63 results on '"Jan-Lukas, Robertus"'
Search Results
2. Efficient Parameter Optimisation for Quantum Kernel Alignment: A Sub-sampling Approach in Variational Training.
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Mustafa Emre Sahin, Benjamin C. B. Symons, Pushpak Pati, Fayyaz Minhas, Declan Millar, Maria Gabrani, Jan Lukas Robertus, and Stefano Mensa
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- 2024
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3. Towards quantum computing for clinical trial design and optimization: A perspective on new opportunities and challenges.
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Hakan Doga, M. Emre Sahin, Joao H. Bettencourt-Silva, Anh Pham, Eunyoung Kim, Alan Andress, Sudhir Saxena, Aritra Bose, Laxmi Parida, Jan Lukas Robertus, Hideaki Kawaguchi, Radwa Soliman, and Daniel Blankenberg
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- 2024
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4. The genetic basis of thoracic aortic disease: The future of aneurysm classification?
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M Yousuf Salmasi, Shehani Alwis, Shabnam Cyclewala, Omar A. Jarral, Heba Mohamed, David Mozalbat, Christoph A. Nienaber, Thanos Athanasiou, Deborah Morris-Rosendahl, James Moore Jr, Yun Xu, John Pepper, Declan O'Regan, Jan-Lukas Robertus, Aung Oo, Sumesh Sasidharan, Selene Pirola, Michael Sabetai, Richard Gibbs, and Rakesh Uppal
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Thoracic aortic aneurysms (TAA) ,aortic dissection ,genotype ,syndromic ,polymorphisms ,hereditary aortic aneurysms and dissection ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The expansion in the repertoire of genes linked to thoracic aortic aneurysms (TAA) has revolutionised our understanding of the disease process. The clinical benefits of such progress are numerous, particularly helping our understanding of non-syndromic hereditary causes of TAA (HTAAD) and further refinement in the subclassification of disease. Furthermore, the understanding of aortic biomechanics and mechanical homeostasis has been significantly informed by the discovery of deleterious mutations and their effect on aortic phenotype. The drawbacks in genetic testing in TAA lie with the inability to translate genotype to accurate prognostication in the risk of thoracic aortic dissection (TAD), which is a life-threatening condition. Under current guidelines, there are no metrics by which those at risk for dissection with normal aortic diameters may undergo preventive surgery. Future research lies with more advanced genetic diagnosis of HTAAD and investigation of the diverse pathways involved in its pathophysiology, which will i) serve to improve our understanding of the underlying mechanisms, ii) improve guidelines for treatment and iii) prevent complications for HTAAD and sporadic aortopathies.
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- 2023
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5. Malignant Mesothelioma Subtyping of Tissue Images via Sampling Driven Multiple Instance Prediction.
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Mark Eastwood, Silviu Tudor Marc, Xiaohong Gao, Heba Sailem, Judith Offman, Emmanouil Karteris, Angeles Montero Fernandez, Danny Jonigk, William Cookson, Miriam Moffatt, Sanjay Popat, Fayyaz A. Minhas, and Jan Lukas Robertus
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- 2022
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6. MesoGraph: Automatic Profiling of Malignant Mesothelioma Subtypes from Histological Images.
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Mark Eastwood, Heba Sailem, Silviu Tudor Marc, Xiaohong Gao, Judith Offman, Emmanouil Karteris, Angeles Montero Fernandez, Danny Jonigk, William Cookson, Miriam Moffatt, Sanjay Popat, Fayyaz ul Amir Afsar Minhas, and Jan Lukas Robertus
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- 2023
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7. Malignant Mesothelioma subtyping via sampling driven multiple instance prediction on tissue image and cell morphology data.
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Mark Eastwood, Silviu Tudor Marc, Xiaohong Gao, Heba Sailem, Judith Offman, Emmanouil Karteris, Angeles Montero Fernandez, Danny Jonigk, William Cookson, Miriam Moffatt, Sanjay Popat, Fayyaz Minhas, and Jan Lukas Robertus
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- 2023
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8. ATGL Deficiency-Induced Triglyceride Deposit Cardiomyovasculopathy Requiring Heart Transplant
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Prina Rajani, MBBS, Jan Lukas Robertus, PhD, Joyce Wong, PhD, Tessa Homfray, MBBS, Fernando Riesgo Gil, MD, and Mayooran Shanmuganathan, MBBS
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cardiac magnetic resonance ,cardiac transplant ,cardiomyopathy ,chronic heart failure ,genetic disorders ,lipid metabolism disorders ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
A young man presented with syncope. He was diagnosed with triglyceride deposit cardiomyovasculopathy and skeletal myopathy secondary to adipose triglyceride lipase (ATGL) deficiency. Despite optimal medical therapy, he required heart transplantation to treat his heart failure. Five years post-transplant, the graft function was normal with no evidence of triglyceride deposits. (Level of Difficulty: Intermediate.)
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- 2020
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9. Type II Endoleaks and Culprit Vessels: Will 4D MRI Change the Paradigm?
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Lydia Hanna, Richard G.J. Gibbs, Thanos Athanasiou, James Moore, Xiao Yun Xu, Christoph Nienaber, John Pepper, Declan O'Regan, Jan-Lukas Robertus, Deborah Morris-Rosendahl, Aung Oo, Sumesh Sasidharan, Selene Pirola, M. Yousuf Salmasi, Omar Jarral, Michael Sabetai, George Asimakopoulos, Richard Gibbs, and Rakesh Uppal
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Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2023
10. Prediction of next generation sequencing test failure in lung adenocarcinoma in a genomic laboratory hub setting
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Yu Zhi Zhang, Stuart Sherlock, Suzanne MacMahon, Cecilia Brambilla, Alexandra Rice, Jan Lukas Robertus, Katharina Wassilew, Eric Lim, Sofina Begum, Silviu Buderi, Simon Jordan, Vladimir Anikin, Jonathan Finch, Nizar Asadi, Emma Beddow, Justin L Garner, Jaymin Morjaria, Richard Lee, Fiona McDonald, Georgios Antoniou, Carole Ridge, Simon Padley, Paras Dalal, Deborah Morris-Rosendahl, Mikel Valganon-Petrizan, Pallav L Shah, Anand Devaraj, Sanjay Popat, and Andrew G Nicholson
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Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology - Published
- 2023
11. Genetic Architecture of Acute Myocarditis and the Overlap with Inherited Cardiomyopathy
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Amrit S. Lota, Mark R. Hazebroek, Pantazis Theotokis, Rebecca Wassall, Sara Salmi, Brian P. Halliday, Upasana Tayal, Job Verdonschot, Devendra Meena, Ruth Owen, Antonio de Marvao, Alma Iacob, Momina Yazdani, Daniel J. Hammersley, Richard E. Jones, Riccardo Wage, Rachel Buchan, Fredrik Vivian, Yakeen Hafouda, Michela Noseda, John Gregson, Tarun Mittal, Joyce Wong, Jan Lukas Robertus, A. John Baksi, Vassilios Vassiliou, Ioanna Tzoulaki, Antonis Pantazis, John G.F. Cleland, Paul J.R. Barton, Stuart A. Cook, Dudley J. Pennell, Pablo Garcia-Pavia, Leslie T. Cooper, Stephane Heymans, James S. Ware, Sanjay K. Prasad, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), British Heart Foundation, Medical Research Council (Reino Unido), Wellcome Trust, Fondation Leducq, Instituto de Salud Carlos III, Fundación ProCNIC, Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España), and Ministerio de Ciencia (España)
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Cardiomyopathy, Dilated ,Adult ,Male ,Cardiomyopathy ,Arrhythmogenic right ventricular dysplasia ,Heart failure ,Heart ,Stroke Volume ,Middle Aged ,Ventricular Function, Left ,Myocarditis ,Desmoplakins ,Physiology (medical) ,Dilated ,Humans ,Female ,Cardiology and Cardiovascular Medicine - Abstract
Acute myocarditis is an inflammatory condition that may herald the onset of dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis. This was a population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterized cardiomyopathy-associated genes with comparison to healthy controls (n=1053) sequenced on the same platform. Case ascertainment in England was assessed against national hospital admission data. The primary outcome was all-cause mortality. Variants that would be considered pathogenic if found in a patient with DCM or ACM were identified in 8% of myocarditis cases compared with
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- 2022
12. Artificial intelligence in the diagnosis and management of arrhythmias
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Christoph A. Nienaber, Sabine Ernst, Su-Lin Lee, Jan-Lukas Robertus, Natalia A. Trayanova, and Venkat D Nagarajan
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Big Data ,education.field_of_study ,Cardiac electrophysiology ,business.industry ,Population ,Big data ,Cardiac arrhythmia ,Arrhythmias ,Ablation ,Electrophysiology ,Electrocardiography ,Artificial Intelligence ,Artificial intelligence ,Machine learning ,Atrial Fibrillation ,State of the Art Review ,Humans ,Ablation Therapy ,Medicine ,AcademicSubjects/MED00200 ,Cardiology and Cardiovascular Medicine ,education ,business ,Internet of Things - Abstract
The field of cardiac electrophysiology (EP) had adopted simple artificial intelligence (AI) methodologies for decades. Recent renewed interest in deep learning techniques has opened new frontiers in electrocardiography analysis including signature identification of diseased states. Artificial intelligence advances coupled with simultaneous rapid growth in computational power, sensor technology, and availability of web-based platforms have seen the rapid growth of AI-aided applications and big data research. Changing lifestyles with an expansion of the concept of internet of things and advancements in telecommunication technology have opened doors to population-based detection of atrial fibrillation in ways, which were previously unimaginable. Artificial intelligence-aided advances in 3D cardiac imaging heralded the concept of virtual hearts and the simulation of cardiac arrhythmias. Robotics, completely non-invasive ablation therapy, and the concept of extended realities show promise to revolutionize the future of EP. In this review, we discuss the impact of AI and recent technological advances in all aspects of arrhythmia care., Graphical Abstract Artificial intelligence-enhanced arrhythmia care.
