2 N E W S & M A NAG E M E N T Transforming healthcare Necessary change – or destruction? Report: Michael Krassnitzer Dr Clemens Martin Auer knows ‘dis- ruption is an ambivalent concept’. Auer is president of the European Health Forum Gastein (EHFG), in which healthcare policy is discussed annually from a European perspec- tive: ‘For some, disruption is the promise of necessary change whilst for others it means suspicions and fears.’ The term – a synonym for ‘transformation’ but also for ‘destruc- tion’ – was the central topic of this year’s conference titled: ‘A healthy dose of disruption? Transformative change for health and societal well- being’. Auer comes to the point when he asks: ‘How do we find the right measure of transruption in the healthcare sector?’ One of the great disruptors in healthcare is without a doubt dig- itisation. ‘The digital transformation offers the opportunity no longer only to react to disease but rath- er for us to increasingly dedicate ourselves to proactive and preven- tive treatments,’ stresses Professor Ran Balicer, founding director of the Clalit Research Institute (Israel). However, it also brings with it great changes: ‘If we look at the digital transformation, the key word is not “digital” but “transformation”, Balicer emphasises. ‘It makes no sense to promote digitisation of healthcare without first effective- ly revolutionising the fundamental care processes. In other words: if you digitise a defective clinical pro- cess, then you get an expensive defective digitised process.’ AI in healthcare, as Marco Marsella, head of the General Direction Communications Networks, Content, and Technologies (DG CONNECT) explains: ‘The digital transforma- tion will be data driven.’ So, at one conference session one could learn how the European Centre for Disease Control (ECDC) uses ‘big data’ for surveillance of nosocomial infections, or who the World Health Organisation (WHO) localises dis- ease outbreaks in the context of EIOS (Epidemic Intelligence from Open Sources) based on indicators in the media – both classical and social formats. The EU invests in AI The EU invests in and supports the development of the ‘digital trans- formation’ often cited at the EHFG 2019. The European Commission is currently working on a strategy to support artificial intelligence (AI) at EU level that also includes the use of Of course, EHFG 2019 also tries not to forget the human side, the ‘human touch’ in the digital transfor- mation. ‘If these new technologies are implemented, attention must be given not to marginalise parts of the population,’ warns Dr Indra Joshi, who, as Digital Health & AI Clinical Lead in the British National Health Service (NHS), is responsible for the introduction of an app that enables access to a series of services. This is especially important in the case of vulnerable population groups, such as the aged who feel insecure with modern technologies, or migrants who might not speak the local lan- guage: ‘They must be able to choose whether they want to care for their treatment digitally, or prefer to con- sult a physician personally.’ There is a second key word in the conference title: ‘well-being’ – an allusion to Finland’s presiden- cy of the European Council. The Scandinavian country has placed well-being – and hence a health issue in the widest sense – high up on its agenda while currently pre- siding over the EU Council. ‘People who feel well are less frequently ill, work, are innovative and pay taxes,’ Dr Paivi Sillanaukee, General Director of the Finnish Ministry for Social Affairs and Health, explains: Sept. 2019. https://doi.org/10.1016/ S0140-6736(19)31877-X). Although STEMI patients make up a third of primary PCI cases, BIOSTEMI is the first randomised clinical trial, powered for superior- ity, to look at them specifically. ‘BIOSTEMI is not only the first randomised clinical trial to com- pare two contemporary drug-elut- ing stents, it’s also the first ran- domised clinical trial comparing two new devices with high standing platforms in patients with STEMI,’ Iglesias says, adding that he hopes the trial will lead to further research gaps being closed. ‘The use of these stents is mainly supported by non-inferiority trials, including all-comer patients, and for the first time we have a sub-group of patients that’s been shown to benefit from a dedicated stent.’ The ultrathin Orsiro was launched in the CE market in 2011 and received FDA approval in 2019. Orsiro’s safety, efficacy and clinical performance has been investigated in an extensive clinical program Dr Clemens Martin Auer is the special commissioner for health in the Austrian Federal Ministry for Health and Social Affairs, as well as president of the European Health Forum Gastein. The high-ranking Austrian civil servant per- formed a central function in all essential stages of healthcare reform in his coun- try. This also included the introduction of the electronic health file (ELGA) in Austria. Auer, who studied philosophy and political science in Vienna, was most recently co-chair of the eHealth Network, the responsible agency head within the EU and, as coordinator of the EU eHealth Governance Initiative, responsible for the strategic orientation of the common eHealth policy of the Member States. ‘In aging populations well-being has a countervailing effect also for the rise in costs of social services and healthcare.’ The demand for equal status, improved employment options for women, as well as the compatibility of professional and private life, are central objectives of the ‘Economy of well-being’ propa- gated by Finland. The European Semester ‘The instrument for implement- ing our program is the ‘European Semester’, explained Sillanaukee. This is a budgetary instrument that permits the EU to perform an early review of national budget and reform bills before these are adopted by the national parliaments. Every year in May, the European Commission publishes proposals on this basis as to what it feels each individual country could do better. Funds are tied to these ‘recommendations’. So, if a country does not fulfil the demands, then it loses money. The high-ranking Finnish civil servant is convinced that ‘the legitimacy of the Union among the citizenry is strengthened if well-being is given a clear priority among the EU’s long- term objectives.’ Dr Juan F. Iglesias from Geneva University Hospitals, Switzerland, unveiled results of the BIOSTEMI trial at the latest ESC Congress in Paris. with more than 48,500 patients enrolled so far. ‘Based on the data, compared to the Xience stent, Orsiro is a supe- rior solution for STEMI patients. In this patient group, vascular heal- ing is a challenge due to the com- plex environment with the vessel,’ Iglesias explained. ‘With Orsiro, we can incrementally improve patients care path.’ EUROPEAN HOSPITAL Vol 28 Issue 5/19 Drug-eluting stents reduce risk of lesion failure Orsiro DES demonstrates superiority in STEMI patients ciated with a 41 percent lower risk of target lesion failure (TLF) at 12 months, when compared to Abbott’s Xience. The study enrolled 1,300 patients and has since been pub- lished in The Lancet (Lancet online: About 30 percent of patients under- going primary percutaneous cor- onary intervention (PCI) suffer ST-Elevation Myocardial Infarction (STEMI) – the most acute form of coronary artery disease. Caused by a complete thrombotic occlusion, it is associated with sig- nificant morbidity and mortality. Following his presentation at a Late- Breaking session at the European Society of Cardiology Congress, Dr Juan F. Iglesias, from Geneva University Hospitals, has communi- cated the benefits of the Biotronik Orsiro drug-eluting stent (DES) for that challenging STEMI patient group. Iglesias is a co-principal investiga- tor of the BIOSTEMI clinical trial, which found using Orsiro to be asso-

4 N E W S & M A NAG E M E N T Transferring research into daily routine AI possibilities and probabilities Although some people foresee artificial intelligence easing medical workloads, many challenges arise before that dream can begin. Dr Felix Nensa and Dr Bram Stieltjes described such hurdles in an ‘Artificial Intelligence in Medical Imaging’ session held during a SITEM School Symposium in Bern, Switzerland. Report: Daniela Zimmermann Whilst artificial intelligence (AI) has potential, actually delivering that asset into routine medical practice remains a major challenge. Recently discussing ‘Translational AI – from bits to bedside’, radiologist Dr Felix Nensa, from Essen University Hospital in Germany, pointed to headlines that AI had helped to save lives, or that machines were suppos- edly better than radiologists. But, he noted, the tone of those headlines has been changing – indicating a peak in AI development. ‘Now,’ he said, ‘to get to a plateau of produc- tivity, we really need to be transla- tional. We need AI to do something useful for us.’ The hype around AI results from several decades of continuous expo- nential growth in computer hardware, the power of computers, and storage, which brings with it a lot of data. Is big data always big value? However, Nensa added: ‘You have to be careful not to equate big data with big value. Only if we have the ability to analyse this data does it turn into value. We are produc- ing more information but lagging behind in our ability to analyse this data. The big hope is that AI, or methods of machine learning, will help us close this gap and extract more value from our data.’ Sharing examples from radiology, he said decades of information from images had simply gone into archives and nothing further had been done with that valuable data. However, radiomics – among new C a y d a N / k c o t s r e t t u h S : e c r u o S buzzwords in radiology – is seeing information extracted from tumours, in terms of their shape and texture, with machine learning applied to the data to create predictive models or future treatment plans. A tumour’s N- or M-stage, he said, may be predicted by looking at a primary tumour. Or, for brain tumours, where there is reluctance to carry out a biopsy, machine learn- ing on PET-MRI data could be used to predict its mutational status. Yet, he still does not consider radiomics translational, because most methods need a manual tumour segmenta- tion, and there are also issues of standardisation, validation, and clini- cal acceptance. ‘Radiomics is inter- esting research-wise and we should go for it, but there is almost nothing Shaping your business success Daily clinical work means a wide variety of demands and challenges. We help you meet your needs by offering a solution tailored for your individual set-up. Ziehm Vision RFD Hybrid Edition* > Extend your capa bilities in cardiovascular surgery > Take your OR to the next level with a mobile hybrid solution > Start your hybrid procedure with zero room preparation > Reduce exposure significantly www.ziehm.com / RFDHE CMOSline represents a system configu- ration that is based on a Ziehm Imaging CMOS flat-panel detector. * Ziehm Vision RFD Hybrid Edition represents a group of optional hardware and software that creates an option package on the device named Ziehm Vision RFD. I see in five to ten years in clinical routine,’ Nensa said. At the centre for liver transplan- tation in Essen, he said a tool has been created to automatically segment the whole liver and pro- duce reports. He also outlined how machine learning can be used to predict how liver lobe will grow and predict future liver remnant in patients. A good machine learning model starts from a good question, he emphasised. ‘If you identify a clinical problem find what really needs improvement and then under- stand the problem and specify data, you can communicate that with data scientists, who can design a sys- tem. After that, it’s important to get these clinical models back to clini- cal routine early, to validate them.’ While the first try-out will probably not work that well, the process is repeated with further iteration to deliver a tool good enough to work in clinical routine. Nensa outlined the importance of medical informatics in translation and integrating tools into work- flows. ‘Medical informatics is needed to deploy AI tools into a hospital infrastructure because if it doesn’t work in the clinical routine, it’s worth nothing,’ he added. In bone analysis, for example, AI could be used to mimic a radiolo- gist’s workflow with stacked neural networks, harnessing the specialist’s knowledge of workflows into the data science for tools to work better. Is big data always big value? However, Nensa stressed that he does not think AI could or would replace radiologists or radiology. ‘Radiologists using these tools will get much more efficient much faster than those who reject them. In the end, radiologists who refuse to use these methods will be replaced – not by AI, but by other radiologists who do use these tools.’ On AI use theories recently dis- cussed at major radiology confer- ences, as well as the point about radiologists already operating at near capacity and needing new tech- nology to become more effective, he Directly after completing his final school exams, Felix Nensa freelanced as a software developer for the Research Institute for the Diagnosis and Treatment of Early Lung Cancer at the Augusta Hospital in Bochum. At that time he also took a distance learning degree course in IT (2000). His medical studies, at Ruhr University in Bochum (2001-2007), included two semesters at the University of Strasbourg in France. In 2011, Nensa became a registrar at the Institute for Diagnostic and Interventional Radiology and Neuroradiology at Essen University Hospital. He manages research projects on PET/MR, Cardio-MRI and DCEMRI. said: ‘That’s because we are getting more data every day and we cannot scale by just getting more efficient by ourselves, so we need tools to help us to scale and provide real- time diagnostic support.’ Rather than an autopilot, AI will be a co-pilot and leave radiologists to focus on vital tasks. It will not take jobs from radiologists, he confirmed, but will aid efficiency with routine tasks delegated to automation. ‘In the end,’ Nensa concluded, ‘we’ll have super-diagnostics, where all this information will come together and we, with the help of machines, will have oversight of all data, pro- viding better and more sophisticated real-time diagnostics. This is key to personalised medicine.’ Challenges to AI projects from Basel Dr Bram Stieltjes, University, outlined a range of challenges and hurdles involved in developing artificial intelligence projects in a clinical context. As Head of the university’s Research and Analysis Services Department, his presentation ‘AI in a clinical context; get ready to make your hands dirty!’, tempered expec- tations and focused on why AI in a medical context can be so difficult. He warned that a ‘huge over enthusiasm’ is circulating around medical data on what can be done in the context of AI. A key issue with machine learning is having sufficient information and items in reports, in the first place, to be able to extract meaningful information. In a significant proportion of cases, Stieltjes feels reports are incomplete. For structured reporting, he said, standard sentences must be a key element, but the aspect of ‘prob- ability’ is often overlooked, and its lack is a limitation. ‘Probability is the only way for us to know what you are thinking and the only way to use that data afterwards for a machine learning or AI project. If you do not add probability you are lost,’ he observed. Adding probability brings an extra dimension to reports and could help in future learning and thinking. ‘Recording medical think- ing like this not only helps to train algorithms but also to train doctors in a really quantitative way. ‘The whole structuring of medical data not only touches on training algorithms to replace what doctors do, but also trains doctors in a com- pletely different way.’ Bram Stieltjes MD PhD is VC of Research at the Department of Radiology of the University Hospital Basel and has recently formed a new department for research and analytical services in IT. In this role, he aims to integrate technical developments in physics and computer science into medical data science projects. His resident training is in radiology but he also had a year of training in child psychiatry and radiation oncology. He also headed a multidisciplinary group consist- ing of members from physics, medicine and informatics at the German Cancer Research Centre. There should also be a direct con- nection to the image. ‘Today, what you have with AI projects is that you are really looking for a needle in a haystack at best and sometimes, in searching for a needle, you just find hay.’ Within a healthcare setting, he said, clinical data is saved for clinical documentation without much con- sideration of research. ‘It’s relatively easy to find all the data points from one patient, but even the databases that control our clinical applica- tions are not built to find all similar patients, or all patients with the same exams.’ To create an effective machine learning application, he explained that auxiliary tools are needed that incorporate a risk element and tech- nical descriptions. Stieltjes’s team at Basel University reorganised their available data for research purposes and re-indexed technical exams in a re-think on the way they were deal- ing with data. Using the search engine for as many patients as possible who ful- filled their criteria, they could inves- tigate 12,000 MRI scans in 48 hours. ‘It’s a whole different way to work and enables interactive data inter- rogation and maybe drives the hos- pital infrastructure,’ he said. In a healthcare setting, he warned, there can be barriers to sharing data and acquiring it from other depart- ments for an AI project, and also pointed to disappointments in the length of time it takes to develop an AI project. Moving radiology – and other fields – to structured text has intrinsic limitations, he said. Obtaining good data will still not solve all the problems, especially the connection between text and image. However, in a scenario where all data created in a medical context is structured can help with modelling the data, and in making a virtual model of organs and predictions. ‘I think this highly depends on how seriously we take the data-driven organisation of medicine,’ Stieltjes said. ‘We shouldn’t organise our- selves around diseases, doctors and specialties; we should analyse what data elements are important for decision-making and how we get them.’ The focus should be more on the data stream, rather than what is necessarily most convenient for the clinician, he said. ‘If we can turn that thinking error around, I think we’ll see rapid progress. If we don’t, I think we’ll talk like this for decades.’ EUROPEAN HOSPITAL Vol 28 Issue 5/19

