2 M A NAG E M E N T & N E W S Implementing MDR is complex and expensive and holds little reality The new Medical Devices Regulation be happy for the competition to gain access to technical documenta- tion and updates? The legislator has devised something knowing that it is not practicable, which means manufacturers will have to deliver clinical studies to obtain regulatory certification. MDR ignores the user safety problem Manegold criticises the MDR for not picking up real problems. Most incident reports relate to user errors – unlikely to stop even with the new regulation. Take ten ventilators – no two of them will be exactly the same. Unlike the cars that can work in the same way globally, medical devices do not have the same level of assurance. ‘The new regulation now proposes licensing procedures similar to those in the pharmaceuti- cals industry, but this will not lead to more user safety,’ Manegold is certain. The problem with the noti- fied bodies A further problem is that the MDR 2017 has not only increased require- ments for manufacturers but also for the regulatory authorities. The MDR also has applied to the regulatory authorities and notified bodies since 26th November 2017. It contains a re-accreditation of all notified bodies with joint assessments for initial designation, extensions and expansions of the scope, and this is likely to take around 18 months. Therefore, manufacturers will only know in 2019 if the authority previ- ously responsible for them and their products will continue to be so. price. Manegold estimates that ‘the healthcare system will be put under additional financial strain after the end of the transition period; these additional costs will run to around 10-15% for medical devices, depend- ent on risk category and quantity.’ Medical disposables will be less affected than, say, a diagnosis sys- tem only used 100 times a year. Documentation via litera- ture alone is increasingly hard The situation is aggravated because the fourth revision of the MEDDEV 2.7.1. has been tightened. It stipu- lates much more intensive work and redefines equivalence criteria. If there is no system on sale that is 100% equivalent for the intended use, settings and diagnostic pos- sibilities then documentation via literature only is not possible. ‘You can then only compare apples to apples. In the past, the interpreta- tion of this guideline was a little more practical. For instance, several devices could be compared, but in future manufacturers can only com- pare their products with devices they already have on the market – because what manufacturer would The heavy burden: By 2020 medical devices manufacturers must document the clinical effectiveness of their devices more extensively. MDR presents a fundamental impact on innovation and price calculation for medical devices Report: Brigitte Dinkloh Since the faulty PIP breast implants scandal in France (March 2010), there have been frequent calls for tighter licensing regulations for medical devices within the European Union. The new Medical Devices Regulation (MDR) took effect on 25th May 2017. Following a three- year transition period, from 26th May 2020 this will become manda- tory in all EU member states. The new regulation is creating big problems for regulatory authori- ties and particularly for small and medium size manufacturers of medi- cal products. Therefore, engineer Christoph R. Manegold, Partner at AC Controls in Germany’s Lower Rhine area, and an initiator of the federal network MDR Competence*, is calling for greater common sense in the implementation of this new regulation, and particularly for long- er transition periods to master the challenge. Safe and also effective ‘Small and medium size companies are naturally more nervous than global players, which have had their relevant departments preparing for this for a while. For small and medium size businesses the MDR is difficult for two reasons. Licensing requirements for new products will be significantly increased as documenting the clinical effective- ness of products will become more complex,’ the chartered engineer explains. Previously, the main issue around the licensing of medical devices was patient safety. There were many norms so that patients, users and third parties were not exposed to any harm. The question as to wheth- er a product works as described was clearly given lower priority, depend- ing on the level of risk involved. Where previously it was possible to cover the proof of benefit with sim- e g a m I m a r g n I y b d e s n e c i l e g a m I For small and medium size businesses the MDR is especially hard to implement ulations or written documentation, clinical studies are now required. ‘What we used to refer to as risk management,’ Manegold explains, ‘initially only relating to the device, then as risk management for the product life cycle (Norm DIN EN ISO 14971), and what mainly related to technical safety, will now have to be extended with studies to cover clinical data collection on product effectivity, and not only when the product first becomes licensed but continuously.’ However, small-and medium sized companies, which have an 80% market share in Germany, are not prepared for this. Studies also required for existing products The second hurdle manufacturers face is that this will also apply to older devices that have proved their value already. ‘This is the biggest problem, and in my view an unjusti- fied imposition,’ Manegold laments. ‘Clinical data may have to be sup- plied even for devices which have never been involved in any inci- dents. And if the manufacturers can- not do this according to MEDDEV 2.7.1 via documentation only, which is what many will try to do, then in a worst case scenario the legislator is forcing them to carry out studies for a device which has been around for several decades.’ Manufacturers don’t have the staff for this and no experience, and the authorities do not have the resources to scrutinise and moni- tor all these studies simultaneously, not even to mention the additional costs involved which have not really been mentioned so far. These will have to be added to the sales In order to develop a regulatory strategy for the implementation of the MDR a coherent sequence of activities can be critical e t t i o l e D f o y s e t r u o C Documenting the clinical effectiveness of products will become more complex k c o t s r e t t u h S / 6 0 3 t a J : e c r u o S Progressing towards optical biopsy Continued from page 1 patients, the accuracy rate of the diagnoses was 90 percent. (Figure 4) A multi-centre pre-clinical study is currently being designed to ana- lyse several hundred cases. By increasing the number of patients, Bocklitz hopes to increase accuracy to over 95 percent. Moreover, in this upcoming study the team will perform the measurement in a lab right next to the OT, to be able to integrate optical biopsy into the sur- gery workflow. the prelimi- Bocklitz considers nary results of optical biopsy to be very promising. The data that were generated optically contain a lot of information that will improve patient care. ‘Initially, there will be a combination of different measuring methods. Each method provides dif- ferent data, which we will be able to pool. However, this scenario requires the development of suitable and high-performing algorithms for assessment, because we have cre- ated a multidimensional data space that needs to be analysed.’ In the long run, Bocklitz predicts, ‘optical biopsy will surpass conventional biopsy in terms of accuracy and information value.’ Using image analysis algorithms, multi-modal tissue images (left) can be translated into predictive data (centre, left). In the images above, green areas show healthy epithelial tissue, red areas show cancerous tissue. Histopathological diagnosis (centre right) is based on HE stains (right). When multi-modal imaging is integrated into fibre optic probes, in-vivo tissue diagnostics becomes reality. (Copyright: Leibniz-IPHT) EUROPEAN HOSPITAL Vol 27 Issue 1/18

4 M A NAG E M E N T & N E W S Shake-up needs input from students’ and lateral thinkers’ High-tech event aims to push progress Various emergency care repre- sentatives will gather at Xpomet to discuss related issues, among them members of the German Society for Interdisciplinary Emergency and Acute Medicine (DGINA) on the opening day. In addition, undoubted- ly the focus will be on the emergency care specialist. ‘In all other European countries it exists, except for us – we lag behind progress in emergency medicine,’ Schöpke asserts. Industry suppliers see a need for action in this area and offer Xpomet solutions that contribute to increas- ing efficiency with workflow sup- port. In particular, it is a matter of guaranteeing complete data, which in turn makes ‘reliable analyses’ pos- sible. On the one hand, this is intend- ed to relieve the physician’s work- load and, on the other, to provide IT support in his or her judgment. ‘Emergency care in Germany must be centralised and professionalised!’ the Xpomet organisers demand. In addition to cross-professional infor- mation on continuing education and training, and regulations for the allo- cation of resources in line with demand, require the digitisation of supply processes. This question is also addressed within the ‘OP of the future’ show- case, which will show how computer models are used to carry out thera- py. At Xpomet, a virtual operating theatre with ‘phantom patient’, will demonstrate how medical technol- ogy based on computer models rec- ognises a surgeon’s current surgical stage and calculates the next step in advance. Patient demands will shape the future During the event visitors are to be offered ‘mixed reality glasses’ that have been used in surgical proce- dures recently, when two novelneu- In the run-up to Xpomet, deficits in German emergency medicine were outlined Following three-years as head physician in the emergency unit at Berlin’s Vivantes Klinikum am Urban, in 2015 Dr Timo Schöpke MD was appointed for his present role as Director of the Emergency Centre of the Barnim Clinic in Berlin. rosurgical interventions were per- formed in Germany for the first time in 2017. Time and again, a central future medicine topic has been the elec- tronic patient record. The conven- tion aims encourage this by showing what a smooth data flow could be. In an animated video, the network- ing of companies and their interfaces will be illustrated based on three patient histories. During a related think tank, the question of what the prerequisites are that will make Report: Eva Britsch In the German healthcare system, inno- vations are difficult – Xpomet boss Ulrich Pieper is certain of this. Not because the system is different, but because the point of view is wrong. ‘The system assesses innovations according to how much money they save, and not according to whether they achieve healing,’ the industrial engineer explains. Precisely the for this reason, he adds, three-day Convention for Innovation and High-Tech in Medicine, to be held in Leipzig from 21 March, is a great attraction. The organiser is confident – the next three years have already been sol- idly counter-financed. The aim of the event is to look beyond the horizon and motivate the system players to dare to take more risks: ‘Whoever is willing to take risks will take a new approach, open up and dare to venture into unknown realms, such as through collabora- tion outside the sector.’ In terms of medical technology, the congress will present some sur- prising findings, which aim to pro- mote interoperability and better net- working of processes, as well as to create greater efficiency for patients. German emergency medicine needs to become professionalised. In the run-up to Xpomet, Dr Timo Schöpke, Director of the Emergency Centre of the Barnim Clinic, describes deficits in German emergency medi- cine. The processes are too compli- cated; currently there are endless non-necessities, for example in case reports that have to be transcribed up to six times due to a lack of soft- ware interoperability. In this, impor- tant proficiencies are lost. Industrial engineer Ulrich Pieper is the Xpomet Convention’s Chairman. and the founder and CEO of Business Management GmbH. Since graduating his work has focused healthcare sector for more than twenty years. networking interfaces a reality and not simply an imagined Utopia (23 March). Obsolete equipment, paper stacks, fax machines – Xpomet diagnoses an innovation gap in many medi- cal practices. The medical practice of the future would save doctors and employees time. Visitors will be shown how the initiators envisage an ideal future practice, starting with a simple online appointment. Why is it not so easy to install innovations in the German health- care system, when we all handle apps, for example, in many different areas of life? Pieper sees German politicians as too overstretched to make good decisions. However, he assumes that the healthcare system will change because patients will demand inno- vations. Changing communication between doctor and younger generation patients would help them to ask more confidently for innovations and different treatment options. ‘At Xpomet we want a bottom-up process,’ Pieper explains. In concrete terms, this means that the organisers do not rely on top decision-makers and established names, as in other trade fairs, but rather on students, patients and lateral thinkers who will help shape the future in the health- care sector. MT-CONNECT exhibition and MedTech Summit Meeting up with Europe’s med- tech and health experts The international MedTech Summit and MT-CONNECT, an internation- al medical technology exhibition (Nuremberg, 11-12 April 2018) is a key event in Europe. For many years, developments in digitisation and personalised health have been among core elements of the con- gress, the organiser points out. Around 1,900 visitors travelled to Nuremberg for the previous MedTech Summit Congress and MT-CONNECT, which provided 96 specialist presentations in the con- The Matchmaking Event will be included again in 2018 to provide an opportunity for participants to network their ideas and needs e s s e M g r e b n r ü N : e c r u o S gress and exhibition, which had 189 exhibitors from 11 countries. Medical practitioners and other healtcare and industry experts will benefit from the networking opportunities at this year’s event, too, according to Dr Matthias Schier, Managing Director of MedTech Pharma e.V. Connected Health, Neurostimu- lation, Personalised Medical Technology, Drug Delivery as well as Implant Technologies are just some of the headliners at the Summit. Besides technological contents, the congress increasingly focuses on IP Management, Supplier Manufacturer Relations, reimbursement and busi- ness models, aiming to build a bridge between development and production on the one hand and application in research and clinics on the other. The speakers are from renowned companies such as Siemens, Philips, Aesculap, Medtronic und TÜV SÜD Product Service GmbH, and univer- sities and research institutes such as Munich’s Technical University in Germany, University Zürich in e s s e M g r e b n r ü N : e c r u o S The previous MedTech Summit and MT-CONNECT included ninety-six specialist presentations in the congress and exhibition forum Switzerland, and several Fraunhofer Institutes, plus clinical application specialists. The Partnering event The parallel ‘Partnering’ event offers a strong chance to network. In 30-minute cycles, this popular for- mat brings together exhibitors, con- gress visitors and others. A software program is available to enable participants to arrange appointments quickly. Details: www.medtech-summit.com EUROPEAN HOSPITAL Vol 27 Issue 1/18

