competing interest XHTW is a consultant for Pfizer and Rocket Pharmaceuticals, and a founding partner and board member of Elex Biotech Inc., a start-up company that developed drug molecules that target ryanodine receptors to treat cardiac arrhythmia disorders. LZ is the co-founder and consultant for Pelagos Pharma Inc., a start-up company that develop drug molecules that target nuclear receptors to treat heart failure and neurodegenerative disorders. Other authors have no potential conflicts to disclose. AI-assisted technology is not used in the preparation of this work (except checking grammar and spelling)., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs., (© 2024. The Author(s).)

Background: Visceral obesity is directly linked to increased cardiovascular risk, including heart failure., Objectives: This study explored the ability of human epicardial adipose tissue (EAT)-derived microRNAs (miRNAs) to regulate the myocardial redox state and clinical outcomes., Methods: This study screened for miRNAs expressed and released from human EAT and tested for correlations with the redox state in the adjacent myocardium in paired EAT/atrial biopsy specimens from patients undergoing cardiac surgery. Three miRNAs were then tested for causality in an in vitro model of cardiomyocytes. At a clinical level, causality/directionality were tested using genome-wide association screening, and the underlying mechanisms were explored using human biopsy specimens, as well as overexpression of the candidate miRNAs and their targets in vitro and in vivo using a transgenic mouse model. The final prognostic value of the discovered targets was tested in patients undergoing cardiac surgery, followed up for a median of 8 years., Results: EAT miR-92a-3p was related to lower oxidative stress in human myocardium, a finding confirmed by using genetic regulators of miR-92a-3p in the human heart and EAT. miR-92a-3p reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase-derived superoxide (O 2 .- ) by targeting myocardial expression of WNT5A, which regulated Rac1-dependent activation of NADPH oxidases. Finally, high miR-92a-3p levels in EAT were independently related with lower risk of adverse cardiovascular events., Conclusions: EAT-derived miRNAs exert paracrine effects on the human heart. Indeed miR-92a-3p suppresses the wingless-type MMTV integration site family, member 5a/Rac1/NADPH oxidase axis and improves the myocardial redox state. EAT-derived miR-92a-3p is related to improved clinical outcomes and is a rational therapeutic target for the prevention and treatment of obesity-related heart disease., Competing Interests: Funding Support and Author Disclosures This study was supported by a Marie Skłodowska-Curie Early Stage Researcher fellowship to Dr Carena; the CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) consortium (grant number 633196); the British Heart Foundation (FS/16/15/32047, RG/F/21/110040 and CH/F/21/90009 to Dr Antoniades; CH/16/1/32013 to Dr Channon; CH/12/3/29609 to Dr Casadei); Oxford BHF Centre of Research Excellence RE/18/3/34214, the Oxford NIHR Biomedical Research Centre, the National Institute for Health Research Oxford Biomedical Research Centre, and the Novo Nordisk Foundation (NNF15CC0018486) to Dr Antoniades. Dr Antoniades has had consultancy agreements with Mitsubishi Tanabe and Silence Therapeutics; has received grants from Sanofi and Novo Nordisk; is the Chair of the British Atherosclerosis Society; and has received honoraria from Amarin and Covance. Drs Antoniades and Channon are founders, shareholders, and directors of Caristo Diagnostics. Dr Casadei is the past president of the European Society of Cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Brain injury is common following open heart valve surgery. Carbon dioxide insufflation (CDI) has been proposed to reduce the incidence of brain injury by reducing the number of air microemboli entering the bloodstream in surgery. The CO2 Study will evaluate the efficacy and safety of CDI in patients undergoing planned left-sided open heart valve surgery., Methods and Analysis: The CO2 Study is a multicentre, blinded, placebo-controlled, randomised controlled trial. Seven-hundred and four patients aged 50 years and over undergoing planned left-sided heart valve surgery will be recruited to the study, from at least eight UK National Health Service hospitals, and randomised in a 1:1 ratio to receive CDI or medical air insufflation (placebo) in addition to standard de-airing. Insufflation will be delivered at a flow rate of 5 L/min from before the initiation of cardiopulmonary bypass until 10 min after cardiopulmonary bypass weaning. Participants will be followed up until 3 months post-surgery. The primary outcome is acute ischaemic brain injury within 10 days post-surgery based on new brain lesions identified with diffusion-weighted MRI or clinical evidence of permanent brain injury according to the current definition of stroke., Ethics and Dissemination: The study was approved by the East Midlands-Nottingham 2 Research Ethics Committee in June 2020 and the Medicines and Healthcare products Regulatory Agency in May 2020. All participants will provide written informed consent prior to undertaking any study assessments. Consent will be obtained by the principal investigator or a delegated member of the research team who has been trained in the study and undergone Good Clinical Practice training. Results will be disseminated through peer-reviewed publications and presentations at national and international meetings. Study participants will be informed of results through study notifications and patient organisations., Trial Registration Number: ISRCTN30671536., Competing Interests: Competing interests: CR, GDA and BG received support from the National Institute for Health and Care Research for the project associated with this manuscript, which was paid to the University of Bristol. RT, MP, LC, ML and SK received support from the National Institute for Health and Care Research for the project associated with this manuscript, which contributed to their salary. PP, NV and RS received support from the National Institute for Health and Care Research for the project associated with this manuscript, which was paid to the University of Oxford. EA received support from the National Institute for Health and Care Research for the project associated with this manuscript, which was paid to the RS reports ad hoc payments for providing expert testimony for the Parliamentary & Health Service Ombudsman. RS is the director and shareholder of Oxford Heart Surgery, chairs the Intercollegiate Speciality Board on Cardiothoracic Surgery, and is a member of the Special Advisory Committee in Cardiothoracic Surgery for the Royal Surgery Colleges. RS is an honorary secretary of the Society for Cardiothoracic Surgery in Great Britain and Ireland. No other conflicts were reported., (© 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.)

