2 R A D I O L O G Y Predicting the future of imaging What will ultrasound practice look like in the year 2030? in Rapid technical advances ultrasound and increasingly tight healthcare budgets call for a change in ultrasound practice, experts explained in a session at the European Congress of Radiology in Vienna. Two experts presented possible models for the next two decades. Ultrasound has become less pop- ular among young radiologists, according to Professor Paul Sidhu, a consultant radiologist in the Department of Radiology at King’s College Hospital, UK. ‘Trainees are less interested in performing ultra- sound than CT or MR,’ he said. In the UK, 90% of the ultrasound is performed by sonographers, near- ly all of whom have undergone radiographer training, followed by a two-year apprenticeship in ultra- sound, and often also a postgradu- ate diploma or MSc in ultrasound. This allows for many years of experience prior to independent practice. By contrast, radiologists have less formal training and tend to use ultrasound only in specialized settings, such as musculoskeletal, paediatrics or contrast-enhanced ultrasound (CEUS). ‘Very few of the large teaching centres in the UK would have radiologists perfor- ming general ultrasound anymore,’ Sidhu said. ‘In district hospitals, they’re more likely to do gener- al ultrasound once a week, but often only once or twice a week, contrasting with the sonographer’s daily practice.’ Unlike most European countries, sonographers in the UK perform both the examination and the reporting, but they’re accounta- ble to radiologists, who are still responsible for imaging quality and safety. Ultrasound will thus become less of a radiology tool, Sidhu predicted. ‘It’s all going to have to change within 20 years,’ he told the audience. ‘You will get fewer trivial examinations being performed in the radiology-run ultrasound departments. A pleural effusion will be performed at the bedside by the clinician, just prior to the drainage procedure. There will be no need to take a patient to the ultrasound department.’ Finding the right balance This scenario will be more cost effective for healthcare systems, which are increasingly under finan- cial strain. ‘They can’t afford a doc- tor to perform all the ultrasound. The sonographer is less expensive than a radiologist. Healthcare sys- tems have to wonder if it’s efficient or necessary to have a physician perform all of the imaging exam- inations.’ A more sustainable scenario would be to have an ultrasound depart- ment run by the radiologists, but used by other practitioners of ultra- sound, and staffed by doctors and sonographers. ‘The future will be a balance,’ Sidhu predicted. ‘It takes a lot of training to be able to scan properly. We will see that radiolo- gists delegate more and more ultra- sound to well-trained technicians.’ This model will expand slowly and will be initially hospital based, he added. ‘The radiologists will always ultimately be in charge because of their imaging background, but it will be a hybrid department where other specialists can use the equipment within the umbrella of the department, which will look at clinical governance, and safety and quality of the imaging,’ he said. This is where the strength of radi- ology remains in retaining ultra- sound, he explained. ‘Radiology should not lose it because it’s a modality that’s so ubiquitous and so useful as a point of care tool that you need it. But trying to convince the younger doctors to understand that is difficult,’ he concluded. The German example In Germany, some institutions have already established such interdis- ciplinary ultrasound centres to counter structural problems and high maintenance costs, accord- ing to Professor Thomas Fischer, Interdisciplinary Head of the More than just MRI accessories Ultrasound Center of Charité – Universitätsmedizin Berlin, Germany, who also spoke in the session. ‘The targeted and time-in- tensive training of ultrasound spe- cialists, the personnel-intensive staffing of small ultrasound depart- ments, and availability for on-call duty are urgent problems in many departments,’ he said. ‘Equipment fleets are maintenance- and cost-in- tensive, and in some cases out- dated.’ In a recent article, Fischer and col- leagues observed how institutions in Berlin, Munich, Regensburg, Rostock, and Trier set up and ben- efit from an interdisciplinary ultra- sound centre. ‘They’ve been able to reduce the number of devices needed in a hospital and more effi- cient use of available equipment through bedside time optimiza- tion,’ he said. Establishing such a centre results in further potential for economic opti- mization. ‘The DEGUM multicentre study PRIMUS showed that hospi- tal stay could be reduced from 8 to 5 days by using ultrasound within the first 24 hours in the emergen- cy department,’ he said. ‘In some cases, inpatient admission can be avoided, and the number of out- patient treatments can be reduced. The effect on possible therapeutic consequences and targeted dia- gnostics is high.’ CEUS or image fusion for com- plex interventions, as well as trai- ning of younger colleagues can be centrally organized through the multidisciplinary experience available at such centres, Fischer noted. ‘Interdisciplinary centraliza- tion also allows standardization and better control of hygiene qual- ity standards. The creation of an interdisciplinary image database based on standardized ultrasound protocols can significantly improve research,’ he said. The challenge will be to coordinate the centralization of the modality with specific organ and disease related processes depending on the local conditions and require- ments of the hospital. ‘Functional areas have been created in many departments in recent years and are spatially and organizationally oriented on the clinical pathway of the patient – for example, interdis- ciplinary outpatient breast cancer centres. A high volume of patients and examinations could limit the ability of an ultrasound centre to provide comprehensive sono- graphic resources,’ he concluded. Report: Mélisande Rouger www.allmri.com Nephrology: Example of cooperation with nephrology. CT/US image fusion in renal vein thrombosis. The image planes correspond to an axial section at the level of the left renal vein. r e h c s i F s a m o h T © r e h c s i F s a m o h T © Liver: Cooperation with hemato oncology. A patient comes to the examination of a focal liver lesion. A split-screen mode with B-mode right and special doppler method SMI left after contrast medium administration. The wheel spoke pattern of the FNH is particularly good to recognize. Aneurysm: Splenic pseudo-aneurysm following trauma with CEUS u h d i S l u a P © Paul Sidhu Thomas Fischer Paul Sidhu is professor of imaging sciences at King’s College London and a consultant radiologist in the Department of Radiology at King’s College Hospital. His research has focused on ultrasound and interven- tional radiology, and he has published extensively on many aspects of ultra- sound, particularly in relation to male health and liver transplantation. Sidhu notably pioneered the introduction of contrast-enhanced ultrasound (CEUS) in the United Kingdom in 1996 and is recognized as an authority in the application of this technique in clini- cal practice. the is Professor Thomas Fischer Interdisciplinary Head of Ultrasound Center of Charité – Universitätsmedizin Berlin, Germany, where he founded the Ultrasound Research Laboratory. With a research focus on breast imaging, ultrasound contrast media, US/CT-MRI image fusion, rheumatic diseases, and pros- tate cancer diagnosis and treatment, Fischer has made important con- tributions to the development and improvement of new ultrasound techniques like elastography, image fusion, and ultrasound-guided pros- tate biopsy. EUROPEAN HOSPITAL Vol 31 Issue 3/22

4 R A D I O L O G Y Sponsored · Expansion to AI market Improving prioritization, quantification and productivity recently Bayer announced the launch of Calantic Digital Solutions, a new platform deliv- ering access to digital applica- tions, including artificial intelli- gence (AI) enabled programs for medical imaging. The offering contains tools which aid radiologists and their teams to improve prioritization, lesion detection, quantification, and pro- ductivity. By providing access to AI radiology applications through the Calantic Digital Solutions platform Bayer expands its portfolio beyond contrast media, medical devices, software, and services. Gerd Krueger, Head of Radiology at Bayer Pharmaceuticals, said: ‘With Calantic Digital Solutions, we are entering the fastest growing segment in the radiology market and taking the next step on our way from a product provider to a solution provider, following our mission to provide an ecosystem of third-party and Bayer products to deliver state-of-the-art disease-ori- ented solutions for radiologists and their teams.’ Providing assistance at critical steps Calantic Digital Solutions is a suite of digital radiology AI-enabled applications which provide assis- tance at critical steps within a patient’s treatment journey. The vendor-neutral, cloud-hosted plat- form includes a growing number of applications designed to aid in prioritization, lesion detection and quantification, as well as apps that automate routine tasks and meas- urements, improve the radiology suites’ workflow, and free up time for radiology staff. The offering is orchestrated by body region and procedure, ini- tially focusing on thoracic and neurological diseases, such as pul- monary nodule detection. Another area of application is the triage of potential intracerebral hemorrhage (ICH) and large vessel occlusions (LVO), both of which can be asso- ciated with stroke. More disease-specific application packages will be added moving forward, the company announces. Bayer provides services around installation, configuration, and training of the platform and its applications. First launch markets will include the US and sever- al European countries, with more regions to follow. The Calantic Digital Solutions platform r e y a B © Increasing demand for AI The company sees increasing demand for innovation powered by AI: aging populations and changing lifestyles are leading to an increase in chronic conditions such as cardiovascular disease and cancer. Consequently, the need for medical imaging to detect dis- eases, guide treatment decisions and support therapy planning is growing. AI is the technology to meet these challenges, Bayer con- cludes, as it comes with the value proposition to accelerate diag- nosis and increase the through- put of radiological examinations. More information: www.calantic.com Diversity, transparency, flexibility Building trustworthy AI systems for cancer imaging Building artificial intelligence (AI) tools that clinicians and patients can trust, and easily use and understand, are core to the technology being successfully deployed in healthcare settings. AI expert Dr Karim Lekadir focused on the importance of these elements during a pres- entation at ECR in Vienna, as developers seek to create new AI models to support image-based diagnosis and care. Lekadir