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- 2021
13. Vascular histopathology and connective tissue ultrastructure in spontaneous coronary artery dissection: pathophysiological and clinical implications
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Francesca Saini, Aryan Vink, Sarah Parsons, Mary N. Sheppard, Nilesh J. Samani, Ania A Baranowska-Clarke, David Adlam, Marios Margaritis, Charley A. Budgeon, Bart E. Wagner, Natalie Alcock, Jan H. von der Thüsen, and Jan Lukas Robertus
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Male ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,Physiology ,Coronary Vessel Anomalies ,Myocardial Infarction ,Connective tissue ,Autopsy ,Fibromuscular dysplasia ,030204 cardiovascular system & hematology ,Coronary Angiography ,Sudden death ,Sudden cardiac death ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,medicine ,Fibromuscular Dysplasia ,Humans ,Vascular Diseases ,Myocardial infarction ,Inflammation ,business.industry ,medicine.disease ,Coronary Vessels ,030104 developmental biology ,medicine.anatomical_structure ,Connective Tissue ,Vasa vasorum ,Histopathology ,Cardiology and Cardiovascular Medicine ,business - Abstract
AIMS Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndromes and in rare cases sudden cardiac death (SCD). Connective tissue abnormalities, coronary inflammation, increased coronary vasa vasorum density and coronary fibromuscular dysplasia have all been implicated in the pathophysiology of SCAD but have not previously been systematically assessed. We designed a study to investigate the coronary histological and dermal collagen ultrastructural findings in SCAD. METHODS AND RESULTS 36 autopsy SCAD cases were compared with 359 SCAD survivors. Coronary and myocardial histology and immunohistochemistry were undertaken. Transmission electron microscopy (TEM) of dermal extracellular matrix components (ECM) of n = 31 SCAD survivors and n = 16 healthy volunteers were compared. Autopsy cases were more likely male (19% versus 5%; p = 0.0004) with greater proximal left coronary involvement (56% versus 18%; p
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- 2021
14. Inflammation and vascular remodeling in COVID-19 hearts
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Christopher Werlein, Maximilian Ackermann, Helge Stark, Harshit R. Shah, Alexandar Tzankov, Jasmin Dinonne Haslbauer, Saskia von Stillfried, Roman David Bülow, Ali El-Armouche, Stephan Kuenzel, Jan Lukas Robertus, Marius Reichardt, Axel Haverich, Anne Höfer, Lavinia Neubert, Edith Plucinski, Peter Braubach, Stijn Verleden, Tim Salditt, Nikolaus Marx, Tobias Welte, Johann Bauersachs, Hans-Heinrich Kreipe, Steven J. Mentzer, Peter Boor, Stephen M. Black, Florian Länger, Mark Kuehnel, and Danny Jonigk
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Cancer Research ,Physiology ,Clinical Biochemistry ,Human medicine ,ddc:610 - Abstract
Angiogenesis 26(2), 233 - 248 (2022). doi:10.1007/s10456-022-09860-7, A wide range of cardiac symptoms have been observed in COVID-19 patients, often significantly influencing the clinical outcome. While the pathophysiology of pulmonary COVID-19 manifestation has been substantially unraveled, the underlying pathomechanisms of cardiac involvement in COVID-19 are largely unknown. In this multicentre study, we performed a comprehensive analysis of heart samples from 24 autopsies with confirmed SARS-CoV-2 infection and compared them to samples of age-matched Influenza H1N1 A (n = 16), lymphocytic non-influenza myocarditis cases (n = 8), and non-inflamed heart tissue (n = 9). We employed conventional histopathology, multiplexed immunohistochemistry (MPX), microvascular corrosion casting, scanning electron microscopy, X-ray phase-contrast tomography using synchrotron radiation, and direct multiplexed measurements of gene expression, to assess morphological and molecular changes holistically. Based on histopathology, none of the COVID-19 samples fulfilled the established diagnostic criteria of viral myocarditis. However, quantification via MPX showed a significant increase in perivascular CD11b/TIE2 + —macrophages in COVID-19 over time, which was not observed in influenza or non-SARS-CoV-2 viral myocarditis patients. Ultrastructurally, a significant increase in intussusceptive angiogenesis as well as multifocal thrombi, inapparent in conventional morphological analysis, could be demonstrated. In line with this, on a molecular level, COVID-19 hearts displayed a distinct expression pattern of genes primarily coding for factors involved in angiogenesis and epithelial-mesenchymal transition (EMT), changes not seen in any of the other patient groups. We conclude that cardiac involvement in COVID-19 is an angiocentric macrophage-driven inflammatory process, distinct from classical anti-viral inflammatory responses, and substantially underappreciated by conventional histopathologic analysis. For the first time, we have observed intussusceptive angiogenesis in cardiac tissue, which we previously identified as the linchpin of vascular remodeling in COVID-19 pneumonia, as a pathognomic sign in affected hearts. Moreover, we identified CD11b + /TIE2 + macrophages as the drivers of intussusceptive angiogenesis and set forward a putative model for the molecular regulation of vascular alterations., Published by Springer Science + Business Media B.V, Dordrecht [u.a.]
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- 2022
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15. Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2‐tier nuclear grade
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Eric Lim, Michael Dusmet, S Begum, Loic Lang-Lazdunski, Aliya N. Husain, William O.C.M. Cookson, Miriam F. Moffatt, Jan Lukas Robertus, Emma Beddow, Vladimir Anikin, Yu Zhi Zhang, Andrew G. Nicholson, Sanjay Popat, Philip L. Molyneaux, Alexandra Rice, John Le Quesne, Jonathan Finch, Simon Jordan, Nizar Asadi, C. Brambilla, and Action for Pulmonary Fibrosis
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Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Histology ,Composite score ,Pleural Neoplasms ,pleomorphic features ,nuclear grade ,Prognostic stratification ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pathology ,Overall survival ,medicine ,Humans ,Mesothelioma ,growth patterns ,Nuclear grade ,Aged ,Aged, 80 and over ,Science & Technology ,Pleural mesothelioma ,business.industry ,Epithelioid Cells ,Mesothelioma, Malignant ,1103 Clinical Sciences ,Cell Biology ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Micropapillary pattern ,030104 developmental biology ,mesothelioma ,030220 oncology & carcinogenesis ,Female ,Neoplasm Grading ,heterogeneity ,business ,Life Sciences & Biomedicine - Abstract
AIMS: Nuclear grade has been recently validated as a powerful prognostic tool in epithelioid malignant pleural mesothelioma (E-MPM). In other studies histological parameters including pleomorphic features and growth patterns were also shown to exert prognostic impact. The primary aims of our study are (1) externally validate the prognostic role of pleomorphic features in E-MPM and (2) investigate if evaluating growth pattern in addition to 2-tier nuclear grade improves prognostication. METHODS AND RESULTS: 614 consecutive cases of E-MPM from our institution over a period of 15 years were retrospectively reviewed, of which 51 showed pleomorphic features. E-MPM with pleomorphic features showed significantly worse overall survival compared those without (5.4 months vs 14.7 months). Tumours with predominantly micropapillary pattern showed the worst survival (6.2 months) followed by solid (10.5 months), microcystic (15.3 months), discohesive (16.1 months), trabecular (17.6 months) and tubulo-papillary (18.6 months). Sub-classification of growth patterns into high grade (solid, micropapillary) and low grade (all others) led to good separation of overall survival (10.5 months vs. 18.0 months) but did not predict survival independent of 2-tier nuclear grade. A composite score comprised of growth pattern and 2-tier nuclear grade did not improve prognostication compared with nuclear grade alone. Intra-tumoural heterogeneity in growth patterns is ubiquitous. CONCLUSIONS: Our findings support the incorporation of E-MPM with pleomorphic features in the epithelioid subtype as a highly aggressive variant distinct from 2-tier nuclear grade. E-MPM demonstrates extensive heterogeneity in growth pattern but its evaluation does not offer additional prognostic utility to 2-tier nuclear grade.