This study sought to compare the morbidity and mortality of redo aortic valve replacement (redo-AVR) versus valve-in-valve trans-catheter aortic valve implantation (valve-in-valve TAVI) for patients with a failing bioprosthetic valve. A multicenter UK retrospective study of redo-AVR or valve-in-valve TAVI for patients referred for redo aortic valve intervention due to a degenerated aortic bioprosthesis. Propensity score matching was performed for confounding factors. From July 2005 to April 2021, 911 patients underwent redo-AVR and 411 patients underwent valve-in-valve TAVI. There were 125 pairs for analysis after propensity score matching. The mean age was 75.2±8.5 years. In-hospital mortality was 7.2% (n=9) for redo-AVR versus 0 for valve-in-valve TAVI, p=0.002. Surgical patients suffered more post-operative complications, including intra-aortic balloon pump support (p=0.02), early re-operation (p<0.001), arrhythmias (p<0.001), respiratory and neurological complications (p=0.02 and p=0.03) and multi-organ failure (p=0.01). The valve-in-valve TAVI group had a shorter intensive care unit and hospital stay (p<0.001 for both). However, moderate aortic regurgitation at discharge and higher post-procedural gradients were more common after valve-in-valve TAVI (p<0.001 for both). Survival probabilities in patients who were successfully discharged from the hospital were similar after valve-in-valve TAVI and redo-AVR over the 6-year follow-up (log-rank p=0.26). In elderly patients with a degenerated aortic bioprosthesis, valve-in-valve TAVI provides better early outcomes as opposed to redo-AVR, although there was no difference in mid-term survival in patients successfully discharged from the hospital.

The coronavirus (COVID-19) pandemic disrupted all surgical specialties significantly and exerted additional pressures on the overburdened United Kingdom (UK) National Health Service. Healthcare professionals in the UK have had to adapt their practice. In particular, surgeons have faced organisational and technical challenges treating patients who carried higher risks, were more urgent and could not wait for prehabilitation or optimisation before their intervention. Furthermore, there were implications for blood transfusion with uncertain patterns of demand, reductions in donations and loss of crucial staff because of sickness and public health restrictions. Previous guidelines have attempted to address the control of bleeding and its consequences after cardiothoracic surgery, but there have been no targeted recommendations in light of the recent COVID-19 challenges. In this context, and with a focus on the perioperative period, an expert multidisciplinary Task Force reviewed the impact of bleeding in cardiothoracic surgery, explored different aspects of patient blood management with a focus on the use of haemostats as adjuncts to conventional surgical techniques and proposed best practice recommendations in the UK., (© 2023. The Author(s).)