concentrated on different methods for building and vali- dating artificial intelligence work- flows, and how federated big data repositories can enhance future AI applications in cancer imaging. Questioning the performance primacy He highlighted the creation of trustworthy systems as a key step in AI development. That, he added, has to take into consideration all aspects of the system. ‘I will focus on the value of trust in future AI solutions because it is one thing to build an AI solution that is performant, but quite another to build AI solutions that people can trust and will deploy and use,’ said Lekadir, who is Director of the University of Barcelona’s Artificial Intelligence in Medicine laboratory. ‘Until now, people have focused on the performance in relation to accuracy and robustness, but that is not enough. We need to go beyond that and take in other elements, such as fairness. An AI solution may be robust but may discriminate against certain underrepresented groups. It may work well with white patients but not so much with black patients, for example, or with men but not female patients.’ Bringing light into the AI black box He also pointed out the value of usability and explainability, for both clinicians and patients. ‘Because AI models are often com- plex, users can sometimes be resist- ant to using them, so we need to make the AI decisions understand- able,’ he said. Transparency and traceability are also important in light of constantly changing data and users. Models that do not take these factors into account run the risk of quickly losing their robust- ness, becoming unusable. ‘We need to monitor and trace these tools over time, because something that makes AI different from other tech- nologies is that it is highly dynamic and changing over time,’ he added. m o c . k c o t S e b o d A – a v o k h s e p © Inclusive approach to anticipate barriers The expert argued that adopting a ‘highly-inclusive approach when designing, building, validating and deploying the AI solution’ is piv- otal in its successful introduction into a clinical setting. A crucial oversight of the past, he suggested, was that engagement with clini- cians and other stakeholders had been minimal when AI tools were being developed. ‘We are realising the importance of having a mul- ti-stakeholder and human-centred approach where we involve devel- opers, clinicians, patients, data experts, ethicists, social scientists, and regulators so we can anticipate some of the implementation barri- ers,’ added Lekadir. This co-creation enhances techni- cal robustness, applicability, and clinical safety and means problems can be anticipated in advance with appropriate solutions designed and implemented. Thorough evaluation of AI He emphasised the role of thor- ough evaluation, such as ensuring a system covers patients of differ- ent ethnic backgrounds. ‘If you evaluate without paying attention to ethnic diversity, you may run into problems later when the tool is deployed in practice,’ he cau- tioned. ‘It may not work well for certain populations.’ External eval- uation, in a hospital or centre dif- ferent to the one where the model was built in, is therefore critical. He also underlined the need for com- pliance with AI regulations. For the development of AI, it is important that clinical, techni- cal, ethical and legal aspects are taken into account and that all stakeholders and end users are involved, problems are anticipated and measures are taken to mitigate risks, he concluded. Report: Mark Nicholls Karim Lekadir is Dr Karim Lekadir from the Department of Mathematics and Computer Science at the University of Barcelona, and Director of the univer- sity’s Artificial Intelligence in Medicine laboratory. His research interests focus on big data and AI for biomedical applications. EUROPEAN HOSPITAL Vol 31 Issue 3/22

6 Overheard at AACC L A B O R AT O RY The complexities of drug testing in urine and hair Urine screening tests using only immunoassays are the most common procedures used to identify drug abuse. They are inexpensive, automated, and pro- duce rapid results. But they may produce false-positive or false- negative results, which vary based on the drug, drug class, and the assay used. Hair toxicol- ogy analysis is another form of drug testing, which unlike urine tests, enable analysis of drug use over a period of time. Hair tox- icology tests complement urine tests but can be just as challeng- ing to interpret. Mass spectrometry, specifically liq- uid chromatography with tandem mass spectrometry (LC-MS/MS), is a powerful tool for toxicolo- gy analysis. Although more labour intensive, more time consuming, and much more expensive that hair and urine tests, LC-MS/MS is recommended for drug confirma- tion testing following a positive or inconclusive immunoassay screen. It is highly complex and requires significant expertise but provides definitive results due to its superior sensitivity and specificity. At the 2022 AACC Annual Scientific Meeting Joe M. El-Khoury, PhD, director of the Clinical Chemistry Laboratory at Yale-New Haven Health, discussed the challenges of interpreting com- plex urine toxicology cases. in Chicago, ‘When in doubt, mass spec it out’ El-Khoury discussed a routine urine test ordered for a patient prescribed opioids and other med- ications for multiple, chronic, and complex medical problems. Her physician wanted to verify that this patient was not taking addi- tional types of painkillers. The test results were positive for heroine, but other findings were contradic- tory and confusing. ‘Immunoassay screening may not produce accu- rate results, because antibodies used in the assays for the targeted Publisher Mediengruppe Oberfranken – Fachverlage GmbH & Co. KG E.