6 L A B O R AT O RY Lab services: Don’t cut the cost! In recent years, whenever the German media reported on laboratory medicine, questions consistently arose: ‘How can excessive costs for lab services be cut?’ and ‘How could money saved be distributed among other medical specialists and general medicine practitioners (GPs)?’ Specialist lab physicians raise quality of car The questions are myopic in their failure to address two important aspects of laboratory medicine – its significance for patient well-being and the preconditions that should be fulfilled to operate a lab successfully. These are closely intertwined, since lab medicine drives and is driven by innovation and thus requires ongo- ing and high capital investments. Without those investments medical Chemist and physician Dr Andreas Bobrowski chairs the Association of German Laboratory Physicians, and pro- motes the rational handling of lab diag- nostics by developing and implementing diagnostic pathways in healthcare. Early in his career, he joined a Lübeck-based laboratory group of which, 12 years later he became head (2005). A delegate to the regional Association of Statutory Health Insurance Physicians Schleswig- Holstein since 1999, he has been the only lab physician delegate in the National Association of Statutory Health Insurance Physicians since 2011. progress cannot arrive. There is a third neglected aspect: innovative tests – even if expensive – might well reduce overall healthcare costs. 66% of medical diagnoses are made by lab physicians* Roughly 2.5 percent of healthcare costs reimbursed by German statu- tory health insurers are generated in the laboratory. No doubt this money could be spent more wisely if pay- ers and politicians drew the right conclusions. Over recent years, lab medicine has developed from a care- relevant to a system-relevant cross- sectoral discipline, which greatly influences the direction of the healthcare system as a whole: two thirds of all diagnoses are made, or confirmed by, approximately 1,000 hospital-based and office-based lab physicians. Specialist lab physicians, aware of their influence in healthcare, are drafting lab diagnostic pathways and guidelines for their discipline. Inspired by the USA initiated cam- paign ‘Choosing wisely’ – based on preparatory work in the German Society for Clinical Chemistry and Laboratory – the National Association of Statutory Health Insurance Physicians, along with the Association of German Laboratory, are developing ways to introduce those pathways and guidelines into medical practice. Their recommendations explic- itly aim to enable high quality and cost-efficient care, particularly when complex and expensive therapies are involved. teamwork Teamwork is crucial is necessary Close between referring GPs and hospital- based physicians on the one hand and lab physicians on the other. In this well-structured landscape of diagnostic and treatment pathways the ‘four-eyes’ principle (approval by at least two people) is the alpha and omega of patient safety, being a safeguard against wrong diagnoses and waste of resources. However, benefits culled from this kind of cooperation depend, to a large extent, on the significance of lab physicians and the appreciation they receive. For instance, in the Netherlands cooperation with micro- biology has contributed significantly to one of the lowest MRSA rates worldwide. In Germany, Austria and Italy, lab services can be provided and assessed only by a lab physician, which creates a communication structure where the doctors involved are on equal footing, ensuring high diagnostic quality and treatment safety. In countries where lab services are not necessarily provided by lab physicians, but by medical techni- cians, results are forwarded to the referrer without further assessment. Thus the referrers cannot discuss them with a lab physician who is well versed in all issues surrounding lab analytics. e t z r ä r o b a L r e h c s t u e D d n a b r e v s f u r e B : e c r u o S Andreas Bobrowski and colleague evaluate a SDS electrophoresis to differentiate proteinurias. On the European level, healthcare systems remain very different, even in diagnostic-technical disciplines, although medical diagnostics manu- facturers, as well as professional associations, have long pushed for Europe-wide standards. In several EU Member States, and Switzerland, clinical-chemical and haematology basic services are provided on site, while, in Northern European coun- tries, Benelux, Germany and Austria, large service provider groups with large catchment areas have evolved. These significant differences in services provision have created a wide variety of reimbursement struc- tures within the EU. The number of tests have also increased and innovation pressure has intensified, while all healthcare systems record shrinking resources and increasing morbidity rates. Which current system is therefore best-suited to overcome future chal- lenges? In terms of sheer numbers, lab medicine in Germany is facing the biggest task because, with 18 visits per person per year, Germans spend far more time with their doc- A peek in the medical lab: receipt and handling of test samples e t z r ä r o b a L r e h c s t u e D d n a b r e v s f u r e B : e c r u o S Human/Computer Interaction challenges Designing lab automation and environments The key challenge of Human- Computer Interaction (HCI) in cre- ating a productive and efficient Andreas Schuller currently leads the Interaction Design and Technologies team at the Fraunhofer Institute for Industrial Engineering in Stuttgart. He studied Computer Science and Media at the University of Ulm and Interactive Systems (Programming) at Monash University in Melbourne. In research and industrial projects, his interest is on the connection of the human-centred design process with the technical development of innovative user interfaces. His research focuses on the development of new interaction pos- sibilities for industry 4.0, the implementa- tion of mobile networked applications and intelligent user interfaces as well as design patterns for security and privacy of users. During future laboratory was examined in detail by Andreas Schuller from the Fraunhofer Institute for Industrial Engineering in Stuttgart, Germany, during the recent SLASEurope2019 conference in Barcelona, which drew in more than 1,000 scientists and technologists. his presentation, ‘Workplaces of the Future: Future Topics and Trends for Human- Machine Interaction – Implications for Lab Automation’, Schuller looked at three key areas that would impact on the laboratory of tomorrow. These are: the driving forces that shape how workplaces will look; relevant research themes his team is working on; and what the implica- tions are for Lab automation. ‘In a nutshell,’ he said, ‘it is essen- tial to address HCI and interaction design for lab automation equip- ment and environments due to its increasing future importance and major upsides and benefits for com- panies. Driving forces that will shape how workplaces will look in the future include: demographic and shortage of skilled workers; effects of globali- sation and demand for more speed and flexibility from companies; cul- tural changes at the workplace try to find a better work-life balance; and advancements in digitisation and Artificial Intelligence (AI). ‘Due to these factors,’ Schuller added, ‘it’s increasingly important for interactions between workers and their instruments to take place in a frictionless manner. Workers need to grasp interfaces quickly. Additionally, the technical advance- ments must allow for closer col- laboration between workers and smart systems, where the worker complements these systems by train- ing them, and AI and machine learn- ing allow for better assistance of employees than ever before.’ Focus on conception, design and development Schuller heads Interaction the Design and Technologies team at the Fraunhofer Institute for Industrial Engineering, which develops strate- gies, business models and solutions for digital transformation. Their focus is on the conception, design and development of human-technol- ogy interaction, aiming to make the most of the opportunities offered by digitisation through novel forms of interaction. Current research themes being developed by his team include adap- tion and personalisation of user interfaces; creating shared know- ledge spaces between employees and AI systems; making digital information available on the spot (through augmented and virtual reality, such as in a medical setting); and quantifying physiological data. ‘Sensors allow for a novel kind of context detection of the user,’ he explained. ‘Systems can automati- cally set themselves up to accommo- date for different tasks within the work context, or different person- alised input modalities for the user, also enabling accessibility features. ‘In increasing collaboration envi- ronments between employees and smart systems, the aim is to foster common knowledge and informa- tion data set. The important ques- tion here is: how can we incentivise users to provide this kind of infor- mation?’ By quantifying physiologi- cal data such as heart rate, brain activity and galvanic skin response, researchers can attempt to derive conclusions towards the emotional components in design, or identify cognitive dimensions such as aware- ness during a certain task. However, he stressed that there are implications for lab automation. ‘To create effective and innovative interactions that also work for the coming years, it’s important to gain an understanding and overview of the technical options available,’ he explained. ‘We have created a tax- onomy of interactions or interaction space that can serve as a kind of guideline. When it comes to evaluat- ing technology fit, it is important to be aware of relevant standards that play a role for the context and task. Employees must be involved in the process ‘The second point is to methodically involve the employees or existing system users in the design process. Only they have the perspective and Virtual Reality interaction in the lab EUROPEAN HOSPITAL Vol 28 Issue 5/19

