V O L 2 7 I S S U E 5 / 1 8 O c t / N o v 2 0 1 8 T H E E U R O P E A N F O R U M F O R T H O S E I N T H E B U S I N E S S O F M A K I N G H E A L T H C A R E W O R K 8-15 RADIOLOGY • Artifical intelligence shapes future radiology • Research with 7-Tesla MRI • New 1.5 Tesla MR: fine images despite movements LAB & PATHOLOGY 18-22 • Challenges for liquid biopsy • Automation liberates labs from manual processes • Hungary and Belgium advance digitised systems DRESS FOR SUCCESS Introducing the World’s First Barrier and Securement Dressing The revolution escalates New procedures in medical image analysis based on artificial intelligence offer numerous opportunities but still have their limitations, Michael Krassnitzer reports. Face reconstruction from solely contextual properties (a set of gene variants responsible for facial development, supplemented with age, BMI and gender). Top: reconstructed face. Bottom: real face, unknown at the time of the reconstruction. The model was built using a database of 3-D pictures, DNA, age, BMI, and gender of an admixed population. (Courtesy of Professor M. Shriver, Pennsylvania State University, and Dr Peter Claes, KU Leuven. Reprinted from Paul Suetens, Fundamentals of Medical Imaging 3rd edition, Cambridge University Press, 2017.) ‘Is image computing an opportunity or a threat?’ asked Dr Paul Suetens, professor of Medical Imaging and Image Processing at University Hospital Leuven. During the recent European Radiology Congress 2018 held in Vienna he also provided his own answer: ‘It’s an opportunity if the radiologist takes advantage of this supporting technology. It’s a threat if it is discarded by the radiologist – “I am too busy now” are words I often hear; then it’s other specialists who are gratefully adopting this technology. ‘Image Computing, including image analysis, artificial intelligence, artificial neural networks und deep learning, is starting a revolution,’ Suetens is convinced. Artificial Intelligence (AI) is not new – research in this field was carried out as far back as the 1950s – but, whilst in the early days AI learnt from image descriptions, it now learns directly from the images, such as pho- tometric image characteristics. Suetens was involved in a project that used MRI images with BOLD con- trast – with the image signal depend- ing on the oxygen content in red blood cells – for a detailed investiga- tion into which areas of the brain are active during hearing and processing of language. Other types of image computing are based on geometric image characteristics, such as segmen- tation of thoracic images. Detecting mutations via facial analysis Image computing also includes the exciting field of image genetics, in which Suetens is also involved. As a member of an international research team, he linked a database contain- ing 3-D facial images with genetic information. One of the results was that biomarkers, which point towards genetic mutations, were found in the image data. Certain characteristics of human faces suggest a mutation of the SLC35D1 gene, which is associat- ed with chondrodysplasia with snail- like pelvis, a very rare, lethal form of skeletal dysplasia. A further use of this link between facial images and genetic information is the reconstruction of faces from Result of a study of a selected set of SNP genotypes in a normal population. Faces A and B show the effect of two extreme SNP variants in gene SLC35D1. Mutations in this gene cause Schneckenbecken dysplasia. The colour images show the differences between faces A and B of some local features (from left to right: strain, curvature change and distance). Significant local differences, such as at the orbits, may define characteristic biomarkers for this particular genetic disorder. (Courtesy of Dr Peter Claes, KU Leuven. Reprinted from Paul Suetens, Fundamentals of Medical Imaging 3rd edition, Cambridge University Press, 2017.) human DNA, making it possible for instance to reconstruct the features of well-known persons of whom, long after they have died, only artistic Continued on page 5 www.healthcare-in-europe.com CONTENTS NEWS & RESEARCH INTENSIVE CARE CARDIOLOGY 1-5 6-7 8-9 RADIOLOGY 10-11 NUCLEAR MEDICINE 14-15 LABORATORY 16-19 DIGITAL PATHOLOGY 20-22 Example of deep learning to predict thrombectomy outcome in acute stroke based on CT perfusion images. A Convolutional Neural Network was trained on the following data: 180 CT perfusion images in the acute phase. Y/N followed by an intra-arterial thrombectomy. About 50% of the training set received an endovascular treatment. The time between imaging and the end of the thrombectomy. Occlusion present Y/N. A follow-up CT scan after 5 days with a delineation of the final lesion. Left three images: the prognosis showing 3 cases: (left) a complete reperfusion except for the core; (middle) no treatment, hence, the final lesion consists of core and penumbra; (right) predicted lesion after thrombectomy 3h after imaging with a presumed mTICI grade 2a. Right image: the follow-up scan after 5 days with the final lesion. Thrombectomy was performed 3h after imaging with mTICI grade 2a. d n a , n e v u e L U K , n e b b o R d i v a D r D f o y s e t r u o C s r o t a g i t s e v n I N A E L C R M www.healthcare-in-europe.com
N E W S & R E S E A RC H 5 The revolution escalates Continued from page 1 plex forms and deformations, neural networks do not function very well. ‘A neural network is nothing other than a large number of individual data processors which are linked with one another – comparable to neurons in the human brain,’ explains Suetens. However, the human brain has around 86 billion nerve cells, whilst an artificial neural network only has 20 million nodes. ‘When we increase the number of nodes the results become worse – and we don’t yet know why this is,’ Suetens admits. Activation areas in fMRI language study. Column 1 and 3: hearing and seeing words (red) during respectively auditory and visual stimulation. Column 2 and 4: subsequent semantic decision (green) and right-hand response (blue). The yellow colour is a mixture of red (perception) and green (interpretation). (Figure courtesy of Professor S Sunaert, Department of Radiology, UZ Leuven. Reprinted from Paul Suetens, Fundamentals of Medical Imaging 3rd edition, Cambridge University Press, 2017.) representations have been available. Respective reconstructions based on saliva samples from living test subjects achieve astonishing resemblances. These applications are based on deep learning, which entails an arti- ficial system learning from examples, then itself recognising inherent pat- terns and regularities. The basis of this is so-called artificial neural networks that are modelled on the workings of the human brain. ‘Deep learning is a new paradigm with a strong impact on medical image analysis. It is suf- ficiently accurate and fast to compete with the human expert for specific narrowly defined tasks,’ says Suetens. However, deep learning still has its limitations. ‘Deep learning is still in its infancy,’ admits Suetens. If only a limited amount of data is available, or where the issue is around com- Professor Paul Suetens heads the Division Image and Speech Processing in the Department of Electrical Engineering at Katholieke Universiteit (KU) Leuven, Belgium. He is also chairman of the Medical Imaging Research Centre at University Hospital Leuven. His research focuses on medical imaging and medical image computing, which methodologically lies in the domains of computational science and machine learning. He has authored more than 500 peer-reviewed papers in international journals and conference proceedings and is author of the book ‘Fundamentals of Medical Imaging’ (3 editions, 2002, 2009, 2017). Jos de Blok was awarded the prestigious Albert Medal from The Royal Society of Arts (RSA). ‘I received a letter from London about the nomination. I thought it was a joke, until they called me and explained they wanted to recognise the innovation and global impact of the concept. So, in 2014, I received this award, placing me on the same list as physicist Stephen Hawking. I feel really honoured.’ reliance and well-being. ‘I predict that, in five to 10 years many organisations worldwide will have reversed their approach, defeat- ed by their own weapons: saving. And those savings will not be at the expense of healthcare providers and healthcare receivers.’ Buurtzorg is essentially a mod- ern form of old Dutch community nursing. Now it is the largest pro- vider of care. In addition, there is Buurtdiensten for community ser- vice, household and family assis- tance, like family care in the past. www.healthcare-in-europe.com Vereos Digital PET/CTProven accuracyinspires confidenceIn the transition from volume- to value-based care, accurate treatment pathways are essential. Philips Vereos Digital PET/CT is the world’s first and only fully digital PET/CT solution—and its accuracy is supported by rigorous clinical evidence measured in years, not months.There is always a way to make life better.