-C.-Baumann-Str. 5 95326 Kulmbach/Germany Phone +49 (0) 9221 949-311 Fax +49 (0) 9221 949-377 Editor and Production Manager: Sonja Buske (SB) Editorial team: Wolfgang Behrends (WB) Sascha Keutel (SKE) Senior Writer: Mark Nicholls (MN), Great Britain Mélisande Rouger (MR), Spain Managing Directors: Walter Schweinsberg, Bernd Müller m o c . k c o t S e b o d A – n o i t c u d o r P a i d e M k c o t S © drug may exhibit cross-reactivity toward other closely related com- pounds,’ said El-Khoury. ‘Patients maintained on chronic opioids are often at risk of false positives. The LC-MS/MS test determined that the patient was only taking exactly what she’d been prescribed. When in doubt, mass spec it out.’ He noted that patients taking Suboxone, a drug widely used for treatment of patients with opi- oid use disorder, are high-risk, and may attempt to stimulate compliance by spiking the pill in urine to pass the screening test. Immunoassays are not spe- cific enough to detect this sample adulteration and patients may get away with it. El-Khoury recom- mends that quantitative LC-MS/MS testing be the only method used for assessing adherence in patients taking Suboxone. When concentra- tions of drugs in urine are high, he advised the audience to make sure to rule out pharmaceutical impuri- ties, and to rule out enzyme inhi- bitors when metabolite patterns are unusual. Jacqueline Hubbard, PhD, the Laboratory Director of Three Rivers Diagnostics in Pittsburgh, Pennsylvania, gave deeper insights into hair toxicology analysis. Hair grows an average of 1 cm each month. When hair samples are seg- mented into sections, it is possible to obtain a detailed historic profile of an individual’s drug exposure over a specified amount of time. However, the accuracy of the anal- ysis may be impacted by ultravi- olet light exposure and diffusion of sweat, which may occur at any time. Cosmetic hair treatments may strip analytes or increase environ- mental contamination. Melanin must be considered A person with higher melanin may show a greater accumulation of drugs compared to a person with low melanin, so this needs to be considered when testing dark hair. Hubbard explained that the Society of Hair Testing (SHT) recommends that hair first be segmented prior to decontamination. The Society re- commends use of aqueous washes and an organic solvent to remove oil and external contaminants from the hair. But these processes may still be insufficient. Recent research has suggested that such proce- dures may lead to the swelling of the hair and may promote incor- poration of analytes into the hair itself. Cleansed hair samples need to be cut, ground, and pulverized before they are analysed. ‘When drugs are detected in a panel, I recommend metabolite detection to confirm ingestion,’ she said. ‘The detected presence of drugs in hair may be due to ingestion, incidental exposure from contaminated sur- faces, impurities found in the drug, Founded by Heinz-Jürgen Witzke ISSN 0942-9085 Correspondents Austria: Michael Krassnitzer (MK) France: Jane MacDougall (JMD) Germany: Cornelia Wels-Maug (CWM) Karoline Laarmann (KL) Katrin Schreiter (KS) Dr Christina Czeschik (CC) The Netherlands: Madeleine van de Wouw (MvW) USA: Cynthia E. Keen (CEK) Subscriptions Simone Sesselmann kundenservice@mgo-fachverlage.de Subscription rate 4 issues: 32 Euro, Single copy: 8 Euro. Printed by: mgo360 GmbH & Co. KG, Bamberg, Germany Publication frequency: quarterly Representatives Germany, Austria, Switzerland: Ralf Mateblowski Phone: +49 6735 912 993 E-Mail: r.mateblowski@mgo-fachverlage.de France, Italy, Spain: Eric Jund Phone: +33 493 58 77 43 E-Mail: jund@european-hospital.com GB, Scandinavia, BeNeLux: Simon Kramer Phone: +31 180 6200 20 E-Mail: kramer@european-hospital.com 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 Maria Kaiser Phone: +1 250 726 4007 E-Mail: mkads@mac.com All company, brand and product names in this publication are the property of their respective holders. Users must obtain per- mission from those holders before copying or using the owner’s trademarks, product and company names or logos. and/or decomposition products of drugs.’ ‘Hair toxicology interpretation to determine the frequency of use and if a person used specific drugs is not that simple. The amount of drugs detected in hair may not be equivalent to the actual con- centration present in hair, and the relationship between the concen- tration in hair and the amount ingested is not well established,’ cautioned Hubbard. ‘Drugs in hair are indicative of repeated use and/ or exposure, and not of a single use or recent use. Hair as a matrix for toxicology testing has impli- cit biases, including seeing higher drug concentrations in pigmented toxicology analysis showed that the child had ingested two drugs, including methamphetamine. A two-year-old boy was admitted to a hospital emergency department with acute encephalopathy and seizures. His urine and lab tests were negative, but when the hair toxicology reports became availa- ble 30 days later, they had tested positive for exposure to oxycodone and methamphetamine ‘Hair toxi- cology helped identify an unstable home situation from drug use for both children. For the boy, whose parents were separated, it provided definitive evidence that the mother of the child was a drug abuser, enabling the child to stay with his m o c . k c o t S e b o d A – y l f y t t i k © father. These tests