Background: Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19., Methods: For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes., Findings: Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43-6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17-3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [<6·99] C19-RS; hazard ratio [HR] 3·31 [95% CI 1·49-7·33], p=0·0033; and 2·58 [1·10-6·05], p=0·028), adjusted for clinical factors, biochemical biomarkers of inflammation and myocardial injury, and technical parameters. The adjusted HR for in-hospital mortality was 8·24 (95% CI 2·16-31·36, p=0·0019) in patients who received no dexamethasone treatment, but 2·27 (0·69-7·55, p=0·18) in those who received dexamethasone after the scan, suggesting that vascular inflammation might have been a therapeutic target of dexamethasone in COVID-19. Finally, C19-RS was strongly associated (r=0·61, p=0·00031) with a whole blood transcriptional module representing dysregulation of coagulation and platelet aggregation pathways., Interpretation: Radiotranscriptomic analysis of CT angiography scans introduces a potentially powerful new platform for the development of non-invasive imaging biomarkers. Application of this platform in routine CT pulmonary angiography scans done in patients with COVID-19 produced the radiotranscriptomic signature C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation and responsible for adverse clinical outcomes, which predicts in-hospital mortality and might allow targeted therapy., Funding: Engineering and Physical Sciences Research Council, British Heart Foundation, Oxford BHF Centre of Research Excellence, Innovate UK, NIHR Oxford Biomedical Research Centre, Wellcome Trust, Onassis Foundation., Competing Interests: Declaration of Interests CA, KC, CS, and SN are founders, shareholders, and directors of Caristo Diagnostics, a CT image analysis company. CS is a full-time employee and MS is a part-time employee of Caristo diagnostics. JD is shareholder and chair of the advisory board of Caristo Diagnostics. EKO is a consultant and minor shareholder of Caristo Diagnostics. The technology described in this work is subject to patent US10,695,023B2 and patent applications PCT/GB2017/053262, GB2018/1818049.7, GR20180100490, and GR20180100510, licensed through exclusive license to Caristo Diagnostics. Caristo Diagnostics and the authors linked to it have no further conflicts of interest, beyond the above. JD is CMO of Our Future Health; Senior Advisor for Cardiovascular Disease Prevention, NHS Healthcheck Expert Scientific and Clinical Advisory Panel; and Chair of the Review of the National Health Check Programme for Public Health England. JCLR received a Research for Patient Benefit Grant from NIHR, and consulting fees from HeartFlow for physician services. DAd received support from Leicester NIHR Biomedical Research Unit and Innovate UK; grants and contracts from the Medical Research Council; and has two patents issued (Cardiac assist device: EP3277337A1; and angioplasty of calcified arteries: PCT/GB2017/050877) outside the scope of the current study. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction(NIHR Health Informatics Collaborative:TROP-CABG study). Benedetto et al. BACKGROUND: The optimal timing of coronary artery bypass grafting (CABG) in patients with non-ST elevation myocardial infarction (NSTEMI) and the utility of pre-operative troponin levels in decision-making remains unclear. We investigated (a) the association between peak pre-operative troponin and survival post-CABG in a large cohort of NSTEMI patients and (b) the interaction between troponin and time-to-surgery. METHODS AND RESULTS: Our cohort consisted of 1746 patients (1684 NSTEMI; 62 unstable angina) (mean age 69 ± 11 years,21% female) with recorded troponins that had CABG at five United Kingdom centers between 2010 and 2017. Time-segmented Cox regression was used to investigate the interaction of peak troponin and time-to-surgery on early (within 30 days) and late (beyond 30 days) survival. Average interval from peak troponin to surgery was 9 ± 15 days, with 1466 (84.0%) patients having CABG during the same admission. Sixty patients died within 30-days and another 211 died after a mean follow-up of 4 ± 2 years (30-day survival 0.97 ± 0.004 and 5-year survival 0.83 ± 0.01). Peak troponin was a strong predictor of early survival (adjusted P = 0.002) with a significant interaction with time-to-surgery (P interaction = 0.007). For peak troponin levels <100 times the upper limit of normal, there was no improvement in early survival with longer time-to-surgery. However, in patients with higher troponins, early survival increased progressively with a longer time-to-surgery, till day 10. Peak troponin did not influence survival beyond 30 days (adjusted P = 0.64). CONCLUSIONS: Peak troponin in NSTEMI patients undergoing CABG was a significant predictor of early mortality, strongly influenced the time-to-surgery and may prove to be a clinically useful biomarker in the management of these patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear., Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk., Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019., Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455)., Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation., Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75])., Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year., Trial Registration: isrctn.com Identifier: ISRCTN57819173.

The effects of miniaturization on theoretically predicted performance of dual-period guided mode resonance (GMR) transmission filters, which demonstrate immense potential for multispectral imaging in short wave infrared (SWIR), have been compared with experimental findings. With reducing filter size from 112 periods (90 µm) to 12 periods (10 µm), peak transmittance (Tpeak) of simulated and measured filters reduced gradually from 84% to 55% and from 76% to 65%, respectively, with a moderate change of 1 - 3 nm in full width at half maximum (FWHM). For 6 period filters (5 µm), simulations predict drastically reduced Tpeak = 14% accompanied by increase in FWHM by 12 nm. The Tpeak value is theoretically shown to increase to 46% with FWHM reduced by 7 nm upon placing metal reflectors at the optimum positions to increase the optical path length. Our findings indicate that four 5 µm × 5 µm size filters with metal reflectors designed for different resonance wavelengths can be used to form a single, 20 µm × 20 µm mosaic pixel for SWIR multispectral imaging.