6 I N T E N S I V E CA R E Discharged ICU patients need careful rehabilitation Aftercare after intensive care Care models that go beyond rehabilitation services and are aimed at a smooth transition from intensive to aftercare are not established in Germany. A working group around Professor Dr Christian Apfelbacher at the Institute for Epidemiology and Preventive Medicine, Regensburg University, is currently develop- ing a concept for intensive out-patient aftercare. ‘The project is to help improve the care of patients after prolonged treatment in the intensive care unit (ICU) and to close the gap in the transition from intensive care to aftercare,’ the professor explained during an interview with Sascha Keutel. Prolonged treatment in intensive care frequently leads to chronic physi- cal and psychological impairments, also described as Post Intensive Care Syndrome (PICS). This descrip- tion relates to new or worsening physical (pulmonary, neuromuscu- lar, physical-functional), cognitive (such as memory- or concentration problems) and psychological (anxi- ety disorders, post-traumatic stress disorder and depression) problems in patients, which occur due to ill- ness requiring treatment in inten- sive care and persist after hospi- tal treatment,’ Professor Christian Apfelbacher explains. ‘On-going, comprehensive diag- nostic investigation, as well as ade- quate multidisciplinary care with coordination of services, are impera- tive for patients who have received intensive care. Patients find coor- dinated, needs-based medical care after being discharged helpful. It can also help to reduce the large share of patients who have to be readmitted after being discharged: Care models would be desirable that go beyond the services provided by rehabilitation clinics and are cus- tomised to patients’ needs during the post-ICU phase.’ A continuum of care Patients who are discharged after a lengthy stay in intensive care are rarely completely recovered and most are still dependent on help. Therefore, the study project is not only aimed at patients but explic- itly also their relatives, as ‘they are also affected by the continuous morbidity. PTSD, depression, anxi- ety and adjustment disorders can be potential implications. In recent publications these psycho-patholog- ical reactions among relatives have also been described as PICS-Family (PICS-F),’ Apfelbacher adds. However, persistent psychologi- cal - and physical morbidity after discharge, or transfer, has so far not been sufficiently addressed; this is where the study comes in. The working group wants to specify patients and relatives needs, with the help of primary and second- ary data and to develop a concept for intensive out-patient aftercare on this basis. ‘Intensive out-patient aftercare would improve the pro- cesses - coordination of therapeutic services, referrals based on spe- cific medical needs, contact with GPs, involvement of relatives – and close the gap in care,’ Apfelbacher said, who also explained that the project is carried out along- side Professor Dr Thomas Bein from the Anaesthesiology Clinic at Regensburg University Hospital. A participative approach The study includes adult patients who have spent more than five days in intensive care, have had organ replacements and have a predicted life expectancy of more than six months. The first step is to inves- tigate the uptake of care as well as existing care requirements of patients and their relatives after dis- charge from the ICU, with the help of guided interviews. Recruitment of around 25 patients, plus their The interdisciplinary challenge In 2003, Professor Christian Apfelbacher PhD gained a master’s degree in philosophy at the Munich School of Philosophy, followed by a Master of Science in Public Health at the London School of Hygiene and Tropical Medicine (DLSHTM) in 2006. Two years later he became a Doctor of Humanistic Sciences at the Medical Faculty of Heidelberg University. Then came a PhD in Philosophy at Brighton & Sussex Medical School in 2013. In the same year he qualified to teach medical sociology. In spring 2014, Apfelbacher became Professor for Medical Sociology at the Institute for Epidemiology and Preventive Medicine at Regensburg University. relatives, is done via stratified quota sampling with regards to age, gen- der and severity of illness among the participants and consortium partners. In parallel, an analysis of Evaluating ICU care for cancer patients Progressive treatments offer new chances for cancer patients, but also could result in as yet unknown complications. The number of cancer patients transferred to the ICU for cancer-specific and internal medi- cine related reasons is on the increase. Caring for them on the ICU is a complex challenge, with interdis- ciplinary cooperation playing an essential part. Certain criteria need to be met for the admission of a cancer patient to the ICU, according to Dr Peter Schellongowski, specialist in internal medicine and intensive care and sen- ior consultant in the ICU at Vienna’s Medical University. The Austrian ICU specialises in the care of critically ill cancer patients suffering from, for instance, acute respiratory failure and infection related problems such as sepsis or toxic reaction. Admission criteria ‘We need to consider several fac- tors when deciding whether criti- cally ill cancer patients should be cared for in the ICU. Apart from the patient’s general condition, we must evaluate the probability of surviving acute organ failure(s) along with the expected long-term survival and therapy options after intensive care treatment. The latter can be very strenuous and even traumatising and affect the remaining quality of life, which is why the admission crite- ria are important,’ Schellongowski explains. ‘Patients in the early stage of a still treatable disease, whose life expectancy is likely to be more than a year, patients who should receive curative treatment, and patients in remission from their pri- mary disease are usually admitted. They are given a full code manage- ment, receiving the entire range of intensive care treatments available. However, if treatment options have been exhausted or intensive care is unlikely to improve a patient’s life expectancy or condition we would refrain from treatment.’ For patients receiving pallia- tive care who may have a good chance of longer-term survival due to treatment progression, such as patients with low-grade non-Hodg- kin Lymphoma, for instance, or patients in partial remission from diseases like multiple myeloma or solid tumours, admission to the ICU can also make sense. ‘The group of patients who may benefit from intensive care continu- ously expands due to the broad range of cancer treatments avail- able. Oncology is continuously evolv- ing, making a close cooperation between intensive care medics and oncologists so important: It guar- antees the best treatment for the patient,’ Schellongowski explains. Close examination Despite structured criteria and guide- lines, the decision-making process on treatment and admission objectives is often very complex. ‘A minimum “one-year survival” objective obvious- ly does not mean that a patient with an 11-months survival prognosis will immediately fall outside the scope. Each case is intensively examined. ‘If the situation is not clear-cut,’ he adds, ‘we often start a multi-day ICU trial to examine whether the patient responds positively to the treatment. Then we decide if it makes sense to continue with intensive care.’ the disease. Further, up to 18% of patients with aggressive, haematolog- ical cancers require intensive medical care during the early disease stage, either because of early complications or because of aggressive initial treat- ment that has caused secondary com- plications, both ultimately leading to organ dysfunction. Specific treatment The most common cause for ICU admission is acute respiratory failure, followed by complications from sep- sis. Haematological diseases in par- ticular often lead to pulmonary com- plications, caused by infections or complications arising from leukaemia itself. ‘This complicates treatment, because chemotherapy can aggra- vate an infection. At the same time, chemotherapy cannot be suspended for too long. In some cases, limited intensive care treatment is considered, exclud- ing certain procedures such as intu- bation. ‘A study has confirmed that this approach also helps many and that survivors suffer from post inten- sive care syndrome (leading to anxie- ty, depression or post-traumatic stress syndrome) no more frequently than patients without therapy limitations.’ Frequent ICU admissions Patients in the early stages of a can- cerous disease are in particular need of intensive care. Five to six percent of cancer patients with solid tumours are admitted to the ICU for primary surgical care in the early stage of ‘Close cooperation between haema- tologists and oncologists is therefore of extraordinary importance and very desirable,’ Schellongowski empha- sises. ‘It’s scientifically well docu- mented that intensive care patients with cancer, who receive intensive A a G K . o C & G A k r e w r e g ä r D f o y s e t r u o C EUROPEAN HOSPITAL Vol 27 Issue 5/18 ACEM SPA | Medical Company DivisionARGELATO, BO - ITALYPH +39 051 721844 | FAX +39 051 email@example.com | WWW.ACEM.ITMEDICAL LIGHTING SYSTEM12-15 NOV 2018DÜSSELDORFHALL 10 | STAND B60ACEMSO15FFOCUSABLE LED LAMPFOR EXAMINATIONAND MINOR SURGERY