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- 2020
16. ATGL Deficiency-Induced Triglyceride Deposit Cardiomyovasculopathy Requiring Heart Transplant
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Fernando Riesgo Gil, Tessa Homfray, Prina Rajani, Jan Lukas Robertus, Mayooran Shanmuganathan, and Joyce Wong
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0301 basic medicine ,medicine.medical_specialty ,5 year follow up ,Lipid Metabolism Disorder ,Cardiomyopathy ,Case Report ,030105 genetics & heredity ,Graft function ,cardiac magnetic resonance ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Clinical Case ,CMR, cardiac magnetic resonance ,Internal medicine ,medicine ,Diseases of the circulatory (Cardiovascular) system ,genetic disorders ,ATGL, adipose triglyceride lipase ,biology ,Triglyceride ,business.industry ,Syncope (genus) ,medicine.disease ,biology.organism_classification ,PNPLA2, patatin-like phospholipase domain containing 2 ,chronic heart failure ,chemistry ,lipid metabolism disorders ,Heart failure ,RC666-701 ,Adipose triglyceride lipase ,Cardiology ,EMB, endomyocardial biopsy ,Cardiology and Cardiovascular Medicine ,business ,cardiac transplant ,cardiomyopathy ,030217 neurology & neurosurgery ,CK, creatine kinase - Abstract
A young man presented with syncope. He was diagnosed with triglyceride deposit cardiomyovasculopathy and skeletal myopathy secondary to adipose triglyceride lipase (ATGL) deficiency. Despite optimal medical therapy, he required heart transplantation to treat his heart failure. Five years post-transplant, the graft function was normal with no evidence of triglyceride deposits. (Level of Difficulty: Intermediate.), Graphical abstract, A young man presented with syncope. He was diagnosed with triglyceride deposit cardiomyovasculopathy and skeletal myopathy secondary to adipose…
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- 2020
17. Primary Tumors of the Aorta and Pulmonary Arteries
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Monika Arzanauskaite, Jan Lukas Robertus, Raad Mohiaddin, and Vassilios S. Vassiliou
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medicine.medical_specialty ,Aorta ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Tissue characterization ,Late diagnosis ,medicine.artery ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Cardiac imaging - Abstract
As the access to advanced cardiac imaging grows, primary cardiovascular tumors are increasingly encountered despite being very rare [(1)][1]. Primary tumors of the aorta and pulmonary arteries have nonspecific clinical manifestations that often lead to a late diagnosis. These tumors are most
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- 2019
18. Abstract 10960: Genetic Overlap of Acute Myocarditis and Inherited Cardiomyopathy
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Amrit S Lota, Mark Hazebroek, Pantazis Theotokis, Rebecca Wassall, Sara Salmi, Brian Halliday, Upasana Tayal, Job Verdonschot, Devendra Meena, Antonio de Marvao, Alma Iacob, Daniel Hammersley, Richard Jones, Rick Wage, Rachel Buchan, Momina Yazdani, Michela Noseda, Tarun Mittal, Joyce Wong, Jan Lukas Robertus, John Baksi, Vassilios Vassiliou, Ioanna Tzoulaki, Antonios Pantazis, John Cleland, Paul J Barton, stuart cook, Dudley J Pennell, Pablo Garcia-Pavia, Leslie T Cooper, Stephane Heymans, James S Ware, and Sanjay K Prasad
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: Myocarditis may predispose to dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Familial data indicate a potential genetic susceptibility shared with arrhythmogenic cardiomyopathy (ACM). We present the first large-scale genotype-phenotype study of adults with acute myocarditis. Methods: A cohort comprising 336 consecutive patients with acute myocarditis was enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterised cardiomyopathy-associated genes. The burden of rare protein altering variants (PAV) in ACM genes, DCM genes, and TTN specifically, were compared with local healthy controls sequenced on the same platform (n=1053). Case ascertainment was assessed against national hospital admission data. Results: We identified rare protein-altering variants in 23% of cases compared to 16% in controls (Δ+6.8%; p=0.021), with rare truncating variants (tv) in 6% of cases compared to Conclusion: We identified enrichment of cardiomyopathy gene variants in acute myocarditis patients, dominated by DSP-tv in those with normal LVEF and TTN-tv in those with reduced LVEF. Incorporation of genetic testing may be beneficial to identify such high-risk individuals and guide family screening in acute myocarditis patients.
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- 2021
19. Erratum to: Vascular histopathology and connective tissue ultrastructure in spontaneous coronary artery dissection: pathophysiological and clinical implications
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Marios Margaritis, Francesca Saini, Ania A Baranowska-Clarke, Sarah Parsons, Aryan Vink, Charley Budgeon, Natalie Allcock, Bart E Wagner, Nilesh J Samani, Jan von der Thüsen, Jan Lukas Robertus, Mary N Sheppard, and David Adlam
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Physiology ,Physiology (medical) ,Cardiology and Cardiovascular Medicine - Published
- 2022
20. COVID‑19 and SARS‑CoV‑2 host cell entry mediators: Expression profiling of TMRSS4 in health and disease
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Emmanouil Karteris, Harpal S. Randeva, Demetrios A. Spandidos, Julie Davies, Marcia Hall, Rachel Kerslake, Kamaljit Chatha, Andreas Polychronis, Vladimir Anikin, Periklis Katopodis, Jan Lukas Robertus, and Ioannis Kyrou
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0301 basic medicine ,Central Nervous System ,Male ,pan-cancer ,transmembrane protease serine 4 ,TMPRSS2 ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,Neoplasms ,COVID‑19 ,Databases, Genetic ,Genetics ,Carcinoma ,medicine ,Humans ,Computer Simulation ,Pandemics ,SARS‑CoV‑2 ,Tropism ,Host Microbial Interactions ,business.industry ,SARS-CoV-2 ,Gene Expression Profiling ,pan‑cancer ,tropism ,Serine Endopeptidases ,Cancer ,COVID-19 ,Brain ,Membrane Proteins ,General Medicine ,Articles ,Cell cycle ,Virus Internalization ,medicine.disease ,Gastrointestinal Tract ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Adenocarcinoma ,Female ,Ovarian cancer ,business - Abstract
Copyright: © Katopodis et al. Severe acute respiratory syndrome (SARS) coronavirus‑2 (SARS‑CoV‑2), the causative viral agent for the ongoing COVID‑19 pandemic, enters its host cells primarily via the binding of the SARS‑CoV‑2 spike (S) proteins to the angiotensin‑converting enzyme 2 (ACE2). A number of other cell entry mediators have also been identified, including neuropilin‑1 (NRP1) and transmembrane protease serine 2 (TMPRSS2). More recently, it has been demonstrated that transmembrane protease serine 4 (TMPRSS4) along with TMPRSS2 activate the SARS‑CoV‑2 S proteins, and enhance the viral infection of human small intestinal enterocytes. To date, a systematic analysis of TMPRSS4 in health and disease is lacking. In the present study, using in silico tools, the gene expression and genetic alteration of TMPRSS4 were analysed across numerous tumours and compared to controls. The observations were also expanded to the level of the central nervous system (CNS). The findings revealed that TMPRSS4 was overexpressed in 11 types of cancer, including lung adenocarcinoma, lung squamous cell carcinoma, cervical squamous cell carcinoma, thyroid carcinoma, ovarian cancer, cancer of the rectum, pancreatic cancer, colon and stomach adenocarcinoma, uterine carcinosarcoma and uterine corpus endometrial carcinoma, whilst it was significantly downregulated in kidney carcinomas, acute myeloid leukaemia, skin cutaneous melanoma and testicular germ cell tumours. Finally, a high TMPRSS4 expression was documented in the olfactory tubercle, paraolfactory gyrus and frontal operculum, all brain regions which are associated with the sense of smell and taste. Collectively, these data suggest that TMPRSS4 may play a role in COVID‑19 symptomatology as another SARS‑CoV‑2 host cell entry mediator responsible for the tropism of this coronavirus both in the periphery and the CNS.
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- 2021
21. Genetic Overlap of Acute Myocarditis and Inherited Cardiomyopathy
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Vass Vassiliou, Ioanna Tzoulaki, Alma Iacob, Leslie T. Cooper, Riccardo Wage, Pantazis Theotokis, John Baksi, Paul J.R. Barton, John Gf Cleland, Richard E. Jones, D.J. Pennell, Antonis Pantazis, Tarun Mittal, Devendra Meena, Momina Yazdani, Joyce Wong, Sara Salmi, Jan Lukas Robertus, Pablo García-Pavía, Brian P. Halliday, James S. Ware, Antonio de Marvao, Amrit S. Lota, Upasana Tayal, Mark R. Hazebroek, Sanjay K. Prasad, Rachel Buchan, Rebecca Wassall, Stuart A. Cook, Michela Noseda, Stephane Heymans, Job Verdonschot, and Daniel J. Hammersley
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History ,medicine.medical_specialty ,education.field_of_study ,Ejection fraction ,Myocarditis ,Polymers and Plastics ,medicine.diagnostic_test ,business.industry ,Population ,Cardiomyopathy ,Dilated cardiomyopathy ,Odds ratio ,medicine.disease ,Industrial and Manufacturing Engineering ,Internal medicine ,Cohort ,medicine ,Business and International Management ,business ,education ,Genetic testing - Abstract
Background: Acute myocarditis is a complex inflammatory disease increasingly associated with dilated cardiomyopathy (DCM) and arrhythmogenic ventricular cardiomyopathy (ACM), but its underlying genetic basis is unknown. We sought to determine if there is a genetic overlap between myocarditis and inherited forms of cardiomyopathy. Methods: Population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA-sequencing for well-characterised cardiomyopathy-associated genes with comparison to healthy controls (n=1053). Case ascertainment was assessed against national admission data. Findings: Variants of known or likely pathogenicity were identified in 6% of cases compared to
- Published
- 2021
22. On the role of artificial intelligence in medical imaging of COVID-19
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Deepta Rajan, Vandana Mukherjee, Pallav L. Shah, Emmanouil Karteris, Matteo Manica, Jan Lukas Robertus, Dorith Shaham, Michal Guindy, Michal Rosen-Zvi, Deddeh Ballah, Maria Gabrani, Jannis Born, Adam Coy, Prasanth Prasanna, and David Beymer
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Chest ultrasound ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Chest X-Ray ,MEDLINE ,CT, (Computed Tomography) ,medical imaging ,General Decision Sciences ,chest CT ,PRISMA ,Review ,ACR, (American College of Radiology) ,chest ultrasound ,Patient care ,Imaging modalities ,US, (Ultrasound) ,PRISMA, (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) ,QA76.75-76.765 ,Chest CT ,Medical imaging ,Medicine ,Medical physics ,Computer software ,DL, (Deep Learning) ,meta-review ,MI, (Medical Imaging) ,digital healthcare ,CXR, (Chest Radiographs) ,Meta Review ,artificial intelligence ,COVID-19 ,Coronavirus ,machine learning ,deep learning ,SARS-CoV-2 ,lung imaging ,business.industry ,Published Erratum ,AI, (Artificial Intelligence) ,Correction ,RT-PCR, (Reverse Transcriptase Polymerase Chain reaction) ,chest X-ray ,Clinical Practice ,LUS, (Lung Ultrasound) ,Clinical value ,business - Abstract
Although a plethora of research articles on AI methods on COVID-19 medical imaging are published, their clinical value remains unclear. We conducted the largest systematic review of the literature addressing the utility of AI in imaging for COVID-19 patient care. By keyword searches on PubMed and preprint servers throughout 2020, we identified 463 manuscripts and performed a systematic meta-analysis to assess their technical merit and clinical relevance. Our analysis evidences a significant disparity between clinical and AI communities, both in the focus on imaging modalities (AI experts neglected CT and Ultrasound, favoring X-Ray) and performed tasks (71.9% of AI papers centered on diagnosis). The vast majority of manuscripts were found deficient regarding potential use in clinical practice, but 2.7% (N=12) publications were assigned a high maturity level and are summarized in greater detail. We provide an itemized discussion of the challenges in developing clinically relevant AI solutions with recommendations and remedies., Graphical Abstract, In medical imaging, artificial intelligence (AI) has the potential to save time and cost in the healthcare system by advancing rapid patient stratification. We conducted the largest systematic review (N=463) of AI methodology on medical imaging data from COVID-19 patients. AI experts largely failed to focus on clinically relevant tasks and imaging modalities and only few publications are found valuable. On the roadmap toward developing robust and clinically valuable AI solutions, we identify key challenges and provide possible remedies.