Although robotics is now an established arm of medical technology – with the Da Vinci surgical system a trailblazer – many basic issues need to be resolved before nurse Robot can report for the morning shift in a ward. Surprisingly, among the major problems is the fact that a robot becomes a bit weak at the knees quite easily, explained Mathias Hofmann, researcher at the Robotics Research Institute at Technical University Dortmund, Germany, during an IVAM Microtechnology Network conference. Since centre-forward Robot and nurse Robot are closely related, EH spoke with the developer of soccer robots about current progress ‘Camera settings are another head- ache: when light incidence changes, the perception of the robot changes. In well-lit rooms this is not so much of a problem, but a service robot also has to function when the light is dimmed or in the dark.’ is being tested in specific therapies aimed at addiction patients or autistic people. Having said that, one thing remains clear: robots will never be able to replace clinical staff. ‘ Then why waste energy on develop- ing service robots? ‘The major advantage of service robots is that they relieve staff work- load. With their very specific skills, What problems are you currently trying to tackle? ‘We are working on several issues. As a football player, and as a robot, you have to be able to recognise your sur- roundings; you have to orient your- self; communicate with your team mates, make split-second decisions and move your body accordingly. For our research we use NAO, a two-legged humanoid robot that is 58 Beyond technical challenges, are there others? ‘Indeed, the legal and ethical obsta- cles are high. Should robots be allowed at all to act autonomously and take on responsibilities? Take the example above – robots that provide medical information. What about pri- vacy and data security issues when a robot performs administrative tasks? Interview: Lena Petzold ‘Service robots in Germany are still quite rare. The robotics industry is new and very few companies offer products suitable for daily use – primarily because a number of basic problems remain to be solved,’ explained robot- ics expert Mathias Hofmann, when asked about their role in healthcare. ‘The developers must go back to the drawing board and deal with func- tions such as language recognition and context awareness. If they don’t work properly in a robust and stable system, there will be no marketable products. Service robots, unlike pre- cision systems in the OR, have to perform tasks autonomously – they are much more than a surgeon’s extended arm.’ Where can service robots be used? ‘They can be used in many areas: obviously, they can monitor and help patients, but they also can bridge waiting times and take over adminis- trative tasks. Theoretically, a robot can perform any task with a low degree of autonomy. In the hospital or the waiting room a robot can entertain patients by playing games with them. Robots can “man” the reception desk – collect data or answer routine ques- tions. ‘In the future, robots will also be used to convey information on procedures, or to help children over- come their fear of surgical inter- vention or certain therapies. Robots might as well monitor the hospi- tal for emergencies and alert the staff. Furthermore, the use of robots 6 I T & T E L E M E D I C I N E Soon service robots will find their healthcare niche Robots: Weak knees and hard facts performance is still inadequate. On a smooth surface, NAO can walk without a problem, but what happens when there’s carpet on the floor or, even worse, steps? Mathias Hofmann is a researcher at the Robotics Research Institute at Dortmund Technical University in Germany. Following training as an informatics specialist at Deutsche Telekom AG in Bonn, Germany, in 2005, while also working, he began an informatics BA programme with a focus on business informatics in Darmstadt, Germany. In 2008, he enrolled in an MA programme in informatics with a focus on Intelligent Systems at Dortmund Technical University, while working at the Department of Geo-information Systems at Wupperverband. In 2011, he gained his Master’s degree and was offered a position at the Robotics Research Institute. In 2014, he held a six-month research fellowship at the University of Miami in the USA. robots are well suited to perform repetitive tasks. In 2014, “Pepper” was introduced, a robot with humanoid features, which, to a certain degree can interpret human emotions and respond appropriately. It is available 24/7 and never under pressure.’ Which technical challenges need to be overcome? ‘On the technical side, a number of things remain to be done. Advanced recognition and language understand- ing is a highly complex process. Language, with its ambivalences and double meanings, is extremely dif- ficult to process – as most people would confirm who have ever used an online translation sys- tem. Just like a human being, a robot needs to hear and record language, convert it phonetically into words and respond to it on the cognitive level. ‘For a machine to perform those semantic pro- cesses and respond to nuances is much more difficult than for human. Context awareness is another issue: the ability to recognise the environment and adjust the behaviour accordingly. Last but not least, the hardware has to be par- ticularly sturdy – as we can see in soccer robotics every day.’ a Humanoid features are designed to make it easier for humans to interact with these machines NAO robots are equipped with cameras, microphones, a gyroscope and acceleration sensors. cm tall and equipped with two cam- eras, four microphones and speak- ers as well as several sensors – for example four ultrasound and eight pressure sensors. Just like its human counterpart a robot needs a sense of equilibrium, tactile sense and muscle sense. Under stress the robot’s joints run hot and it literally gets weak at the knees. Consequently, NAO needs a system that prevents it from over- heating, so to speak. This is one of the crucial challeng- es: developing robust systems. In a lab – or on our in-house soccer pitch – the robots tend to function pretty nicely. But, take them out of the lab and things get tricky: the transfer Source: Softbank Robotics NAO camera settings determine images the robot can record and process What happens in case of an accident? Who is liable – the manufacturer or the operator of the robot? All of these questions are highly complex and none of them has been answered satisfactorily. ‘We are confronted with these issues now with autonomous cars – they are nothing but service robots. Hope for telemedical ward rounds There are daily tele-intensive ward rounds, handovers and case confer- ences. ‘Only around 300 specialists in infectious diseases work in hospi- tals nationwide,’ Marx points out; not enough to provide comprehen- sive, personal care. TELnet@NRW is to bridge this gap ‘because early and joint diagnosis is better and ensures adherence to guidelines’. of the Clinic Professor Alexander Zarbock, for Director Anaesthesiology, Surgical Intensive Care Medicine and Pain Therapy at Muenster University Hospital is par- ticularly pleased about cooperation between the hospitals: ‘By making scientific expertise available to col- Continued from page 5 leagues at any time we support the best possible, close-to-home patient care.’ Next to Aachen and Muenster university hospitals, a further 17 hospitals within the Aachen and Muenster regions are also in the con- sortium, along with the Techniker Krankenkasse (Technical Health Insurance) and the medical networks Gesundheitsnetz Köln-Süd (GKS), and MuM – Medizin und Mehr. The consortium is supported by partnerships with the hospital asso- ciation North Rhine-Westphalia, the Medical Associations North-Rhine and Westphalia-Lippe as well as all statutory medical insurers in North Rhine-Westphalia. Short, quick movements, as necessary on a football pitch, put strain on robot joints The use of service robots is moreover a cost issue. It won’t suffice to invest in the device; a suitable infrastructure has to be developed at the same time. ‘A robot needs to move and orien- tate itself. Even a human being has difficulties finding his or her way in a hospital where all the hallways look the same. A robot needs unambigu- ous machine-readable signs, such as beacons or QR codes. This signage has to be developed and implement- ed. ‘A lot remains to be done but I am confident that we will develop suit- able solutions. Service robots, I am sure, will soon find their niche in healthcare.’ The University of Bielefeld and the Centre provide scientific guidance for Telematics and Telemedicine GmbH (ZTG) in Bochum. The evalu- ation phases will run to three years. The data collection method via cluster randomisation and a stepped wedge design allows the project team to compare each hospital with itself and other hospitals over time. Together with continuous data col- lection this facilitates calculation of the causalities between changes in therapy and diagnosis and the tele- medical intervention. After this evaluation a decision will be taken as to whether telemedical ward rounds can become part of standard medical care. EUROPEAN HOSPITAL Vol 27 Issue 1/18

8 E H @ E C R Big Data in cohort studies analysis will boost disease prediction Population imaging Population imaging is key to determining disease prediction and risk prevention, and Big Data will be key to extracting information and drawing analysis from imaging results, experts high- lighted during the annual meeting of the European Society of Magnetic Resonance in Medicine and Biology (ESMRMB) held in Barcelona in October. in questionnaires. In 2019, partici- pants will be re-invited for a second examination five years after baseline recruitment. The participants will undergo com- plex whole-body imaging sequences – MRA, T-1 mapping of the myocar- dium, and high-resolution imaging of the neurocranium, torso, hip, and spine – to provide a comprehen- sive image of the human body and help answer longstanding questions. Results will go along developments in Big Data, radiology, IT and radi- omics, to achieve comprehensive characterisation of disease-pheno- types using advanced image-analysis, Bamberg forecasted. ‘All this detailed information will help us characterise disease and early disease states much better. For instance, we can cluster patients with lung cancer by apply- ing advanced post-processing meth- ods with similar radiomic expression patterns. Results obtained with this type of imaging analysis are much more relevant and precise for pre- dicting clinical outcome and genetic tumour type,’ he pointed out. Two major challenges to the GNC study remain incidental findings and the internal variability of the MRI studies – although the latter has been addressed by implementing similar MR technology with identical proto- cols, he explained. One solution may be related to deep learning, and the field is cur- rently growing exponentially. For instance, convolutional neural net- work (CNN) has already helped develop and validate a deep learning algorithm to detect diabetic retin- opathy in retinal fundus photographs (JAMA, 2017, Gutshan et al.). ‘Prevention of disease is increas- ingly relevant and there’s a high potential of subclinical disease assessment. MRI is an ideal tool for whole-body phenomapping and radi- omics is an ideal target for big data approaches,’ he concluded. Paul Matthews, from Imperial College London, presented the UK Biobank prospective longitudi- nal study, which includes 500,000 women and men aged 40-69 years at the time of the baseline assessment in 2006-2010. The study, which is supported by independent academ- ics, includes extensive baseline ques- tions and measurements, follows up a wide range of disease outcomes by linking to health record systems and direct contact, and will offer adjudication of health outcomes to confirm or refute and to sub classify phenotype. ‘Sufficiently large numbers of people will develop many different Examples of MR images acquired as part of the cardiovascular protocol: A–C: Long-axis MR images obtained with the cine steady-state free precession sequence D: Short-axis MR image obtained with cine steady-state free procession sequence E: MR image obtained with T1 mapping (modified look-locker inversion recovery) F: Native thoracic MR angiogram Source: Bamberg F, Kauczor H-U, Weckbach S, et al. Whole-body MR imaging in the German national cohort: Rationale, design, and technical background. Radiology 2015;277:206-220. Interest in cohort studies has been increasing over the years and popu- lation imaging is on the verge of becoming a major medical topic, according to radiologist Professor Fabian Bamberg from Tübingen University. ‘Most of our services are based on delivering care to people who are already sick, but a more meaningful approach would be to identify sub- jects who are at risk for early disease or death at a very early point in time, to modify lifestyle, medication, and just prevent the future development of disease. Ideally, we’d assess genet- ic determinants right at birth and act accordingly,’ Bamberg suggests. For 15 years the professor has been involved in improving and develop- ing imaging tools. While knowing the determinants – genetic, physiologi- cal and environmental information – and outcomes, cancer, dementia, etc., is a key, the issue remains the determination of what occurs in the meantime. ‘We don’t really know what’s in between. I’m convinced that, between determinants and out- come, there is something else to disease, and imaging is a powerful mean to assess and quantify it, and come out with a more individualised risk assessment over time – and this is due to new achievements in MRI.’ MRI can provide new information, but researchers need large data to derive these parameters. Cohort stud- ies can help prove that those imaging biomarkers are really predictive for the occurrence of disease over time. Famous studies have already stressed the power of population imaging. The Framingham heart study, which observed 3 generations between 1948 and 2017 to predict the occurrence of cardiovascular dis- ease, has helped identify various risk factors, such as high blood pres- sure, increased cholesterol, diabetes, smoking and family history, by nota- bly using imaging. More recently, the Rotterdam study, which used brain MRI, has revealed that the presence of silent brain infarcts is associated with cognitive decline and increased risk of dementia over time. The next big thing will be the German National Cohort MRI study, Bamberg said, as it will provide com- prehensive characterisation and phe- notyping in more than 30,000 partici- pants with 3-T whole-body MRI. ‘It’s a unique opportunity to substantially impact on imaging-based risk strati- fication leading to personalised and precision medicine,’ he explained. The study is part of a national, government-funded effort: the GNC study (in German: NAKO), which includes 200,000 participants recruit- ed through 18 centres (and 8 clus- ters). All participants are invited to take part in physical and medical examinations, collection of biomate- rials, personal interviews, and to fill Brain regions showing age-related atrophy from the initial 5,000 individuals imaged for UK Biobank. To generate this figure, T-1 structural brain MRI images from each of the participants were represented in a common, standard brain space. Age related differences in brain volume across the population were assessed. Those areas showing the greatest change with age are illustrated with a dark brown wash. (Image courtesy of Dr Hideaki Suzuki, Imperial College London). Professor Fabian Bamberg MPH is currently Associate Chair of Radiology at the Department of Diagnostic and Interventional Radiology at the University of Tübingen, Germany. He received his medical degree from the University of Witten-Herdecke, Germany and gained a Masters in Public Health from Harvard School of Public Health in 2007. After serving as a faculty member in the Cardiac MR PET CT Program at Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, he joined the Department of Radiology in Munich, Germany, in 2008, where he completed Residency and Fellowship at the Ludwig-Maximilians University and subsequently directed the MRI program as an attending physician. ers and longer-term outcomes. We need to understand disease from the start, decades before they appear. Lifestyle and environment interact with underlying genetic susceptibili- ties to influence the risks of brain disease. We need to understand how these factors – the exposome* – influ- ence the brain through life,’ Matthews explained. ‘We can’t change your genes, but we can change the envi- ronment; people are motivated to do so if we define the risks.’ MR * Exposome: a potential vehicle the better to incorporate environmental components into the study of disease and health. Paul Matthews OBE, DPhil, FRCP, FMedSci is the Edmond and Lily Safra Professor of Translational Neuroscience and Therapeutics, and Head of the Division of Brain Sciences at Imperial College London, and Associate Director of the UK Dementia Research Institute. He is an NIHR Senior Investigator and lead researcher for the Im perial College Healthcare Trust Bio- medical Research Centre Neuroscience Theme. He is also a Fellow by Special Election of St. Edmund Hall, Oxford, UK, and holds other honorary academic appointments in Oxford, Maastricht, McGill and the LKC Medical School of Nanyang Technological University, Singapore. conditions to assess causes reliably. Having 500,000 volunteers in the study will provide enough power for future cohort designs,’ Matthews said. He also highlighted the role of popu- lation imaging in defining risk fac- tors, biomarkers of presymptomatic disease and contributory mechanisms for important and common disease. ‘Cohort studies create opportuni- ties to investigate gene-environment associations with phenotypic mark- MR images obtained as part of the neurologic MR imaging protocol A: T1-weighted 3-D magnetisation-prepared rapid acquisition gradient-echo sequence B: Two-dimensional fluid-attenuated inversion recovery sequence C: 2-D gradient-recalled-echo echo-planar imaging blood oxygen level–dependent sequence (for resting-state functional MR imaging) Source: Bamberg F, Kauczor H-U, Weckbach S, et al. Whole-body MR imaging in the German national cohort: Rationale, design, and technical background. Radiology 2015;277:206-220. Hopes for AD prediction remain Continued from page 7 Meeting the challenges of harmonisation Genome-wide association stud- ies (GWAS) may contribute to find- ing associations between genetic alterations and particular imaging biomarkers. However, there are many chal- lenges ahead. ‘You need extremely large populations and to pull the data from different cohort studies possibly including 20-50,000 sub- jects, to find significant genotypic alterations related to certain imag- ing phenotypes. You also need a high level of harmonisation in terms of image acquisition, sequencing and data processing,’ he added. The Rotterdam Study collaborates in the CHARGE consortium, includ- ing large population cohorts in the Netherlands, Iceland and the USA. A network of researchers in epi- demiology genetics and imaging that cooperates to better understand neurodegenerative brain disease. For instance, they found a mutation on chromosome 17, which is associ- ated with WML. They are not sure how to interpret this information yet. ‘Is this genetically determined? Is the presence of such mutations associated with earlier dementia onset? We don’t know,’ Krestin said. GWAS are only showing asso- ciations with and increased risks of developing certain diseases, but not necessarily the cause of disease, he pointed out. ‘The utility of these studies is unclear. We find out some- thing about pathophysiology, but not really the cause of this associa- tion yet.’ EUROPEAN HOSPITAL Vol 27 Issue 1/18