8 CA R D I O LO G Y Multidisciplinary care is key to cardiac disease management Research with 7-Tesla MRI Figure 1 Figure 2 Sodium mapping of the heart using 7 Tesla MRI Higher signal-to-noise ratio (SNR) using 7 Tesla MRI allows to map sodium in the human heart. The isolation of the long relaxation sodium component (using a long echo time) and the compen- sation of concomitant signal modulation (T2star and B1+/B1- from transmit-receive coil) allows for a single slice to be mapped within 5min at a resolution of 2x2x10 mm3. Reference sodium concentration vials attached to the coil serve as calibration of the sodium MRI signal. Figure 1: Top-left is B1+/B1- map, Top-right is T2star map, Bottom-left is anatomical MRI image of the heart using conventional 1H-MRI, and bottom-left is the map of long- relaxation sodium concentration after corrections of the sodium MRI signal using the maps at the top. Figure 2: Overlay of long-relaxation sodium map onto the anatomical MRI. New 7-T MR methods could potentially shed light on cardio- myopathies’ principles, according to a leading French radiologist who also stresses the importance of teamwork between radiolo- gists, cardiologists, surgeons and anaesthesiologists. Report: Mélisande Rouger Morphologic and dynamic informa- tion of the myocardium is achieved with millimetric resolution (0.9x0.9 mm2). Strong intensity variations characteristic of 7-Tesla MRI can be observed from anterior to posterior myocardial segments. New tools provided by indus- trial partners and used by cardio- vascular surgeons and radiologists are improving treatment of thoracic aorta pathologies. An increasingly used technique is fusion imaging, in which pre-treatment MR and CT scans of the patient are being fused with angiography images to guide stent-graft navigation through the vascular structures of the patient during the intervention, according to Alexis Jacquier, cardiovascular radiologist at Timone University Hospital in Marseille. ‘Fusion imaging enables to lower radiation dose and to reduce the amount of contrast media that are traditionally required in this type of surgery. It avoids having to inject iodine to know where we’re at,’ he explained. The hospital also hosts the Timone Aortic Centre (CAT in French), a leading regional multidisciplinary centre that covers full aortic pathol- ogy management, from diagnosis to patient care and follow-up, with a strong connection with the univer- sity. The CAT includes vascular and cardiac surgeons, radiologists, car- diologists, vascular physicians and anaesthesiologists. The objective is to provide a mul- tidisciplinary approach to provide the best medical care; for instance all thoracic stent-graft procedures are performed by a multidiscipli- nary team comprised of vascular surgeons, radiologists and anaesthe- siologists at CAT. Imaging has become key in tho- racic aorta treatment with the boom of minimally invasive procedures. Besides thoracic disease, Timone Hospital is one of the main cen- tres in France offering endovascu- lar interventional radiology skills to treat patients with carotid and renal disease, which Jacquier and colleague Vincent Vidal perform daily, along with the full suite of cardiovascular interventional radi- ology procedures – endoprosthe- ses and stent placement, small ves- sels and tumour embolisation, etc. Furthermore, the hospital is located close to the medical and biology MR centre (CRMBM), one of the few labs in Europe that work with 7-T MRI for diagnostic imaging research. This proximity enables Jacquier Accutron® CT-D New with Pre-Inject Testing of the patient’s access prior to the injection! Easy activation with a single keystroke! Automatic profile adjustment! Update now! Contrast medium injectors and consumables for CT, MRI and angiography Hauptstrasse 255 · 66128 Saarbruecken For more info: www.medtron.com Cardiovascular radiologist Professor Alexis Jacquier, at Timone University Hospital, Marseille, France, trained in Marseille and Lyon and gained his PhD in San Francisco, USA, supervised by Maythem Saeed and Charles Higgins. In 2006 he integrated the cardiovascular group in the CEMEREM research lab (http://crmbm.univ-amu.fr). He is author and co-author of more than 90 peer-reviewed publications and has presented numerous lectures, tutorials and refresher courses internationally. He also chaired the European Society of Cardiac Radiology membership committee and is current vice president of the French Society of Cardio-Vascular Radiology (Société Française d’Imagerie CardioVasculaire, SFICV). French Society of Radiology estab- lished a working protocol in 2005; according to this, the cardiologist prescribes the CT and MR scans and radiologist performs the technical assessment and writes the report – and then sends it to the cardiolo- gist. Jacquier: ‘This division of tasks promotes the best possible medical care, but everything really depends on the physician’s skills. A lot of things may need to be updated as we gradually introduce artificial intelligence.’ Radiologists must also homoge- nise the way they write the imaging report. Introducing the structured report to exploit data at nation- al level will prove essential for their future. Another priority is to improve communication not only with patients but also other medical specialties, he said. Jacquier will participate in the International Day of Radiology (8 November 2018), an initiative to highlight the radiologist’s role in cardiac care. ‘Radiology is not a medico-tech- nical specialty, although French administration still classifies us as such. We’re a medical discipline. The old-fashioned image of the radiolo- gist reading scans alone in a base- ment and not having contact with anyone else in a hospital is outdat- ed. The radiologist,’ he emphasised, ‘is now at the centre of patient care and healthcare.’ and team to test 7-T methods using sodium instead of proton imag- ing, a possibility that opens brand new perspectives in heart imaging. ‘Sodium electrolytic disorganisation in the myocardium can have an electrical and mechanical impact on heart function. 7-T will enable the development of new applications in the field. It is still a complex task, but we are working hard on differ- ent papers on sodium quantification in the myocardium and potential clinical applications’ he explained. Cooperation with cardiologists is essential in myocardial disease man- agement, according to Jacquier, who again stressed the importance of the multidisciplinary approach dur- ing patient treatment. ‘Patients are now being care for within the heart team, a model increasingly followed by healthcare facilities in France and beyond,’ he explained, adding, ‘whether it’s for TAVI procedures, diagnosis or follow-up. Medicine is becoming hyper specialised and mixing profiles and specialties ena- bles us to significantly improve patient care.’ Another significant develop- ment in France was the reform of the radiology residents’ train- ing scheme, which was introduced in 2017. Radiology residents must The Council now undergo a three-step training, including successively: base training (one year), dedicated to emergency radiology; in-depth training (three years), to ensure that every subspe- cialty in radiology has been covered in their education; and consolida- tion training (one or two years), providing certification for one or two subspecialties. French of the Teachers of Radiology (CERF) has been piloting the change for radiology. The French Society of Cardiovascular Radiology now pro- vides e-learning material to ensure homogeneous teaching and train- ing program across the country. In September, the series became freely available for French residents on the CERF website, and also available for all radiologists on the website of the French Society of Radiology. This change is a substantial improvement in the training scheme, because it reflects daily routine bet- ter, Jacquier added. ‘Cardiac imaging studies are being prescribed every day by all sorts of physicians: GPs, endocrinologists, surgeons, and even oncologists, for instance in pre- and post-chemotherapy evalu- ation.’ As for cardiology, the French the Society of Cardiology and High-resolution Simultaneous Multi-Slice (SMS) dynamic MRI of the heart at 7 Tesla Increased signal-to-noise ratio from the 7 Tesla MRI is harnessed for refined imaging of heart. Simultaneous Multi-Slice (SMS) cardiac dynamic MRI (cine) permits the acquisition of three thin- slices (4 mm) within a 10 s breath-hold. Robustness to patients motion and limited breath-hold capacity is guaranteed through a dedicated self-calibrated SMS technique tailored for cardiac imaging. Morphologic and dynamic information of the myocardium Figure 3: SMS cine acquired within 10s showing diastole (relaxed phase of the cardiac cycle) of the apex (a) mid- ventricular (b) and base (c) slices. is achieved with millimetric resolution (0.9x0.9 mm2). Strong intensity variations characteristic of 7 Tesla MRI can be observed from anterior to posterior myocardial segments. a b c EUROPEAN HOSPITAL Vol 27 Issue 5/18
CA R D I O LO G Y 9 David Newby is the British Heart Foundation Professor of Cardiology at the University of Edinburgh, and Director of the Edinburgh Clinical Research Facility, plus a Consultant Interventional Cardiologist at the Edinburgh’s Royal Infirmary. His principal research interests are in advanced imaging with particular relevance to acute coronary syndromes, valvular heart disease and heart failure. too much then you get remodelling and heart failure.’ Work with nanomedicine in this area, he said ‘are the first steps towards trying to understand how the heart is responding to injury from a heart attack.’ The speakers also included Dr Iwona Cicha, from the University Hospital Erlangen, Germany, who focused on magnetic nanoparticles for atherosclerosis - in vitro and in vivo preclinical studies. Also, Professor Patrick Hsieh, research fellow and affiliate attending sur- geon at the Institute of Biomedical Sciences, Academia Sinica, Taiwan spoke of nanomaterials for cardio- vascular repair and regeneration. The development of novel MRI tools assessing atheromatous plaque inflammation and stress analysis was the focus of Professor Jonathan Gillard, Professor of Neuroradiology at the University of Cambridge, United Kingdom. ysmal atrial fibrillation only once every three months and I have an implantable device, why do I have to take anti-coagulants all the time? ‘If I see an alert on my phone say- ing I have to take an action to avoid a thrombolytic event, that would be a step forward. ‘The second thing is to train nurses to see what’s important in telemonitoring and to act on that information as independently of the physician as possible. Nanomedicine is deemed valuable in cardiovascular care Manipulating atoms and molecules Report: Mark Nicholls Nanomedicine is set to play an increas- ingly important role in the future diagnosis and treatment of cardio- vascular disease. Understanding the importance of nanomedicine was enhanced by four experts who spoke at the British Cardiovascular Society conference held in June. The technology – deal- ing with dimensions and tolerances of less than 100 nanometres and especially the manipulation of indi- vidual atoms and molecules – is a critical component in increasingly more precise detailed approaches to cardiac care. The speakers tackled areas such as nanomaterials for cardiovascular repair and regeneration, magnetic nanoparticles for atherosclerosis and the development of novel MRI tools to assess atheromatous plaque inflammation and stress analysis. Professor Dave Newby spoke of ‘magnetic nanoparticles in clinical cardiovascular disease’ highlighting how magnetic resonance imaging USPIO imaging in the Abdominal Aortic Aneurysm agents have an application to car- diovascular disease, predominantly with macrophages. Nanoparticles can tell us about where there is active inflammation and where macrophages are active. ‘That can be useful because it helps us understand disease biology – where injury is happening, how diseases are occurring and how the body heals.’ Experts are using MRI, PET and other technologies to exploit the role of nanomedicine in this field as they assess arterial blockages and the disease dimension. ‘What we need to know is whether the biology is dormant, is it just going to lie there and stay unchanged for the next 10 years and never cause a problem, or is there a heart attack around the corner and what can we do to stop it happening?’ Newby outlined his work to iden- tify ongoing inflammation using ultra-small superparamagnetic iron oxides (USPIOs) to identify hot areas within the aneurysm that are growing. His study showed that, if the aneurysm lights up with the MR agent, it will grow bigger and t sur- gery is necessary, or the likelihood of the aneurysm bursting increased. Tracking active inflammation ‘Macrophages are important in lots of cardiovascular diseases – plaque rupture, heart attacks and aneu- rysms, for example – and resolution of injury and inflammation within that,’ said Newby, who is Professor of Cardiology at the University of Edinburgh in Scotland. Nanomedicine and advanced imaging to study biology are cur- rently particularly topical. ‘It’s not just body structure,’ he said. ‘It’s also about what the tis- sue in the body is actually doing. Understanding cardiac injury Newby also described how the heart heals after myocardial infarction and how, via iron nanoparticles, imaging can show how much inflammation there is in the heart and how this activity relates to the resolution and scarring of the heart attack. ‘We do not know yet whether modifying cellular inflammation will make things better or worse, because it could go either way,’ Newby pointed out. ‘If a heart does not heal well, it can burst and rup- ture but if it overdoes it and heals Looking again at IN-TIME What kind of workflow can maximise clinical benefit? The IN-TIME study remains the only major trial to show a clear mortality benefit for remote monitoring in heart failure (HF) patients. A recent analysis by Hussar et al. suggests workflow processes such as daily, multipar- ametric data transmitted using Biotronik Home Monitoring, may be key to this benefit. Dr Wilfried Mullens, Head of the Heart Failure and Cardiac Rehabilitation Section at Ziekenhuis Oost- Limburg, in Genk, Belgium looks at the implications for telemoni- toring in the future. Dr Wilfried Mullens heads the Heart Failure and Cardiac Rehabilitation Section at Ziekenhuis Oost-Limburg, in Genk, Belgium be a challenge in a lot of hospitals because it can take a lot of time to process technical alerts. We would look to manufacturers to make that more efficient. ‘At hospitals, we need to improve the way we look at data, by train- ing two types of nurses—those who handle device problems and those who specialise in heart failure.’ For telemonitoring, what should the next step be? ‘I think telemonitoring is here to stay and it’s going to expand. I think patients want some kind of self-empowerment and we’re almost there. For example, if I had parox- According to the recent Hussar et al. analysis, workflow processes might make a clear difference in remote monitoring’s clinical ben- efit. How should we now look at the IN-TIME? Wilfried Mullens: ‘IN-TIME is a great study, but you have to incorporate it into a disease management strategy. Telemonitoring is a great tool if you know how to use it within a daily work schedule. If the study showed something, it was that when you react to telemonitoring signals in an appropriate and individualised man- ner, it can be beneficial. ‘There’s a lot of technical signals coming out of devices that don’t lead to a lot of clinical benefit. You need someone to filter those before they reach the physician or health- care professional. You have to get to know your patient as well because some alarms will be important for some patients but not for others.’ How is an efficient remote moni- toring workflow managed in your practice? ‘We’ve installed mandatory phone calls for certain alerts. In these phone calls, the nurses ask patients specific questions. Our EP nurses, who are absolutely fantastic, will sometimes say everything is fine. My heart failure nurse might call later for the same alert and be able to tell whether something’s wrong. ‘If you keep a direct link to that patient, you can then reinforce bet- ter adherence to medical therapy, for example. 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R A D I O LO G Y 1 1 AI shapes the future of radiology System allocates cases to the right radiologist With 14 years’ experience in developing, launching and marketing medical techno logy solutions, Tomer Zonens is Worldwide Product Manager at Carestream and responsible for three product lines in the Healthcare Information Solutions division. Formerly an algorithm engineer, he developed automated sleep medicine analysis systems following studies in Biomedical Engineering at Technion, Israel Institute of Technology. far in the future. Until we get to that point we need to consider if we truly want to maximise the value from AI. ‘We will only achieve this by inte- grating AI within an enterprise plat- form while also working to create better reports and optimise workflow, making radiologists more productive and improving results by allowing them to focus on their main task: treating the patient.’ AI Orchestrator details: carestream.com o r i / m i s a C m o c . e b o d a . k c o t s / / : s p t t h the machine will scan the patient and the reports will come directly out of the system,’ he said. ‘They will not even need images; all the information will be in the machine, and AI will do everything. But I think this is very and as it is interactive they can make comparisons more easily, which is much better than just getting a piece of paper,’ Zonens pointed out. Findings can be added and filters created, with access made possi- ble across multiple facilities and for multiple subspecialists at multiple locations. Going to the best specialist Above all, Zonens affirmed, the new technology avoids wasted time for radiologists. This is largely because Carestream’s Workflow Orchestrator directs the study to the best radiolo- gist for each case, based on subspe- cialty, location and affiliation. ‘We want studies to find the radi- ologist rather than the radiologist having to look for a study,’ Zonens continued. ‘We therefore have a sys- tem for matching exams to radiolo- gists, based on intelligent rules, and we are working on applying AI to this process. We can imagine a sys- tem where an AI algorithm actually guides or directs the flow of studies in the optimum way towards the radiologist.’ Carestream’s AI Orchestrator tool also has the ability to automati- cally spread hospital workloads more effectively. ‘If, in the hospital, there is some division of the workload, the system will use this as feedback and optimise the load in future until the best result is achieved.’ AI can already use the informa- tion in scans and text to ‘extract more value’ from reports, by taking the clinical data and plainly making sense of it. Yet, Zonens sees far more potential for AI within radiology in the years ahead. ‘Maybe in the future Real Python code developing screen. Programing workflow abstract algorithm concept. Lines of Python code visible under magnifying lens. Report: Daniela Zimmermann Synergy is key to ensuring Artificial Intelligence (AI) can play a critical role in helping radiologists raise their game. Integrating AI with innovative platforms to optimise workflow and make diagnosis more efficient, whilst also creating more accurate reports, offers enormous potential benefits to patients, clinicians and hospi- tals, according to industry specialist Tomer Zonens, Worldwide Product Manager at Carestream. Thus it is among the latest systems the compa- ny is developing to speed up report- ing and eliminate the most mundane tasks radiologists undertake. Speaking at the recent Roeko German Congress of Radiology, Zonens discussed AI radiology solu- tions and the challenges to overcome in order to achieve the advances radiologists and patients need and demand. Carestream, which delivers medical and dental imaging and IT solutions, has worked with Zebra Analytics, a third-party software company that provides tools to enhance the quality and speed of diagnosis and report- ing for radiology imaging exams. The resulting algorithm-enabled Radiology Assistant can boost diag- nostic confidence while simultane- ously improving productivity and containing costs. AI can quickly cal- culate and provide incidental find- ings, critical findings and quantitative assessments, which can help stream- line radiologists’ reading workflow and allow earlier treatment. Zonens pointed out a range of ways in which Carestream’s AI applications can support the radiologist, stating that ‘Synergy is the key.’ While the automotive industry has been a driv- er within the AI space, followed by the gaming sector, he explained the technology also has huge potential within healthcare, and particularly in radiology. Carestream is collaborating with a number of centres to harness AI and deep learning to identify and analyse mainstream images. These include customers, university health systems and private practices. The company’s AI systems can already automatically populate reports and even offer triage. ‘For example,’ said Zonens, ‘If the AI algorithm detects a brain bleed, Carestream’s new Workflow Orchestrator system automatically escalates the exam. The radiologist may be seeing an out- or in-patient for a non-urgent exam, but once the brain bleed is spotted, that patient will jump to the top of the list and, thanks to a particular icon on the system, the radiologist will already know something has been identified.’ Carestream is constantly working to add more algorithms to the system. It will, for example, soon be possible to search all a patient’s data who is being screened in hospital, perhaps for an un-related event, so as to tell the clinician and patient if there are any signs that need follow-up. With interactive reports, hyperlinks to findings can be included, leading to more comprehensive reports and increased patient confidence. ‘The viewer can see the report, www.healthcare-in-europe.com The new standard in the pre-cleaning of robotic instruments • Modular compilation of the system according to the types of instruments • Time optimized and coordinated cleaning processes depending on the types of instruments • Cleaning – gentle and in shortest time• Robotic and rinsable MIS instruments: safety by rinsing of single channel and single examinationMore information about our ultrasonic baths and the cleaning of medical instruments you will find on the website bandelin.com/branchen/medicineor by phone +49-30-768 80-212.T Ultrasonic baths for robotic instruments, rinsable MIS and standard instrumentsMade in GermanyYou meet us here: Hall 12 A30