Aims: Systemic inflammation and increased activity of atrial NOX2-containing NADPH oxidases have been associated with the new onset of atrial fibrillation (AF) after cardiac surgery. In addition to lowering LDL-cholesterol, statins exert rapid anti-inflammatory and antioxidant effects, the clinical significance of which remains controversial., Methods and Results: We first assessed the impact of cardiac surgery and cardiopulmonary bypass (CPB) on atrial nitroso-redox balance by measuring NO synthase (NOS) and GTP cyclohydrolase-1 (GCH-1) activity, biopterin content, and superoxide production in paired samples of the right atrial appendage obtained before (PRE) and after CPB and reperfusion (POST) in 116 patients. The effect of perioperative treatment with atorvastatin (80 mg once daily) on these parameters, blood biomarkers, and the post-operative atrial effective refractory period (AERP) was then evaluated in a randomized, double-blind, placebo-controlled study in 80 patients undergoing cardiac surgery on CPB. CPB and reperfusion led to a significant increase in atrial superoxide production (74% CI 71-76%, n = 46 paired samples, P < 0.0001) and a reduction in atrial tetrahydrobiopterin (BH4) (34% CI 33-35%, n = 36 paired samples, P < 0.01), and in GCH-1 (56% CI 55-58%, n = 26 paired samples, P < 0.001) and NOS activity (58% CI 52-67%, n = 20 paired samples, P < 0.001). Perioperative atorvastatin treatment prevented the effect of CPB and reperfusion on all parameters but had no significant effect on the postoperative right AERP, troponin release, or NT-proBNP after cardiac surgery., Conclusion: Perioperative statin therapy prevents post-reperfusion atrial nitroso-redox imbalance in patients undergoing on-pump cardiac surgery but has no significant impact on postoperative atrial refractoriness, perioperative myocardial injury, or markers of postoperative LV function., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01780740., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Recent clinical trials indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in heart failure patients, but the underlying mechanisms remain unknown. We explored the direct effects of canagliflozin, an SGLT2 inhibitor with mild SGLT1 inhibitory effects, on myocardial redox signalling in humans., Methods and Results: Study 1 included 364 patients undergoing cardiac surgery. Right atrial appendage biopsies were harvested to quantify superoxide (O2.-) sources and the expression of inflammation, fibrosis, and myocardial stretch genes. In Study 2, atrial tissue from 51 patients was used ex vivo to study the direct effects of canagliflozin on NADPH oxidase activity and nitric oxide synthase (NOS) uncoupling. Differentiated H9C2 and primary human cardiomyocytes (hCM) were used to further characterize the underlying mechanisms (Study 3). SGLT1 was abundantly expressed in human atrial tissue and hCM, contrary to SGLT2. Myocardial SGLT1 expression was positively associated with O2.- production and pro-fibrotic, pro-inflammatory, and wall stretch gene expression. Canagliflozin reduced NADPH oxidase activity via AMP kinase (AMPK)/Rac1signalling and improved NOS coupling via increased tetrahydrobiopterin bioavailability ex vivo and in vitro. These were attenuated by knocking down SGLT1 in hCM. Canagliflozin had striking ex vivo transcriptomic effects on myocardial redox signalling, suppressing apoptotic and inflammatory pathways in hCM., Conclusions: We demonstrate for the first time that canagliflozin suppresses myocardial NADPH oxidase activity and improves NOS coupling via SGLT1/AMPK/Rac1 signalling, leading to global anti-inflammatory and anti-apoptotic effects in the human myocardium. These findings reveal a novel mechanism contributing to the beneficial cardiac effects of canagliflozin., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Under the 21st Century Cures Act and the Office of the National Coordinator for Health Information Technology (ONC) rule implementing its interoperability provisions, a patient's rights to easily request and obtain digital access to portions of their medical records are now supported by both technology and policy. Data, once directed by a patient to leave a Health Insurance Portability and Accountability Act-covered health entity and enter a consumer app, will usually fall under Federal Trade Commission oversight. Because the statutory authority of the ONC does not extend to health data protection, there is not yet regulation to specifically address privacy protections for consumer apps. A technologically feasible workflow that could be widely adopted and permissible under ONC's rule, involves using the SMART on FHIR OAuth authorization routine to present standardized information about app behavior. This approach would not bias the patient in a way that triggers penalties under information blocking provisions of the rule., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Kinase oxidation is a critical signaling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, PKARIα (type-1 protein kinase A) can be reversibly oxidized, forming interprotein disulfide bonds in the holoenzyme complex. However, the effect of PKARIα disulfide formation on downstream signaling in the heart, particularly under states of oxidative stress such as ischemia and reperfusion (I/R), remains unexplored., Methods: Atrial tissue obtained from patients before and after cardiopulmonary bypass and reperfusion and left ventricular (LV) tissue from mice subjected to I/R or sham surgery were used to assess PKARIα disulfide formation by immunoblot. To determine the effect of disulfide formation on PKARIα catalytic activity and subcellular localization, live-cell fluorescence imaging and stimulated emission depletion super-resolution microscopy were performed in prkar1 knock-out mouse embryonic fibroblasts, neonatal myocytes, or adult LV myocytes isolated from "redox dead" (Cys17Ser) PKARIα knock-in mice and their wild-type littermates. Comparison of intracellular calcium dynamics between genotypes was assessed in fura2-loaded LV myocytes, whereas I/R-injury was assessed ex vivo., Results: In both humans and mice, myocardial PKARIα disulfide formation was found to be significantly increased (2-fold in humans, P =0.023; 2.4-fold in mice, P <0.001) in response to I/R in vivo. In mouse LV cardiomyocytes, disulfide-containing PKARIα was not found to impact catalytic activity, but instead led to enhanced AKAP (A-kinase anchoring protein) binding with preferential localization of the holoenzyme to the lysosome. Redox-dependent regulation of lysosomal two-pore channels by PKARIα was sufficient to prevent global calcium release from the sarcoplasmic reticulum in LV myocytes, without affecting intrinsic ryanodine receptor leak or phosphorylation. Absence of I/R-induced PKARIα disulfide formation in "redox dead" knock-in mouse hearts resulted in larger infarcts (2-fold, P <0.001) and a concomitant reduction in LV contractile recovery (1.6-fold, P <0.001), which was prevented by administering the lysosomal two-pore channel inhibitor Ned-19 at the time of reperfusion., Conclusions: Disulfide modification targets PKARIα to the lysosome, where it acts as a gatekeeper for two-pore channel-mediated triggering of global calcium release. In the postischemic heart, this regulatory mechanism is critical for protection from extensive injury and offers a novel target for the design of cardioprotective therapeutics.