8 L A B O R AT O RY Sharing four crucial perspectives Pre-analytics and patient safety BD, a global medical technology company, participated in the 5th European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) conference on pre-analytical phase in Zagreb, Croatia, 22-23 March 2019. At the conference, they met with Steve McManus, Professor Ana-Maria Simundic, EFLM conference chair, Professor Mario Plebani and Dr Alexander von Meyer, member of the EFLM conference scientific committee. Mr Steve McManus, of the Royal Berkshire Hospitals National Health Service (NHS) Foundation Trust, Reading, United Kingdom Professor Ana-Maria Simundic, from the Department of Medical Laboratory Diagnostics, University Hospital Sveti Duh, Zagreb, Croatia Professor Simundic and Dr von Meyer belong to the EFLM Working Group for Pre-analytical Phase (WG-PRE). They gave us their views on patient safety, the pre-analytical phase and its impact on the emergency depart- ment (ED). Healthcare’s purpose is to maintain or improve patients’ health. With the introduction of new technologies, medicines and treatments, healthcare is becoming more complex. There is growing awareness that human and systemic factors can harm patients through preventable adverse events. Medical errors that lead to these adverse events are a major burden on healthcare systems across Europe. Up to 70% of all medical decisions are based on the results of laboratory tests and up to 66% of diagnostic errors occur during the pre-analytical phase. This is why these errors have the potential to cause great harm to patients according to Professor Plebani. The challenge of haemolysis and other pre-analytical errors For Simundic, there is a lot to be done to prevent pre-analytical errors in the ED. Haemolysis is by far the most frequent pre-analytical error and the main reason for rejected samples. It occurs when red blood cells rupture and release haemoglo- bin and other intra-cellular compo- nents into the plasma or serum. Causes include drawing blood incorrectly, underfilling tubes, shak- ing of samples and using intra- venous catheters to collect blood samples. Haemolysis may lead to unreliable results, delayed diagnosis and avoidable harm to patients. But, as Simundic pointed out during her presentation at the EFLM confer- ence, not all clinical laboratories in Europe use the same haemolysis index cut-offs, or the same detection techniques. She pointed out that the visual detection of haemolysis has been found to be highly unreliable and extremely inconsistent. According to Simundic and Plebani, the highest rates of haemolysis are in the emergency department (ED), with 65% of samples rejected for this reason. Simundic said the ED is the hospital department where most pre- analytical errors (e.g. patient misi- dentification) occur. Plebani found it is more difficult to identify haemoly- sis with point of care testing (POCT) than testing performed in central laboratories. With the rapid growth of POCT in clinical settings such as the ED, the role of the pre-analytical phase in POCT may therefore pose an increasing challenge. It is also common in the ED. Up to 70% of all medical decisions are based on the results of laboratory tests Up to 66% of laboratory errors occur Up to 65% of emergency department sample rejection is due to haemolysis during the pre-analytical phase Measuring pre-analytical quality Pre-analytical quality indicators are used to measure performance in the ED and other hospital wards. Dr von Meyer identified the most important quality indicator for healthcare sys- tems as being turnaround time (TAT). Though definitions vary, we define it here as the time from test request to reporting of results. von Meyer mentioned that we do not always know the exact sam- pling time, and this is important for calculating TAT. Some reference values are correlated to the time of day and sampling time is needed to calculate drug doses. However, clinical laboratories do not agree on a standardised way to use qual- ity indicators to measure laboratory performance during the total testing process (TTP). Preventing errors and improving pre-analytical quality Solutions exist to reduce pre-ana- lytical errors and positively impact on patient safety. Better haemolysis management requires using auto- matic detection systems instead of visual identification; defining hae- molysis index cut-offs based on bio- logically variable data instead of using one cut-off for all tests and all patients, and informing clinicians when results are from haemolysed samples. If automatic detection sys- tems are not available, the laboratory should use a colour chart for visual identification. Von Meyer stressed the importance of knowing sampling time to improve TAT and to ensure sample stability. The exact sampling time should be documented and included with each sample. Faster TATs may lead to more timely treatment and improved clinical outcomes. Techniques used to reduce centrifugation time may also have an impact on TAT. Since 2008, Plebani’s team has been working on the harmonisation of quality indicator management. Over the past five years, laboratories have uploaded data on the model of quality indicators (MQI) web- site: http://217.148.121.44/ MqiWeb/ Page_Presentation.jsf. This is a free service. Plebani’s team has collected and analysed this data, from which they have identified 26 quality indicators and 53 measurements, with defined benchmarks. Their final goal is to create an MQI that could be used by clinical laboratories all over the world to help increase sample qual- ity while reducing laboratory errors. Professor Mario Plebani is at the Department of Laboratory Medicine, University-Hospital of Padua, Italy Dr Alexander von Meyer, from the Institute for Laboratory Medicine, Kliniken Nord oberpfalz AG, Weiden, and Klinikum St. Marien, Amberg, Germany Future perspectives: POCT testing and a culture of safety For von Meyer and Simundic, the future of pre-analytics will be in POCT. POCT has been shown to reduce TAT, while providing rapid answers for decision-making in the intensive care unit (ICU). However, it presents specific challenges because POCT sample collection is usually performed by clinical staff who have varying levels of experience with sample analysers. Care settings where POCT is used tend to have heavy workloads and the pre-analytical phase varies from patient to patient, based on level of urgency. This makes minimising human error an added challenge. Effectively training clinical staff in quality control and ensuring close collaboration with laboratory staff are important to maintain the reli- ability of results from POCT. According to Mr McManus, learn- ing is at the heart of a culture of safety. By learning from mistakes and applying that knowledge to workflows, we can improve patient safety. McManus and Simundic also said it is important to create the right conditions for this kind of organisa- tional culture. Healthcare workers and laboratory staff should feel com- fortable about reporting errors and suggesting ways to improve these workflows. Another way to improve patient the pre-analytical safety during phase is through clinician-lab coop- eration. A recent study by McKeeman et al showed that having a laboratory technician processing samples in the ED can reduce TAT and improve communication with the laboratory. Clinicians should feel free to come to the laboratory and lab workers to meet with their colleagues in care settings to improve communication between these important stakehold- ers along the care continuum and enhance patient safety. Preventing haemolysis, keeping TAT as short as possible, reducing pre-analytical errors, harmonising quality indicators, maintaining the reliability of POCT results and build- ing a culture of safety are all ways to ensure patient safety throughout the pre-analytical phase in the ED and beyond. *References may be requested from the author Discover BD Patient Safety: eu.bd.com/ patient-safety The transcription factor GATA-3 Switching off chronic inflammations e n i M r o t c e V / k c o t s r e t t u h S : e c r u o S Chronic inflammatory diseases, such as allergies and asthma, are not only an acute problem but also a major research and prevention chal- lenge. When our EH correspondent spoke with Professor Harald Renz, Director of the Institute for Laboratory Medicine at the University Hospital Gießen/Marburg, Germany, they discussed the major reason for increases in the number of these widespread diseases. Interview: Walter Depner ‘Allergies such as asthma, neuroder- matitis and hay fever,’ observed Professor Harald Renz, ‘are so-called non-communicable diseases – NCDs. All NCDs, including auto-immune, cardio-vascular and neuropsychiat- ric diseases, are rising worldwide. This group of diseases is associated with a genetic disposition. Genes, however, do not lead to the out- break of NCDs, including allergies. Outbreak is triggered by certain environmental and lifestyle factors. ‘Most experts seem to agree that NCDs, and thus allergies, are increas- ing because the lifestyles in the Western industrialised world poses a major challenge for the immune system: it produces an abnormally vigorous response to rather benign environmental substances, the aller- gens. Why this excessive reaction? Due to the Western lifestyles the immune system lacks sufficient training, particularly during child- hood. This training is necessary to induce immunological and clinical tolerance. Microbes, harmless bac- teria from the environment, trigger tolerance induction.’ Figures and stats? ‘Since World War II, the prevalence of allergies has been escalating sig- nificantly – in the Western industri- alised world. We estimate that each third child is born with an allergy risk. Recent studies at the Robert Koch Institute show this increase to continue unabatedly. Approximately 10 percent of the population suffer EUROPEAN HOSPITAL Vol 28 Issue 5/19