1 4 N U C L E A R M E D I C I N E Comparison is still pending On-going malignant astrocytoma vaccine tests A new vaccination for malignant astrocytoma brings such patients hope. However, research is still in its infancy. Eva Britsch of European Hospital spoke with Professor Michael Platten, Medical Director of the Neurological Clinic at Medical University Mannheim, about the present state of research and the serious opportunities this presents. During the interview, he also revealed how cooperation with the pharmaceu- tical industry is developing and why the current results are only conditionally resilient. From July 2015 to July 2017 Professor Michael Platten and colleagues treated 33 patients with newly diag- nosed malignant astrocytoma with a novel vaccine. What is the current state of affairs? MP: ‘We have completed the study and are in the follow-up phase. The patient data are currently evaluated. However, over the next few months we will collect and evaluate further data on the patients’ progress. At the same time, we are currently conducting intensive research on the patients’ blood samples to gain a better understanding of the immune reactions.’ EB: Can definitive statements be made about the vaccination reducing the risk for astrocytoma and oligodendroglioma* patients to recur? ‘No. In addition to vaccination all patients received effective radia- tion and chemotherapy, which also prevents recurrent tumour growth, even if only for au limited period. Whether this recurrence risk is fur- ther reduced by vaccination can only be answered in a comparative study. We can start such a study once we have fully evaluated the current study.’ How does the new vaccination work and how can it be seen in combination with previously known treatment options? p039P p031P 15 μm 15 μm 15 μm 15 μm I P A D A L P I P A D H 2 3 1 R 1 H D I A L P Brain tumour cells producing the mutated protein molecule IDH1R132H (green) carry this on their cell surface (seen in red). Thus, tumour-specific changes are visible to the immune system ‘The vaccination is intended to sen- sitise the immune system of patients concerned to a protein molecule that is characteristically altered in the tumours of the patients, name- ly by the exchange of a single building block. We call this change IDH1R132H. With the vaccination we can sen- sitize the immune system so spe- cifically that only the altered pro- tein molecule in the tumour cells, IDH1R132H, but not the healthy form, IDH1wt, which can be found in all healthy body cells, is recog- nized. We hope that this specific sensitization of the immune system through vaccination will lead to the targeted treatment of tumours, as we have observed in animal experi- ments. We also assume that radia- tion therapy of the tumour, a proven therapy for these tumours, helps the sensitized immune system to fight the tumour. You and colleagues are currently evaluating the immune reactions of patients to the vaccine – how do you evaluate the reactions? Very positive. The vast majority of patients develop specific antibod- ies against IDH1R132H as a result of vaccination, but also T-cells, two important components of the immune system. We are currently evaluating which factors influence the strength of the immune reac- tions and, of course, whether these have an influence on the further course, i.e. freedom from recur- rence. We are also interested in finding out why individual patients have not experienced an adequate or delayed immune reaction.’ Does the vaccination have (previ- ously known) risks? ‘The only relevant risks we have observed are vaccination reactions at the injection site with redness and itching. This reaction is to be expected and is mainly the result of the necessary vaccination booster.’ Could a similar vaccine be devel- oped for other cancers? ‘In rare cases IDH1R132H can also occur in other types of tumours, for example in bile duct carcinomas. In principle, all tumour types in which IDH1R132H is present are suitable for vaccination. ‘On a super-ordinate level, mutat- ed protein molecules are found in practically all tumours, but they are usually patient-specific. If we succeed in defining these specifi- cally modified protein molecules for each individual patient and in developing a tailor-made vaccina- tion therapy, then such a vaccina- tion could in principle be used for all types of tumours. However, this would then be a real individualised cancer immunotherapy that could Michael Platten MD is Medical Director of the Manheim Medical University Neurological Clinic and professor of clinical neurology, neuroimmunology and neuro-oncology at Heidelberg University. In recent years he has also led brain tumour immunology at the German Cancer Research Centre (DKFZ) in Heidelberg, Germany. not simply be taken out of the medi- cine cabinet.’ Could your research lead to new treatments for multiple sclerosis, which you are also researching? ‘We always try to learn from other diseases. For the current vaccination we use many findings and models, including multiple sclerosis, because an unwanted excessive immune reaction occurs in the brain there. If we understand the mechanisms that lead to this excessive immune response, then we can better con- trol the immune responses in brain tumours. ‘Conversely, many of the break- through technologies we use to analyse immune responses in brain tumour patients can also contribute to a better understanding of multi- ple sclerosis.’ How does the pharmaceuti- cal industry respond to your research? ‘Let’s say: with cautious interest. But, we have now begun a cooperation with the industry that combines our vaccination approach with an approved cancer immunotherapy drug. Through this intelligent com- bination, we hope to make our vac- cination therapy even more effec- tive. This clinical trial will start in the next few weeks.’ What hampers your work? ‘Financing is certainly a major obsta- cle; so far we have financed all studies from public subsidies. The German Cancer Research Centre, the National Centre for Tumour Disease, German Cancer Aid and the Federal Ministry of Education and Research have given us considerable sup- port, for which we are very grateful. Without this support, implementa- tion would not have been possible. ‘We are also very grateful for the good cooperation with the Paul Ehrlich Institute, which actively sup- ports us in these innovative thera- peutic approaches.’ Could patients hope to receive vac- cination beyond their research status? ‘It’s probably too early for now. We are currently focusing all our efforts on the follow-up study. Until we can say for sure whether the vaccination therapy will actually work and, if so, in which patients and under what conditions, research in the form of clinical studies will be a priority. ‘However, we are very pleased that the patients affected and their relatives are supporting us by par- ticipating in the studies.’ * A rare, slow-growing tumour that begins in oligodendrocytes – the cells covering and protecting nerve cells in brain and spinal cord. EUROPEAN HOSPITAL Vol 27 Issue 5/18 Main Themes Medical Imaging Compuyed Maxillofacial Imaging Image Processing and Visualizayion Mulyidisciplinary Compuyayional Anayomy E-Healyh and IHE Compuyer Aided Diagnosis Compuyer Assisyed Radiayion Therapy Image and Model Guided Therapy Personalized Medicine Surgical Navigayion Surgical Roboyics and Insyrumenyayion Surgical Simulayion and Educayion Compuyer Assisyed Oryhopaedic and Spinal Surgery Compuyer Assisyed Head and Neck, and ENT Surgery Image Guided Neurosurgery Minimally Invasive Cardiovascular and Thoracoabdominal Surgery Informayion Processing in Compuyer-Assisyed Inyervenyion Digiyal Operaying Room Human-Machine Inyerface Payhology Informayics Machine Inyelligence Inyegrayed Payieny Care Tumor Boards Innovayive Clinical InvesyigayionsCoMpuTer AssisTed rAdiology And surgeryCARS 201933rd Inyernayional Congress and Exhibiyionwww.cars-iny.orgCArs 2019 presidentPierre Jannin, PhD (F)Congress organizing Committee Christos Angelopoulos, DDS (USA)Elicabeth Beckmann, BSc (UK)Leonard Berliner, MD (USA)Ulrich Bick, MD (D)Davide Caramella, MD (I)Kevin Cleary, PhD (USA)Mario A. Cypko, PhD (NL)Takeyoshi Dohi, PhD (J)Kunio Doi, PhD (USA)Volkmar Falk, MD, PhD (D)Allan G. Farman, PhD, DSc (USA)Hubertus Feussner, MD (D)Guy Frija, MD (F)Miguel Ángel Goncálec Ballester, PhD (E)Makoto Hashicume, MD, PhD (J)Yoshihiko Hayakawa, PhD (J)Javier Herrero Jover, PhD (E)David Hilderbrand (USA)Kiyonari Inamura, PhD (J)Pierre Jannin, PhD (F)Leo Joskowicc, PhD (IL)Tina Kapur, PhD (USA)Heinc U. Lemke, PhD (D) (Chair)Kensaku Mori, PhD (J)Hironobu Nakamura, MD, PhD (J)Nassir Navab, PhD (D)Terry M. Peters, PhD (CDN)Osman M. Ratib, MD, PhD (CH)Hans G. Ringertc, MD, PhD (S)Yoshinobu Sato, PhD (J)Ramin Shahidi, PhD (USA)Akinobu Shimicu, PhD (J)Hiroyuki Yoshida, PhD (USA)June 18–21, 2019Rennes, France