can be invalu- able in help keeping vulnerable children safe,’ she concluded. Report: Cynthia E. Keen versus non-pigmented hair after the same systemic exposure. This test frequently has a longer turn- around time compared to urine tests. But it may be useful to identify if children who have unex- plained conditions or may be expe- riencing developmental delays are living in unhealthy situations,’ she said. Hubbard described two cases that demonstrate the utility of hair toxicology testing. A malnourished two-year-old girl showing signs of neglect and developmental delays had a negative urine drug screen- ing test for 11 drugs. However, hair Jacqueline Hubbard Joe El-Khoury Jacqueline Hubbard, PhD, joined QualiTox Laboratories, now Three Rivers Diagnostics, in 2022 as its Laboratory Director. Her interests include toxicology interpretations, test utilization, and mass spectrometry. She also serves as an MSACL Practical Training scientific committee member and is actively involved in training new users on mass spectrometry. Her research has also focused on devel- oping and validating drugs of abuse assays, driving under the influence of marijuana, and Covid-19 serology research. Joe El-Khoury is Director of the Clinical Chemistry Laboratory at Yale New Haven Health in New Haven, Connecticut, and Associate Professor of Laboratory Medicine at Yale University School of Medicine. A fellow of the AACC Academy, his research interests include indicators for monitoring clinical laboratory per- formance, investigating biomarkers of acute kidney injury and chronic kid- ney disease, and development of new mass spectrometry-based methods for the measurement of markers in bio- logical fluids. EUROPEAN HOSPITAL Vol 31 Issue 3/22

8 L A B O R AT O RY Modelling systems for human biology Organoid technology: new opportunities for drug discovery for Two-dimensional (2D) cultured cell lines and animal models have been the principal research tools the past decade. ‘However, a variety of biologi- cal processes unique to humans cannot be fully replicated in animal models or immortalized cell lines,’ said Munir Al-Zeer from the Department of Applied Biochemistry at the Technical University of Berlin, Germany. Since successfully isolating human embryonic stem cells (ESCs) and reprogramming human soma- tic cells into induced pluripotent stem cells (iPSCs), three-dimen- sional (3D) cell cultures have become very popular. Classed as one of these new structures, orga- noids can mimic stem cell niches more closely than 2D cell cul- tures, particularly gene and pro- tein expression, metabolic func- tion, and host-microbe interactions. ‘Organoids are capable of self- renewal, self-organisation, and exhibit functionality. Biologists call them organ-like aggregate cell structures,’ said Jürgen Knoblich, Scientific Director at Institute of Molecular Biotechnology the Austrian Academy of Sciences in Vienna. (IMBA) at organ the 35 human organoids reported for 15 organs Organoid culture allows specific cell types to be generated that were previously unachievable using 2D cultures. To date, a total of 35 human organoid systems have been reported associated with some fifteen organs from the brain to the bladder, including the retina, the thyroid gland, blood vessels, mammary glands, and the stomach. Consequently, pancreatic, liver, and cardiac organoids have been used for disease modelling, drug efficacy testing and toxicity analysis. Brain organoids are helpful for model- ling various neuropsychiatric disor- ders and neurodegenerative brain conditions. One recent study from the Department of Human Biology at the University of Cape Town Faculty of Health Sciences in South Africa, published in Gene Therapy, has opened up progress in under- standing autism spectrum disorders. Lung organoids have been devel- oped from various cell types such as human pluripotent stem cells (PSCs) and alveolar epithelial progenitor cells. These organoids were devel- oped either from PSCs, or adult stem cells (AdSC) and biobanks. Infections, respiratory diseases, cystic fibrosis, and colorectal cancer Following the development of human stem cell-based organoids, various human diseases have been modelled using these systems. ‘Today, human brain organoids are mainly being used to successful- ly model human diseases such as microcephaly, a neurological dis- order seen during the Zika virus outbreak,’ said Jihoon Kim from the Institute of Molecular Biotechnology at the Austrian Academy of Sciences. Parasitic diseases such as life-threat- ening cryptosporium diarrhoea L AT E S T H E A D L I N E N E W S plement cascade. A rare autoimmune disease that causes muscle weakness and impairs walking and hand function. CIDP is characterized by immune system hyperactivity sparked by auto antibody production, leading to peripheral nerve demyelination and reduction in nerve conduction velocity. The data generated provided the ration- ale for testing Sanofi SA’s sutimlimab, a humanized monoclonal antibody used to target C1s in treating CIDP. The product gained US FDA approval under the brand name Enjaymo in February 2022 for the treatment of cold agglutinin disease, in which activation of the complement cas- cade leads the immune system to destroy healthy red blood cells. Hesperos aims to replicate that success in other rare diseases for which there are no animal models. ‘There are 7,000 rare diseases and only 400 research programs looking at them, as there are no animal models. In some cases, these systems fill a void where animal models don’t exist,’ said James Hickman, CEO of