1 0 R O B OT I C S Myths and misconceptions Robotic surgery: good for some, not all Report: Sascha Keutel The first use of a robot-supported surgical intervention was reported in 1985, when the robot arm PUMA 560 placed a needle for a cerebral biopsy using CT guidance. Since then, strong growth in the market for robotic surgery has occurred, due to an increasing automation demand in the healthcare as a whole and greater concentration on minimally invasive surgery (MIS) for faster recovery. Robot-supported surgery is now applied in many disciplines. In neu- rosurgery, for example, image-con- trolled robots aid in the examination of brain lesions without serious damage to adjacent tissue. General surgeons can perform gall bladder, hernia, cancer and colon opera- tions with a robot. Robots are used in orthopaedic surgery to form the femur bone so that a prosthetic hip joint replacement fits exactly. However, some patients still find the concept of robot operations unsettling or intimidating, not least because of a few widespread myths. One such myth is that the proce- dure is programmed and the robot performs the operation on its own, i o e d V r e t s a M / k c o t s r e t t u h S : e c r u o S automatically, without any human involvement. In reality, robot sur- gery is an operation that the sur- geon performs aided by a robot system through which he controls 100 percent of what happens. Surgical robotic systems are composed of miniaturised surgi- cal instruments mounted on robot arms. The surgeon controls every movement of the robot arm and instrument directly in real-time. Every movement the surgeon per- forms with hands on the console is performed simultaneously by the robot control. In other words, the robot acts as the extended arm of the surgeon. Another frequently propagated myth is that the surgeon performs the operation in another room. The surgeon is always pre- sent in the room and the console used to control the robot is only a few meters away from the patient. Moreover, the patient is constantly monitored by an assistant next to the bed, along with members of the anaesthesia team and a nurse. The advantages Robot systems permit outstanding visualisation and very precise move- Surgical breakthrough in France ments. These properties enable the surgeon to perform minimally inva- sive interventions with high pre- cision, control and flexibility. All this leads to a generally shorter hospitalisation, less post-operative pain and a faster return to active life compared to laparoscopy or open operations. However, robot-supported surgi- cal systems are expensive and, as a rule, require longer operating times as well as intensive training and fre- quent practice. Often, the evidence for the advan- tages of such surgical techniques is unconvincing. The risks of robot- supported operations are compara- ble with those of common surgery. In fact, clinical studies of robot- supported surgery for indications in the chest and abdomen as yet have only exhibited a few advantages for this cost-intensive surgical method, according to a current analysis by the Ludwig-Boltzmann-Institute for Health Technology Assessment (LBI- HTA), in which the relevant inter- national clinical studies have been assessed. ‘Altogether, it can be said that, in the case of the indications analysed, there are few signs of clear advantages for the effective- ness and safety of this new surgical technique,’ said PD Dr Claudia Wild, director of the LBI-HTA. One example is a study by researchers for UNSW Medicine, at the Ingham Institute and the South Western Sydney Local Health District. These show that prostate cancer patients believed errone- ously that the robot operation con- stituted a more definitive cure for prostate cancer than other treat- ments, such as radiation therapy. ‘The robot-supported radical pros- tatectomy is becoming the treat- ment of choice more frequently by many men, despite the potentially higher cost and limited evidence of its superiority over other treat- ments,’ Dr Ben Smith of the Ingham Institute pointed out. The study also found that patients often disregard the various side effects of their treatment options but, above all, follow only their phy- sicians’ recommendations. However, robot technology might not be the right option for every patient. Therefore, patients ought to gath- er information about all treatment options before they make a decision that has a substantial impact on their quality of life. Robot enables lumbar spine repair Is it possible to repair the rachis without having to open the abdomen or the back? A team of French surgeons has done just that. Thanks to minimally invasive robotic surgery, exposing the patient to risky spine interventions may soon be avoidable, a leading surgeon explained. Report: Mélisande Rouger Neurosurgeons and vascular surgeons in France have, for the first time, suc- cessfully repaired the lumbar spine with the help of a da Vinci robot. This pioneering intervention results from a cooperation between Nancy University Hospital and Timone University Hospital in Marseille. The patient, a 36-year-old man with a complex vertebrae fracture caused by lumbar trauma, received an iliac bone fragment implant and prosthe- sis and is recovering quickly. This minimally invasive robotic technique is a game changer in spine trauma surgery, which tradi- tionally requires opening the patient quite extensively either in the abdo- men or the back, to access the lesion and secure the surrounding vertebrae, aorta and blood vessels. With this new type of surgery, sur- geons can now repair the fractured or damaged vertebrae by doing an incision of just a few millimetres, Serguei Malikov, professor of vas- cular surgery at Nancy University Hospital, explained. ‘We did the same radical and final gesture as in classical sur- gery, only with a simple puncture of the abdominal wall. We did not have to open the wall to repair the rachis,’ he said. ‘We just placed the robot’s arms inside the cav- ity, without damaging the abdomi- nal wall or moving the organs.’ A surgeon controls the robot via a control console Like seeing spine and nerves under a microscope Working with the robot tremendous- ly improves surgical vision during the intervention, thanks to a power- The da Vinci assisted in an anterior lumbar repair From left, the robotic spinal surgery team. Neurosurgery - Professor S Fuentes, Doctor N Mansouri. Vascular Surgery - Professor S Malikov, Doctor N Settembre, Doctor C Saba surgery, but without any risks. The intervention time is shorter and the patient does not need to be opened and closed, prompting better surgi- cal outcome and earlier recovery. ful camera, excellent resolution and the possibility to zoom in. ‘It’s like seeing the spine and the nerves, the part that wraps up the bone mar- row, through a microscope,’ he said, adding, ‘with much more detail than traditional surgery,’ Robotic surgery fast and expands the surgeon’s field of action without touching surround- ing tissues. ‘The robot improves our precision and movement amplitude, allowing us to repair areas that used to be complicated to access,’ he said. With the robot, the minimally invasive approach is as radical as is Cooperation is key Experts foresee a wide variety of applications for repair of rachis lesions caused by trauma, infection, degeneration or cancer. Robotic sur- gery of the spine is bubbling. Other patients have been treated with the technique in Nancy and Marseille. Their evaluation will help determine how much the technique can be expanded to wider surgical practice. As for the lumbar spine in particu- lar, Malikov said he found only two publications – in the USA but none in Europe – on similar interventions, but at other rachis levels. Serguei Malikov studied medicine at the University of St Petersburg, Russia. He carried out his research in experimental surgery in Marseille and currently heads the Vascular Surgery Department in Nancy University Hospital, France In France, vascular surgery has been a well-established subspecialty (founded 1984) much earlier than in other European countries. This seniority, combined with the pos- sibilities offered by technology, is promising, and boosts collaboration with other subspecialties, especially neurosurgery, Malikov believes. ‘We are very proud of our break- through. We’ve been working on the topic for the past five years, first in animals, then cadavers. ‘It’s the result of a close coop- eration between two hospitals, and two subspecialties: neurosurgery and vascular surgery. The key in rachis reconstruction is vessels and aorta control. It’s the access, not the disease, that demands vascular sur- geons to step in.’ Experimental works have been carried out at Nancy Surgery School, within the Lorraine Virtual Hospital, a reference centre in Europe for training and research in medico- surgical innovation (notably tele- surgery, robotic, coelioscopic, endo- scopic and endoluminal surgery) and evaluation of therapeutic pro- cesses validation based on surgical expertise. EUROPEAN HOSPITAL Vol 28 Issue 5/19