N U C L E A R M E D I C I N E 1 5 Digital Photon Counting (DPC) Surmounting conventional photomultiplier limits Interview: Daniela Zimmermann Built as the first commercially avail- able scanner to deliver truly digi- tal PET, the Vereos PET/CT, from Philips, offers revolutionary Digital Photon Counting technology. The science behind this scanner evolu- tion is ‘quite complicated’, agrees Piotr Maniawski, Director of Clinical Science Nuclear Medicine at Philips Healthcare, yet the improved per- formance is significant, particularly when compared with an analogue system. The primary benefit of the improved resolution is the detect- ability of smaller lesions and that eventually translates into more acute diagnostic accuracy.’ Additional to DPC, other advances making digital PET possible are 1:1 coupling between the scintillator and the light-sensing element and faster Time-of-Flight (TOF) technol- ogy. Philips’ DPC technology was developed to overcome the limita- tions of conventional photomultipli- er technology and the 1:1 coupling detectability of the disease.’ PET tracers are enhancing person- alised medicine in, for example, the area of immunotherapy and mark- ing antibodies with PET imaging isotopes. ‘These antibodies will go only to places where they are sent; that’s a very targeted, personalised precise therapy. However, before therapy, we can image to make sure the patient receiving this immuno- therapy is going to respond,’ he said, adding that the latest clinical evi- dence for cancers that utilise glucose for growth is that PET and PET/CT is with Philips, using those tracers for investigational and clinical applica- tions. Other areas where Vereos is appli- cable, in addition to oncology, are cardiology and neurology, such in diagnosis of different types of dementia, where various tracers are used, such as amyloid tracers of amyloid plaque, and tau (an anti- body that expresses in dementia). ‘What you want in a PET scan for dementia is high resolution,’ Maniawski pointed out, ‘because we are looking at very small changes Vereos PET/CT study performed with RB-82 Chloride to classify the state of myocardial perfusion at rest and with pharmacologic stress. With the highest count rate in the industry, Vereos Digital PET/CT provides enhanced diagnostic confidence with applications that use short half-life tracers. That performance includes a reduction in scan time, lower dose, improved diagnostic accuracy and better detection of small lesions as well as applicability across oncology, cardiology and neurology, for exam- ple in dementia assessment. Maniawski outlined how propri- etary Digital Photon Counting (DPC) technology sits at the core of the new Philips PET system, and was developed to overcome the limita- tions of conventional photomulti- plier technology. With PET, scintillating crystals are used to collect high-energy photons and convert them to visible light, which is then picked up by a light sensor, and the output constructs the resulting image. With DPC technol- ogy, light is counted as individual single photons. and enhanced TOF allow the Vereos system to offer approximately dou- ble the volumetric resolution, sensi- tivity gain, and accuracy of a compa- rable analogue system. Maniawski emphasised how better images benefit patient management with the ability to see disease that has traditionally been difficult to image or the recurrence of disease. ‘This can change patient manage- ment if, for example, there are extra lymph nodes that were not seen before. Significant patient decisions are made on the accuracy of the the most accurate staging modality. With immuno-PET developed to help guide immunotherapy, research- ers investigate if a therapy works in tumour response. ‘Here again digital PET has potential, because it’s much more quantitative, more reliable in absolute uptake. We can do studies and track if a patient is responding in the way we anticipate,’ Maniawski explained. A number of academic sites are currently using Vereos PET/CT for high-end research and have devel- oped their own radio tracers to work and we want to detect these changes before clinical symptoms of cogni- tive dementia show up.’ Another key area of evaluation from Vereos is in coronary artery disease (CAD) with heart scans con- ducted at peak exercise and at rest to assess the supply of blood in the myocardium. An issue with conventional PET myocardial perfusion imaging is that, in patients with multi-vessel disease, it cannot fully distinguish where the coronary arteries are dis- eased. ‘However, if we are able to Piotr Maniawski is a clinical physicist and Director of clinical science for nuclear medicine and advanced molecular imaging at Philips Healthcare. He worked in a multitude of positions, including as radiation safety officer in Zabrze, Poland, as research associate at Yale University and as software engineer in Cleveland. The focus of his work is in nuclear imaging, especially PET/CT, for which he develops clinical protocols and quality control tools. characterise the absolute flow in millilitres per minute per gram of tissue, we can then see in absolute terms if the flow is normal or not – even in patients with multi-vessel disease – with new PET/CT scan- ners,’ Maniawski said. This is where the 1:1 coupling offers a critical benefit, because it allows more accurate quantification of the flow. Artificial Intelligence (AI) – or adaptive intelligence as Philips pre- fers to call it – also undergoes signifi- cant developments with PET, notably for example with adaptive protocols that are specific to patients. ‘Patient image quality suffers with larger patients,’ Maniawski observed, ‘but the system can adapt the proto- col either through automisation or reconstruction.’ ‘This is very technical talk,’ Maniawski concedes, ‘but what it means is that we have far more pre- cise information about the character- istics of that light signal. We have a better way of determining when the signal was detected and also more precise localisation of that signal. Vereos PET/CT study performed with F18-PSMA on patient with prostate ca for staging. Increased activity in prostate identified and multiple areas of increased uptake in the pelvis are consistent with lymph nodes. Also identified is a very small lesion anterior to the spine in the upper abdomen www.healthcare-in-europe.com
1 6 L A B O R AT O RY This research is as vital as understanding the human genome Exploring the human microbiome During the International Forum for Laboratory Medicine, being held at MEDICA 2018, one seminar (on 12 November} will focus on infectious diseases. Professor André Gessner, from the Medical Microbiology and Hygiene Department at Regensburg University, will lecture on ‘The human microbiome, an explosive ‘climate’ topic,’ he explained to EH reporter Walter Depner. WD: Generally you know the kind of audience you face during gatherings of specialists in your field. However, there’s no certain- ty about who will be among the MEDICA delegates attending your lecture. Could this make your job difficult or perhaps more exciting? AG: I have given many lectures to heterogeneous audiences and find the challenge of explaining complex relationships in the most compre- hensible way to be very exciting and positive. Often, I have received very stimulat- ing questions – especially from col- leagues in other fields. About three years ago, at the University of Regensburg, you lec- tured on The Intestinal Microbiom as the Centre of Health and Illness, and included in the invitations physicians, chemists, nutrition- ists, microbiologists, dieticians, technical consultants and health journalists – a very heterogeneous audience. Could that experience help with the Düsseldorf seminar? Yes, certainly. The conference is a good example for what the partici- pants see as a successful interdisci- plinary forum. Modern medicine and healthcare demands an interdisciplinary approach. Do such events, as in Regensburg and now Dusseldorf, help to reach this goal? The challenge is to transmit the latest scientific knowledge, with a critical appraisal, in such a way that it is well understood and to ‘condense’ without over-simplification, which distorts the information. For me it is important to stay realistic and above all not to raise hopes among physi- cians and their patients too early that cannot (yet) be fulfilled. There is considerable focus on the role of microbial intestinal flora as a basic component for staying healthy. You have described mod- ern, high-throughput sequencing technology as a source of dramat- ic knowledge growth. Why? Without high throughput sequencing technology, together with appropri- ately qualified bioinformatics, micro- biome analysis would be impossible. It was this technology that first made this enormous knowledge growth possible – currently more than 65,000 publications in just over ten years. MEDICA’S LABMED FORUM Monday, 12 Nov 2018 10.45 – 11.15 a.m. The human microbiome – diagnostic and therapeutic aspects Speaker: Prof. André Gessner, Director of the Institute for Medical Microbiology and Hygiene at Regensburg University Are their approaches going in the right direction? The technological potential in analy- sis is developing rapidly. Here we need improved standardisation of analyses, quality controls and hope to gain ever increasing ‘read lengths’, that is to say DNA sections that can be sequenced in one piece, lower sequencing error rates and naturally lower costs for examinations. Especially important here is also a significantly better comprehension of the functional relationships between microbiome and various diseases, so that rational new therapies can be developed in the future. Along with interdisciplinary scope, the internationality ques- tion plays an important role. What is the state of cooperation, exchange in research, teaching and practice? Microbiome research is particu- larly characterised by numerous already well-established international cooperation efforts, among academic institutions such as universities, and increasingly among very many firms. The exchange is extremely inten- Having studied medicine and molecular biology at the University of Hamburg, Professor André Gessner received his medical doctorate in infection immunology and a PhD in molecular virology. Following five years’ basic research at the Heinrich- Pette Institute, Hamburg, he established his research group at the University of Erlangen, where he qualified as a specialist in medical microbiology and infectious disease epidemiology. His scientific work focuses on molecular infection immunology, infectious diseases and the role of the microbiome for diseases. He is an expert and reviewer for several international journals and scientific societies and, between 2008 and 2010 he received four calls regarding chairs for medical microbiology. Since 2010 he has been a professor and director of the Institute for Medical Microbiology and Hygiene at Regensburg University, where 150 employees focus on all aspects of infectious diseases. In 2015, Gessner became the Dean of research at the Regensburg medical faculty. sive, not only through scientific pub- lications but also via Internet fora and more than a dozen international congresses annually on microbiome