This study was undertaken to investigate the nutritional value, chemical characterization and in-vitro antioxidant activity of Celosia cristata Linn. inflorescences, a culturally significant plant of Kashmir valley, India. The results revealed that the flower contained variety of vitamins (A, B-complex, C and E) with Vitamin E (tocopherol) showing the highest concentration. Among minerals, potassium was found to be present in significant amounts, the amino acid and fatty acid profile of the flower was also found to be satisfactory. The antioxidant activity of flower extract was evaluated by various in-vitro analytical methods: DPPH free radical scavenging activity, lipid peroxidation, reducing power, and metal chelating ability. Therefore, the present research brings into focus, the nutritional and antioxidant potential of C. cristata flower and its extract., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors.)

The 21st Century Cures Act requires that certified health information technology have an application programming interface (API) giving access to all data elements of a patient's electronic health record, "without special effort". In the spring of 2020, the Office of the National Coordinator of Health Information Technology (ONC) published a rule-21st Century Cures Act Interoperability, Information Blocking, and the ONC Health IT Certification Program-regulating the API requirement along with protections against information blocking. The rule specifies the SMART/HL7 FHIR Bulk Data Access API, which enables access to patient-level data across a patient population, supporting myriad use cases across healthcare, research, and public health ecosystems. The API enables "push button population health" in that core data elements can readily and standardly be extracted from electronic health records, enabling local, regional, and national-scale data-driven innovation.

Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans 1 . Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warrant investigation given the inadequacy of present therapies 2 . Here we show that calcitonin, a hormone product of the thyroid gland involved in bone metabolism 3 , is also produced by atrial cardiomyocytes in substantial quantities and acts as a paracrine signal that affects neighbouring collagen-producing fibroblasts to control their proliferation and secretion of extracellular matrix proteins. Global disruption of calcitonin receptor signalling in mice causes atrial fibrosis and increases susceptibility to atrial fibrillation. In mice in which liver kinase B1 is knocked down specifically in the atria, atrial-specific knockdown of calcitonin promotes atrial fibrosis and increases and prolongs spontaneous episodes of atrial fibrillation, whereas atrial-specific overexpression of calcitonin prevents both atrial fibrosis and fibrillation. Human patients with persistent atrial fibrillation show sixfold lower levels of myocardial calcitonin compared to control individuals with normal heart rhythm, with loss of calcitonin receptors in the fibroblast membrane. Although transcriptome analysis of human atrial fibroblasts reveals little change after exposure to calcitonin, proteomic analysis shows extensive alterations in extracellular matrix proteins and pathways related to fibrogenesis, infection and immune responses, and transcriptional regulation. Strategies to restore disrupted myocardial calcitonin signalling thus may offer therapeutic avenues for patients with atrial fibrillation.

Based on current guidelines, 15% to 20% of patients undergoing mitral valve repair for regurgitation develop left ventricular dysfunction (ejection fraction < 50%-55%) despite a normal baseline. Two schools of thought have been debated: preexisting myocardial disease or suboptimal intraoperative myocardial protection. In our view, they could be reconciled. It is well recognized that left ventricular ejection fraction with a standard cut off at 50%-55% has limited sensitivity in detecting early systolic impairment in mitral regurgitation patients. Mitral regurgitation also leads to mitochondrial oxidative stress, thus rendering the myocardium more susceptible to ischemia-reperfusion injury and precipitating postoperative cardiac dysfunction. The fall in left ventricular ejection fraction early after mitral valve repair was shown to be caused by the reduction in both myocardial contractility and left ventricular stroke volume. To mitigate the risk to myocardial reperfusion injury, appropriate cardioplegia volume and distribution and well-defined surgical repair processes are equally important. We use transesophageal echocardiography-guided cardioplegia delivery, imaging the intramyocardial flow and ensuring adequate protection of the subendocardium during mitral valve repair. Mild aortic regurgitation on a beating heart often leads to left ventricular dilatation with diminished cardioplegia flow in the myocardium, thus requiring direct ostia cardioplegia. Systematic transesophageal echocardiography assessment before surgery is essential for establishing the mitral regurgitation mechanisms and translating them into precise surgical repair strategies. The benefits of transesophageal echocardiography-guided cardioplegia delivery warrant further clinical trials in order to evolve into part of a high surgical standard.