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- 2021
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23. A case with two faces: noncompaction or phospholamban cardiomyopathy?
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Sip Wijchers, Jan Lukas Robertus, Kadir Caliskan, Jan H. von der Thüsen, Cardiology, and Pathology
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medicine.medical_specialty ,Noncompaction cardiomyopathy ,medicine.diagnostic_test ,business.industry ,Cardiomyopathy ,Dilated cardiomyopathy ,General Medicine ,Gene mutation ,medicine.disease ,Pathology and Forensic Medicine ,Phospholamban ,Internal medicine ,Heart failure ,Mutation (genetic algorithm) ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Genetic testing - Abstract
Noncompaction cardiomyopathy is a well-known clinical entity, whereas phospholamban gene mutation is a relatively recently known mutation with phenotypes as arrhythmogenic cardiomyopathy and dilated cardiomyopathy. We report the case of a 15-year-old girl that presents with rapid progressive heart failure based on a noncompaction cardiomyopathy as confirmed through cardiovascular imaging. As a result of her progressive heart failure 22 months later she received a heart transplant. Genetic testing showed a phospholamban gene mutation. We present cardiovascular images together with macroscopic and microscopic anatomy. This case shows the importance of considering phospholamban gene mutation in a case of severe noncompaction cardiomyopathy.
- Published
- 2022
24. On the Role of Artificial Intelligence in Medical Imaging of COVID-19
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Vandana Mukherjee, Deddeh Ballah, Maria Gabrani, Matteo Manica, Jan Lukas Robertus, Michal Rosen-Zvi, Prasanth Prasanna, Adam Coy, Jannis Born, Michal Guindy, David Beymer, Pallav L. Shah, Deepta Rajan, Dorith Shaham, and Emmanouil Karteris
- Subjects
Telemedicine ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Algorithmic complexity ,Disease detection ,business.industry ,Medical imaging ,Medicine ,Clinical significance ,Medical physics ,Disease ,Patient data ,business - Abstract
The global COVID-19 pandemic has accelerated the development of numerous digital technologies in medicine from telemedicine to remote monitoring. Concurrently, the pandemic has resulted in huge pressures on healthcare systems. Medical imaging (MI) from chest radiographs to computed tomography and ultrasound of the thorax have played an important role in the diagnosis and management of the coronavirus infection.We conducted the, to date, largest systematic review of the literature addressing the utility of Artificial Intelligence (AI) in MI for COVID-19 management. Through keyword matching on PubMed and preprint servers, including arXiv, bioRxiv and medRxiv, 463 papers were selected for a meta-analysis, with manual reviews to assess the clinical relevance of AI solutions. Further, we evaluated the maturity of the papers based on five criteria assessing the state of the field: peer-review, patient dataset size and origin, algorithmic complexity, experimental rigor and clinical deployment.In 2020, we identified 4977 papers on MI in COVID-19, of which 872 mentioned the term AI. 2039 papers of the 4977 were specific to imaging modalities with a majority of 83.8% focusing on CT, while 10% involved CXR and 6.2% used LUS. Meanwhile, the AI literature predominantly analyzed CXR data (49.7%), with 38.7% using CT and 1.5% LUS. Only a small portion of the papers were judged as mature (2.7 %). 71.9% of AI papers centered on disease detection.This review evidences a disparity between clinicians and the AI community, both in the focus on imaging modalities and performed tasks. Therefore, in order to develop clinically relevant AI solutions, rigorously validated on large-scale patient data, we foresee a need for improved collaboration between the two communities ensuring optimal outcomes and allocation of resources. AI may aid clinicians and radiologists by providing better tools for localization and quantification of disease features and changes thereof, and, with integration of clinical data, may provide better diagnostic performance and prognostic value.
- Published
- 2020
25. Utility of Nuclear Grading System in Epithelioid Malignant Pleural Mesothelioma in Biopsy-heavy Setting: An External Validation Study of 563 Cases
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Jan Lukas Robertus, Loic Lang-Lazdunski, C. Brambilla, Andrew G. Nicholson, Jonathan Finch, Yu Zhi Zhang, William O.C.M. Cookson, S Begum, Sanjay Popat, Emma Beddow, Nizar Asadi, Simon Jordan, Philip L. Molyneaux, Miriam F. Moffatt, Vladimir Anikin, Michael Dusmet, Alexandra Rice, and Eric Lim
- Subjects
0301 basic medicine ,Adult ,Male ,Mesothelioma ,Lung Neoplasms ,medicine.medical_treatment ,Biopsy ,Pleural Neoplasms ,Pathology and Forensic Medicine ,03 medical and health sciences ,Pneumonectomy ,0302 clinical medicine ,medicine ,Humans ,Grading (education) ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Neoplasm Grading ,medicine.diagnostic_test ,business.industry ,Pleural mesothelioma ,Mesothelioma, Malignant ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Survival Analysis ,030104 developmental biology ,030220 oncology & carcinogenesis ,Pleura ,Surgery ,Female ,Anatomy ,Nuclear medicine ,business ,Follow-Up Studies - Abstract
Nuclear grading systems for epithelioid malignant pleural mesothelioma (MPM) have been proposed but it remains uncertain if they could be applied in a biopsy-heavy setting. Using the proposed system, we conducted an independent, external validation study using 563 consecutive cases of epithelioid MPM diagnosed at our institution between 2003 and 2017, of which 87% of patients underwent biopsies only. The median number of sites sampled was 1, with a median maximum tissue dimension of 17 mm (biopsy) and 150 mm (resection). The median overall survival (OS) was 14.7 months. The frequencies of grade I, II, and III tumors were 31% (132/563), 52% (292/563), and 17% (94/563). Grade I tumors were associated with the most favorable median OS (24.7 mo) followed by grades II (12.7 mo) and III (7.2 mo). The 2-tier nuclear grade separated tumors into low grade (19.3 mo) and high grade (8.9 mo). In multivariate analysis, 3-tier nuclear grade, 2-tier nuclear grade, and mitosis-necrosis score predicted OS independent of age, procedural type, solid-predominant growth pattern, necrosis, and atypical mitosis (all P
- Published
- 2020
26. Initial 2-year results of CardioCel® patch implantation in children
- Author
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Jan Lukas Robertus, Carine Pavy, Guido Michielon, Olivier Ghez, and François Lacour-Gayet
- Subjects
Heart Defects, Congenital ,Male ,Reoperation ,Pulmonary and Respiratory Medicine ,Aortic arch ,medicine.medical_specialty ,Time Factors ,Adolescent ,Heart disease ,Persistent truncus arteriosus ,030204 cardiovascular system & hematology ,Aortopulmonary window ,Blood Vessel Prosthesis Implantation ,03 medical and health sciences ,0302 clinical medicine ,Blood vessel prosthesis ,medicine.artery ,medicine ,Humans ,Child ,Retrospective Studies ,Bioprosthesis ,business.industry ,Infant, Newborn ,Infant ,Retrospective cohort study ,medicine.disease ,Hypoplasia ,Blood Vessel Prosthesis ,Surgery ,Treatment Outcome ,030228 respiratory system ,Child, Preschool ,Pulmonary artery ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objectives We present the initial 2-year results of CardioCel® patch (Admedus Regen Pty Ltd, Perth, WA, Australia) implantation in paediatric patients with congenital heart diseases. Methods This was a single-centre retrospective study with prospectively collected data of all patients aged 18 years and under operated for congenital heart disease. The patch was introduced in 2014, with clinical practice committee approval and a special consent in case of an Ozaki procedure. Standard follow-up was performed with systematic clinical exams and echocardiograms. In case of reoperation or graft failure, the patch was removed and sent for a histological examination. Results Between March 2014 and April 2016, 101 patients had surgical repair using a CardioCel patch. The mean age was 22 (±36.3) months, and the mean weight was 9.7 (±10.3) kg. No infections and no intraoperative implantation difficulties were associated with the patch. The median follow-up period was 212 (range 4-726) days. The overall 30-day postoperative mortality was 3.8% (n = 4), none of which were related to graft failure. Five children were reoperated because of graft failure, 4 of whom had the patch implanted for aortic and were aged less than 10 days. The indications for patch implantation in the aortic position were aortopulmonary window, truncus arteriosus, coarctation and aortic arch hypoplasia repair. The median time between the first and the second operation for graft failure was 245 (range 5-480) days. Conclusions Our experience shows that the patch is well tolerated in the septal, valvar and pulmonary artery positions. However, we experienced graft failures in infants in the aortic position.