1 2 R O B OT I C S Aiding well-being and future surgical training Robotic surgery is expanding Report: Mark Nicholls is seeing Standardisation of robotic surgery procedures increased usage and improved outcomes for patients and could also play a role in helping with the overall well- being of surgeons in terms of, for example, ergonomic benefits that could reduce repetitive strain injury (RSI) and back conditions. Change of surgical care Richard Kerr from the Royal College of Surgeons (England) recently chaired the RCS Commission on Future Surgery, which focused on advances in medicine and technol- ogy, plus robotics, that are likely to change surgical care in the next 20 years. Areas considered included innovations in data analytics, artifi- cial intelligence, genomics, regen- erative medicine, virtual and aug- mented reality, 3-D printing and planning. y r r e b d a r B m a y l l i W / k c o t s e t t u h S : e c r u o S ‘Perhaps the most important thing to say is that the use of a robot effectively adds to the surgical arma- mentarium,” Kerr explained. “It’s about adding to the instruments that we have available to help patients, not about robots doing operations in isolation from surgeons. This is a very sophisticated tool, where the surgeon is in an ergonomically-com- fortable position. It’s a very precise instrument and therefore eliminates any sort of human frailty like tremor or fatigue.’ Lengthy surgical procedures can be physically tiring; surgeons move into awkward positions to gain a line of sight into a patient, or they use microscopes or manipu- late instruments during laparoscopic procedures. Using a robot, the sur- geon is seated in front of a screen and can manipulate the robotic arm with his hands from a console. ‘You have a very precise instru- ment that you can navigate to dif- ficult spaces and places within the human body, which gives us improved access, visualisation and illumination,’ Kerr pointed out. ‘Because you are using minimally invasive techniques, it’s also a huge benefit to the patient, hopefully with improved recovery times and less pain. What‘s also important is that there is the potential to use robots to begin to standardise what we surgeons do. “Naturally, there’s a variation in outcomes. I think use of the robot potentially allows us to reduce the variation and hopefully improve the level of care that we give patients.” Training platform ‘The training issue is very important. We need to ensure there is a defined training platform that makes sure that we can reap all the benefit and hopefully eliminate any of the risks that come with bringing new tech- nology into our ways of working.’ And, Kerr emphasised, ‘I think the Neurosurgeon Richard Kerr, at the John Radcliffe Hospital, Oxford, has been a consultant for 30 years. He devised and ran the Oxford Skull Base Practice and his subspecialty interests lie in skull base tumours, oncology and vascular disease. A former president of the Society of British Neurological Surgeons (SBNS), he sits on the council of The Royal College of Surgeons of England and chaired the independent Commission on the Future of Surgery. take-up of robotics needs to be con- ducted in a structured way, with a structured training programme.’ RCS England is keen to work with NHS England to achieve this. In conclusion, the neurosurgeon sees the use of robotic surgery expanding from the more com- monplace use in urology to colo- rectal surgery, gynaecology, cardio- thoracic surgery, ophthalmology, and potentially into his own field: neurosurgery. The vital element in successful joint replacement Bone cement: a key factor Bone cements made of polymethyl methacrylate (PMMA) are well established in joint arthroplasty, particularly for hip and knee joint implantations. PALACOS was introduced in 1959 as one of the first bone cements and has proven very successful to this day. The history goes way back. The first patent based on cold-curing plastics was issued in 1943. No one had any idea that this would lay the founda- tion for the unique success story of bone cements in orthopaedics. The bone cement breakthrough in orthopaedic surgery happened in the 1950s to anchor acrylic glass caps to the femoral head after removal of the joint cartilage. After further product develop- ment, the first bone cement for orthopaedic surgery was launched in Germany in 1959 under the name Palacos. The brand has since become the gold standard among bone cements. idea from Following an the Hamburg surgeon Professor Hans Wilhelm Buchholz, antibiotics were added to this bone cement for the first time in 1969. Palacos R with gentamicin has been available since 1972, as the first antibiotic-loaded cement produced commercially with added gentamicin. Evidence as the basis for quality The development of Palacos bone cement is founded upon numer- ous clinical studies and investiga- tions to achieve the desired medical and mechanical properties of the cement. Factors such as strength, creep resistance and longevity are relevant to ensure optimal load transfer of the endoprosthesis to the bone. Decisive factors for the highly reproducible and reliable quality of the cement are the special polymer structure and the manufacturing and sterilisation process used and vali- dated by Heraeus Medical, which has remained unchanged since its introduction in 1959. The most studied bone cement worldwide Numerous registers, meta- and long- term studies from the past decades document that cemented knee and hip joint prostheses, especially for an older population, have consid- erably longer survival rates and reduce the risk of revision. In par- ticular, Palacos products with anti- biotic additive are superior to other bone cement manufacturers thanks to their longer and higher antibiotic release, the manufacturer adds. ‘Over the past 60 years, Palacos has been used with and without antibiotic additives in more than 30 million joint replacement proce- dures worldwide. Palacos cements are therefore the most frequently used bone cements to date – in more than 90 countries,’ Hereaus confirms. The reproducible quality of this cement is documented by evidence from more than 130 clinical stud- ies published since the 1950s in renowned international scientific publications and involving over 9,000 patients, the firm adds. ‘The first long-term studies on the use of Palacos were already available in the 1980s, and no fewer than 20 studies have been added since 2010. A literature analysis from 2018 shows that Palacos is not only the most often used bone cement in the world, but also the best inves- tigated.’ Committed to the gold standard ‘Cements with different properties are needed depending on the field of application in joint arthroplasty. Users can now turn to Palacos cements in various viscosities (flow properties). The high- and medium- viscosity variants, for example, are fast-curing and can be inserted eas- ily into the bone or applied to the implant,’ Heraeus reports. Additionally, the company con- firms, handling and mixing of Palacos has been further simplified and the portfolio also supplemented by the modern ready-to-mix Palacos pro system. * Source: Heraeus Medical EUROPEAN HOSPITAL Vol 28 Issue 5/19

1 4 R A D I O LO G Y Multidisciplinary care is key to cardiac disease management Research with 7-Tesla MRI New 7-T MR methods could potentially shed light on cardio- myopathies’ principles, according to a leading French radiologist who also stresses the importance of teamwork between radiolo- gists, cardiologists, surgeons and anaesthesiologists. Morphologic and dynamic informa- tion of the myocardium is achieved with millimetric resolution (0.9x0.9 mm2). Strong intensity variations characteristic of 7-Tesla MRI can be observed from anterior to posterior myocardial segments. New tools provided by indus- trial partners and used by cardio- vascular surgeons and radiologists are improving treatment of thoracic aorta pathologies. An increasingly used technique is fusion imaging, in which pre- treatment MR and CT scans of the patient are being fused with angi- ography images to guide stent-graft Figure 1 Figure 2 Sodium mapping of the heart using 7-Tesla MRI Higher signal-to-noise ratio (SNR) using 7-Tesla MRI allows to map sodium in the human heart. The isolation of the long relaxation sodium component (using a long echo time) and the compen- sation of concomitant signal modulation (T2star and B1+/B1- from transmit-receive coil) allows for a single slice to be mapped within 5min at a resolution of 2x2x10 mm3. Reference sodium con- centration vials attached to the coil serve as calibration of the sodium MRI signal. Figure 1: Top-left is B1+/B1- map, Top-right is T2star map, Bottom-left is anatomical MRI image of the heart using conventional 1H-MRI, and bottom-left is the map of long- relaxation sodium concentration after corrections of the sodium MRI signal using the maps at the top. Figure 2: Overlay of long-relaxation sodium map onto the anatomical MRI. High-resolution Simultaneous Multi-Slice (SMS) dynamic MRI of the heart at 7-Tesla Increased signal-to-noise ratio from the 7-Tesla MRI is harnessed for refined imaging of heart. Simultaneous Multi-Slice (SMS) cardiac dynamic MRI (cine) permits the acquisition of three thin- slices (4 mm) within a 10 s breath-hold. Robustness to patients motion and limited breath-hold capacity is guaranteed through a dedicated self-calibrated SMS technique tailored for cardiac imag- ing. Morphologic and dynamic information of the myocardium is achieved with millimetric resolution (0.9x0.9 mm2). Strong inten- sity variations characteristic of 7-Tesla MRI can be observed from anterior to posterior myocardial segments. Figure 3: SMS cine acquired within 10s showing diastole (relaxed phase of the cardiac cycle) of the apex (a) mid- ventricular (b) and base (c) slices. a b c navigation through the vascular structures of the patient during the intervention, according to Alexis Jacquier, cardiovascular radiologist at Timone University Hospital in Marseille. ‘Fusion imaging enables to lower radiation dose and to reduce the amount of contrast media that are traditionally required in this type of surgery. It avoids having to inject iodine to know where we’re at,’ he explained. Covering full aortic pathology management, from diagnosis to care and follow-up The hospital also hosts the Timone Aortic Centre (CAT in French), a leading regional multidisciplinary centre that covers full aortic pathol- ogy management, from diagnosis to patient care and follow-up, with a strong connection with the univer- sity. The CAT includes vascular and cardiac surgeons, radiologists, car- More than just MRI accessories www.allmri.com diologists, vascular physicians and anaesthesiologists. The objective is to provide a mul- tidisciplinary approach to provide the best medical care; for instance all thoracic stent-graft procedures are performed by a multidiscipli- nary team comprised of vascular surgeons, radiologists and anaesthe- siologists at CAT. Imaging has become key in tho- racic aorta treatment with the boom of minimally invasive procedures. Besides thoracic disease, Timone Hospital is one of the main cen- tres in France offering endovascular interventional radiology skills to treat patients with carotid and renal disease, which Jacquier and col- league Vincent Vidal perform daily, along with the full suite of car- diovascular interventional radiology procedures – endoprostheses and stent placement, small vessels and tumour embolisation, etc. Furthermore, the hospital is locat- ed close to the medical and biology MR centre (CRMBM), one of the few laboratories in Europe that work with 7-T MRI for diagnostic imaging research. This proximity enables Jacquier and team to test 7-T methods using sodium instead of proton imag- ing, a possibility that opens brand new perspectives in heart imaging. ‘Sodium electrolytic disorganisation in the myocardium can have an electrical and mechanical impact on heart function. 