1 0 E H @ E C R Emergency radiology advances Despite shortages and low recognition Emergency radiology is no longer a babbling field; professionalisa- tion will bring more recognition to this young subspecialty, according to Elizabeth Dick, a London-based consultant, who will coordinate part of the new European Diploma in Emergency Radiology (EDER), the European Society of Radiology’s new tool. During the International Day of Radiology (IDoR) in November 2017, which focused on emergency radiology, Mélisande Rouger inter- viewed the radiologist, who spoke of her daily practice and why she loves her job. In London, the Imperial National Health Service (NHS) Trust is a major trauma centre, covering a radius of over 12 miles (20km). ‘In the capital this means a lot of people. We also treat abdominal and chest pain, and paediatric emergencies, explained Dr Elizabeth Dick, who estimates her radiology department carries around 20-30 emergency CT scans a day. A consultant for the past 15 years, she has worked in emergency radiology for as long as she can remember. ‘I have grown with the specialty, which wasn’t established until the late 1990s,’ she said. What’s so special about emergen- cy radiology? ‘I like the fact that we can make a difference and we are really crucial to the patient pathway. Everybody wants to know what’s on CT, so we really influence patient manage- ment. ‘I enjoy the team approach. We are 15 people in the room, all trying to figure out together how to best treat the patient. Being in emer- gency radiology myself, I know it’s k c o t s r e t t u h S / s u k r i B r o t k i V : e c r u o S Emergency radiology is a young specialty; as such, this field needs more recognition according to radiology consultant Elizabeth Dick really important in a person’s life. No one wants to be there, but if we can make a difference, it’s really inspiring.’ How do you cope with staff short- age? ‘This is not just a local problem; it’s a worldwide issue. We prioritise our patients and try to train our juniors very well. We encourage them to ask questions and support them as much as we can. In the end we try to provide a full seven-day ser- vice, but we’re not able to do that. We provide a full five-day service with emergency cover out of hours, which I find frustrating. ‘The hospital is open 24/7 and you will always get good care. But we should have at least daytime consultant lists every day and we’re far from that. We have resident jun- iors with back up from consultants who come into the hospital and are always at the end of a phone.’ Is teleradiology helpful in this context? ‘Like every other hospital in the UK, we use teleradiology for all kinds of out-patient imaging. If we can sort those out, that gives us more time for emergency work. We don’t use teleradiology at night, but other hospitals do. It’s obviously a very good short-term solution. However, it doesn’t really solve the problem of not having enough radiologists. ‘I know that a lot of people work- ing in teleradiology work in the NHS, so they are working less directly in their hospital. Additionally, however great Skype or the phone is, it’s not quite the same as working together with someone you’ve known for a while. You lose a lot in translation.’ What other challenges exist for emergency radiologists? ‘ER is a young specialty and needs more recognition as such. People often think within their own special- ty and that’s it. In ER, the skills you need are very broad. Pretty much everyone I know has other interests and that’s good because you can bring in different skills. You end up covering the whole body between the staff.’ Is cooperation good with other emergency specialists? ‘It’s one of the things I really love about emergency medicine in gener- al: teamwork is amazing. Emergency medicine is very young too; we are very much on the same line. Emergency physicians are fantastic to work with; they really want to communicate. That’s a real attrac- tion: who wants to work with grumpy colleagues?’ Will Brexit impact on ER? ‘Personally I believe Brexit will be a disaster for UK Healthcare. It will have a big impact on our work because about 20% of our health- care staff comes from Europe. The uncertainty is already driving peo- ple home. Instead of thinking of building a future here, people head back. For everyone, their income dropped by 20% when the pound devalued. The impact of the loss of European funding for research and development has already been felt so Brexit is already impacting on healthcare in a variety of ways.’ Are there European trends in emergency radiology? ‘More radiology studies are being done. When I started as a radi- ologist, if people came with an appendicitis they’d go straight to the operating theatre. Now they undergo CT, unless the clinicians Dr Elizabeth Dick is consultant radiologist and lead for emergency radiology at the Imperial College NHS Trust in London, UK. She is president of the British Society of Emergency Radiology and president elect of the European Society of Emergency Radiology (ESER). are very certain. Imaging defi- nitely increases diagnostic con- fidence in clinicians before they come to the theatre. Postoperative outcomes are also much better. ‘Emergency radiology is not a sub- specialty everywhere in Europe. In the UK it is a less established and probably the youngest radiology subspecialty. ‘Another big trend is profession- alisation within radiology. The ESR has produced diplomas in chest, neuro and now emergency radiol- ogy.’ What is the European Diploma in Emergency Radiology? ‘This diploma began in January. It consists of 10 webinars and 10 workshops and one exam, so the first candidates will graduate in 2019. ‘The idea of having a Europe-wide diploma is great, because it means that wherever you go in the world you’ll find someone with the same experience as in your country. This also brings international recognition of their skills to radiologists, and improves their career perspectives abroad.’ At the scene: point-of-care ultrasound Size and mobility is saving time and lives Time is of the essence in an emer- gency, and can be the difference between life and death. Ambulance crews on the front line must decide rapidly whether or not a patient is suffering from a life-threatening condition requiring specialist treat- ment, and point-of-care ultrasound can provide vital guidance. SonoSite is at ECR 2018 Hall X5, Stand 503 Geert-Jan Deddens, an emergency care nurse practitioner with the Rotterdam Ambulance Service in the Netherlands, describes the ben- efits of using hand-carried ultra- sound systems to assess suspected abdominal aortic aneurysms, allow- ing patients to be taken to the most appropriate hospital immedi- ately, avoiding delays due to onward transfer to another medical facility. ‘I joined the Rotterdam Ambulance Service in 2006 as an ambulance nurse, going on to train as a nurse practitioner in emergency care five years later. We look after a popu- lation in the region of 1.2 million people, covering a large area in and around the city. As a nurse practi- tioner, I attend emergency call-outs to provide additional support to the ambulance crews when needed, for Geert-Jan Deddens scanning a patient via point-of-care ultrasound example, in cases of cardiac arrest. ‘A couple of years ago, a vascu- lar surgeon at one of Rotterdam’s hospitals contacted the ambulance service to discuss the potential ben- efits of using point-of-care ultra- sound to identify and assess patients with an abdominal aortic aneu- rysm (AAA) in a pre-hospital set- ting. Without ultrasound, we might suspect the patient has an aneu- rysm, but we can’t be sure. This means that the hospital has to be prepared to carry out emergency surgery, with an operating thea- tre and emergency room staff on standby to treat this life-threatening condition, when the patient may have a completely different abdomi- nal pathology that is less serious.’ More accurate assessments ‘We realised that introducing ultra- sound into pre-hospital care would allow us to scan the aorta in the ambulance and make a more accu- rate assessment of whether or not the patient has an aneurysm, and also to estimate its size. Once we know that, we can quickly transfer the patient to the most appropriate hospital, and provide more exact information to the surgeon much earlier. ‘This means that the hospital is better prepared, and does not tie up resources unnecessarily. It also elim- inates potentially life-threatening delays caused by avoidable transfers between hospitals, as the patient is taken to the correct medical facility first time. ‘At the end of 2015, we began a pilot study – Pre-hospital Assessment Rotterdam Aortic Aneurysm (PARA2) – to evaluate pre-hospital assess- ment of the abdominal aorta using point-of-care ultrasound (POCUS). ‘Fujifilm SonoSite provided two hand-carried ultrasound systems and, together with an emergency physician with extensive POCUS experience, trained three ambulance nurses and two nurse practition- ers to scan the abdominal aorta. It quickly became part of our daily routine to scan patients’ aortas, gain- ing as much practice as possible. ‘As nurse practitioners, we also received more advanced training in point-of-care ultrasound, including Extended Focused Assessment with Sonography for Trauma (eFAST), to allow additional conditions to be triaged. 950 abdominal scans in the first 16 months During the pilot study we scanned as many patients as possible, evalu- ating how easy it was to perform the procedure and the length of time it took to obtain a good view of the aorta. We carried out 950 abdominal scans during the first 16 months, finding 14 patients with an AAA where the aorta measured more than 3 cm. ‘Of these, four patients were immediately directed to a vascular surgery team for urgent treatment, potentially saving their lives. At the same time, we were able to iden- tify other life-threatening conditions pre-hospital, for example, differen- tiating between wet and dry lung problems, looking for blood in the abdomen following an accident, as well as using ultrasound during a cardiac arrest. ‘This all helps to ensure the patient is directed to the right facil- ity first time, whether that’s a spe- cialist trauma or cardiac centre, ensuring that they receive the most appropriate treatment at the earliest possible opportunity. For patients with an acute AAA, this may well be a life saver.’ EUROPEAN HOSPITAL Vol 27 Issue 1/18

1 2 E H @ E C R Seeking a leaky blood-brain bar New MRI technique visualises seepage that might cause AD Report: Madeleine van de Wouw ‘With our new MRI method, we can finally visualise tiny leaks in the blood-brain barrier. They shed light on the vascular contribu- tion to dementia and may indicate Alzheimer’s disease. However, the MRI scan is only a tool to diagnose cerebrovascular damage. We have not yet found a cure for Alzheimer’s,’ confirms Walter H Backes, medical physicist and professor at Maastricht University Medical Centre. The blood-brain barrier (BBB) separates blood from the brain tis- sue and protects the brain by allow- ing certain substances to pass while keeping others out. Backes, with his interdisciplinary team of Maastricht UMC and Leiden UMC, are hot on the tracks of Alzheimer’s disease (AD) as they aim to visualise small vessel leakage in BBB. Contrast-enhanced MRI While conventional MRI visualises neither small vessels nor markers or leakage, the dynamic scan trac- es even extremely low concentra- tions of the marker fluid everywhere through the bloodstream and brain tissues, no matter how small the vessels are. ‘Contrast-enhanced MRI is a combination of vision, technical knowledge and computer power,’ says Backes, adding: ‘We now can investigate with medical imaging in a non-invasive way and we don’t have to rely on post-mortem tissue or spi- nal tap samples anymore.’ Initial clinical tests yielded exciting insights: ‘Since we couldn’t test our new scanning method in healthy vol- unteers with an intact BBB we imme- diately scanned Alzheimer patients and saw damages in the barrier with fluid leaking from the smallest blood vessels to the brain.’ New insights in the vascular contribution of dementia Due to the leakage, unwanted sub- stances can enter the brain and damage the tissue. ‘At first, blood vessels were not considered a player in the development of AD. While ani- mal experiments had shown leaking blood vessels, these leaks were not thought to be associated with cogni- tive decline and dementia. What we discovered in the human brain is somewhat of a fluke, an accidental breakthrough. While we can show the leak, we cannot determine yet whether it is AD. This requires fur- ther research. Nevertheless, the con- nection between BBB impairment and AD pathology was strengthened by the fact that the addition of diabe- tes and other non-cerebral vascular diseases did not change the results.’ The condition of the blood vessel system, Backes concludes, seems to play a very important – and previ- ously underestimated – role in the development of Alzheimer’s disease. ‘Earlier research focused the deposi- tion of amyloid-beta proteins as a possible cause of AD. This theory appears to be disproven today: When we wipe out the protein stack with medication, the condition of the patient remains unchanged. Finding this leakage is therefore an important contribution to the research on the development of AD. We have shown that in people with Alzheimer’s dis- ease not only the brain but also blood vessels are damaged, and that the damage is substantial.’ While there is no cure yet for Alzheimer’s, Backes’ research might indicate that keeping our vascular system in good condition – with good nutrition and physical as well as mental exercise – could help stave off AD. Further research Unfortunately, the new MRI method is not yet widely available. Therefore, as the physicist explains, ‘We are focusing on making the technique easier to apply, so more people can be examined, even those who do not yet show symptoms. With our new knowledge of the leaks, we might be able to send medication to certain places in the brain. However, we don’t yet exactly know how vascular medication works in vascular disor- ders. This will need further investi- gation.’ Indeed, two follow-up studies are planned, each lasting about four years. Backes: ‘In eight years we should have a better understand- ing of the cause of Alzheimer’s. Approximately one hundred people with and without diagnosed AD will participate in each trial.’ Award-winning research During RSNA 2017, the article Backes and his team published in ‘Radiology’* received the Alexander R Margulis Award for the best sci- entific article of the past year. For Backes the award did not come as a surprise because his research had attracted considerable attention: ‘It AI – Radiology’s next frontier Healthcare artificial intelligence Artificial intelligence (AI) technology and its role and future impact on the radiology profession was the dominant theme at RSNA 2017, whether in scientific presentations or in the technical exhibitions. Keith J Dreyer DO PhD addressed this subject head-on in his presen- tation ‘Healthcare AI – Radiology’s Next Frontier.’ Report: Cynthia E. Keen Dr Keith Dreyer, vice chairman of radiology informatics and chief data science officer at Massachusetts General Hospital in Boston, is an acknowledged expert on informa- tion technology (IT) innovations in radiology. His prediction, at a packed lecture hall during the joint RSNA/AAPM scientific session, was that an AI future is very bright for radiology and radiologists. Once AI becomes an established technology in radiology, it will allow radiolo- gists more time to work with both clinicians and their patients. Rather than being diminished, radiologists will assume the leadership role of being aggregators of all data that passes through the diagnostic pro- cess. Acknowledging the large num- ber of AI-oriented companies exhib- iting for the first time and veteran vendors incorporating the subject of AI into their exhibition booths, Dreyer rhetorically asked where the radiology profession is on the path- way to AI expectations? At the very beginning, he answered. Potentially diagnostic imag- ing AI will take decades Building an AI algorithm can be surprisingly easy, but converting an algorithm into a sophisticated product that works consistently in clinical use is very complex. He dis- agrees with deep learning pioneer Professor Geoffrey Hinton, a com- puter scientist at the University of Toronto, whose remarks at the 2016 Machine Learning and Market for Intelligence Conference that medical schools should stop training radiol- ogists now because they will not be displaced by AI technology in five to 10 years made global headlines. More than just MRI accessories www.allmri.com k c o t s r e t t u h S / w e r d n a s g a : e c r u o S Digital technology has radically changed the radiology profession: with increasing complex modali- ties, with electronic health records and the more specialised radiol- ogy information systems, with digi- tal imaging and PACS, with cloud storage and global digital image exchange capabilities, and with speech recognition dictation sys- tems and auto-populating structured reporting templates. But these tech- nologies and their adoption have evolved over decades. Diagnostic imaging AI will also potentially take decades because there is a stagger- ingly large amount of work to do. The potential for AI has stirred excitement since the 1950’s, but deep learning only began to flourish in 2010. The growth in AI applica- tions over the past five years has been fuelled by rapid advances in technology, growth, data, and mas- sive investment from tech titans, by powerful new applications for known AI techniques, the prolifera- tion of open source software, and sharing of advances. Imaging diag- nostics is a hot area for investment, and it behoves organisations like the American College of Radiology (ACR) and the RSNA to get very involved. ‘What you see on the exhibition floor are very narrow applications of AI, focusing on a very specific radiology application. Is this appli- cation needed? Just how good does it need to be? What can it solve better than a radiologist?’ Dreyer compared the global diagnostic per- formance of radiologists to a bell- shaped curve, ranging from random guesses to perfection. What should the standard for an AI algorithm be? He observed that there are many places on the globe where good AI assistance in a very narrow applica- tion would be adequate. Complex work and interaction by multidisciplinary community is needed to have clinical AI take place on a broader scale, and a platform to support all the development of algorithms to deal with thousands of findings and tens of thousands of medical conditions. AI will need to focus on image interpretation, patient care and safety, and radiol- ogy practice optimisation for pro- ductivity and quality. To show how these AI products reduce costs and improve outcomes will require clini- cal translation and industrial-grade integration into routine workflow. Current obstacles include lack of a healthcare AI ecosystem. No standard methods exist to annotate data for AI model training and test- ing, nor is there a standard mecha- nism for clinical integration into existing systems and modalities and future ones. AI healthcare standards need to be developed. This is a role that the recent- ly established ACR Data Science Institute (www.acrdsi.org) is tack- ling. Its objective is to advance data science solutions for radiol- ogy care that are clinically relevant, safe and effective. The Institute is working with the USA’s Congress, federal agencies, the healthcare AI industry, professional societies and the healthcare community. Dreyer discussed in detail the numerous issues that need to be addressed with respect to clinically viable AI applications. Easing the AI premarket approval process Radiology has an enormous oppor- tunity to leverage AI to become a centre of intelligently aggregated, quantitative, diagnostic information. This is of great interest to the USA’s Food and Drug Administration (FDA), which sees the potential for medical device development tools to ease the process of AI premar- ket approval and programs such as the National Evaluation System for Health Technology (NEST) to improve post market surveillance through a continuous data feedback loop, as is being implemented by EUROPEAN HOSPITAL Vol 27 Issue 1/18

1 4 E H @ E C R We need to determine the benefits and potential risks Reason must prevail in debates on GCCAs use Radiologists must ensure pre- cise scientific data and radiol- ogy-based evidence are used to regulate the use of Gadolinium Containing Contrast Agents (GCCAs), a Spanish leading radi- ologist explained in closed-door leadership meeting earlier this year in Barcelona. not involved in these discussions, so it’s not easy to form an initial opin- ion,’ Martí-Bonmatí explained. In the past three years, concern has grown about gadolinium deposits in the brain of patients undergoing GBCA-enhanced MR examinations. In 2017, the Pharmaco-vigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recommended suspension of some GCCAs marketing authori- sations based on linear chelators, due to the potential risk of gad- olinium retention in the human body; the recommendation was fur- ther extended by EMA’s Committee for Medicinal Products for Human Use. As a result, four linear GCCAs are no longer marketed in the EU Findings showing GCCAs deposits in different parts of the body have triggered a profusion of publica- tions and decisions that now direct- ly affect radiology practice. The good news is that radiologists can use their abilities to bring science back into the discussion, accord- ing to Luis Martí-Bonmatí, Director of the Medical Imaging Department and Biomedical Imaging Research Group at La Fe University Hospital in Valencia, who addressed a panel from the academy and the industry. ‘There’s been a real tsunami; large quantities of diverse information and opinions that have pushed the authorities to make decisions, which affect our daily practice but are based on neither accurate nor pre- cise data,’ he said. Radiologists now understand the full extent of the deluge. ‘We may not have valued these decisions properly at the time. Usually we are Luis Martí-Bonmatí MD PhD is Director of the Medical Imaging Department and Biomedical Imaging Research Group (GIBI230) at La Fe Polytechnics and University Hospital and Health Research Institute in Valencia, Spain. He is also professor of radiology at Valencia University lions of patients. GCCAs have been administered more than 300 million times, with a very low frequency of acute adverse events. People tend to overestimate the occurrence of very unlikely events and magnify them in the decisions they make. And generally, people lack abilities to correctly interpret statistical prob- abilities,’ Martí-Bonmatí pointed out. evaluation on statistical probability and we can’t or don’t know how to, or haven’t properly extrapolated small samples’ results from the gen- eral population. And,’ he added, ‘we haven’t been able to properly man- age these small probabilities.’ To this day the only known adverse effect linked with GCCAs use is nephrogenic systemic fibrosis, which had a very low incidence; the risk has almost disappeared since doses are now tailored to each patient. Recent research even suggests it has no effect in patients undergoing dialysis or with chronic renal disease.* Differentiation is important Martí-Bonmatí recommends evaluat- ing contrast agents separately, as they have different retention pro- files, and conducting prospective controlled trials. Radiologists should also be aware of poorly controlled CA administration numbers and doses, and of the importance of con- fusion variables, such as age, sex, patient condition and the interval between dose administrations. ‘Patients with different diseases and treatments should not be mixed and the effect of pharmacokinetics should be taken into account. We also need histological and/or mass spectroscopy confirmation, as it is absent from most series,’ he added. Last but not least, radiologists use different MR equipment and param- eters, and therefore have to watch out for T1 signal variations. ‘Retention in bones, skin, liver, or central nervous system is different depending on which CA is being used,’ he said. Instead of fighting over which CA is safe to use or not, radiologists should use their energy and skills to determine benefit-risk ratio. Finally, Martí-Bonmatí con- cluded: ‘Political appreciation has ruled in risk management evalua- tion so far. The time has come to determine which are the benefits and potential risks when using con- trast agents.’ MR *https://www.ncbi.nlm.nih.gov/ pubmed/28731375 ECR 2018 Wednesday 28, February 16:00-17:30 Room G Special Focus Session, Level II SF 4 Gadolinium deposition: is it harmful? EUROPEAN HOSPITAL Vol 27 Issue 1/18 Administration of gadolinium containing contrast agents (Omniscan, Magnevist, Optimark and MultiHance). Clear clinical evidence is missing However, even if long-term safety of GCCAs remains unclear, current scientific evidence for gadolinium retention has several methodologi- cal limitations, most experts feel. ‘No clear clinical evidence exists indicating that gadolinium retention causes neurotoxicity. We need this evidence to formulate a hypothesis,’ Martí-Bonmatí said. ‘If we don’t use that approach, hypotheses simply do not stand.’ In Spain, the Medicine and Medical Devices Agency is follow- ing the EMA recommendation, argu- ing that clinical benefits do not overcome potential risks. But it still enables the use of Primovist and MultiHance for hepatic studies, an exemption Martí-Bonmatí finds intriguing. ‘That’s a backroom door! If risks do exist, then they should be relevant in any application and in all contrast media,’ he said. ‘Even more importantly,’ he added, ‘we know today that all GCCAs are retained in tracer quantities in different com- partments, but without any histo- logical toxicity or clinical sign.’ Debates on potential risks of cut- ting-edge technology had spurred in the past over the use of radio- frequency and, more recently, mag- netic resonance imaging, as an EU directive planned to limit the expo- sure of workers to magnetic reso- nance. Eventually, the proposal was withdrawn. ‘This draft would have significant- ly restricted the use of a technique that has showed its benefits in mil- Precise data to evaluate risks is needed Radiologists can help evaluate reli- ability and relevance of risk man- agement investigation using their scientific reasoning. ‘What the world needs now are cool, reason-based facts to evaluate risks appropri- ately. We need to use the scientific method, i.e. to carry out consequent observation using experimentation, measurements, formulation, analysis and hypothesis renovation, to gen- erate evidence,’ he said. However, as they offer their exper- tise to help advance knowledge, radiologists must demand strong data in return. ‘Us radiologists should have a clear idea on how to evaluate data precision, and trust our critical and criteria appraisal for the patients benefit. Each time an institution, academy, committee, person or group approaches us with recom- mendations on how to act in our clinical practice, we should ask which data and evidence they base their opinion on, to be able to use our reasoning,’ he said. Bias awareness When faced with the vast amount of studies on the potential risk of GCCAs, radiologists must be aware of bias inherent to scientific investi- gation. In radiology, bias can origi- nate from samples, tools and data used in measurements and analyses. But even when trials are carried out properly, results often prove useless, Martí-Bonmatí explained. ‘Not only are most investigation results false but also, when they are accurate, they are useless. That’s because, deep down, we base our www.braccoimaging.comOptimizing the use of gadolinium-based contrast: expert opinionChairman: Louis Martí-Bonmatí• Retention of gadolinium-based molecules following exposure to macrocyclic GBCAs Josef Vymazal• Optimizing contrast dose: safety and efficacy considerations Francesco Sardanelli• Immediate-type adverse events: how to prevent them, how to manage them Fulvio StaculECR 2018 Vienna, AustriaThursday, March 112:30-13:30 (Room E1)You are invited!Bracco Satellite SymposiumFacultyLouis Martí-BonmatíLa Fe Polytechnics and University Hospital. Valencia, SpainJosef VymazalCharles University and Na Homolce Hospital Prague, The Czech RepublicFrancesco SardanelliUniversity Hospital San Donato, Milan, ItalyFulvio StaculUniversity Hospital “Ospedali Riuniti”, Trieste, ItalyA light lunch will be offered

1 8 E H @ E C R The race is on – radiologists must pick up the ball and run! Liquid biopsy versus radiomics The development of new procedures to monitor cancer treatments is gathering momentum. One such innovation is liquid biopsy. This new lab technique allows non-invasive identification, characterisation and monitoring of circulating tumour DNA. Thus, liquid biopsy can potentially revolutionise oncological diag- nostics – and put a spoke in the wheel of radiology. High time to act, says Professor Dr Jens Ricke, Chair of Radiology at Ludwig Maximilian University (LMU), Munich, and Director of the Clinic and Polyclinic of Radiology at LMU Hospital. He is confident that radiology has several aces up its sleeve – one is radiomics. (Response Evaluation Criteria in Solid Tumours) criteria and accept- ed their imprecisions. However, we do need unambiguous standards. The current procedure relies on mere volume measurement: tumour growth or regression, however min- ute, is evaluated. This, however, does not allow a reliable predic- tion of therapy response. There are better parameters, which have not yet been clinically validated and are thus not accepted as follow-up variables. ‘Enter radiomics: future develop- ments in radiomics may well yield suitable criteria to gauge therapy response in oncology. However, as yet there is no proof that the parameters really predict patient survival linked to therapy response. Current data are incomplete and their analysis and successful trans- formation into criteria will take years. Therefore, we must hurry up. ‘The competition is on the ball. This is why we should invest more resources in radiomics. I’m sure we do have the means and the possibili- ties to create useful alternatives.’ What exactly needs to be done to shape this future? ‘Above all, we need validation stud- ies. Firstly, imaging methods need to be established, which might encom- pass entirely new forms of analyses. The idea underlying radiomics is to cull more information from image data than meet the human eye. This involves complex statistical analy- ses, what’s usually subsumed under the buzzword Big Data: computa- tional drudgery. Every large data set has to be analysed over and over until patterns with predictive value regarding therapy response – or the lack thereof – become visible. ‘MRI has already offered promis- ing techniques. But this is just the beginning. The more methods are being developed, the more impor- tant is the validation of those meth- ods. Prospective clinical studies that define and show innovative imaging endpoints for therapy response are indispensable. ‘Today, FDA and EMA require clin- ical trials for regulatory approval of a pharmaceutical to be based on the RECIST criteria. However, we also have to think about the validation of potentially new imaging endpoints.’ How quickly can results be pro- duced? ‘The validation of such procedures is time-consuming. This is another reason why the projects have to be launched as soon as possible. Validation is always tied to a spe- cific endpoint of the study as such, which might also include long-term survival studies. However, not only Radiomics: Radiology images (below, left) undergo feature extraction and quantitative image analysis in order to be converted into a high-dimensional data space (centre). A correlation between this data space and a clinical outcome, such as overall survival (right), is identified with the help of machine learning. This correlation can be used to analyse new image data Interview: Daniela Zimmermann Why is liquid biopsy such a suc- cess? ‘As soon as liquid biopsy has iden- tified circulating tumour DNA, it’s also possible to identify gene muta- tions that might influence the ther- apy,’ the Professor explains. ‘This effect can be seen in the personal- ised therapy of colorectal cancer: an RAS or RAF mutation of the metas- tasising colorectal tumour impacts systemic therapy. Liquid biopsy can indeed detect this mutation in circu- lating tumour DNA.’ What does that mean for imag- ing? ‘That’s exactly the sore point. Methods such as liquid biopsy are mere lab procedures. They have only recently been introduced and are still under development. This phase, no doubt, will continue for a while. Nevertheless, we radiolo- gists have to get a move on today if we want to actively shape the future of oncological imaging. If liquid biopsy keeps its promise, it may well replace the tight imaging follow-up in oncology. Obviously, that won’t mean that radiologists will be out of work. But, we do have to think about our future now and, above all, we need to tap the full potential of radiology. For a long time, we have applied RECIST studies themselves can take years, the preparation also takes a lot of time.’ Is there political or industry sup- port for these methods? ‘Such studies are eligible for public funding; but even more interesting is the interest of the pharmaceutical industry. Validation would require clinical trials that include new imag- ing standards. These studies are rarely publicly funded. ‘By the way, within the pharma- ceutical industry the awareness that new imaging endpoints need to be defined has markedly increased with the success of immunothera- pies. This is because, in the initial phase of immunotherapy, a response in the traditional sense cannot be determined. Quite to the contrary: tumours tend to grow despite an initially positive response. This is caused by tumour infiltrating lym- phocytes, which in fact trigger an inflammation. This is an accom- panying effect of immunotherapy. These lymphocytes cause pseudo- progression of the tumour, which a conventionally trained radiologist or oncologist might interpret as tumour growth – an undesired out- come – and discontinue the therapy. However, in many cases, initial tumour growth during immunother- apy turns into tumour regression – the therapy should have continued rather than stopped. To account for these new insights RECIST criteria were expanded: the new so-called iRECIST criteria recommend a dif- ferent evaluation of immunotherapy response. ‘If tumour growth is recorded, further controls are performed in The birth and rebirth of imaging Radiology: An era of turbulence and innovation The New Horizons Lecture at the RSNA annual meeting is a keynote address that looks to the future, and the inventor of a major innovation in magnetic resonance imaging (MRI) technology, Daniel K Sodickson MD PhD, did just that. His lecture enti- tled ‘A New Light: The Birth and Rebirth of Imaging’ looked back at how MRI has evolved and forward at what it will become. radiology The change will be radical. Today’s images may be irrelevant. MR protocols will become obsolete – but radiologists will not be, Sodickson emphasised, because radiologists are in a posi- tion to transform the field. ‘We invented diagnostic imaging. We figured out how to visualise and understand human inner space. This is both a turbulent age for imaging and a golden age for innovation. We need to embrace the theme of RSNA 2017, and ‘Explore, Invent, Transform.’ Modern imaging science is information science. Let us be the scientists who create new forms of information. In a world increas- ingly dominated by information, what more valuable contribution can we make?’ Sodickson explained that the era of continuous, comprehensive imag- ing data has arrived, and that with this change, the era of the ‘carefully framed snapshot’ of a high-resolu- tion image will pass. ‘Radiology is Courtesy of Daniel Sodickson MD and NYU School of Medicine not just copying our eyes. Instead, it is starting to emulate the way that our brains process multiple, stream- ing multi-sensory experiences.’ In his lecture Sodickson described the building blocks that created MR technology, from 1973 when the idea was first published to the revolutionary changes and relent- less innovation that have ensued. This rapid-fire overview clearly illustrated how radiology progress- es, adapts, and advances diagnoses through imaging. Dramatic improvements of the 1990s Sodickson spoke of the evolution from the first magnetic field gra- dients to diffusion imaging. The introduction of functional MRI, Daniel Sodickson and the Radiology Research team of NYU School of Medicine, who are involved in the development of new techniques for biomedical imaging implemented in 1990, enabled radi- ologists to see different types of biophysics, reflecting brain activ- ity. In the 1990’s, some dramatic improvements were made to gra- dients and to radiofrequency coils, enabling advances in speed and image information content. The con- cept of moving from a sequential imaging device to a parallel acquisi- tion device decreased the time to acquire images. Parallel acquisition made it possible to reduce corrup- tion of images by motion from the abdomen and heart, and also to make the process easier for patients. In 2007, compressed sensing was introduced. In addition to making the acquisition of images faster, it made feasible the use of multiple dimensions of data, which could be integrated together. Non-traditional data sampling patterns, such as radi- al patterns, gained new prominence. One particular example Sodickson described used a golden angle radi- al pattern, which enabled motion robustness during continuous data acquisition. With the introduction of con- tinuous three-dimensional acquisi- tion, it became possible to perform multidimensional sorting along dis- tinct motion dimensions. This ena- bled the creation of unique cardiac motion dimensions or respiratory motion dimensions, as an example. More innovations enabled radiolo- gists to determine how the heart contracts and relaxes at any stage, or to look at the morphology of the great vessels or coronary arteries and freeze the images at any stage, thus enabling better heart disease diagnoses. Creating a dictionary of pre- simulated fingerprints The addition of 4-D, 5-D, and 6-D image processing algorithms led radiologists away from a mode of carefully tailored and adjusted snapshots toward a much simpler paradigm of rapid and continuous Source: Courtesy of Daniel Sodickson MD EUROPEAN HOSPITAL Vol 27 Issue 1/18

2 0 E H @ E C R New cancer treatments present radiologists with new imaging questions Understand the treatment to understand an image Conventional chemotherapy in oncology is increasingly yielding to new procedures such as targeted therapy and immunotherapy. The result is changes for radiologists because new procedures require famil- iarisation with certain imaging to ensure that the treatment process is interpreted correctly. During a recent CT symposium Professor Hans-Christoph Becker, radiologist at Stanford University Medical Centre in California, USA, discussed aspects of such changes. Wolfgang Behrends reports ‘To begin with it’s important to under- stand how the new therapies actual- ly work,’ radiologist Professor Hans- Christoph Becker advised, speaking at the CT-Symposium 2018 held in Garmisch, Germany. Targeted treat- ment and immunotherapy attack tumours in a very different way from chemotherapy. ‘The point of chemotherapy is to destroy tumour cells. Targeted, i.e. specific can- cer therapy works, for exam- ple, with specific messenger substances that activate signal paths, and explicitly interfere with the metabolism of tumour cells.’ The advantage of the new treatments lies in their higher precision. ‘Chemotherapy is com- paratively non-selective,’ Becker explains. ‘It damages tumour cells as well as healthy tissue, which means it causes collateral damage.’ By comparison, targeted therapies attack the tumour cells, which can be identified with high specific- ity with the help of surface anti- gens, for instance. This can help to reduce the severity of side effects for patients. Therefore, the objective for researchers is to make the treatment as precise as possible. ‘Each patient has tumours with a certain, individ- ual combination of characteristics,’ Becker points out. These markers are determined histologically via biopsies. ‘We can now differentiate with much more precision which treatments tumours are most likely A: Melanoma reaction to Ipilimumab treatment. Although the CT images initially suggest tumour growth (B) this in fact signals therapy success (C) A B C to respond to and can there- fore target ther- apy much more i n d i v i d u a l l y . ’ Treatment success is monitored clini- cally as well as through imaging. The high precision of thera- pies, however, also entails some new difficulties: ‘With chemother- apy, treatment success is usually confirmed by the fact that a tumour shrinks,’ the expert adds. ‘This is different with the new targeted therapies. The objective is not necessarily only the destruction of the tumour tissue but also a sig- nificant impact on its metabolism.’ This reduces the blood supply to the tumour. ‘It leads to effects which look different from those of conven- tional chemotherapy.’ Tumours are usually heterogeneous, i.e. they con- sist of different cell lines. Targeted therapy has become so specific that sometimes only some of these lines respond to it, but not oth- ers. ‘This leads to a peculiar response where some tumours and metastases may shrink, whilst others even grow at the same time.’ With other procedures, such as immunotherapy, the tumour initially clear- ly looks bigger in the CT image – however, this does not mean that the tumour is not responding to treat- ment. ‘To the contrary, this is a classic phenomenon of immunotherapy and the result of a deliberately induced inflammatory reaction,’ Becker explains. ‘Some of these therapies release the hand- brake of the body’s immune cells. The immune system then attacks the tumour with leucocytes, which makes the tumour appear larger on the image. What it really means though is that the treatment is work- ing. ‘Radiologists must be able to recognise these effects to evaluate the CT images correctly.’ Understanding how different therapies work is also essential for correct interpretation of images. ‘The interaction between pathol- ogy, tumour treatment and image analysis is increasingly complex,’ says Becker. ‘Linking these areas in a meaningful way will be among the big challenges in the future.’ BERUF und KARRIERE mit Bildung managen! rtaustria ist zertifizierter Bildungsanbieter nach ISO 29990:2010. • Fortbildungsangebot • Approbation von Lehr- und Lerninhalten • Akkreditierung von Lehr- und Lerninhalten Die gesamte Kursübersicht finden Sie auf www.radiologietechnologen.at/kurse. From 2001-2014 Professor Hans- Christoph Becker was a senior consultant at the Institute for Clinical Radiology at Ludwig-Maximilian- University (LMU), in Munich, Germany. In 2009 he was appointed Professor of Radiology, focusing on non-invasive cancer imaging. About three years ago he received a generous budget to set up a cancer research laboratory at Stanford University, California, USA, similar to the one he established at LMU in Munich. AI analysis presents great potential Automated evaluation of such imag- ing phenomena is also conceiv- able. Artificial intelligence (AI) could detect the specific reactions of tumours in the data sets and therefore measure treatment suc- cess. Stanford University Medical Center is already working on the development of such algorithms. ‘The procedure is still in its infancy, but it’s very exciting. It is likely that AI-supported evaluation will soon have a major impact in radiology.’ The ‘new’ cancer therapies refer- red to here are actually not that new: ‘Hormone therapy was already in clinical use 20 years ago,’ Becker points out. ‘However, subsequent- ly, more and more therapies have been discovered and the number of licensed targeted therapies also continues to increase. ‘Many different drugs are cur- rently being trialled, and studies into combining these with conven- tional treatment, as well as dose- ranging studies will continue to run.’ Fundamentally, the new therapies can be used anywhere that conven- tional chemotherapy is used. ECR 2018 Friday 2, March 08:30-10:00 Room C New Horizons Session, Level III NH 9 Immunotherapy: a revolution in cancer care? » Chairperson’s introduction: What the radiologist needs to know [A-385] V.J. Goh; London/UK » CT: looks bigger, but it’s better [A-386] C. Dromain; Lausanne/CH » The MR armoury in follow-up [A-387] D.-M. Koh; Sutton/UK » Systemic and immunologic effects of image-guided interventions in oncology [A-388] S.N. Goldberg; Jerusalem/IL » Panel discussion: How should radiology improve imaging to support this revolutionary care? EUROPEAN HOSPITAL Vol 27 Issue 1/18

2 2 E H @ E C R The clinical implications of breast tomosynthesis Catching more invasive cancers earlier What beats digital mammography to detect breast cancer in asymptomat- ic women? Digital breast tomosyn- thesis (DBT) – was a big discussion at RSNA 2017. Sarah M Friedewald MD, medical director of the Lynn Sage Comprehensive Breast Center of Northwestern Memorial Hospital in Chicago and its division chief of breast and women’s imaging, discussed the clinical implications of DBT for routine mammography screening. When digital mammography (DM) equipment was introduced in the USA its adoption by accred- ited women’s imaging centres and hospital radiology departments was cautiously slow. By comparison, the adoption of digital breast tomos- ynthesis technology skyrocketed, fuelled by studies that prove its superiority in breast cancer detec- tion. s e t a i l i f f a d n a . c n I , c i g o o H f o l y s e t r u o C s e t a i l i f f a d n a . c n I , c i g o o H f o l y s e t r u o C A B Digital screening mammography shows no definite lesion at the area of interest, left 8-9:00 position. Breast tomosynthesis demonstrates architectural distortion and shows the area for targeting for image-guided biopsy or localization. Histopathology revealed Radial scar and Ductal Carcinoma in Situ. This lesion, seen on breast tomosynthesis imaging (B), was occult (not visualized) on routine digital screening mammography (A) In June 2005, five years after the first full-field DM system received 510(k) clearance from the USA’s Food and Drug Administration (FDA), out of the 13,621 mam- mography systems in use at 8,911 facilities, only 6.4% systems were digital. In June 2016, five years after clearance of the first DBT technol- ogy systems, 20.8% of 16,155 sys- tems in use were DBT capable. Just 18 months later, this has increased to 29%, with 43% of all accredited facilities having at least one DBT- capable system. This surge is based in part on radiologists’ familiarity with and rec- ognition of the fact that full-field DM systems do increase early stage cancer detection rates. Numerous studies conducted in Europe and North America show that DBT offers even greater benefits. The USA’s National Comprehensive Cancer Network (NCCN) 2016 guidelines recommend that DBT be considered for breast cancer screening exams Courtesy of Hologic, Inc. and affiliates significant improvement in recall rate reduction for both categories. And, when we divided patients into the four den- sity breast categories, we discovered that more cancers were being identi- fied with DBT use in women with fatty breasts. The fat surrounding the cancers enabled us to see them better with DBT,’ said Friedewald. ‘For this group, the use of mammog- raphy plus DBT identified 38.2% more cancers.’ Further analysis based on stratify- ing the patient cohort in 10 year age groups, adjusted for breast density, showed performance outcome in identifying cancers with the use of digital mammography plus DBT screening, for women aged 40-49, was almost equivalent to digital mammography alone of women in their 50s. While there were gains from DBT use in all age catego- ries, the relative increase in detect- ing invasive cancers was 69% for women in their 40s. Friedewald also referenced a study conducted at the University of Pennsylvania in Philadelphia evalua- ting recall rates over three years breast screening examinations using DBT. This demonstrated that, over time, the benefit of imaging patients with DBT shifts from cancer detec- tion to recall rate reduction. In the study, there were only 59 recalls per 1,000 examinations in the third year compared to 130 recalls per 1,000 exams in the first year of imaging. Complicated transition from DM to DBT In addition to cost, the disadvan- tages of adopting DBT technology is that radiologist need a learning curve, which may also result in increased recall rates during the time it takes for them to become proficient with the technology. ‘The transition from DM to DBT is com- plicated because there are many more images to interpret. The time it takes to read a screening exami- nation is two to three times as long as digital mammography. However, with the reduction in recall after screening with DBT, the volume of diagnostic imaging should decrease concomitantly, and radiologist inter- pretation time can then be shifted to screening,’ Friedewald explained. She advised that the way her breast centre made the adjustment and incorporated DBT into the breast imaging practice was with the initial purchase of a single sys- tem. This was used to image patients in the diagnostic setting. Because a longer amount of time was allocated for patients having diagnostic imag- ing, this extended time enabled the physicians to become accustomed to the new images and reading times. It also allowed the breast radiographers time to become famil- iar with the technology. Today, DBT is used for all routine and diagnostic breast screening examinations. ‘There are many ways to deploy this exciting technology,’ she said. Sarah M Friedewald MD is medical director of the Lynn Sage Comprehensive Breast Center of Northwestern Memorial Hospital in Chicago, USA and its division chief of breast and women’s imaging. She is also an Assistant Professor of Radiology at Chicago’s Feinberg School of Medicine. In 1998 she gained her doctorate at the Columbia College of Physicians and Surgeons in New York City, followed by her internship in the surgical department at Union Memorial Hospital, in Baltimore, USA. After her residency in radiology at Johns Hopkins Hospital, she started her Women’s Imaging fellowship at the University of Pennsylvania Hospitals. ‘The women’s imaging centre at Baylor College of Medicine in Houston, TX, began by using DBT for routine screening to maximise the technology’s benefits in increas- ing detection of early cancer and reducing recalls. After 24 months, a hybrid model was adopted based on room availability and specific scenarios that needed DBT, such as asymmetries and architectural distortion.’ Friedewald did not present statis- tics relating to digital breast tomo- synthesis adoption in Europe, but expressed hope that imaging cen- tres in all countries that have con- verted to digital mammography will add DBT to their cancer-fighting arsenal of imaging examinations: ‘It’s a very exciting technology that is helping to save lives.’ CK Editor-in-Chief: Brenda Marsh Art Director: Olaf Skrober Editorial team: Wolfgang Behrends, Lena Petzold, Marcel Rasch Senior Writer: John Brosky Executive Director: Daniela Zimmermann Founded by Heinz-Jürgen Witzke ISSN 0942-9085 Correspondents Austria: Michael Kraßnitzer, Christian Pruszinsky.China: Nat Whitney France: Jane MacDougall. Germany: Anja Behringer, Eva Britsch, Annette Bus, Walter Depner, Cornelia Wels-Maug, Holger Zorn. Great Britain: Brenda Marsh, Mark Nicholls. Malta: Moira Mizzi. Spain: Mélisande Rouger, Eduardo de la Sota. The Netherlands: Madeleine van de Wouw. USA: Cynthia E. Keen, i.t. Communications, Lisa Chamoff. Subscriptions Liane Kaiser, Theodor-Althoff-Str. 45, 45133 Essen, Germany Subscription rate 6 issues: 42 Euro, Single copy: 7 Euro. Send order and cheque to: European Hospital Subscription Dept s e t a i l i f f a d n a . c n I , c i g o o H f o l y s e t r u o C Occult cancer obscured on conventional mammogram is easily seen with tomosynthesis in average-risk patients over the age of 40, thus increasing payment coverage for many women through private health insurance. Advantages of digital breast tomosynthesis DBT improves on mammograph- ic performance by minimising the impact of overlapping breast struc- tures, making it easier to see inva- sive cancers. It improves lesion con- spicuity and by removing tissue superimposition, improves evalua- tion of margins and localisation. Recall rates for additional testing are lower. And, for some patients, when suspicious findings of screen- ing mammograms merit additional testing, breast ultrasound exams may be performed in lieu of diag- nostic mammograms, thus avoid- ing additional exposure to ionising radiation. While many think DBT is only useful to identify cancers, this is not the case. Friedewald explained that findings from a study of over 450,000 women showed that, while DBT did identify more cancers than DM, recall rates also reduced sig- nificantly. This 2014 study evaluated mammography findings and recall rates of 281,187 screening exams at 13 institutions for 12 months before they implemented DBT, with mam- mography plus DBT from the date of implementation through December 2012, for 173,663 screening exams. The 13 participating facilities were geographically diverse, both aca- demic and non-academic, and with breast specialists and non-specialist radiologists interpreting the exams. ‘The results from this diversity of screening centres were very excit- ing – they confirmed that DBT increased cancer detection and reduced recall rates, the two main criticisms of screening mammogra- phy. After tomosynthesis implemen- tation, the invasive cancer detection rate increased from 2.9 to 4.1 per 1,000 women screened, a relative increase of 41%,’ she said. Recall rates reduced by 15% overall, Lowering the recall rate ‘Of particular interest was that, when recalls were divided into cat- egories of dense-breasted and non- dense women, there was statistically Artificial Intelligence helps to detect breast cancer Scientists are using Artificial Intelligence to suppor detection. The researchers at Massachusetts Institute of Science and Artificial Intelligence Laborator (MGH), and Harvard Medical School, are using the machine lear whether breast lesions identified from a biopsy will tur From left: Manisha Bahl MD is a breast imaging radiologist and director of the Breast Imaging Fellowship Program at Massachusetts General Hospital/Harvard Medical School in Boston, USA. After graduating from the Harvard School of Public Health with an MPH in Health Policy and Management, she completed a radiology residency and breast imaging fellowship at Duke University Medical Centre and joined the faculty at Massachusetts General Hospital/Harvard Medical School in July 2016. Regina Barzilay MD is a Delta Electronics Professor in the Department of Electrical Engineering and Computer Science and Printed by: WVD, Möhrfelden, Germany Publication frequency: bi-monthly Representatives China & Hongkong: Gavin Hua, Sun China Media Co, Ltd. Phone: +86-0755-81 324 036 E-Mail: gavin_hua@163.com Germany, Austria, Switzerland: Ralf Mateblowski Phone: +49 6735 912 993, E-Mail: rm@european-hospital.com France, Italy, Spain: Eric Jund Phone: +33 493 58 77 43, E-Mail: ej@european-hospital.com GB, Scandinavia, BeNeLux: Simon Kramer Phone/Fax: +31 180 6200 20 E-Mail: sk@european-hospital.com Israel: Hannah Wizer, International Media Dep. of El-Ron Adv. & PR Co., Ltd., Phone: +972-3-6 955 367 E-Mail: hw@european-hospital.com South Korea: CH Park, MCI Phone: +82 2 730 1234, E-Mail: mci@unitel.co.kr Taiwan: Charles Yang, Phone: +886 4 232 236 33, E-Mail: medianet@ms13.hinet.net USA & Canada: Hanna Politis, Media International Phone: +1 301 869 66 10, E-Mail: hanna@media-intl.com All company, brand and product names in this publication are the property of their respective holders. Users must obtain permis- sion from those holders before copying or using the owner’s trademarks, product and company names or logos. 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2 4 E H @ E C R A valuable tool for reconstruction Augmented reality lets surgeons ‘see’ inside limbs Report: Mark Nicholls Researchers at Imperial College London (ICL) have shown how the Microsoft HoloLens headset can be used during reconstructive lower limb surgery. Surgeons at London’s St Mary’s Hospital are using the device, a self-contained computer headset that immerses the wearer in ‘mixed reality’, enabling them to interact with holograms visible through the visor. In effect, the limb’s interior is visible during the procedure. Identifying critical blood vessels under the skin Testing the technology, the ICL team used the system to overlay images of CT scans – including the posi- tion of bones and key blood ves- sels – on to each patient’s leg so the surgeon could better locate and reconnect key blood vessels during reconstructive surgery. ‘We are one of the first groups in the world to use the HoloLens successfully in the operating theatre,’ Dr Philip Pratt, a Research Fellow in the Department of Surgery and Cancer, confirmed. ‘Through this initial series of patient cases we have shown that the technology is practical, and that it can provide a benefit to the surgi- cal team. With the HoloLens, you look at the leg and essentially see inside of it. You see the bones, the course of the blood vessels, and can identify exactly where the targets are located.’ When a patient sustains serious injury, with tissue damage or open wounds, they may require recon- structive surgery using fasciocutane- ous flaps of tissue taken from else- where on the body, including the skin and blood vessels, to be used to cover the wound and enable it to close and heal properly. Successfully Your partner for medical devices European Congress of Radiology Vienna · Booth X1/139 Feb 28 – March 4 connecting the blood vessels of the new tissue to those at the wound is a vital step in the process. Presently, handheld scanners using ultrasound are used to identify blood vessels under the skin. ‘Augmented real- ity offers a new way to find these blood vessels under the skin accu- rately and quickly by overlaying scan images onto the patient dur- ing the operation,’ Pratt explained. Virtual 3-D arrows guide the surgeon During initial trials of the technol- ogy, five patients requiring recon- structive leg surgery underwent CT scans to map the structure of the limb, including the position of bones and blood vessels. Images from the scans were then segmented into bone, muscle, fatty tissue and blood vessels by Dr Dimitri Amiras, a consultant radiolo- gist at Imperial College Healthcare NHS Trust (ICHNT), and loaded into intermediary software to cre- ate 3-D models of the leg. These models were then fed into specially designed software that renders the images for the HoloLens headset, which in turn overlays the model onto what the surgeon can see in the operating theatre. www.leoni-healthcare.com www.leoni-healthcare.com As a system provider, LEONI works to support development and supplies innovative cable solutions for medical devices: Antimicrobial cables and systems Tailor-made cable systems with UL/CSA approval System solutions with add-on services like engineering or testing Business Unit Healthcare · healthcare@leoni.com a) Yellow arrows in CTA image indicate perforating arteries arrows; b) example of HoloLens rendering of segmental polygonal models a) AIR overlay of models as viewed from remote HoloLens; b) co-ordination of perforator location with audible Doppler ultrasonography c) Case with overlay of bounding box with arrows highlighting position of d) Sural metal and e) posterior tibial perforators The HoloLens is used to identify where the blood vessels are in 3-D space and uses virtual 3-D arrows to guide the surgeon. Clinical staff can then manipulate the augment- ed reality images to make fine adjustments to correctly line up the model with surgical landmarks on the patient’s limbs. Jon Simmons, plastic and recon- structive surgeon at Imperial College Healthcare NHS Trust, carried out the trial procedures. Already, the hospital’s surgical teams believe that the HoloLens approach is more reli- able and less time-consuming than the ultrasound method of locating the blood vessels. Dr Philip Pratt is a Research Fellow in the Faculty of Medicine, Department of Surgery & Cancer at Imperial College London, UK. Initially working in the banking sector, he began to explore research opportunities at the Institute of Biomedical Engineering, Imperial College, which ultimately led to a career change. He was appointed Research Fellow at the Hamlyn Centre for Robotic Surgery, Imperial College. From within the Department of Surgery and Cancer, he now undertakes very active research in image-guided surgery, and has successfully translated new technology and software into clinical practice in the operating theatre. Improving the system for future use While the first cases have been car- ried out on legs, which have clearly visible surgical ‘landmarks’, using this technique for surgery on the abdomen may be more complicated. However, as the technique is refined it could be used in other areas of reconstructive surgery requiring tis- sue flaps, such as breast reconstruc- tion following mastectomy. ‘In future we hope to automate the process further,’ Pratt added. ‘We can use software to improve the alignment and will attach markers to the patient when they have the scan, with the same markers present during the operation to use as addi- tional points of reference.’ With further trials planned in a larger set of patients, he acknowl- edged that further improvements are needed, but said that from the number of cases so far the tech- nique could be a valuable tool dur- ing reconstructive surgery. Superior functionality and driv MobileDaRt Evolution MX8 Digital Mobile X-Ra ‘With Your Stories – lifetime healthcare support’: this future-driven approach combines the best of two worlds, using Shimadzu’s insights and exper- tise in medical imaging systems and laboratory instrumentation to ben- efit patients through ever improving prevention, diagnosis, treatment and follow-up. In 2018, the year of the 50th anni- versary of the opening of Shimadzu’s European headquarters, the compa- ny has released the new MobileDaRt Evolution MX8 version digital mobile X-ray system. This features its first tel- escoping support column to increase convenient drivability and improve forward visibility; a large completely flat monitor screen; a lockable FPD housing compartment; an extensive selection of options and improved operability. Digital mobile X-ray systems become increasingly essential for qualified radiography in hospital rounds, or to examine emergency patients, in neonatal intensive care units or other highly urgent medical applications. Shimadzu MobileDaRt series digital mobile X-ray systems are already used in over 60 countries around the world, with more than 3,500 units sold to date. Shimadzu is at ECR 2018 Expo Hall X2, Stand 218 the In September 2017, Shimadzu received ‘Global General Radiography Product Line Strategy Leadership Award 2017’. The award is presented to a company that intro- duced products and services dem- onstrating the highest leadership in international markets for diagnostic X-ray imaging systems in the previ- ous year and for employing the best strategies for success. A part of the company’s portfolio contributing to this award has been covered by its DR solutions. Multifaceted support The newly redesigned MobileDaRt Evolution MX8 version has been developed to provide users with multifaceted support based on Shimadzu’s extensive technology and track record cultivated thus far. important The most features: Collapsible column enhances for- ward visibility and drivability. The new design features an X-ray tube support column that can be extend- ed or retracted and a more compact system width. The previous model was 1930 mm tall during travel; the new design is only 1270 mm tall and 560 mm wide, becoming 20 mm narrower. This shorter profile due to the collapsible column dramatically improves forward visibility during travel and the more compact size makes it easier to use the system in narrow spaces such as bedside. Various functionalities and options help to improve hospital round effi- ciency. The MX8 features a new com- pletely flat 19-inch monitor, which improves operability. The maximum X-ray focal point height is also increased by 15 mm, making it easier to examine patients on higher beds. Security features are also con- sidered, such as the addition of a new locking function for the FPD housing compartment. New optional features, such as a wireless hand switch for X-ray exposure operations EUROPEAN HOSPITAL Vol 27 Issue 1/18