- Published
- 2017
27. An audit of compliance with NOLCP in the GLH era
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Fabrice Ly, Georgios Antoniou, Lisa Thompson, Sanjay Popat, C. Brambilla, Jan Lukas Robertus, Suzanne MacMahon, Alexandra Rice, and Andrew G. Nicholson
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Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology ,Nursing ,business.industry ,Medicine ,Audit ,business ,Compliance (psychology) - Published
- 2021
28. Predicting Significant Right Ventricular Failure Post-LVAD Implantation Using CMR Compared to Echocardiography and Right Heart Catheterisation
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Verónica Rial Bastón, O. Dar, U. Stock, Fernando Riesgo-Gil, Prina Rajani, E. Androulakis, G. Sarri, Jan Lukas Robertus, Joyce Wong, Mayooran Shanmuganathan, Andre R. Simon, K. Kiff, and Saadiq Moledina
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Pulmonary and Respiratory Medicine ,Inotrope ,Transplantation ,medicine.medical_specialty ,Ejection fraction ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Dilated cardiomyopathy ,medicine.disease ,Pulmonary hypertension ,Heart failure ,Internal medicine ,medicine ,Etiology ,Cardiology ,Surgery ,Implant ,Cardiology and Cardiovascular Medicine ,business - Abstract
Purpose Right ventricular failure (RVF) complicates 10-40% of LVAD implants. Significant RVF is associated with increased mortality and reduced chance of being bridged to transplant. It is therefore crucial to identify patients at high risk of RVF using pre-operative investigations. We investigated markers of RV function on pre-LVAD echocardiography (echo), right heart catheterization (RHC) and cardiovascular magnetic resonance imaging (CMR) in predicting significant post-LVAD RVF. Methods We performed a single centre retrospective analysis of 220 patients who underwent LVAD implantation between 2011-18. 33 patients had CMR within 15 months pre-LVAD implantation. CMR was used to derive RV volumes, TAPSE, RV ejection fraction, strain and scar burden. RV function parameters were derived from echo and RHC just prior the LVAD implantation. INTERMACS criteria was used to categorize RVF based on duration of pharmaceutical support (post-implant IV inotropes/vasodilators/inhaled nitrous oxide) - mild ( 14 days). The latter also included the need for RVAD or death due to RVF. Moderate and severe RVF were considered as significant RVF. Results The median age was 49 (IQR 39-56). 31 were males. 18 patients had no/mild RVF; 14 had significant RVF (8 moderate RVF, 6 severe RVF); 1 patient was not categorised due to incomplete data. 29 survived to discharge. Dilated cardiomyopathy was the commonest aetiology of heart failure (17/33) followed by ischaemic heart disease (11/33). Echo derived pulmonary hypertension (42 vs 36mmHg) and proportion of those with tricuspid regurgitation (83.3% vs 92.8%) were not different in the two groups. PVR on RHC was not different between the groups (2.82 vs 3.68 WU). CMR derived volumes, TAPSE (12.2 vs 12.1mm), Global longitudinal strain (-9.1% vs -7.2%) and radial strain (-12.4% vs -10.0%) and the presence of scar were not different between the two groups. CMR-RVEF however was lower in the group significant RVF (23.5 ± 8.2%) when compared to the group with no/mild RVF (31.0 ± 10.7%) (p=0.03). Conclusion When compared to indices from RHC and echo, pre-operative RVEF on CMR is the only marker that differentiated the group who developed significant post-LVAD RVF from the group that did not. A larger study with CMR closer to the time of LVAD implant is needed to validate this.
- Published
- 2021
29. Acute fulminant necrotizing eosinophilic myocarditis: early diagnosis and treatment
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Nicholas R. Banner, Rebecca Lane, Jan Lukas Robertus, Mohammed Kamal, Aigul Baltabaeva, Paul David Callan, and Joyce Wong
- Subjects
Cardiac function curve ,medicine.medical_specialty ,Myocarditis ,medicine.diagnostic_test ,business.industry ,Fulminant ,030208 emergency & critical care medicine ,Magnetic resonance imaging ,030204 cardiovascular system & hematology ,medicine.disease ,Chest pain ,Eosinophilic myocarditis ,03 medical and health sciences ,0302 clinical medicine ,Cardiac magnetic resonance imaging ,Heart failure ,Internal medicine ,medicine ,Cardiology ,Radiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Necrotizing eosinophilic myocarditis is a rare but potentially fatal condition that requires prompt recognition and treatment. We describe a case of a young athlete presenting with chest pain and breathlessness, with evidence of rapidly deteriorating cardiac function. The condition was successfully treated with corticosteroids, with no evidence of residual myocardial damage. This is the first reported case to demonstrate the utility of cardiac magnetic resonance imaging for diagnosis and monitoring response to treatment. It also highlights the value of endomyocardial biopsy in establishing a tissue diagnosis in cases of fulminant myocarditis, in order to direct treatment appropriately.
- Published
- 2017
30. Airway remodelling in the transplanted lung
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Jens Vogel-Claussen, Danny Jonigk, Lavinia Maegel, Jan Lukas Robertus, and Mark Kuehnel
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Pathology ,medicine.medical_specialty ,Histology ,medicine.medical_treatment ,Bronchiolitis obliterans ,Vascular Remodeling ,030230 surgery ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Animals ,Humans ,Medicine ,Lung transplantation ,Lung ,Survival rate ,business.industry ,Cell Biology ,Allografts ,medicine.disease ,Molecular medicine ,medicine.anatomical_structure ,030228 respiratory system ,Airway Remodeling ,Solid organ ,business ,Airway ,Lung Transplantation - Abstract
Following lung transplantation, fibrotic remodelling of the small airways has been recognized for almost 5 decades as the main correlate of chronic graft failure and a major obstacle to long-term survival. Mainly due to airway fibrosis, pulmonary allografts currently show the highest attrition rate of all solid organ transplants, with a 5-year survival rate of 58 % on a worldwide scale. The observation that these morphological changes are not just the hallmark of chronic rejection but rather represent a manifestation of a multitude of alloimmune-dependent and -independent injuries was made more recently, as was the discovery that chronic lung allograft dysfunction manifests in different clinical phenotypes of respiratory impairment and corresponding morphological subentities. Although recent years have seen considerable advances in identifying and categorizing these subgroups on the basis of clinical, functional and histomorphological changes, as well as susceptibility to medicinal treatment, this process is far from over. Since the actual pathophysiological mechanisms governing airway remodelling are still only poorly understood, diagnosis and therapy of chronic lung allograft dysfunction presents a major challenge to clinicians, radiologists and pathologists alike. Here, we review and discuss the current state of the literature on chronic lung allograft dysfunction and shed light on classification systems, corresponding clinical and morphological changes, key cellular players and underlying molecular pathways, as well as on emerging diagnostic and therapeutic approaches.
- Published
- 2016
31. Early Insight Into In Vivo Recellularization of Cell-Free Allogenic Heart Valves
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Jan Lukas Robertus, Karolina Theodoridis, Dietmar Boethig, Dmitry Bobylev, Günther Laufer, Alexander Horke, Lavinia Neubert, Igor Tudorache, Axel Haverich, Serghei Cebotari, Philipp Beerbaum, Andres Hilfiker, Martin Andreas, Samir Sarikouch, Kristin Teiken, and Danny Jonigk
- Subjects
Adult ,Male ,Reoperation ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Transplantation, Heterologous ,Heart Valve Diseases ,030204 cardiovascular system & hematology ,Prosthesis Design ,Young Adult ,03 medical and health sciences ,Animal data ,0302 clinical medicine ,In vivo ,medicine ,Humans ,Transplantation, Homologous ,Endocarditis ,Child ,Retrospective Studies ,Cryopreservation ,Heart transplantation ,Pulmonary Valve ,Decellularization ,business.industry ,Infant, Newborn ,Infant ,Middle Aged ,medicine.disease ,Surgery ,Transplantation ,Stenosis ,Procollagen peptidase ,030228 respiratory system ,Aortic Valve ,Child, Preschool ,Heart Valve Prosthesis ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Background Unlike the vast amount of animal data available on the recellularization of allogenic decellularized heart valves (DHVs), there have only been sporadic histologic reports on such grafts in humans. Methods Two experienced cardiac pathologists independently evaluated human specimens obtained during reoperation between December 2010 and April 2017 DHVs in seven categories after automated staining (scores: 0 to 6) in comparison with published data. An optimal result of 42 points was classified as 100%. Results We found that 364 DHVs, 236 decellularized pulmonary homografts (DPHs), and 128 decellularized aortic homografts (DAHs) were implanted, and freedom from explantation was 96.1% (DAH) and 98.7% (DPH). Reoperations were because of (suspected) endocarditis in 5 of 11 patients, stenosis at the subvalvular or valvular or supravalvular level in 3 of 11 patients, planned staged reoperation in 2 of 11 patients, and 1 heart transplantation. Good reader agreement was reflected by an interagreement weighted κ of 0.783 (95% confidence interval: 0.707 to 0.859). The relative histologic score in nonendocarditis specimens was 76% ± 4.3% (maximum 81%). Intracellular procollagen type 1 production was found in recipient mesenchymal cells within the transplanted grafts. In endocarditis specimens the histologic score was significantly lower with 48% ± 7.3% (minimum 41%, p = 0.0004) because of leucocyte infiltration and matrix degradation. One DPH showed immune system-mediated graft failure. Grafts obtained during the first 12 months after implantation were not evenly repopulated with less recellularization in the inner parts; no difference was found between DAH and DPH with respect to extent of recellularization. Conclusions Substantial in vivo recellularization with noninflammatory cells was observed in this study. Spontaneous recellularization appears to require multiple months, which correspondingly has an impact on size selection for growing patients.