7-T will enable the development of new applications in the field. It is still a complex task, but we are working hard on different papers on sodium quantification in the myocardium and potential clinical applications’ he explained. Cooperation with cardiologists is essential in myocardial disease man- agement, according to Jacquier, who again stressed the importance of the multidisciplinary approach during patient treatment. ‘Patients are now being cared for within the heart team, a model increasingly followed by healthcare facilities in France and beyond,’ he explained. ‘Whether it’s for TAVI procedure, diagnosis or follow-up. Medicine is becoming hyper specialised and mixing profiles and specialties ena- bles us to significantly improve patient care.’ Obligatory three-step training for residents in emergency radiology Another significant development in France was the reform of the radiolo- gy residents’ training scheme, which was introduced in 2017. Radiology residents must now undergo a three- step training, including successively: base training (one year), dedicated to emergency radiology; in-depth training (three years), to ensure that every subspecialty in radiology has been covered in their education; and consolidation training (one or two years), providing certification for one or two subspecialties. The French Council of the Teachers of Radiology (CERF) has been piloting the change for radiology. The French Society of Cardiovascular Radiology now pro- vides e-learning material to ensure homogeneous teaching and training program across the country. Last September, the series became freely available for French residents on the CERF website, and also available for all radiologists on the Cardiovascular radiologist Professor Alexis Jacquier, at Timone University Hospital, Marseille, France, trained in Marseille and Lyon and gained his PhD in San Francisco, USA, supervised by Maythem Saeed and Charles Higgins. In 2006 he integrated the cardiovas- cular group in the CEMEREM research lab (http://crmbm.univ-amu.fr). He is author and co-author of more than 90 peer-reviewed publications and has presented numerous lectures, tutorials and refresher courses internationally. He also chaired the European Society of Cardiac Radiology membership com- mittee and is current vice president of the French Society of Cardio-Vascular Radiology (Société Française d’Imagerie CardioVasculaire, SFICV). website of the French Society of Radiology. This change is a substantial improvement in the training scheme, because it reflects daily routine bet- ter, Jacquier added. ‘Cardiac imaging studies are being prescribed every day by all sorts of physicians: GPs, endocrinologists, surgeons, and even oncologists, for instance in pre- and post-chemotherapy evalu- ation.’ Many things may need updatewing for AI As for cardiology, the French Society of Cardiology and the French Society of Radiology estab- lished a working protocol in 2005; according to this, the cardiologist prescribes the CT and MR scans and radiologist performs the tech- nical assessment and writes the report – and then sends it to the cardiologist. Jacquier: ‘This division of tasks promotes the best possible medical care, but everything really depends on the physician’s skills. A lot of things may need to be updated as we gradually introduce artificial intelligence.’ Radiologists must also homoge- nise the way they write the imaging report. Introducing the structured report to exploit data at national level will prove essential for their future. Another priority is to improve communication not only with patients but also other medical spe- cialties, he said. The radiologist is no longer alone in a basement reading scans,with no contact Jacquier will participate in the International Day of Radiology (8 November 2018), an initiative to highlight the radiologist’s role in cardiac care. ‘Radiology is not a medico-tech- nical specialty, although French administration still classifies us as such. We’re a medical discipline. The old-fashioned image of the radiologist reading scans alone in a basement and not having contact with anyone else in a hospital is outdated. ‘The radiologist,’ he emphasised, ‘is now at the centre of patient care and healthcare.’ (MR) EUROPEAN HOSPITAL Vol 28 Issue 5/19

1 6 R A D I O LO G Y The only chance of a lung cancer cure is early diagnosis Can we afford not to offer lung screening? For lung cancer patients life expectancy has hardly improved since 1970. A ten-year survival is 5%, making this the leading cause of death among all cancers. One reason is that, in most cases, the disease is diagnosed far too late. Interview: Daniela Zimmermann Previous evidence on the benefits of screening programmes to detect lung cancer early, was mainly based on data from the NLST study in the US (National Lung Screening Trial; N Engl J Med 2011), was considered insufficient. However, the publica- tion of the Belgian-Dutch NELSON study (De Koning et. al, 2018) has just changed this. For the first time, lung cancer screening has moved within reach. Professor Mathias Prokop, head of the Department of Radiology at Radboud University Hospital Nijmegen is among leading advo- cates of low-dose CT screening for lung cancer for high risk patients. At this year’s congress he explained aspects of the current debate in the context of the Holzknecht Lecture. Considering present evalua- tion by the Federal Office for Radiation Protection (BfS) as to whether lung screening makes sense, what might be the main concerns? ‘First, the BfS obviously deals with radiation protection. As a result of new technology, radiation expo- sure during chest CTs now poses an almost negligible risk,’ Prokop explained. ‘In the NLST study, the dose per examination was between one and three mSv; in the NELSON study it was lower than one mSv. How does the radiologist detect lung cancer on a CT scan? ‘There are basically two methods that help us. There is morphology, where the size or the volume of a suspicious region plays the most important part. ‘Then there are other morphologi- cal criteria that help with tumour determination, such as the shape or the localisation. A biopsy is only rec- ommended for patients with large, high-risk pulmonary nodules. All other patients just receive follow- up examinations. This is where the second category comes into play: changes over time. The rate of growth is significant in terms of mortality ‘If the pulmonary nodule grows very fast, it is most likely to be a malig- nant tumour; if it grows slowly, it is likely to be either a benign tumour or a malignant tumour which the patient will live with until their death (from causes other than lung cancer). ‘We must not forget that many patients who are recruited for lung screening are already multimorbid, because of their age and addition- ally they may, for instance, be at higher risk of a heart attack or a stroke.’ Would you say that lung screen- ing helps to save lives? ‘Well, it depends how you define saving lives. If you mean that patients do not die from lung can- cer, then yes. The NELSON study showed that mortality among men decreased by 26% and among women even by 61%. Lung cancer screening appears to work better among female patients. This is prob- ably because comorbidity amongst Some experts even say that they can screen with 0.2 - 0.1 mSv. ‘What the current evaluation pro- cedure is really about is the assess- ment of the risk/benefit ratio, given false positives and over- diagnosis and treatment. There is a danger that patients who would never have died of lung cancer are exposed to the potential complications of an invasive medical procedure. If there is no need to intervene it should not be done.’ What is the false positive rate? ‘It depends what you define as positive. The NLST study classed all nodules larger than 4mm as posi- tive, which leads to an extremely high false positive rate of 96.4%. Source: Shutterstock/Semnic Those who carried out the study simply lacked empirical values because they were the first to ana- lyse this. In all later trials, results were only classed as positive where further examinations were carried out because lung cancer was explic- itly suspected. ‘Therefore, the false positive rate for the NELSON study was only 10-15%, depending on which screen- ing round you looked at. There are now new suggestions as to how the false positive test results can be pushed below five percent. Then definitely this would be acceptable and considerably better than the results achieved in breast cancer screening.’ women is lower, and they more fre- quently have slow-growing tumours. ‘What is important is that, if we screen for long enough, the opti- mum effect on survival will devel- op. First data from the German LUSI (Lung Tumour Screening and Intervention Trial) confirms that the advanced tumour stages only disap- pear from about the third round of screening. It just takes a while until all tumours within the population have been captured and for new tumours to have been detected early enough. Weighing up the costs of life- extending therpies ‘Can we afford not to offer screen- ing? Although life-extending treat- ment procedures for advanced tumour stages, such as immuno- therapy, work well, they are also very expensive and a significant burden for the healthcare system. The cost per life saved by a screen- ing programme is therefore much lower. The only chance of a cure is to diagnose lung cancer as early as possible.’ Radiology Professor Mathias Prokop heads the Department of Radiology and Nuclear Medicine at Radboud University Nijmegen, in the Netherlands. Over the last decade he has extensively researched chest screening with CT and he was signifi- cantly involved in the Dutch-Belgian lung cancer screening study (NELSON). He has been vice chairman of the Dutch Radiology Society and has repeatedly received awards from the Radiological Society of North America and the German Radiological Society. Aiming to work without radioac The search for new MRI contrast agents MRI is now indispensable for diagnosing diseases and monitor- ing therapies. However, the ongoing discussion on gadolinium deposits in the brain has intensified the search for alternatives. Dr Daniel Paech of the German Cancer Research Centre in Heidelberg, Germany, discussed potential solutions to acquire high-quality images without contrast agents. Interview: Sascha Keutel Dr Paech, you found a way to detect brain tumours using glu- cose. Could you describe your method? ‘Conventional MRI measures pro- ton signals in water. Since about 60 percent of our body consists of water, a clear image can be gener- ated. Contrast agents intensify the signals in the vessels and between the cells, albeit they do not enter the cells themselves. Glucose on the other hand is taken up by the cells and metabolised. Tumour cells need sugar to meet their high energy demand. ‘To visualise the much lower levels of glucose, my colleagues Patrick Schünke and Moritz Zaiss from the Division of Medical Physics in Radiology and I have developed a method to selec- tively intensify the glucose sig- nal. It’s based on the physical process of magnetisation transfer, which means the signal of the glucose protons is transferred to the body water measured during the MRI procedure. This effect is proportional to the local glucose level and thus maps the regional change in the glucose level. ‘After completion of the initial technical developments, we con- ducted a proof-of-concept study with a group of ten glioblastoma patients. In this study, we could confirm increased glucose signals in the tumours.’ T1w (Contrast agent) APT (Proteins) for the patient. However, there is one difference to radioactive trac- ers: we don’t know yet whether our images contain metabolism information or, as in conventional Left: conventional morphological contrast-enhanced image of a brain tumour at 3 Tesla; Right: contrast-free protein measurement at 7 Tesla. © D. Paech/DKFZ PET has long been used to vis- ualise sugar metabolism in tumours. How does your meth- od differ from those techniques? ‘PET uses radioactively marked glucose molecules. We work with- out radioactivity, which means there is zero radiation exposure EUROPEAN HOSPITAL Vol 28 Issue 5/19

1 8 O N C O LO G Y R research on treatment response – growing brain tumours in the petri dish 3-D organoids for glioblastoma patients Report: Brigitte Dinkloh Research that might lead to new treatment options and longer sur- vival for patients with glioblastoma – a malignant and particularly inva- sive type of brain tumour – is ongo- ing at ZHT, the Centre for Brain Tumours, and the Wilhelm Sander Neuro-oncology Treatment Unit at University Hospital Regensburg, which form one of the largest and most modern facilities for brain tumour treatment in Germany. The hospital’s head of neuro- pathology, Professor Markus Riemenschneider, is a key member of the interdisciplinary clinical and research team, who studies the in vitro growth of glioblastoma tumour cells which behave like tumour cells in the human body. ‘These tumour organoids offer new insights into tumour growth. One day, we might even be able to translate this approach to personalised medi- cine and test for individual treat- ment response,’ Riemenschneider explained. Maintaining variety in the cells The Centre for Brain Tumours researchers have long been interest- ed in molecular changes in cells. To start a cell culture, they use tissue samples that were isolated during surgery (with prior patient’s con- sent). Previously, this method had a major drawback: the cell heteroge- neity could not be maintained – all cells were ‘harmonised’. ‘A typical feature of glioblastoma is cell heter- ogeneity,’ Riemenschneider pointed out. ‘There are different types of cells in a tumour, some are hypoxic, others are normoxic; that is, they differ in terms of oxygen concen- Tumour organoids in the Petri dish tration. Furthermore, you will see necrotic as well as perfused tissue areas. This variety of active tumour cells means a variety of genetic pro- grams are running. When we isolate these cells and turn them into a cell culture, we only have one of these conditions – the variety is lost.’ The new 3-D organoid models can overcome this hurdle. Currently, there are few studies on this issue – and these mostly on gastrointestinal and colorectal tumours. However, these models are crucial for glio- blastoma research since all cells grow, interact and assume differ- ent functions – just like in a real tumour. ‘We use an extracellular matrix which provides a surface for these cells to dock on. The matrix is metabolised after a while, but the cells retain their structure and integ- rity. This is promising because it might enable us to model the actual patient situation more realistically: when we can map the gradients, for example regarding oxygen satura- tion and nutrient supply, we will be able to see much more than in a normal cell culture,’ the neuro- pathologist added. Producing a brain Tumour organoids are limited nei- ther by species barriers nor artefacts – two obstacles in research that uses tumour cells implanted in mouse brains. Moreover, interindividual barriers don’t exist in a purely autologous system. The researchers, who cooperate with colleagues at the University of Erlangen, are not only able to produce tumour orga- noids in a Petri dish; they can even produce miniature brains, using a procedure which received the 2012 Nobel Prize for medicine: all cells of the human body can be produced from healthy cells via induced pluri- potent stem cells. ‘This procedure,’ said Riemen- schneider, ‘opens up entirely new options to confront cultured patient tumour cells with own miniature brains. This allows us to observe tumour cells’ growth onto and into the brain cells – this is what, de facto, determines healthy and patho- logical cells. In the long run, we hope to develop treatment options.’ The research project is still in an early phase, but the goal is a stand- ardised procedure that tests treat- ment response and effectiveness on the individual patient level. Insights may come into rare brain tumours In turn, this might yield insights rel- evant to the treatment of rare brain tumours that are difficult to assess in conventional cell cultures. Since there are more than 100 types of brain tumours, a highly differenti- ated approach is needed. The Wilhelm Sander Treatment Unit appears to be heading in the right direction as shown in the enhanced patient survival rate recorded since the facility was set up. Whilst over- all glioblastoma prognosis remains poor, at the centre we could sig- nificantly prolong average survival rates. 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 Dr Markus Riemenschneider, a University Professor and Head of Neuropathology at the University Hospital Regensburg since 2010, received his medical training as well as specialist training in neuropathology at the University of Düsseldorf. A Mildred Scheel Scholarship of the Deutsche Krebshilfe Foundation enabled him to become a researcher in the Department of Pathology at the Massachusetts General Hospital and Harvard Medical School, Boston, USA. In 2008, he com- pleted his specialist physician training in neuropathology and headed the independent Max-Eder Junior Working Group of the Deutsche Krebshilfe in Düsseldorf until his present appointment in Regensburg. Riemenschneider has received a number of awards for molecular neuro-oncology research, and was, inter alia, appointed a member of the Junge Kolleg (Young Scholars Group) of the North Rhine- Westphalian Academy of Sciences, Humanities and the Arts. In 2011, he received the Sibylle Assmus Award for neuro-oncology. Another focus of the professor’s work is quality control in neuropathology. He is an expert for DAkkS – the national accreditation body for the Federal Republic of Germany – and a member of the Scientific Board of QuIP GmbH – Quality Assurance Pathology Initiative GmbH, in Berlin. ‘We aim to ensure a longer good quality life for our patients,’ Riemenschneider stressed. With his Regensburg team, he has taken the first successful steps towards this goal: two to three months post-surgery tumour orga- noid cultures are available for cer- tain patients. These can be used to test treatment response in the lab should a tumour return. 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