topics. Local antibiotics improve results Infection control in orthopaedics and trauma surgery ble for PJI should be considered. The COPAL bone cements Copal G+C and Copal G+V, for instance, contain combinations of antibiot- ics (gentamicin and clindamycin and gentamicin and vancomycin respectively) that tackle most of the microorganisms responsible for PJI. Synergistic effects of the combina- tions of antibiotics enable a high local antibiotic concentration in situ. In revision, the range of treatments includes one-stage replacement with good soft tissue conditions and known susceptible pathogens, as 69% reduction in the rate of deep infections following femoral neck fracture when using high-dose antibiotic-loaded bone cement. Source: Sprowson et al. well as two-stage replacement with precarious soft tissue conditions and unknown resistant pathogens. In both cases the effectiveness of the treatment can be increased by using bone cement with combinations of antibiotics. The combination of anti- biotics used should be determined after completing diagnostics and an antibiogram. Hip and knee joint surgeries are among the most common proce- dures in orthopaedics and trau- ma surgery and complications can occur. Rare, but serious, among these is periprosthetic infection (PJI), which causes high costs in healthcare and stress for patients. PJI is caused by microorganisms that form a biofilm on the surface of the implant and, in this sessile state, they are difficult to diagnose and treat. Successful management of a PJI is therefore based on prevention and prophylaxis so that infections cannot develop in the first place. Antibiotic prophylaxis using antibiotic-loaded bone cement Polymethylmethacrylate (PMMA) bone cement, which is primarily used to fix prosthetic implants, can support effective infection manage- ment in primary arthroplasty, revi- sion and the treatment of peripros- thetic infections. The local release of the antibiotic from the bone cement supplements standard systemic anti- biotic prophylaxis. The advantage lies in the considerably higher local concentration of the antibiotics with a low systemic load. Choosing the right treatment algo- rithm is a critical factor for success- ful prevention and reduction of PJI. Combinations of antibiotics – sys- temic and local – are advantageous for effective infection management for revisions, in trauma cases after femoral neck fracture and occasion- ally in primary arthroplasty. When choosing the antibiotic, the cur- rent resistance situation and preva- lence of microorganisms responsi- For revisions due to verified resist- ant microorganisms (MRSA/MRSE), the use of Copal ® G+V is recom- mended. This contains the antibiotic gentamicin combined with vanco- mycin which, as a reserve antibiotic, is an option for use with known bacterial resistance to MRSA/MRSE, for example. For septic loosening or chron- ic infections, a spacer made of antibiotic-loaded bone cement is often inserted as a temporary joint replacement to eliminate infec- tion. Articulating spacers with an implant-like design, e.g. from Copal knee moulds, should be given pref- erence here to preserve the joint function and to prevent the forma- tion of contractures and scar tissue. Risk of deep infections can be considerably reduced In primary arthroplasty patients, who are particularly at a high risk of infection, are recommended for combinations of antibiotics for anti- biotic prophylaxis, and thus the use of Copal G+C bone cement. The risk factors that can increase the likelihood of infections include dia- betes, osteoporosis, limited mobility, excess weight and dementia. When treating femoral neck frac- tures with a cemented hemiarthro- plasty using Copal G+C, it can be verifiably demonstrated that the risk of deep infections (surgical site infections, SSI) can be considerably reduced by using dual antibiotic- loaded bone cement. EUROPEAN HOSPITAL Vol 27 Issue 5/18
L A B O R AT O RY 1 7 Pioneering the clinical use of mass spectrometry Mass spec needs experienced operators Professor Ruth Andrew is Personal Chair of Pharmaceutical Endocrinology Centre for Cardiovascular Science, University of Edinburgh, and Director at the Mass Spectrometry Core Facility, where her main role is to facilitate, lead and conduct biomedical research in the MS Core in all stages of clinical research projects, including preclinical development. Within the MS Core she assesses the potential of new innovations and brings new ideas forward that may then be consolidated in clinical research. also warned not to expect the same pace in advances in quantitative tan- dem MS/MS over the next decade as in the previous 10 years. ‘Accurate mass systems offer improved specificity but are not yet as sensitive or as accepted for quan- titation (e.g. narrower linear range). However, these instruments may in time take a bigger role in the clinical lab but are not common place.’ The new technique of REIMS (Rapid Evaporative Ionisation Mass Spectrometry) to sample from sur- faces is highly exciting for real-time surgical diagnostics and also for pathology. ‘REIMS may also gain a role in rapid microbiological testing,’ she said. ‘These approaches are speed- ing up diagnostics and I expect to see these applications extended with improvements in MS imaging. However, again, these are highly- specialised and expensive and, to my knowledge, only one manufac- turer is building instruments that are specifically designed to meet the quality requirements for clinical diagnostics.’ the instrument companies have invested in kits and software to make the system more user-friendly, such that less experienced operators can use the system. However, the systems still need to be embedded in labs with expert staff to ensure efficient running, method develop- ment and to troubleshoot problems.’ While MS is more precise, albeit more complicated, there are clear advantages, particularly with speci- ficity, which allows greater repro- ducibility and reliability of data. ‘For hormone analysis, for exam- ple, this means there is less like- lihood that other components in the blood can artificially raise the results,’ Andrew explained. ‘In the research field, metabo- lomic profiling of the fingerprint of a large number of biochemical spe- cies by MS may be used to predict disease risk or drug responses, but this approach is in its infancy and the data hard to handle in a stand- ardised manner, so some way from clinic. However, this could pave the way for personalised medicine.’ There is a promising future for MS in diagnostics, she confirmed, but Report: Mark Nicholls As mass spectrometry proves to be a more consistent and accu- rate tool in biochemical measures, with acknowledged advantages over immunoassays, its role in diagnos- tics has escalated. Headed by Professor Ruth Andrew, the pioneering Mass Spectrometry Core Facility at the University of Edinburgh, aims to offer researchers access to expert scientists and spe- cialist resources to support clinical research. With high-cost state-of-the-art equipment hosted through a Core lab, the costs of installation, main- tenance and on-going support can be shared. The facility is staffed by mass spectrometry specialist sci- entists who can advise researchers on the correct way to address their scientific questions at all stages of the project. They also assess the potential of innovations that could benefit clinical research and find ways to resource and incorporate new tech- nologies. Mass spectrometry is already playing a greater role in diagnos- tics. ‘Over the last decade,’ Andrew pointed out, ‘MS has become more extensively utilised in clinical bio- chemistry, primarily because it is recognised that other biochemical measures – such as immunoassay – have inherent errors and can be variable between manufacturers. This causes offsets between data generated by different hospitals. ‘MS overcomes the non-specificity of antibodies used in immunoassays, generating more accurate results that can be standardised nationally. MS instruments have improved in their sensitivity and robustness, making them more attractive and approach- able to clinical labs. Investment in warranty contracts will enable a lab to operate with less downtime, but are costly.’ In the UK, analysis of testosterone and Vitamin D are now routinely conducted by MS, while the US Endocrine Society has recommend- ed that MS should become used across hospital labs for steroids assays. There are various quality control schemes in the USA, EU and UK to align data between labs with samples being sent to multiple cen- tres and compared. However, MS is still generally only available in regional hospitals and sites of specialist expertise, such as for use in paediatric labs to diagnose inborn errors. ‘MS is complementary to other techniques but, due to the expertise required, it cannot be easily managed by non- specialist scientists and normally does not have as high a through- put as other analytical approaches,’ Andrew added. ‘However, this may be offset by the fact that multiple components can be measured in one run. Making MS more user friendly ‘With time, sample preparation has become more automated and throughput is increasing. Some of www.healthcare-in-europe.com PENTA Medical Panel Computers MLC 8 Series for Critical Care PENTAVisit us at Hall 10, Booth F40ADLINK TECHNOLOGY GmbHTel: +49-991-2909410 -Germany@adlinktech.com -www.adlinktech.comUlrichsberger Strasse 17, 94469 Deggendorf -Medical Class I Certification