Hesperos. James Hickmann The FDA announced, that this summer, it is allowed an existing drug to be repurposed based on efficacy data gen- erated using these advanced cell mod- els, or organoids. This represents a true breakthrough in validating the utility of these microphysiological systems and an important advance in finding treatments for rare diseases. Orlando, Florida-based Hesperos Inc. showed that exposing its model of peripheral motor neuron conduction velocity to serum from chronic inflam- matory demyelinating polyneuropathy (CIDP) patients led to increased anti- body binding and activation of the com- e n i c i d e m o B i r a l u c e l o m r o f e t u t i t s n I k c n a l P x a M , r e n n e R k i r n e H © The automated pipetting robots could produce large quantities of organoids and bacterial infections caused by Salmonella typhi and Clostridium difficile have been successfully modelled thanks to organoid sys- tems. More recently in respiratory di- sease, lung organoids infected with SARS-CoV-2 were used to demonstrate that the expression of transmembrane serine pro- tease 2 (TMPRSS2) is essential for priming the spike protein of angiotensin-converting enzyme 2 (ACE2) in coronavirus. ‘The high-throughput screening of lung organoids has also enabled identification of drugs that inhibit the entry of various coronavirus- es into host cells,’ observed Yun Kee Jo, from the department of Biomedical Convergence Science & Technology, Kyungpook National University, Daegu, South Korea, in an article published recently in Materials Today Bio. Resources for precision medicine Human organoids are becoming important resources for precision medicine They can be useful for selecting an appropriate drug for patients with genetic disorders such as cystic fibrosis, a relatively common specific genetic disorder with approximately 90,000 suffer- ers worldwide. Organoids can also be used as in vitro cancer mod- els, with high morphological and molecular similarity to their origin, that can be generated from a wide variety of tumours and normal tis- sue. They can be used as a prom- ising preclinical model for gastro- intestinal cancer, and particularly colorectal cancer. The team from the DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Germany, collected data relating to around 5.5 million single orga- noids from 11 different colon can- cer patients with more than 500 distinct small molecule perturba- tions. Laboratory robots capable of generating up to 20,000 brain organoids a day A team of scientists at the Max Planck Institute for Molecular Biomedicine in Münster, Germany, has succeeded in using human cells to produce midbrain orga- noids using a fully automated pro- cess. First, a strategy was devised that created mid-brain organoids from small molecule neural pre- cursor cells which can generate all relevant mid-brain cells more quickly and with greater repro- ducibility than current methods. Henrik Renner’s team there then demonstrated that their automat- ed pipetting robots could produce large quantities of organoids. This fully automated high-throughput workflow for 3D-based chemical screening in human midbrain orga- noids allows scientists to gener- ate, culture and test up to 20,000 brain organoids a day. This tech- nology has been licensed to the American biotech firm StemoniX, which has developed iPSC-based 3D micro-organ tissue constructs, disease models and advanced ana- lytical techniques to ensure that only the safest and most effective compounds progress through the discovery pipelines of their bio- pharma partners. ‘3D organoids are likely to become an indispensable tool for biolog- ical research, drug discovery and drug screening within a few years,’ said Agnieszka Zuchowska, Chair of Medical Biotechnology at the Warsaw University of Technology Faculty of Chemistry in Poland. New drug development is a long (15 years) and costly process. The average cost of each new drug launched onto the pharmaceutical market is over $1 billion. According to US-based Insight Partners, the market for organoids is projected to reach $3.43 billion globally by 2027. It is expected to grow at a CAGR of 22.1 % over the next five years. Some limitations still to overcome Although organoids are robust research tools for the study of human development and disease, there are hurdles and limitations associated with using organ-like aggregate cell structures. First, cul- ture techniques are not standard- ized, hence their heterogeneous nature. Second, the absence of blood vessels impedes the mat- uration and function of orga- noids. Lastly, the lack of a native micro-environment precludes stud- ies concerning the interaction of stem cells with their niche or immune cells. Challenges and limitations While still in their infancy, orga- noids face many challenges. They merely imitate a small part of the human body, not the whole thing. Human organoids still lack com- munication with nearby organs or tissues and are limited to studying the reproduction of organ-specific or tissue-specific microphysiology in comparison to 2D culture and animal models. ‘There is a long way to go before implementing the first human multiorganoid model in vitro’, Zuchowska concluded. Report: Bernard Banga EUROPEAN HOSPITAL Vol 31 Issue 3/22