Objectives: To identify clinical and procedural practice predictors of avoidable complications during transcatheter aortic valve replacement (TAVR)., Background: TAVR is evolving as a viable strategy for treatment of aortic stenosis (AS). Vascular complications, major bleeding, or pericardial tamponade may be influenced by procedural practice., Methods: The Oxford TAVR (OxTAVI) prospective registry was retrospectively analyzed to identify predictors of avoidable procedural complications in a contemporary cohort of transfemoral TAVR between January 2015 and September 2018. The primary endpoint was defined as a hierarchic composite of in-hospital mortality, pericardial effusion/cardiac tamponade, major bleeding, and vascular access complications. Individual components of the primary endpoint have been analyzed separately., Results: Five-hundred-twenty-nine patients underwent transfemoral TAVR using contemporary techniques during the study period and were enrolled in the OxTAVI registry. Female sex and high frailty were associated with a higher risk of death, major bleeding, vascular complication or pericardial tamponade. The use of ultrasound (US) guidance for vascular access management was independently associated with a reduced composite primary endpoint (OR = 0.35, CI:0.14-0.86, p = .02) after adjustment for clinical confounders, largely driven by a threefold reduction in vascular access complication (OR = 0.29, CI:0.15-0.55, p < .001). Performing rapid pacing via the left ventricle guidewire (LV-GW) was associated with a significant decrease in the risk of cardiac tamponade/pericardial effusion (OR = 0.19, CI:0.05-0.66, p = .009)., Conclusion: US-guided vascular access management and rapid pacing via the LV-GW are important determinants of reduced procedural complications during TAVR., (© 2019 Wiley Periodicals, Inc.)

In vitro cultures play a promising role for production of pharmaceutically important plant secondary metabolites and the use of elicitation can mitigate the low productivity of active compounds. In the present study, the influence of cadmium chloride (CdCl 2 ) elicitation on alkaloid yield was investigated in Rauvolfia serpentina . This heavy metal was employed to enhance the yield of reserpine and ajmalicine in leaf derived callus, leaves, stems and roots of in vitro grown cultures. Different concentrations [0.05 mM (C1), 0.10 mM (C2), 0.15 mM (C3) and 0.20 mM (C4)] of CdCl 2 were added to the MS medium. The elicitor's influence on callus biomass, biochemical attributes and the yield of alkaloids was monitored at regular intervals. The amendment of CdCl 2 improved growth and maximum callus biomass (1.29 g fresh weight and 0.16 g dry weight) was noted at 0.15 mM (C3) after 6 days of elicitation. The addition of elicitor in medium caused cellular stress and to analyse the role of CdCl 2 in plant defence responses various antioxidant enzymes, i.e., superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activities were measured in treated and non-treated cultures. The antioxidant enzyme activity increased linearly with elevated levels of CdCl 2 in medium; highest APX (0.88 EU min -1  mg -1 protein), SOD (5.40 EU min -1  mg -1 protein) and CAT (4.21 EU min -1  mg -1 protein) activity were observed in leaves of in vitro regenerated plants at C4. The quantitative analyses of reserpine and ajmalicine were conducted in different elicitated tissues using high-performance thin-layer chromatography (HPTLC) method. The study reveals enriched level of reserpine and ajmalicine in cultivated tissues and the enhancement was noted up to C3 (0.15 mM) elicitor level. Reserpine yield was maximum (0.191 mg g -1 DW) in roots of in vitro regenerated plants. The accumulation of ajmalicine was, however, better in leaf derived callus at C3 (0.131 mg g -1 DW). Higher elicitor dose (0.20 mM) inhibited callus biomass growth and subsequent alkaloid accumulation. The present study indicates the use of CdCl 2 as a propitious method in enhancing reserpine and ajmalicine yield in R. serpentina ., Competing Interests: Conflict of interestThere is no conflict of interest authors certify., (© King Abdulaziz City for Science and Technology 2020.)

Background: Somatic embryogenesis (SE) is an intricate molecular and biochemical process principally based on cellular totipotency and a model in studying plant development. In this unique embryo-forming process, the vegetative cells acquire embryogenic competence under cellular stress conditions. The stress caused by plant growth regulators (PGRs), nutrient, oxygenic, or other signaling elements makes cellular reprogramming and transforms vegetative cells into embryos through activation/deactivation of a myriad of genes and transcriptional networks. Hundreds of genes have been directly linked to zygotic and somatic embryogeneses; some of them like SOMATIC EMBRYOGENESIS LIKE RECEPTOR KINASE (SERK), LEAFY COTYLEDON (LEC), BABYBOOM (BBM), and AGAMOUS-LIKE 15 (AGL15) are very important and are part of molecular network., Main Text (observation): This article reviews various genes/orthologs isolated from different plants; encoded proteins and their possible role in regulating somatic embryogenesis of plants have been discussed. The role of SERK in regulating embryogenesis is also summarized. Different SE-related proteins identified through LC-MS at various stages of embryogenesis are also described; a few proteins like 14-3-3, chitinase, and LEA are used as potential SE markers. These networks are interconnected in a complicated manner, posing challenges for their complete elucidation., Conclusions: The various gene networks and factors controlling somatic embryogenesis have been discussed and presented. The roles of stress, PGRs, and other signaling elements have been discussed. In the last two-to-three decades' progress, the challenges ahead and its future applications in various fields of research have been highlighted. The review also presents the need of high throughput, innovative techniques, and sensitive instruments in unraveling the mystery of SE.