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- 2019
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32. Etiology of Sudden Death in Sports
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Greg Mellor, Aneil Malhotra, Sanjay Sharma, Alexandros Steriotis, Michael Papadakis, Harshil Dhutia, Elijah R. Behr, Mary N. Sheppard, Jan-Lukas Robertus, Maite Tome, Ahmed Merghani, and Gherardo Finocchiaro
- Subjects
medicine.medical_specialty ,business.industry ,Hypertrophic cardiomyopathy ,Poison control ,030204 cardiovascular system & hematology ,Left ventricular hypertrophy ,medicine.disease ,Sudden death ,Right ventricular cardiomyopathy ,Sudden cardiac death ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Etiology ,Physical therapy ,Cardiology ,cardiovascular diseases ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,Cause of death - Abstract
Background Accurate knowledge of causes of sudden cardiac death (SCD) in athletes and its precipitating factors is necessary to establish preventative strategies. Objectives This study investigated causes of SCD and their association with intensive physical activity in a large cohort of athletes. Methods Between 1994 and 2014, 357 consecutive cases of athletes who died suddenly (mean 29 ± 11 years of age, 92% males, 76% Caucasian, 69% competitive) were referred to our cardiac pathology center. All subjects underwent detailed post-mortem evaluation, including histological analysis by an expert cardiac pathologist. Clinical information was obtained from referring coroners. Results Sudden arrhythmic death syndrome (SADS) was the most prevalent cause of death (n = 149 [42%]). Myocardial disease was detected in 40% of cases, including idiopathic left ventricular hypertrophy (LVH) and/or fibrosis (n = 59, 16%); arrhythmogenic right ventricular cardiomyopathy (ARVC) (13%); and hypertrophic cardiomyopathy (HCM) (6%). Coronary artery anomalies occurred in 5% of cases. SADS and coronary artery anomalies affected predominantly young athletes (≤ 35 years of age), whereas myocardial disease was more common in older individuals. SCD during intense exertion occurred in 61% of cases; ARVC and left ventricular fibrosis most strongly predicted SCD during exertion. Conclusions Conditions predisposing to SCD in sports demonstrate a significant age predilection. The strong association of ARVC and left ventricular fibrosis with exercise-induced SCD reinforces the need for early detection and abstinence from intense exercise. However, almost 40% of athletes die at rest, highlighting the need for complementary preventive strategies.
- Published
- 2016
33. UTILITY OF CARDIAC MRI IN PREDICTION OF ACUTE RIGHT VENTRICULAR FAILURE AFTER LVAD IMPLANTATION
- Author
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Anand Tana, Andre R. Simon, Verónica Rial Bastón, Fernando Riesgo-Gil, Saadiq Moledina, Perviz Asaria, Joyce Wong, Georgina Saari, Mayooran Shanmuganathan, Jan Lukas Robertus, and Mark Peterzan
- Subjects
medicine.medical_specialty ,business.industry ,Ventricular assist device ,medicine.medical_treatment ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,Right ventricular failure ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business - Abstract
Acute right ventricular failure (RVF) complicates 20% to 44% of left ventricular assist device (LVAD) implantations, and is a marker of poor outcomes. Preoperative right ventricular (RV) function has been identified as a predictor of post-implant RVF. Cardiac MRI (CMR) may offer a better assessment
- Published
- 2020
34. P1.13-11 An Audit on IASLC Compliance of Lymph Nodes Dissection and Impact on Survival After Surgery for Non-Small Cell Lung Cancer
- Author
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C. Von Crease, H. Klein, George Ladas, S Begum, M. Nizami, Jan Lukas Robertus, Andrew G. Nicholson, Alexandra Rice, Eric Lim, Simon Jordan, Marcelo Werneck Barbosa, S. Booth, F. Mansour, A. Mani, Emma Beddow, Jonathan Finch, Niall McGonigle, A. Montero-Fernandez, P. De Sousa, Vladimir Anikin, and Nizar Asadi
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Dissection (medical) ,Audit ,medicine.disease ,Surgery ,Compliance (physiology) ,Oncology ,medicine ,Non small cell ,Lymph ,business ,Lung cancer - Published
- 2019
35. Anatomy and Pathology of the Tricuspid Valve
- Author
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S. Yen Ho, Jan Lukas Robertus, and Karen P. McCarthy
- Subjects
medicine.medical_specialty ,Atrioventricular valve ,Tricuspid valve ,business.industry ,Venous blood ,Anatomy ,Regurgitation (circulation) ,030204 cardiovascular system & hematology ,010501 environmental sciences ,01 natural sciences ,Atrioventricular node ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Ventricle ,Internal medicine ,Mitral valve ,Pulmonary valve ,cardiovascular system ,medicine ,Cardiology ,cardiovascular diseases ,business ,0105 earth and related environmental sciences - Abstract
The tricuspid valve (TV), the morphologically right atrioventricular valve, guards the inflow junction between the right atrium and right ventricle. In functional anatomy, the valve does not consist only of leaflets. Instead, the valve complex is comprised of the annulus, leaflets, tendinous cords and papillary muscles occupying the inlet part of the right ventricle. Right sided structures have not had the extensive analysis when viewed in comparison to the systemic mitral valve. This is possibly due to the complexity of measuring the geometrically unusual shape of the right ventricular cavity, tricuspid valve, the curvature of the muscular ventricular septum and the right ventricular cavity wrapping around the systemic left ventricle. The route of inflow to outflow in the low pressure right ventricle (RV) is elongated compared to the left side of the heart. The right ventricle itself is an anterior structure forming the sterno-costal border of the heart beneath the sternum. The tricuspid valve is always associated with a morphological right ventricle. The chamber can be arbitrarily demarcated into three regions: inlet, apical and outlet, hence the concept of a tripartite ventricle. But, there are no anatomic borders for these regions within the right ventricle. The inflow region of the tricuspid valve is separated from the outflow pulmonary valve by several muscular structures; the ventricular infundibular fold (VIF), septomarginal trabeculation (SMT), septoparietal trabeculations (SPT) and the free standing subpulmonary infundibulum musculature (Fig. 1.1). Adjacent along the atrial side tricuspid valve complex are important structures like the triangle of Koch, tendon of Todaro, atrioventricular node continuing into the bundle of His and coronary sinus orifice (Fig. 1.2). Continuing improvements of imaging methods such as echocardiography, cardiac magnetic resonance imaging and computed tomography to examine in detail and analyse these structures and to measure the flow of deoxygenated blood to the lungs from the right heart allows critical analysis and on-going follow up of patients in normal and disease states.
- Published
- 2018
36. National Optimal Lung Cancer Pathway implementation: can pathologists comply with turnaround times?
- Author
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Alexandra Rice, Samuel V. Kemp, Sanjay Popat, T. Newsom-Davis, Andrew G. Nicholson, Pallav L. Shah, Jan Lukas Robertus, K.L. Lloyd, and C. Brambilla
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Lung cancer ,medicine.disease ,business ,Intensive care medicine - Published
- 2019
37. Repeated Measurements of NT-pro-B-Type Natriuretic Peptide, Troponin T or C-Reactive Protein Do Not Predict Future Allograft Rejection in Heart Transplant Recipients
- Author
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Dimitris Rizopoulos, Isabella Kardys, Kadir Caliskan, Martijn Akkerhuis, Eric Boersma, Jan Lukas Robertus, Linda C. Battes, Alina A. Constantinescu, Olivier C. Manintveld, Cardiothoracic Surgery, Cardiology, Epidemiology, and Pathology
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Time Factors ,medicine.drug_class ,Biopsy ,medicine.medical_treatment ,Troponin T ,Internal medicine ,Natriuretic Peptide, Brain ,medicine ,Natriuretic peptide ,Humans ,Lung transplantation ,Retrospective Studies ,Heart Failure ,Heart transplantation ,Transplantation ,biology ,medicine.diagnostic_test ,business.industry ,Myocardium ,Hazard ratio ,C-reactive protein ,Middle Aged ,Allografts ,Peptide Fragments ,Transplant Recipients ,C-Reactive Protein ,Disease Progression ,Cardiology ,biology.protein ,Heart Transplantation ,Biomarker (medicine) ,Female ,business ,Biomarkers - Abstract
Background. Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. Methods. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 +/- 4 (mean +/- standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. Results. The mean age of the patients at HTx was 49 +/- 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after -12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. Conclusion. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.
- Published
- 2015
38. An audit on IASLC compliance of lymph nodes dissection and impact on survival after surgery for non-small cell lung cancer
- Author
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Marcelo Werneck Barbosa, S Begum, Michael Dusmet, N. Asadi, Andrew G. Nicholson, Vladimir Anikin, D. Kyparissopoulos, Jan Lukas Robertus, Emma Beddow, Alexandra Rice, F. Mansour, K. Redmond, Eric Lim, C. Von Crease, M.K. Kuppuswamy, E. Townsend, George Ladas, Simon Jordan, H. Klein, S. Booth, A. Mani, Niall McGonigle, A. Montero-Fernandez, P. De Sousa, M. Nizami, N. Anastasiou, and Jonathan Finch
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,business.industry ,Dissection (medical) ,Audit ,medicine.disease ,Surgery ,Compliance (physiology) ,Oncology ,medicine ,Lymph ,Non small cell ,Lung cancer ,business - Published
- 2019
39. Restrictive allograft syndrome and idiopathic pleuroparenchymal fibroelastosis: do they really have the same histology?