1 0 I N F E C T I O L O G Y Outbreak prevention and management efforts Infectious diseases: new challenges for EU monitoring Avian influenza virus A (H5N1) and A (H7N9), Middle East res- piratory syndrome, coronavirus (MERS-CoV and SARS-CoV) and monkeypox virus: outbreaks of infectious diseases are get- ting more common in Europe. ‘Statistically, it is reckoned that nearly 60 % of pathogens affect- ing humans are of animal ori- gin,’ said Hadi Kazemi-Arpanahi, from the Department of Health Information Technology at the Abadan University of Medical Sciences in Iran. These emerging diseases threaten global security and challenge traditional surveil- lance strategies in the EU. In 2005, the EU established the European Centre for Disease Control and Prevention (ECDC), to help the 27 member states and two of the three remaining European Economic Area coun- tries (Iceland and Norway) devel- op surveillance systems for early warning of infectious disease out- breaks. ‘This surveillance covers 46 diseases, including severe acute respiratory syndrome, West Nile fever and avian influenza,’ said Dr Andrea Ammon, director of the ECDC. The surveillance system is integrated within the national crisis prevention system to support early evaluation and decision-making in response to potential biosecurity threats. independent, New online portal launched by ECDC Last year, the ECDC launched EpiPulse. This online European surveillance portal for infectious disease brings together sever- al surveillance systems that were previously such as the highly flexible metada- ta-driven European Surveillance System (TESSy), the five Epidemic Intelligence Information System (EPIS) platforms and the Threat Tracking Tool (TTT)). This new platform facilitates collection, anal- ysis, and dissemination of indica- tor- and event-based surveillance data regarding infectious diseas- es and associated health issues, including global epidemic intelli- gence, whole-genome sequencing, and health determinants. ‘The plat- form facilitates interdisciplinary collaboration and connects users from different sectors under a One- Health approach,’ said Ammon. The ongoing Covid-19 pandemic, responsible for more than one million deaths in EU countries, ‘convinced us of the necessity of ensuring that real capacity is avail- able in the EU to detect possi- ble new variants sufficiently early as well as to monitor them,’ the ECDC director said. The struggle is constantly starting over, with the continuous emergence of new mutants/variants such as alpha, beta, gamma, omicron and so on. Traditional surveillance is based on case reports. Syndrome-based surveillance systems actively use data from emergency departments, intensive care units and hospital admissions. Event-based internet m o c . k c o t S e b o d A – t e r o c e d s © surveillance systems are expected to be deployed on a large scale, because effective surveillance will have to use multiple data collected and integrated from several sourc- es. This new approach requires integrating multiple technologies and data resources from various fields including social media, la- boratory detection, outpatient or emergency treatment, diagnosis, over-the counter drug sales, insur- ance claims and even absenteeism. ‘The accuracy and timeliness of sur- veillance can be improved by elec- tronic systems and internet connec- tivity which could benefit the reach, visualization, and analysis of various data,’ said Muyang Yan from the First Medical Center of PLA General Hospital in Beijing. The Covid-19 pandemic significantly accelerated the application of big data in emerg- ing infectious diseases surveillance in order to sooner detect, better predict and better control infectious diseases in the EU and elsewhere. However, Big data is not omnipo- tent. It also has to deal with the con- tinuous development of “hard” tech- nologies used to diagnosis infec- tious diseases. Consequently, the rapid development of molecular dia- gnostics, especially next-gener- ation sequencing techniques, are going to help determine wheth- er an emerging infectious disease occurs naturally or due to genet- ically modified micro-organisms. Novel biosensors will be able to automatically identify viral, bacte- rial, and fungal pathogens from patients within a few hours. Novel surveillance systems are improving real-time surveillance capabilities by combining automatic detection techniques with modern network- ing and communication techno- logies. In future, the EU will be fight- ing on two main fronts: emerging and re-emerging infectious diseas- es (EIDs), and climate change. ‘In recent years, we have seen transmission of traditionally “tropi- cal” diseases in continental Europe: Ovid® Synthesis Clinical Evidence Manager B I O S E C U R I T Y E V E N T S I N T H E PA S T C E N T U RY 1918: Spanish flu pandemic leading to several million deaths. 2013: MERS outbreak in Middle East, Avian flu (H7N9) in China 1957 and 1968: Asian flu and Hong Kong flu causing about 1 million and 650k deaths respectively 1980: AIDS discovered in human being 2001: Anthrax attack in US 2003: SARS outbreak in China 2009: Swine flu (H1N1) outbreak 2011: Bird flu (H5N1) increased in viru- lence and transmissibility 2014: Ebola re-emergence in Africa 2020: The Covid-19 pandemic spreads around the world. As of 10 July 2022, just under 586 million confirmed cases and over 6.4 million deaths have been reported globally. 2022: Monkeypox outbreak – geo- graphic areas where monkeypox is not endemic have reported outbreaks of the viral disease. 