Background: Why some but not all patients with severe aortic stenosis (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that reduced creatine kinase (CK) capacity and flux is associated with this transition., Methods: We recruited 102 participants to 5 groups: moderate aortic stenosis (ModAS) (n=13), SevAS, left ventricular (LV) ejection fraction ≥55% (SevAS-preserved ejection fraction, n=37), SevAS, LV ejection fraction <55% (SevAS-reduced ejection fraction, n=15), healthy volunteers with nonhypertrophied hearts with normal systolic function (normal healthy volunteer, n=30), and patients with nonhypertrophied, non-pressure-loaded hearts with normal systolic function undergoing cardiac surgery and donating LV biopsy (non-pressure-loaded heart biopsy, n=7). All underwent cardiac magnetic resonance imaging and 31 P magnetic resonance spectroscopy for myocardial energetics. LV biopsies (AS and non-pressure-loaded heart biopsy) were analyzed for CK total activity, CK isoforms, citrate synthase activity, and total creatine. Mitochondria-sarcomere diffusion distances were calculated by using serial block-face scanning electron microscopy., Results: In the absence of failure, CK flux was lower in the presence of AS (by 32%, P =0.04), driven primarily by reduction in phosphocreatine/ATP (by 17%, P <0.001), with CK k f unchanged ( P =0.46). Although lowest in the SevAS-reduced ejection fraction group, CK flux was not different from the SevAS-preserved ejection fraction group ( P >0.99). Accompanying the fall in CK flux, total CK and citrate synthase activities and the absolute activities of mitochondrial-type CK and CK-MM isoforms were also lower ( P <0.02, all analyses). Median mitochondria-sarcomere diffusion distances correlated well with CK total activity ( r =0.86, P =0.003)., Conclusions: Total CK capacity is reduced in SevAS, with median values lowest in those with systolic failure, consistent with reduced energy supply reserve. Despite this, in vivo magnetic resonance spectroscopy measures of resting CK flux suggest that ATP delivery is reduced earlier, at the moderate AS stage, where LV function remains preserved. These findings show that significant energetic impairment is already established in moderate AS and suggest that a fall in CK flux is not by itself a necessary cause of transition to systolic failure. However, because ATP demands increase with AS severity, this could increase susceptibility to systolic failure. As such, targeting CK capacity and flux may be a therapeutic strategy to prevent and treat systolic failure in AS.

Recent clinical trials have revealed that aggressive insulin treatment has a neutral effect on cardiovascular risk in patients with diabetes despite improved glycemic control, which may suggest confounding direct effects of insulin on the human vasculature. We studied 580 patients with coronary atherosclerosis undergoing coronary artery bypass surgery (CABG), finding that high endogenous insulin was associated with reduced nitric oxide (NO) bioavailability ex vivo in vessels obtained during surgery. Ex vivo experiments with human internal mammary arteries and saphenous veins obtained from 94 patients undergoing CABG revealed that both long-acting insulin analogs and human insulin triggered abnormal responses of post-insulin receptor substrate 1 downstream signaling ex vivo, independently of systemic insulin resistance status. These abnormal responses led to reduced NO bioavailability, activation of NADPH oxidases, and uncoupling of endothelial NO synthase. Treatment with an oral dipeptidyl peptidase 4 inhibitor (DPP4i) in vivo or DPP4i administered to vessels ex vivo restored physiological insulin signaling, reversed vascular insulin responses, reduced vascular oxidative stress, and improved endothelial function in humans. The detrimental effects of insulin on vascular redox state and endothelial function as well as the insulin-sensitizing effect of DPP4i were also validated in high-fat diet-fed ApoE -/- mice treated with DPP4i. High plasma DPP4 activity and high insulin were additively related with higher cardiac mortality in patients with coronary atherosclerosis undergoing CABG. These findings may explain the inability of aggressive insulin treatment to improve cardiovascular outcomes, raising the question whether vascular insulin sensitization with DPP4i should precede initiation of insulin treatment and continue as part of a long-term combination therapy., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Coronary occlusion is a rare but well-described complication of heart valve surgery. The left circumflex coronary artery, especially when it is dominant, is particularly at risk owing to the proximity of the mitral valve annulus. We report three cases of acute coronary complications of different valvular surgical procedures diagnosed and treated in the cardiac catheterization laboratory. Intracoronary optical coherence tomography was used to identify the cause of coronary flow impairment and provided important insights into the mechanism of intraoperative vascular damage., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A patient-centered health system needs precise computable measurements to derive value. While validated patient-reported outcomes (PROs) are increasingly used in trials, their adoption in care remains limited and generally separated from the medical record. Further, absence of systematic processes for patient-led data submission excludes valuable data from digital devices that can potentially aid in contextualizing health status. With prior experience in developing apps for the Patient-Reported Outcomes Measurement Information System (PROMIS), we sought to make collecting patient-generated health data (PGHD) a fundamental property of health information technology at scale, and in an interoperable, standards-compliant fashion. We build upon the open SMART on FHIR (Fast Health Interoperability Resources) specification to create SMART Markers-a mobile device software framework encapsulating functionality needed for rapid deployment of both patient- and practitioner-facing PGHD apps. We refactored previously developed PROMIS apps to use SMART Markers for handling PGHD-request creation, on-device administration, and generation of a variety of PGHD types and submission of results to a FHIR server. Validation and conformance tests were performed on the generated output and app-reusability was demonstrated across two demo servers. App developers can import SMART Markers into their existing or new apps to readily leverage an interoperable PGHD capturing functionality out of the box, without having to reinvent the wheel. Our approach enables the creation of health system integrated, context-specific experiences for both patients and practitioners., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