- Author
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Andrew G. Nicholson, Antonio Roman, Maria Angeles Montero, Maria Teresa Salcedo, Víctor Monforte, Reena Khiroya, Jan Lukas Robertus, Tina Osadolor, and Alexandra Rice
- Subjects
Lung Diseases ,Male ,medicine.medical_specialty ,Pathology ,Histology ,medicine.medical_treatment ,Pulmonary Fibrosis ,Pathology and Forensic Medicine ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Usual interstitial pneumonia ,Medicine ,Lung transplantation ,Humans ,business.industry ,General Medicine ,respiratory system ,Pleural Diseases ,medicine.disease ,Allografts ,Elastic Tissue ,030228 respiratory system ,Bronchiolitis ,030220 oncology & carcinogenesis ,Concomitant ,Histopathology ,Female ,Primary Graft Dysfunction ,business ,Lung Transplantation - Abstract
Aims Restrictive Allograft Syndrome (RAS) and idiopathic pleuroparenchymal fibroelastosis (IPPFE) are two different diseases reported to share the same histology. RAS relates to chronic allograft dysfunction in lung transplantation with IPPFE being a rare condition in native lungs. Our aim is to compare their histologies, alongside biopsies of usual interstitial pneumonia (UIP), to determine if there are differences that might help to elucidate the pathogenesis. Methods and Results We selected 4 post-mortem allograft lungs from patients who developed clear clinical RAS pattern, 5 biopsies diagnosed as IPPFE, 5 UIP biopsies and 5 sections of normal lung. Histopathologic features were described without knowledge of clinical and radiological features. Both RAS allografts and IPPFE biopsies showed intra-alveolar fibrosis and elastosis (IAFE), but RAS allografts also showed concomitant obliterative bronchiolitis, vascular lymphoplasmacytic inflammation within fibro-intimal thickening, less fibroblastic foci at the advancing edge of the fibrosis (1 against 14.4 FF in 2mm2) and a slight reduction of the capillary network compared to UIP (p=0.07) and controls (p=0.06). The main differences seen in UIP were the lack of IAFE and the presence of honeycomb change. Conclusions RAS and PPFE histopathology both show IAFE, but display various differences, particularly in their vascular morphology that may allow further understanding of pathogenesis. This article is protected by copyright. All rights reserved.
- Published
- 2016
40. Reply: How Often Does Athlete Sudden Cardiac Death Occur Outside the Context of Exertion?
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Gherardo, Finocchiaro, Michael, Papadakis, Jan-Lukas, Robertus, Harshil, Dhutia, Alexandros Klavdios, Steriotis, Maite, Tome, Greg, Mellor, Ahmed, Merghani, Aneil, Malhotra, Elijah, Behr, Sanjay, Sharma, and Mary N, Sheppard
- Subjects
Death, Sudden, Cardiac ,Athletes ,Physical Exertion ,Humans ,Sports - Published
- 2016
41. AT1-receptor blockade, but not renin inhibition, reduces aneurysm growth and cardiac failure in fibulin-4 mice
- Author
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Jeroen Essers, Yanto Ridwan, Elza D. van Deel, Luuk te Riet, Els Moltzer, A.H. Jan Danser, Ingrid M. Garrelds, Paula M. van Heijningen, Bibi S. van Thiel, Jan Lukas Robertus, Richard van Veghel, Nicole van Vliet, Marcel Vermeij, Ingrid van der Pluijm, Internal Medicine, Surgery, Cardiology, Molecular Genetics, Pathology, and Radiotherapy
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Physiology ,Stimulation ,Propranolol ,030204 cardiovascular system & hematology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine.artery ,Internal medicine ,Renin–angiotensin system ,Internal Medicine ,Medicine ,Aorta ,Ejection fraction ,business.industry ,Aliskiren ,Blockade ,030104 developmental biology ,Endocrinology ,Losartan ,chemistry ,cardiovascular system ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
textabstractAims: Increasing evidence supports a role for the angiotensin II-AT 1 -receptor axis in aneurysm development. Here, we studied whether counteracting this axis via stimulation of AT 2 receptors is beneficial. Such stimulation occurs naturally during AT 1 -receptor blockade with losartan, but not during renin inhibition with aliskiren. Methods and results: Aneurysmal homozygous fibulin-4 R/R mice, displaying a four-fold reduced fibulin-4 expression, were treated with placebo, losartan, aliskiren, or the β-blocker propranolol from day 35 to 100. Their phenotype includes cystic media degeneration, aortic regurgitation, left ventricular dilation, reduced ejection fraction, and fractional shortening. Although losartan and aliskiren reduced hemodynamic stress and increased renin similarly, only losartan increased survival. Propranolol had no effect. No drug rescued elastic fiber fragmentation in established aneurysms, although losartan did reduce aneurysm size. Losartan also increased ejection fraction, decreased LV diameter, and reduced cardiac pSmad2 signaling. None of these effects were seen with aliskiren or propranolol. Longitudinal micro-CT measurements, a novel method in which each mouse serves as its own control, revealed that losartan reduced LV growth more than aneurysm growth, presumably because the heart profits both from the local (cardiac) effects of losartan and its effects on aortic root remodeling. Conclusion: Losartan, but not aliskiren or propranolol, improved survival in fibulin-4 R/R mice. This most likely relates to its capacity to improve structure and function of both aorta and heart. The absence of this effect during aliskiren treatment, despite a similar degree of blood pressure reduction and renin-angiotensin system blockade, suggests that it might be because of AT 2 -receptor stimulation.
- Published
- 2016
42. Etiology of Sudden Death in Sports: Insights From a United Kingdom Regional Registry
- Author
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Gherardo, Finocchiaro, Michael, Papadakis, Jan-Lukas, Robertus, Harshil, Dhutia, Alexandros Klavdios, Steriotis, Maite, Tome, Greg, Mellor, Ahmed, Merghani, Aneil, Malhotra, Elijah, Behr, Sanjay, Sharma, and Mary N, Sheppard
- Subjects
Adult ,Male ,Adolescent ,Coronary Vessel Anomalies ,Heart Ventricles ,Physical Exertion ,Arrhythmias, Cardiac ,Cardiomyopathy, Hypertrophic ,Fibrosis ,United Kingdom ,Death, Sudden ,Young Adult ,Athletes ,Humans ,Female ,Hypertrophy, Left Ventricular ,Registries ,Arrhythmogenic Right Ventricular Dysplasia ,Retrospective Studies - Abstract
Accurate knowledge of causes of sudden cardiac death (SCD) in athletes and its precipitating factors is necessary to establish preventative strategies.This study investigated causes of SCD and their association with intensive physical activity in a large cohort of athletes.Between 1994 and 2014, 357 consecutive cases of athletes who died suddenly (mean 29 ± 11 years of age, 92% males, 76% Caucasian, 69% competitive) were referred to our cardiac pathology center. All subjects underwent detailed post-mortem evaluation, including histological analysis by an expert cardiac pathologist. Clinical information was obtained from referring coroners.Sudden arrhythmic death syndrome (SADS) was the most prevalent cause of death (n = 149 [42%]). Myocardial disease was detected in 40% of cases, including idiopathic left ventricular hypertrophy (LVH) and/or fibrosis (n = 59, 16%); arrhythmogenic right ventricular cardiomyopathy (ARVC) (13%); and hypertrophic cardiomyopathy (HCM) (6%). Coronary artery anomalies occurred in 5% of cases. SADS and coronary artery anomalies affected predominantly young athletes (≤ 35 years of age), whereas myocardial disease was more common in older individuals. SCD during intense exertion occurred in 61% of cases; ARVC and left ventricular fibrosis most strongly predicted SCD during exertion.Conditions predisposing to SCD in sports demonstrate a significant age predilection. The strong association of ARVC and left ventricular fibrosis with exercise-induced SCD reinforces the need for early detection and abstinence from intense exercise. However, almost 40% of athletes die at rest, highlighting the need for complementary preventive strategies.
- Published
- 2015
43. MiRNA profiling in B non-Hodgkin lymphoma: a MYC-related miRNA profile characterizes Burkitt lymphoma
- Author
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Geert Harms, Yolanthe Swart, Joost Kluiver, Philip M. Kluin, Callista Weggemans, Steven T. Pals, Anke van den Berg, Ed Schuuring, Stefano Rosati, Klaas Kok, Rogier M. Reijmers, Gustaaf W. van Imhoff, and Jan-Lukas Robertus
- Subjects
medicine.medical_specialty ,Hematology ,Cancer ,Biology ,medicine.disease ,Lymphoma ,RNA interference ,Internal medicine ,microRNA ,medicine ,Cancer research ,Gene silencing ,Hodgkin lymphoma ,Mirna profiling - Published
- 2010
44. Histologically Proven Myocardial Carcinoid Metastases: The Value of Multimodality Imaging
- Author
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Daniel Morganstein, Raad Mohiaddin, Ian Chau, Alexander R. Lyon, Kshama Wechalekar, Stuart D. Rosen, Annina A. Studer Bruengger, Rajdeep S. Khattar, Jan Lukas Robertus, Ulrich Rosendahl, and British Heart Foundation
- Subjects
Male ,medicine.medical_specialty ,Cardiac & Cardiovascular Systems ,Nuclear imaging ,Biopsy ,Heart Ventricles ,Magnetic Resonance Imaging, Cine ,Carcinoid Tumor ,030204 cardiovascular system & hematology ,Multimodal Imaging ,1102 Cardiovascular Medicine And Haematology ,Ileal Neoplasm ,030218 nuclear medicine & medical imaging ,Diagnosis, Differential ,Heart Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Cardiac Surgical Procedures ,Multimodal imaging ,Science & Technology ,Ileocecal Valve ,medicine.diagnostic_test ,business.industry ,Myocardium ,Magnetic resonance imaging ,Middle Aged ,equipment and supplies ,Echocardiography, Doppler ,Ileal Neoplasms ,Cardiovascular System & Hematology ,Surgical biopsy ,Cardiovascular System & Cardiology ,HEART ,Radiology ,Differential diagnosis ,Cardiology and Cardiovascular Medicine ,business ,Metabolic activity ,Life Sciences & Biomedicine ,human activities - Abstract
We present a case of a patient with intramyocardial metastases from a carcinoid tumor. These findings were detected using cardiovascular magnetic resonance imaging, with functional metabolic activity analyzed using nuclear imaging and confirmed by histologic findings at surgical biopsy. This case highlights the value of cardiovascular magnetic resonance imaging and the importance of multimodality imaging.