2 6 E H @ E C R Used imaging equipment EU v. USA – a comparison by Phillip F Jacobus I’ve watched the used imag- ing equipment market for the last 40 years and it seems like every year, at ECR, I have a conversation with friends comparing the USA and EU markets. Clearly, the market is more developed in North America than it is in Western Europe. Why? think it’s fair to say Let’s look at the numbers I that DOTmed.com, a company that I started in my apartment almost 20 years ago, is one of the most important medical equipment/parts/ service websites on the internet. People made fun of me because our website was free, but it proved to be a good strategy. Today, out of over 274,521 registered users there are 25,975 used equipment deal- ers. 18,442 are in the USA and 2,640 are in the EU, with another 881 in non-EU, European countries. There are 17,350 service companies in the US, with only 2,806 in the EU. As far as postings of parts or equipment for sale, there are 119,220 total equipment listings with 103,994 DOTmed.com is at ECR Expo Hall X2, Stand 203 in North America and 10,085 in Europe. There are 677,545 total part listings with 369,551 in North America and 83,159 in the EU. So, if your instinct tells you that the mar- ket for used imaging equipment is bigger in the US than in the EU, then you’re probably right. Why? There’s that old conundrum... Which came first, the chicken or the egg? In the US we have a healthy pre-owned equipment industry because we have a healthy independent service indus- try, and we have a healthy independ- ent service industry because we have a healthy independent spare parts industry. All of this is motivat- ed by financial pressure. In the US there’s pressure on healthcare pro- viders to do more with less for more patients. This has c a r r i e d over to in-house d e p a r t m e n t s , where hospitals their provide own mainte- nance. It’s been said that money makes the world go round and hospitals not only found a way to lower their operating costs by servicing the equipment themselves, but now in the US there are alternative parts vendors that help these hospitals. In fact, some of these alternative parts vendors are shipping equipment to Europe and will continue to do so until the independent parts industry in the EU grows big enough to meet demands. In my opinion, it’s all a question of priorities. Europe enjoys a better rail infrastructure than North America because the governments in Europe have made it a priority. Healthcare is also a priority in Europe, even at the cost of higher taxes in some cases. In the US, healthcare is a political football whereas in Europe it seems to be an inalienable right. Or, to put it another way, healthcare providers in Europe are not under the gun to find ways to save and economise to the same extent as they are in the United States. There is an abundance of trained service labour available in the USA. Coupled with an entrepre- neurial spirit, this labour has formed ISOs to offer lower cost quality alter- native service to the OEM prices. Then add a robust spare parts mar- ket and you have strong alternative service options. Will this change? There are more people alive today in the world than there were 100 years ago and we have succeeded in making people live longer. It seems to me that it’s only a matter of time before this larger population plac- es financial pressure on European healthcare providers and they are forced to look for ways to save money. The pre-owned equipment market will be that answer, I predict. As the rest of the world con- tinues to grow, the need for pre-owned equipment and perhaps more importantly, pre-owned parts, will grow as well. The market in Europe will have to develop some independ- ent engineering groups to dismantle equipment and harvest parts without missing a step. Some of these engineer- New monitor generation produces natural, precise colours The i3 series improves diagnosis JVC reports a complete redesign of its display line-up, bringing the i3 series to market. ‘At first glance, the new housing design stands out; the displays bezels are much narrower than in the previous generation,’ JVC points out. ‘Also new are function buttons on the screen with virtual descriptions. These customisable but- tons give users direct access to vari- ous functions.’ Beyond the visual, the devices have been further developed; they also offer some technological innovations. The new 3-D lookup table, for exam- ple, enables the best possible col- our reproduction, the firm reports. ‘By also calibrating primary colours, colours have never been so natural and precise,’ says Marcel Herrmann, Marketing Manager Totoku at JVCKenwood. ‘This also ensures that the image impression is the same on every monitor in the entire facility. In combination with the new colour front sensor, we can guarantee this for the entire life of a display.’ As the first display systems on the market, the www.cars-iny.org CARS 2018 COMPUTER ASSISTED RADIOLOGY AND SURGERY 32nd Inyernayional Congress and Exhibiyion Main Themes Main Th  Medica  Medical Imaging  Compuyed Maxillofacial Imaging  Compu Compu  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  Informayion Processing in Compuyer-Assisyed  Digiyal Operaying Room  Human-Machine Inyerface  Payhology Informayics  Machine Inyelligence  Inyegrayed Payieny Care rayed Payieny Care  Tumor Boards or Boards  Innovayive Clinical Invesyigayions vayive Clinical Invesyigayions Thoracoabdominal Surgery Inyervenyion CARS 2018 President Volkmar Falk, MD, PhD (D) Congress 2018 Organizing Committe Chriutou Angelopoulou, DDS (USA) Elizabeth Beckmann, BSc (UK) Leonard Berliner, MD (USA) Ulrich Bick, MD (D) Davide Caramella, MD (I) Kevin Cleary, PhD (USA) Mario A. Cypko, PhD (NL) Takeyouhi Dohi, PhD (J) Kunio Doi, PhD (USA) Volkmar Falk, MD (D) Allan G. Farman, PhD, DSc (USA) Hubertuu Feuuuner, MD (D) Guy Frija, MD (F) Miguel A. González Balleuter, PhD (E) Makoto Hauhizume, MD, PhD, FACS (J Youhihiko Hayakawa, PhD (J) Javier Herrero Jover, MD, PhD (E) David Hilderbrand (USA) Kiyonari Inamura, PhD (J) Pierre Jannin, PhD (F) Leo Joukowicz, PhD (IL) Tina Kapur, PhD (USA) Heinz U. Lemke, PhD (D) (Chair) Kenuaku Mori, PhD (J) Hironobu Nakamura, MD, PhD (J) Nauuir Navab, PhD (D) Terry M. Peteru, PhD (CDN) Ouman M. Ratib, MD, PhD (CH) Hanu G. Ringertz, MD, PhD (S) Ramin Shahidi, PhD (USA) Hiroyuki Youhida, PhD (USA) June 20–23, 2018 Berlin, Germany The President and Founder of DOTmed.com, Inc., Philip F Jacobus publishes HealthCare Business News magazine and HealthCare Business News online. He is also President of Owen Kane Holdings, Inc. and its sub- sidiaries. Jacobus was a used equipment dealer (1977-1996) and pioneered the exporting these goods to China, visiting that country 70 times. He has also sold equipment in over 30 countries. A business partner/investor in more than 90 imaging centres, he was instrumental in installing the first proton therapy system in Russia. ing groups will be asked to provide maintenance. First, they’ll be asked to provide maintenance in a pinch, and then in the future, they’ll prob- ably be called upon for regular maintenance. It’s my prediction that, just like in the USA, the EU market will have a place for OEM service, in-house service and independent service. It’s only a matter of time. the meantime, just a few companies are going to be big winners, as they domi- nate that space. In JVC is at ECR 2018 Expo Hall X5, Stand 528 calibration is executed autonomously and independently from the PC, the company adds. ‘The procedure is very simple: The user defines the calibra- tion time and date, for example at night. This scheduled calibration will start automatically even if the work- station is not operating.’ The sensor system of the new i3 mon- itors consists of a front sensor and an ambient light sensor. ‘The front sen- sor measures continuously luminance and colour of the display and corrects those in real time. This ensures a very stable brightness and high colour sta- bility,’ Herrmann explains. In addition, the i3 series devices include a human sensor. This detects whether someone is sitting in front of the screen, which helps to save ener- gy when the monitor is not in use. For example, JVC adds, it can be ensured that a doctor is not disturbed by the quality control when he is busy doing his reporting. The i3 series devices include a human sensor that detects whether someone is sitting in front of the screen, which helps save energy when the monitor is not in use EUROPEAN HOSPITAL Vol 27 Issue 1/18

2 8 L A B O R AT O RY & I N F E C T I O N LC-MS/MS enters the medical laboratory Changing analytic parameters Interview: Walter Depner Over the last four years, Dr Thomas Stimpfl and his team have integrat- ed mass spectrometry into routine analysis. The analytical technique liquid chromatography–mass spectrom- etry (LC-MS) combines the physi- cal separation capabilities of liquid chromatography (or HPLC) with the mass analytical capabilities of mass spectrometry (MS). LC- and MS procedures were not originally developed for clinical/ medical diagnosis; their introduc- tion in the diagnostic laboratory has been problematic and taken longer than some had hoped. LC-MS, how- ever, has already enjoyed notable success in Vienna and it is evident that this technology will be much more widely used in medical labo- ratories in the future. Our EH Correspondent spoke with Assistant Professor Thomas Stimpfl, head of Therapeutic Drug Monitoring and Toxicology at the Vienna General Hospital, about the implementation of the new LC/MS procedures. Why was a largely non-medical analysis procedure introduced into the laboratory, and how long did that take? ‘Mass spectrometry, a standard pro- cedure in forensics, was previously used for only a few specific analytes in laboratory medicine here. These analyses were complex, difficult to reproduce and prone to errors. Furthermore, only a few, select specialists in the field of biomedi- cal analysis could carry them out. Making further developments in this field required much persuasion at all levels to prove the qualitative as well as economic superiority of mass spectrometry and its suitability for routine use. This is an on-going process and leads to a continuous expansion of parameters, which we determine via liquid chromatogra- phy–mass spectrometry ’ A fully automated robotic system for the determination of immunosuppressants in Stimpfl’s laboratory observed that manual aliquoting of whole blood leads to significant variability. Moreover, after manu- al sample preparation, the same LC-MS systems are also used to determine psychopharmaceuticals, HIV-therapeutics, antiepileptics, antimycotics and cardiac agents. These analyses will soon be extend- ed to antibiotics and endocrinologi- cal parameters. ‘Its success lies in the enor- mous quality gain due to each sample now being given an iso- tope labelled, internal standard, and the current quality management, which is based on analytical batch- es, becoming focused on individual patients.’ LC-MS procedures need more technical application than con- ventional medical analysis. Was the staff affected? ‘In the beginning it was difficult for LC-MS to find widespread accept- ance for the expansion of the parameter list. We had to use a lot of persuasion and some intensive training to familiarise staff with the more complex technology. Simplifications in handling and data evaluation, but also further devel- opments of LC-MS systems towards classic medical analysers will make them easier to use in the future. Meanwhile, we now have 15 spe- cialists in biomedical analysis in Vienna who can analyse the 85 LC-MS parameters independently (and also on weekends). ’ In your lab, which TDM param- eters have changed to LC-MS/ MS, and with what success? And which are also planned? ‘Immunosuppressants are now determined fully automatically via LC-MS, and this also includes ali- quoting blood from the original sample tubes sent in. This step is essential for the repeatability of the overall process, since it has been will be the automation of sample preparation, reliability and ease of handling of the analysers, complete LIMS integration and fast support from product specialists and service technicians. ‘The development of a robust and easy to use LC-MS analyser will be key to extensive expansion of this new technology, also enabling its use around the clock. As mass spectrometry can be used in very wide-ranging ways, this technology specifically lends itself to the estab- lishment of new parameters and the closure of potential analytical gaps in the parameter spectrum.’ What about the economic aspects of LC-MS? ‘The widespread establishment of LC-MS is still a challenge due to high costs involved (devices, laboratory adaptation), as well as the higher level of staff expertise required. In the long run, how- ever, running costs will be lower, with higher flexibility and quality. The use of commercially available reagent kits offers a wide range of parameters. In our case this has led to a centralisation of services, where the University Hospital is now offering this service to hospi- tals throughout the city of Vienna. ‘This also facilitates new financ- ing concepts – such as including necessary analytical devices in the reagent kits and paying a price per reported result, which lowers the threshold for the establishment of LC-MS considerably.’ Assistant-Professor Thomas Stimpfl PhD studied pharmacy and earned his doctorate in forensic chemistry at the University of Vienna in Austria. He worked as a forensic toxicologist both in Vienna and at the University Hospital Hamburg-Eppendorf in Germany before he moved to the Division of Medical- Chemical Laboratory Diagnostics at the Vienna General Hospital – Europe’s largest university hospital. He also heads a GLP- certified LC-MS laboratory at the Medical University of Vienna. we don’t yet have the appropriate random-access automation. We are beginning to see some promising developments among some of the device manufacturers in this field.’ New device/system/method inte- gration into existing infrastruc- tures is important in the modern laboratory; what happened in yours? ‘The minimum requirement in order to introduce LC-MS was defined as equivalence with the existing sys- tems. Therefore, from the start, we aimed for the full automation of all processes and full integration into the LIMS; for instance there is no longer any manual data transmis- sion. At the same time, we have been able to increase reliability and quality of results considerably.’ Which classic laboratory pro- cedures – e.g. immunoassays (ELISA, RIA), photometry – have MS procedures replaced, or are some earlier procedures still used in parallel? ‘Immunoassays have been replaced, with the different analytic strategies to be viewed as complementary. In the future, qualitative and also economic factors will determine the use of the different technologies. Decisive for the success of LC-MS Which systems do you use to achieve what capacities? ‘We use in-vitro diagnostic reagent kits from Chromsystems. The sam- ple aliquoting and preparation for an annual total of 35,000 immuno- suppressant determinations is car- ried out with a Hamilton device (as a batch) combined with Sciex mass spectrometers. ‘The sample preparation for a fur- ther 15,000 LC-MS determinations a year is done manually because Would you say the reliable and harmonic integration of MS into an existing diagnostic labora- tory is a complete success? ‘We can say that mass spectrometry has been successfully established as a routine procedure in our labora- tory. However, I believe this is only the beginning of an exciting devel- opment – we will see an increasing presence of clinical mass spectrom- etry in medical laboratories in the future.’ Network consolidation continues across the globe The changing face of laboratory medicine k c o t s r e t t u h S / t r a h o e t s e m a j : e c r u o S In Quebec, a provincial reorganisation process of laboratory services is taking place to save millions of dollars a year, requiring the transportation of about 70% of all test samples to centralised hubs Report: Mark Nicholls Laboratory networks are consolidat- ing across the globe as they seek to deliver a more efficient and cost effective service. The latest developments on several continents were outlined at the FiLM 2018 – Frontiers in Laboratory Medicine congress held in Birmingham, UK in January. With consolidation viewed as a way to deliver economies of scale, it was a recurring theme at the con- gress with topics covering the pros and cons of consolidating pathology services, and exploring whether one size fits all when it comes to models of laboratory consolidation. The Dark Report editor-in-chief, Robert Michel, drew on examples of Sonic Healthcare Ltd from Sydney, Australia, as a leader in consol- idation and LabCorp and Quest Diagnostics in the USA as major global players, although he pointed to other examples in Japan, with one major laboratory processing 100,000 patient specimens every night. In a round up that focused less on Europe and Asia, and more on North America, Australia and New Zealand, he offered an insight into what was happening in terms of laboratory consolidation within the sector in these regions. Approaches differ internationally From a situation in 2000, when New Zealand had multiple private lab providers, the country now has ‘sole source’ tenders to reduce com- petition, concentrate testing and lower the cost of pathology whilst, in Australia, hospital clusters have set up regional pathology networks. ‘Canada has been consolidating both hospital and laboratory services since the late 1990s,’ he pointed out, ‘though that concen- tration is generally happening within the boundaries of each province. ‘There is cur- rently tension between pri- vate patholo- gy companies and the public health care sys- EUROPEAN HOSPITAL Vol 27 Issue 1/18