2 0 D I G I TA L PAT H O LO G Y Raising the chances of survival for cancer patients Hungary is steadily digitising pathology In 2004 László Fónyad MD PhD o t o h P y t i s r e v i n U s i e w l e m m e S - s c á v o K a l i t t A : Hungary has one of the worst outcomes when it comes to cancer. Early detection and accurate diagnosis could significantly reduce the costs of oncological treatment. Pathology plays a crucial role in diagnoses, but is crippled by severe shortage and fragmentation. Digital pathology could help overcome those dif- ficulties – and two projects underway seem particularly fit to help, László Fónyad, a pathologist from Semmelweis University, Budapest, explained during ECP 2018 held last September in Bilbao, Spain. The distortion of resources for pathol- ogy impacts on efficiency and simul- taneously worsens the quality of and access to healthcare, according to pathologist László Fónyad. ‘We have 76 hospital pathology departments in Hungary and around 200 patholo- gists, who deal with approximately 550,000 cases per year. ‘In terms of pathology service diversity, the situation is frightening,’ he said. ‘Some labs only have a thou- sand cases while others have 30,000. There are numerous small labs with no fulltime pathologist available, or only one –usually a retired patholo- gist who is still working. It’s unjusti- fiable and everybody knows that the result is long turn around times of findings, which can take two to four weeks, a lack of consultations that would be needed in complicated cases, and lack of rapid diagnostic aid during surgeries,’ he said. Individual digital initiatives Digital pathology solutions could potentially improve the situation, Fónyad explained, and there have been a number of initiatives in that sense in Hungary since 1994, with the implementation of an early tele- pathology network connecting vari- ous hospitals and pathology labs, using still images and sharing live images of robotised microscopes. From the mid 2000s, digitisation has spread to other fields of patholo- gy, such as graduate and postgradu- ate histopathology teaching, research and routine diagnostics, thanks to the cooperation between Semmelweis University and a Hungarian spin- off company in digital pathology. ‘For many years, efforts to introduce telepathology on a local, regional and national level have been driven by enthusiastic volunteer patholo- gists and have not been financed by the Hungarian government,’ Fónyad pointed out. Recent developments In 2015 the European Union and the Hungarian government co-financed the Social Renewal Operational Programme and issued a nationwide comprehensive report on pathology services in Hungary, which high- lighted the importance of enhanced laboratory automatisation, workflow management and digitisation as tools to improve quality. In 2016 the Human Resources Development Operational Program, also co-financed by the EU and Hungary, launched an initiative to develop pathology services through- out the country, with a budget of approximately €11 M. The objective is to provide labs with both traditional and high-end equipment – tissue processors, microtomes, strainers, etc. – and equipment of safe lab sample track- ing, such as cassette and slide print- ers, and barcode readers. Another goal is to develop a nationwide dedicated pathology information system (nwPIS), which will connect all the pathology labs and be interfaced with each lab’s own hospital information system (HIS). ‘The nationwide pathology infor- mation system will enable real time data collection of all aspects of pathology workflow and resource management. Synoptic reporting and solutions for automated or semi- automated medical coding and bill- ing are also planned,’ Fónyad said. The system will be integrated into the Electronic Health Care Service System, a recently installed cloud computing service connecting vari- ous HISs throughout the country. Pathologists will be supplied with computers suitable for digital pathol- ogy with ultra-high resolution large- format displays. A nationwide telepathology consultation network Hungary is also working on a nationwide telepathology consulta- tion network, to digitise, store and share slides for intraoperative fresh frozen specimens, second opinion and primary diagnosis. graduated from the Faculty of Medicine at Semmelweis University (SU), in Budapest. Following his pathology residency, he became a faculty member at the first Department of Pathology and Experimental Cancer Research, in SU. There, in 2015, Fónyad received his PhD in digital pathology, an interest that began when a student. He was the first to introduce digital slides into graduate education in Hungary, and has headed numerous pilot projects to adopt digital slides in routine surgical pathology. As a part of his PhD program he received a grant from the Hungarian-American Enterprise Scholarship Fund’s (HAESF) and was a visiting research fellow at the Pathology Imaging and Communication Technology (PICT) Centre, Massachusetts General Hospital, in Boston, USA, where he worked with Yukako Yagi, and John Gilbertson. matters of patient privacy, security of patient data and informed consent, licensure, malpractice and liability or reimbursement,’ he added. The current decentralised model of pathology departments is a chal- lenge to good service, and digitisa- tion could also help overcome this difficulty, he explained. ‘We have a physically fragmented service. We’re The project is primarily being con- ducted by Semmelweiss University, which recently received a €6.72 million grant from the public health program of the Norwegian Financial Mechanism, an organisation that reg- ularly injects money into EU states initiatives. The project also includes the design of a qualification program for histotechnicians, expanding their competence to handle surgical sam- ples that are intended for intraop- erative pathology telediagnostics, a quality assurance system for the digital network and a detailed pro- ject plan for the implementation of the network when resources become available. Discussions about funding the implementation have begun with the Ministry for Innovation and Technology. Ideally, the teleconsulta- tion system should be fully equipped by 2019, but workshops should be held for users and the medico-legal aspect should be clarified before the network launches, Fónyad point- ed out. ‘If necessary, the pathology community should address the issue and counsel the governing bodies on thinking of a reasonable centralisa- tion of the pre-analytical processes into several labs, and to distribute the task. or several tasks. of the ana- lytical phase. This is where digital pathology comes in. ‘If you want to centralise, you end up with enormous amounts of data and physical samples to process. You need to have a dedicated infor- mation system and software to track your samples and trace back any errors. The planned nationwide tele- pathology consultation network ena- bles distribution of diagnostic tasks between pathologists all around the country.’ The consultation network could improve the human resources capac- ity of pathology services, but will not solve the low-cost effectiveness rooted in fragmentation, Fónyad warned. ‘It has to be clear that implement- ing digital pathology could help to overcome some of our difficulties but not all, while it is a prerequisite for lab centralisation.’ ‘Digital pathology is just a tool, not an end,’ he concluded. MR EUROPEAN HOSPITAL Vol 27 Issue 5/18 We listened.We learned.Now we lead.Find out more atekfdiagnostics.comAnalytical performance of POC instruments for HbA1c can be seen to be continually improving. However, there are still some instruments that do not perform to the desired level when different quality targets are applied.Quo-Lab met all criteria.“ ”Lenters-Westra E, English E. Evaluation of Four HbA1c Point-of-Care Devices Using International Quality Targets: Are They Fit for the Purpose? Journal of Diabetes Science and Technology. 2018; 12: 762-770. WSI Web Slide Portal•ForPC, Tablet, Smartphone•For E-learningor consultation•Any browser, no installations Digital PathologySolutionswww.vmscope.com
D I G I TA L PAT H O LO G Y 2 1 ‘It will be worthy and cost effective’ Belgium sets up a DX pathology platform Professor Isabelle Salmon heads the pathology department at Erasmus Hospital, and directs Curepath (Centre Universitaire inter Régional d´Expertise en Anatomie Pathologique Hospitalière). She is also co-director of DIAPath, a transdisciplinary and interfaculty research unit at Faculties of Medicine and Brussels School of Engi neering, alongside Professor Christine Decaestecker. fied) with the financial support from the ‘Fond Yvonne Boël’, a non–profit organisation, to purchase diagnos- tic solutions and scanners, and to secure the operational budget for the project infrastructures. Continued on page 22 As in many other countries, Belgium faces a significant shortage of health profession- als – particularly pathologists to guarantee the diagnostic quality necessary for adequate therapeu- tic choice. A digital pathology platform can be a true ally; the Brussels Erasmus Hospital opted for that solution. Project man- ager Dr Ali Ramadhan shared his experience – the good, the bad and the ugly – at ECP 2018 last month in Spain. Belgium has a dense population –370 inhabitants/km2– and life expectan- cy is around 81.4 year. Chronic dis- ease numbers, such as diabetes, are rising – in 2018 there were 540,000 diabetics, according to countrym- eter.info. Healthcare expense represents 10.2% of GDP and the main issue is staff shortage, which will increase. ‘By 2035, it is estimated that we will have 40% less workforce. With one pathologist per 56,515 citizens, pathologists are a particularly rare species,’ Ramadhan pointed out. In that context, switching to digi- tal pathology is a relief, he added. ‘We are all aware of the ongoing complexity and burst of demands for the pathological diagnosis. We have become aware of what tech- nology could bring to pathology in terms of benefits, and thought that digitisation could solve most of our issues. The truth is, it is. It’s the cure to most of our problems.’ Therefore, Professor Isabelle Salmon, head of the pathology department at Erasmus Hospital, decided to integrate digital technol- ogy into the existing surgical pathol- ogy services for specific uses. ‘The floor wasn’t ready for full digitisa- tion. So, Professor Salmon thought it more beneficial to use digital and the conventional services together and gradually and partially adopt the new technology,’ Ramadhan explained. SecundOS Four years ago, Erasmus Hospital pathologists stepped in that direc- tion, launching into the creation of a digital pathology platform called SecundOS (second opinion simpli- Ali Ramadhan MD graduated from Mosul University School of Medicine, in Iraq in 2004 and did his residency at Jordan University of Science and Technology, King Abdullah University Hospital between 2007-2011. He is board certified (Jordanian and Arabic) in anatomic pathology and joined Nineveh Medical College as a lecturer in pathology. Beside teaching and mentoring pathology residents, since 2012 he has worked as a pathology consultant in Mosul. He became a postdoctoral fellow at Université Libre de Bruxelles ULB, in Belgium. Ramadhan is also project manager of the digital pathology platform (SecundOS) at the pathology department in Erasmus Hospital. www.healthcare-in-europe.com
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