Obesity is associated with changes in the secretome of adipose tissue (AT), which affects the vasculature through endocrine and paracrine mechanisms. Wingless-related integration site 5A (WNT5A) and secreted frizzled-related protein 5 (SFRP5), adipokines that regulate noncanonical Wnt signaling, are dysregulated in obesity. We hypothesized that WNT5A released from AT exerts endocrine and paracrine effects on the arterial wall through noncanonical RAC1-mediated Wnt signaling. In a cohort of 1004 humans with atherosclerosis, obesity was associated with increased WNT5A bioavailability in the circulation and the AT, higher expression of WNT5A receptors Frizzled 2 and Frizzled 5 in the human arterial wall, and increased vascular oxidative stress due to activation of NADPH oxidases. Plasma concentration of WNT5A was elevated in patients with coronary artery disease compared to matched controls and was independently associated with calcified coronary plaque progression. We further demonstrated that WNT5A induces arterial oxidative stress and redox-sensitive migration of vascular smooth muscle cells via Frizzled 2-mediated activation of a previously uncharacterized pathway involving the deubiquitinating enzyme ubiquitin-specific protease 17 (USP17) and the GTPase RAC1. Our study identifies WNT5A and its downstream vascular signaling as a link between obesity and vascular disease pathogenesis, with translational implications in humans., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Type A aortic dissection is a rare but important cardiac surgical emergency. Few reports exist in the literature describing anterior spinal artery syndrome as a presenting feature. We report a case of anterior spinal artery syndrome due to aortic dissection in a patient with Marfan syndrome caused by a novel fibrillin mutation. A 53-year old female presented with chest pain and sudden-onset paralysis. Neurological examination revealed normal upper limb examination, reduced lower limb power and reflexes but normal sensation. CT scanning revealed type A acute aortic dissection which was treated with emergent cardiac surgical repair. At clinic follow up 3 years later, signs of Marfan syndrome were opportunistically noted and genetic testing revealed a novel mutation in the Fibrillin 1 gene. This case emphasises the importance of a good initial clinical assessment, including thorough neurological examination, as well as a low threshold of clinical suspicion for an aortic dissection in such a constellation of symptoms. The importance of family history should also be emphasised given the coincidental diagnosis of Marfan syndrome in a first-degree relative. Furthermore, this case illustrates the classical signs of anterior spinal artery syndrome., Competing Interests: No conflict of interests declared

Background / Purpose: The Lotus valve (Boston Scientific, Natick, MA, USA) is a contemporary transcatheter aortic valve implantation (TAVI) device that is fully repositionable and retrievable to aid implantation and optimise procedural results. The ability to implant the device without routine pre-dilatation is another possible advantage reducing associated risks and procedure times. The aim of this study is to report procedural and 30-day outcomes following TAVI in a consecutive patient group presenting with severe symptomatic aortic stenosis with the Lotus valve system without routine pre-dilatation., Methods / Materials: 146 consecutive patients that underwent TAVI at the John Radcliffe Hospital, Oxford between January 2015 - December 2016 were retrospectively analysed., Results: The mean age was 81.1±7.4 years and the mean logistic EuroSCORE was 14.6±10. 134 (91.8%) of patients were treated under conscious sedation. 144 (98.6%) of procedures were successful. Two patients (1.4%) died during the follow-up period. None or mild residual aortic regurgitation was achieved in 98.6% of patients. The mean and peak transvalvular gradients were 8.6±3.6mmHg and 16.6±6.6mmHg respectively. Eight patients (5.5%) suffered a stroke. Over time, there was a reduction in major vascular complications (14.3% vs. 2.2%, p=0.03) and a trend toward shorter procedure times (97.6±44.3 vs. 86.8±31.4 minutes, p=0.14) and the administration of less contrast (104.4±45.2 vs. 91.7±37.6 millilitres, p=0.16). The overall new pacemaker implantation rate was 36.3%., Conclusions: The use of the Lotus valve as a 'workhorse' device without routine pre-dilatation is safe and efficacious and is associated with a very low incidence of residual aortic regurgitation and acceptable transvalvular haemodynamics., (Copyright © 2017 Elsevier Inc. All rights reserved.)