3 0 L A B O R AT O RY & I N F E C T I O N AMR: the world’s biggest health threat ‘End animal growth drugs’ A major summit meeting in London, Great Britain, has seen politicians, doctors, scientists, farmers and other experts come together in a bid to tackle the growing global anti- microbial resistance (AMR) crisis. Among these experts was Dame Sally Davies, England’s Chief Medical Officer, who described AMR as a ‘problem without a face’ because most patients are not told they have a resistant infection. She also called for an end to drugs being used for growth promotion within the farming sector within five years. Call for support The event was organised by the Bureau of Investigative Journalism with MP Kevin Hollinrake, who has campaigned on the issue of AMR. ‘AMR,’ he emphasised, ‘is an increas- ingly serious threat to global public health and it requires action from around the world. Without effective antibiotics the success of major surgery is compro- mised, medicines become ineffec- tive, infections persist and spread and the cost of healthcare increases. ‘So, it’s hugely important that we The forum, held in Westminster, aimed to put the issue of AMR on the political agenda and raise awareness to the problem in developing countries continue to build on the UK’s global leadership on this very important issue and continue the momentum which has built up in the UK to tackle it.’ He also called for support for an Innovation Fund, which is helping more small-scale researchers with finances to increase the chances of finding a solution to the AMR crisis. AMR has been called the biggest global health threat the world faces. The forum, held in Westminster, aimed to put the issue on the politi- cal agenda and raise awareness to the problem in developing countries and saw several leading authorities on the subject take part in a discus- sion before opening the floor to questions from the audience. Increasing transparency Lord Jim O’Neill, a former finance minister and economist who chaired the government’s review into AMR and his report published in 2016, said that there had been a lack of action in three areas: pharmaceutical companies developing new antibiot- ics, new diagnostic tests, and using vaccines in livestock to mitigate use of antibiotics. He felt that new diagnostic tests were crucial in the ongoing fight against AMR and that by 2020 all governments should make it man- datory that doctors only prescribe antibiotics if a patient’s infection has been diagnosed by a state-of-the-art test. He called for more transparency from drug companies around antibi- otic effluent released as part of drug manufacturing and said that all anti- biotics important in human medicine should be banned in agriculture. Dr Thomas Van Boeckel, a sci- entist at the Swiss university, ETH Zurich, who has mapped the use of antibiotics in animals, said the reduction of antimicrobial use in animals in the UK was ‘remarkable’ but that this was in stark contrast to the situation across the globe ‘The real tragedy of AMR is that millions of people do not have access to antibiotics because they cannot afford it,’ he said. ‘When these people will finally be able to afford antibiotics they will not work. Not because they misused it, Kevin Hollinrake is a Conservative Party Member of Parliament for Thirsk and Malton constituency in Yorkshire, England. A former businessman, he has held this political seat since May 2015 and has worked to raise awareness of the global threat of Antimicrobial Resistance. but because we did. And because we used a lot of it to raise chicken and pigs.’ Other speakers included Dr James Tibenderana, global technical direc- tor at the Malaria Consortium, which runs health programmes around the world, and Dr Clare Chandler, a medical anthropologist who runs the AMR Centre at London School of Medicine and Tropical Hygiene. She also talked about how antibi- otic use is related to the wider politi- cal and economic context as they speed up recovery so that people can get back to work more quickly, MN and increase productivity. Going for high-performance hospital hygiene H2O2 disinfects air, surfaces and rooms Room decontamination using hydro- gen peroxide (H2O2) has proved to be a powerful solution for complete surface and final disinfection as well as outbreak management in modern hospital hygiene. Most final disinfections in hospi- tals are carried out using the scrub and wipe method, the specialist disinfection company Diop GmbH and Co. KG explains. ‘However,’ the firm adds, ‘this essential disinfect- ing measure entails dangerous risks, such as unnecessary gaps in surface disinfection (up to 70%), incorrect chemical dosages, human errors due to time pressure and lack of vali- dation possibilities. Who seriously wants to take a contamination risk of at least 30%? ‘Inadequate final decontaminations can lead to losses in disinfection quality (contaminated surfaces + equipment), high per- sonnel costs (e.g. by repetition of disinfection processes) as well as to an increasing number of infec- tions, such as Methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile-associated diar- rhea (CDAD) etc. This places heavy financial burdens for economically weak hospitals.’ Validation and difficult, expensive cleaning and dis- infection ‘Mechanical and automated disinfec- tion methods can be reliably vali- dated, such as the hydrogen perox- ide-based room disinfection,’ Diop confirms. ‘In recent years, the so- called cold nebulisation, aerosolised hydrogen peroxide (aHP), or aero- sol disinfection has emerged from these H2O2 procedures as being the most practical, user-friendly and most cost-effective disinfection method for final disinfections and outbreak situations in over 20 appli- cation areas. These include leading pharmaceutical manufacturers, fed- eral institutes in the field of animal health, research centres, hospitals and food production. ‘Especially in highly contaminated patient rooms, toilets, laundry ser- vices and other hospital environ- ments, the residual risks and gaps of the disinfecting work carried out by humans can be mechanically secured by way of validation. These serve as microbiological proof of the disinfection performance,’ Diop assures. Recommendations For the simple, safe and fast imple- mentation of a conclusive validation, closed germ carriers (e.g. DioFog- Controller or DioSpore-Controller) are recommended. These special bio-indicators virtually exclude the risk of recontamination by humans and the environment because they have no handling problems, trans- port complications or storage risks. requirements, bio-indicators for either bacterial activity (incubated with the refer- ence germ Enterococcus faecium or Staphylococcus aureus) or spori- cidal disinfection (inoculated with Geobacillus stearothermophilus) can be used. Depending on ‘The validation itself is quite sim- ple and accompanied by chemical The H2O2 nebulization method can elimi- nate hygiene risks like gasps in surface disinfection and recontamination by humans EUROPEAN HOSPITAL Vol 27 Issue 1/18

3 2 I N T E N S I V E M E D I C I N E Advanced technology results in more difficult and complex interventions Anaesthesia is a story of great success Professor von Goedecke outlined major improvements in anaesthesia practice at the annual ÖGARI meeting warnings and recommendations by the European incident reporting sys- tems. Important as they might be, stand- ards ensuring safety and quality in anaesthesiology as well as recom- mendations to manage critical clini- cal situations are only one success factor. The dramatic reduction of mortality and concomitant progress in patient safety are, to a large extent, due to medical technology innovation: • Pulse oximetry. Continuous and non-invasive measurement of blood oxygen saturation is a parameter of respiratory func- tion and the heart-lung system because it shows the peripheral pulse waves. • Expiratory CO2 monitoring (cap- nometer and capnography) is a gas exchange parameter that provides data on the pulmonary and circulatory function as well as on the correct placement of the ventilation tube. • Neuromuscular monitoring. Intraoperative relaxation moni- Anaesthesia-associated mortality per 100,000 surgery patients 1940s 1960s 1970s 2016 100 80 10-30 0.4 toring of muscle function is important with regard to ven- tilation tube placement and in certain interventions, such as abdominal laparoscopy. • Invasive haemodynamic mon- itoring allows, among others, intra-arterial pressure measure- ment, which in turn offers data on important cardio-vascular parameters. ‘In the past decades, these innova- tions have helped to save many lives and they are contributing signifi- cantly to patient safety,’ Goedecke underlines. A slight perioperative mortality increase ‘Nevertheless, recent figures show a slight increase again in anaesthesia- specific and perioperative mortality in general. ‘This is not related to any deterioration of the safety standards but simply to the fact that more older and multi-morbid patients undergo anaesthesia and surgery,’ the expert points out. In Germany, the number of surgical patients over 75 years rose from 2.3 million in 2006 to 3.9 million in 2016, which trans- lates into an increase from 18 to 23 percent of all patients. ‘In addition, advances in medical technology have led to more difficult and com- plex interventions. Today surgery, as such, is associated with many more risks,’ he explains. Among patients without relevant systemic diseases anaesthesia-associated mortality is stable at 0.0004 percent, whilst in patients with severe multi-morbidity the number increases by factor 100. The conclusion, von Goedecke says, is simple: ‘We have to put even more effort into patient safety.’ Easing ARDS and AECOPD femorally to the body via a vascular access. It is supported by a blood pump that can be adjusted precisely, and instruments to control blood flow. The membrane ventilator can be used on the patient for up to 29 days. Many advantages The ‘artificial lung’ offers a broad range of support tasks – from effi- cient removal of carbon dioxide to full oxygen supply. The approach offers many bene- fits to patient and healthcare staff The membrane ventilator ‘breathes’ for the patient, outside the body Report: Michael Krassnitzer Technical innovations and the imple- mentation of quality standards in anaesthesia have immensely increased patient safety. ‘Over the past 60 years, patient safety dur- ing anaesthesia has improved more than in any other medical disci- pline,’ according to Professor Achim von Goedecke MD MSc, Director of the Institute of Anaesthesiology and Critical Care at Landeskrankenhaus Steyr in Upper Austria. Good news, since anaesthesiol- ogy plays a crucial role in reducing perioperative mortality and increas- ing patient safety. Today, industrial nations report perioperative com- plications in three to 16 percent of surgical interventions; 0.4 to 2.0 per- cent of these cases result in perma- nent damage or death, as explained by von Goedecke at the annual meeting of the Austrian Society of Anaesthesiology, Reanimation and Critical Care (ÖGARI) in Vienna. Major improvement ‘While each incident is one too many, the statistics reflect a remark- able success story: The number of anaesthesia-associated deaths dropped from 100/100,000 cases in the 1940s to the current level of 0.4/100,000,’ he says (see box), and adds that ‘a major improvement has been reported since the late 1980s, when further safety stand- ards and improved training were implemented.’ In 2010, the European Board of Anaesthesiology (EBA) and the European Society of Anaesthesiology (ESA) jointly published the Helsinki Declaration on Patient Safety. At the same time a special Task Force was founded to ensure imple- mentation of the actions identi- fied in the declaration. In 2013, a European platform was established that collects and publishes safety Innovative ‘artificial lungs’, which help the patients to breathe, offer less traumatic treatment for severe diseases such as acute respiratory distress syndrome (ARDS) or chronic obstructive pulmonary disease (COPD/AECOPD). Respiratory failure is one of the most frequent causes of ICU admission. It may occur inter alia in patients with ARDS, a dangerous condition when the respiratory system can no longer provide the important exchange of carbon dioxide and oxygen. Mechanical ventilation Conventional therapy for ARDS patients, and also for patients with exacerbation of chronic obstruc- tive pulmonary disease (AECOPD), relied on invasive mechanical ven- tilation. However, mechanical ventilation has several major drawbacks: seda- tion has to be induced and the air being pressed into the lungs with positive pressure can damage the pulmonary alveoli or the dia- phragm. Moreover, even maximum ventilation frequently does not pro- vide adequate gas exchange. The extracorporeal ‘artificial lung’ An advanced and easy-to-use alter- native to such a trauma-associated invasive procedure is an extracor- poreal ‘artificial lung’. It usually comprises a pump-driven pulmo- nary support system that removes carbon dioxide from the blood and adds oxygen. A key component of such a device is the so-called membrane ventilator which ‘breathes’ outside the body for the patient and carries out some of the gas exchange work of the native lung and at the same time relieves the respiratory muscles. A plasma-tight diffusion mem- brane is, for example, connected g a p s e g : e c r u o S t r a h c s t t e B s a l o h c i N - K & B : e c r u o S Professor Achim von Goedecke MD MSc studied medicine at RWTH in Aachen, Germany. As a medical officer in the air force (1985-95), he became junior physician for anaesthesiology and critical care at the German Armed Forces Hospital in Berlin. He joined the Anaesthesia and Critical Care department at Philipp University Hospital, Marburg, Germany, in 1996, and completed his specialist training. In 2001 he became senior physician at the Anaesthesia and General Critical Care Clinic in Innsbruck University Hospital, Austria. Public health studies and his habilitation thesis were undertaken between 2004-2006. He has directed the Institute of Anaesthesiology and Critical Care at Landeskrankenhaus Steyr in Upper Austria since 2008, and is a board member of the Austrian Society of Anaesthesiology, Reanimation and Critical Care (ÖGARI). alike. Reduced stress on the patient’s respiratory system gives the lungs time to heal and the treatment is significantly less traumatic and more effective than conventional invasive procedures. The lung assist system does not require sedation, which means the patient is actively involved in the therapy and can eat and communi- cate. The entire hardware fits on a trolley, providing patient mobility during therapy. Easy to use Physicians and nurses can quickly height-adjust the membrane ventila- tor as needed in any particular situ- ation, e.g. when the patient wants to lie down, sit up or be moved around. Subsequent therapies can follow sooner which translates into reduced length of stay and thus reduced costs. Source: Xenios AG, Heilbronn, Germany. EUROPEAN HOSPITAL Vol 27 Issue 1/18