- Published
- 2017
45. Intratumoral macrophage phenotype and CD8+ T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma
- Author
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Robin Cornelissen, Joachim G.J.V. Aerts, Henk C. Hoogsteden, Joost P.J.J. Hegmans, Rudi W. Hendriks, Jan-Lukas Robertus, Lysanne A. Lievense, Pulmonary Medicine, and Pathology
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Adult ,Male ,Mesothelioma ,Cancer Research ,medicine.medical_specialty ,Pathology ,Lung Neoplasms ,Pleural Neoplasms ,Cell Count ,CD8-Positive T-Lymphocytes ,chemistry.chemical_compound ,Lymphocytes, Tumor-Infiltrating ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Aged ,Neoplasm Staging ,business.industry ,CD68 ,Tumor-infiltrating lymphocytes ,Macrophages ,Mesothelioma, Malignant ,Middle Aged ,medicine.disease ,Prognosis ,Immunohistochemistry ,Vascular endothelial growth factor ,Phenotype ,Treatment Outcome ,chemistry ,Female ,Complication ,business ,Tomography, X-Ray Computed ,CD163 ,CD8 ,Biomarkers - Abstract
Objectives: In patients with malignant pleural mesothelioma (MPM), local tumor outgrowth (LTO) after invasive procedures is a well-known complication. Currently, no biomarker is available to predict the occurrence of LTO. This study aims to investigate whether the tumor macrophage infiltration and phenotype of and/or the infiltration of CD8(+) T-cells predicts LTO. Materials and methods: Ten mesothelioma patients who developed LTO were clinically and pathologically matched with 10 non-LTO mesothelioma patients. Immunohistochemistry was performed on diagnostic biopsies to determine the total TAM (CD68), the M2 TAM (CD163) and CD8(+) T-cell count (CD8). Results: The mean M2/total TAM ratio differed between the two groups: 0.90 +/- 0.09 in the LTO group versus 0.63 +/- 0.09 in patients without LTO (p < 0.001). In addition, the mean CD8(+) T-cell count was significantly different between the two groups: 30 per 0.025 cm(2) (range 2-60) in the LTO group and 140 per 0.025 cm(2) (range 23-314) in the patients without LTO (p < 0.01). Conclusion: This study shows that patients who develop LTO after a local intervention have a higher M2/total TAM ratio and lower CD8(+) cell count at diagnosis compared to patients who did not develop this outgrowth. We propose that the M2/total TAM ratio and the CD8(+) T-cell amount are potential tools to predict which MPM patients are prone to develop LTO. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2014
46. 66 Sudden Death in Wolf-Parkinson-White. Description of Post-mortem Pathological Findings and Clinical Correlates in 19 Cases: Abstract 66 Table 1
- Author
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Michael Papadakis, Harshil Dhutia, Alexandros Steriotis, Mary N. Sheppard, Jan Lukas Robertus, Gherardo Finocchiaro, Elijah R. Behr, and Sanjay Sharma
- Subjects
medicine.medical_specialty ,business.industry ,Hypertrophic cardiomyopathy ,Autopsy ,Accessory pathway ,medicine.disease ,Left ventricular hypertrophy ,Sudden death ,Asymptomatic ,Surgery ,Sudden cardiac death ,Internal medicine ,medicine ,Palpitations ,Cardiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims The prevalence of pre-excitation (Wolff-Parkinson-White (WPW) pattern) is estimated at 0.3%. The risk of malignant arrhythmias in asymptomatic individuals is low and ablation of the accessory pathway is considered to diminish the risk of sudden cardiac death (SCD). The aim of the study was to describe clinical characteristics and pathological features of SCD victims with a pre-morbid diagnosis of WPW. Methods Between 1994 and 2014, 3684 cases of SCD were referred to our cardiac pathology centre; 19 (0.5%) with known pre-excitation on their ECG. Clinical information were obtained from referring coroners. All subjects underwent detailed post-mortem evaluation including histological analysis by an expert cardiac pathologist. Results The majority of patients were males (n = 16, 84%) of Caucasian descent (n = 17; 89%). The mean age was 31 ± 15 years (2 patients over the age of 50). Five cases (26%) were asymptomatic. Of the 14 symptomatic patients, 13 (68%) reported palpitations, 1 (5%) syncope. Five individuals (26%) had a previous ablation, 4 of which were judged to be successful with resolution of pre-excitation on the ECG. In the majority of cases (n = 15; 79%) SCD occurred at rest. The mean heart weight was 408 ± 105 g. In 10 patients (53%) the post-mortem exam revealed a normal heart, in 5 cases there was a definitive cardiac pathology (n = 4 with hypertrophic cardiomyopathy, n = 1 with cardiac sarcoid), and 4 cases demonstrated autopsy findings of uncertain significance (n = 2 with idiopathic left ventricular hypertrophy, n = 1 with idiopathic fibrosis, and n = 1 with enlarged left ventricle). Out of the 5 asymptomatic patients, the post-mortem revealed HCM in 3 and a normal heart in 2 cases. The patients that underwent previous ablation were characterized by a normal heart in 3 cases and by idiopathic left ventricular hypertrophy at the post-mortem. Conclusions One out of four SCD victims was asymptomatic, raising concerns relating to the value of symptoms in risk stratification of individuals with pre-excitation. In addition, accessory pathway ablation did not eliminate the risk of SCD possibly due to multiple pathways. Finally, pre-excitation was associated with additional structural abnormalities in almost 50% of cases, underscoring the necessity of performing baseline echocardiography in all individuals and suggesting that the combination of pre-excitation with additional cardiac pathology may render individuals at higher risk of SCD.
- Published
- 2016
47. Reply
- Author
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Michael Papadakis, Harshil Dhutia, Maite Tome, Mary N. Sheppard, Ahmed Merghani, Aneil Malhotra, Gherardo Finocchiaro, Alexandros Steriotis, Greg Mellor, Elijah R. Behr, Sanjay Sharma, and Jan-Lukas Robertus
- Subjects
medicine.medical_specialty ,genetic structures ,biology ,Athletes ,business.industry ,Context (language use) ,030204 cardiovascular system & hematology ,biology.organism_classification ,medicine.disease ,Sudden cardiac death ,03 medical and health sciences ,0302 clinical medicine ,Emergency medicine ,medicine ,030212 general & internal medicine ,Exertion ,Medical emergency ,Cardiology and Cardiovascular Medicine ,Death sudden cardiac ,business - Abstract
We are grateful to Dr. Karam and colleagues for their interest in our paper. Their letter focuses on the circumstances of sudden cardiac death (SCD) in our athletes. Previous reports suggest over 80% of SCDs in athletes occur during or immediately after exercise. In contrast, we observed that a
- Published
- 2016
48. 116 Gene mutation profile of non-smokers compared to smokers participating in the CRUK stratified medicines programme at a single institution
- Author
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Chiara Proli, P. De Sousa, Alexandra Rice, Andrew G. Nicholson, H. Raubenheimer, Maria Leung, Eric Lim, Marcelo Werneck Barbosa, Jan Lukas Robertus, A. Montero Fernandez, Maria Elena Cufari, and L. Azcarate
- Subjects
Pulmonary and Respiratory Medicine ,Genetics ,Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,Internal medicine ,medicine ,Gene mutation ,Single institution ,business - Published
- 2016
49. Cutaneous leiomyosarcoma arising in a smallpox scar
- Author
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Jan-Lukas Robertus, Robert J. van Ginkel, Robert A. Pol, Hilde Dannenberg, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Organ Transplantation (GIOT), and Groningen Kidney Center (GKC)
- Subjects
Leiomyosarcoma ,Male ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,lcsh:Surgery ,Case Report ,lcsh:RC254-282 ,FAMILIES ,FH ,Diagnosis, Differential ,Cicatrix ,Scar ,HYDRATASE ,Surgical oncology ,Humans ,Medicine ,Smallpox ,Cutaneous leiomyosarcoma ,SARCOMA ,Aged ,MUTATIONS ,business.industry ,Soft tissue ,Neoplasms, Second Primary ,lcsh:RD1-811 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,GENE ,Smooth muscle tumour ,body regions ,Treatment ,HEREDITARY LEIOMYOMATOSIS ,Oncology ,RENAL-CELL CANCER ,Surgery ,Small pox ,Sarcoma ,Differential diagnosis ,business ,SKIN - Abstract
Background Cutaneous leiomyosarcoma (CLM) is a very rare smooth muscle tumour that accounts for about 2–3% of all superficial soft tissue sarcomas. Although the development of various malignancies in scar tissue is well known, we report the first case of a CLM developing in a small pox scar. Case presentation A 66-year-old man presented with a painless, slow-growing lump in a small pox scar on his left shoulder. Histological biopsies showed the lesion to be a primary, well-differentiated cutaneous leiomyosarcoma. A CT scan of the thorax was conducted, which showed no signs of metastases. The complete lesion was then surgically excised, and histopathological examination revealed a radically excised cutaneous type leiomyosarcoma After 13 months’ review the patient was doing well with no evidence of tumour recurrence. Conclusions This is the first report of a CLM arising in a small pox scar. Although the extended time interval between scarring and malignant changes makes it difficult to advise strict follow-up for patients with small pox scars, one should be aware that atypical changes and/or symptoms occurring in a small pox scar could potentially mean malignant transformation.
- Published
- 2012
50. MiRNA profiling in B non-Hodgkin lymphoma: a MYC-related miRNA profile characterizes Burkitt lymphoma
- Author
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Jan-Lukas, Robertus, Joost, Kluiver, Callista, Weggemans, Geert, Harms, Rogier M, Reijmers, Yolanthe, Swart, Klaas, Kok, Stefano, Rosati, Ed, Schuuring, Gustaaf, van Imhoff, Steven T, Pals, Philip, Kluin, and Anke, van den Berg
- Subjects
Gene Expression Regulation, Neoplastic ,MicroRNAs ,Genes, myc ,Humans ,RNA, Neoplasm ,Burkitt Lymphoma - Published
- 2010
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