11,500 cases confirmed across 60 countries. Chikungunya fever in Italy, large outbreaks of West Nile fever in Greece and Romania, and the first local transmission of dengue fever in both France and Croatia,’ said Jan Semenza, PhD, ECDC Head of the Health Determinants Programme. Major EID drivers that could threaten control efforts in Europe include: • environmental change (climate, travel, migration, global trade) • social and demographic driv- ers (aging population, social in- equality, lifestyles) • public health (antimicrobial resistance, healthcare capacity, animal health, food safety) ‘Climate change is expected to aggravate existing local vulnera- bilities by interacting with a com- plex web of these drivers,’ said Semenza. For instance, increasing global trade and travel, in combi- nation with climate change, are predicted to facilitate the arrival, establishment and dispersal of new pathogens, disease vectors and res- ervoir species. The current acceler- ation of climate change is creating a “new deal” in the surveillance of infectious diseases in Europe. Report: Bernard Banga Workfl ow solution for clinical practice improvement NEW Ovid® Synthesis Clinical Evidence Manager is a workfl ow management solution that organizes, standardizes, and accelerates quality improvement, evidence-based practice, and research projects across your institution. No other solution will take your clinical practice improvement projects to the next level to ensure they are of the highest quality and based on the latest research insights and evidence. To learn more about Ovid® Synthesis, scan the QR code. wltrsklwr.com/ovid-synthesis europe@ovid.com EUROPEAN HOSPITAL Vol 31 Issue 3/22

1 2 I N F E C T I O L O G Y / S U R G E RY is an organ in constant communi- cation with the environment: with each inhale, viruses or bacteria can enter the body. Thus, from the very first day the patient body will try to stave off complications. Good chances for recovery require close cooperation between the transplant pulmonologist and the surgeon. The first few days post transplan- tation will be shaped by unstable blood pressure, hyperacute rejec- tion reactions and intensive care, including ventilation. first year after the transplantation, immunosuppression will be sig- nificantly reduced. Now long-term rather than acute problems need to be managed properly. While the infection risk is sinking, the risk of acute and chronic rejection reactions and side effects of the immunosuppression remain. The immunosuppressive medications are incredibly toxic and can injure any organ. Renal insufficiency or malignant tumours are possible side effects which can appear years after the transplantation.’ ) 0 . 4 A S - Y B C C ( s n o i t a m i n A c i f i t n e i c S © or six years with a lung transplant and now, due to the Covid pandem- ic, they can’t leave the house for more than two of those years.’ Report: Sascha Keutel The ideal patient for transplanta- tion, so to speak, is severely ill but still fulfils the strict criteria, and they have a post-surgery survival prognosis of at least five years. The Covid-19 pandemic has further lim- ited these considerations since all of a sudden many healthy patients suffered from total lung failure and had to be moved to ECMO right away. Currently, it is being discussed whether these patients should also receive a transplant if there is no other regeneration option. But Covid is an infection and at this point we don’t know yet whether the trans- planted organ will also be affected.’ Who decides which patient will receive a donor organ? ‘The allocation of donor organs is exclusively based on medi- cal and ethical considerations. A potential donor organ is regis- tered with the German Foundation for Organ Transplantation, DSO. Eurotransplant, the organisation- al centre for the allocation of donor organs in eight affiliated European countries, is responsible for the actual allocation. It ensures that each organ is transplanted where it is most urgently needed. Unfortunately, Germany has a very small pool of donor organs. From a patient’s point of view it was there- fore incomprehensible that in 2020, the German Parliament did not adopt the so-called double refusal solution. That approach considers every citizen a potential organ and tissue donor who did not explicitly refuse to be a donor during their life or whose closest kin do not refuse an organ donation. This approach is the current legal situation for example in Spain where you have 34 organ donors per 1 million inhabitants. In Germany, there are only 11.2 donors. In the end, the German Parliament adopted the so-called extended consent solution which means organ and tissue removal is only allowed if the donor during their life or their next of kin consented.’ What is the survival rate after a lung transplant and which com- plications might occur? ‘Obviously, the prognosis depends on the underlying disease. Nevertheless, transplantation follow- up is very important since the lung Keratoplasty When the patients have survived the first few acute weeks and have been weaned off the ventilator so they can breathe by themselves, the next major challenge follows: in the first year post surgery, the patients are on high doses of immunosuppres- sive medication in order to avoid rejection of the transplant. That means the body’s own immune sys- tem is suppressed and the stronger the immunosuppression the high- er the probability of an infection. When the patient has survived the What are the specific challenges caused by Covid-19? ‘For the patients corona is obvious- ly a particularly difficult challenge since they are high-risk patients. Some of them don’t react to the vaccination at all because they don’t have the necessary antibodies as the immune reaction is made impossible by the immunosuppressive regimen. Moreover, the patients lose years of their life due to corona. Unlike heart or kidneys, transplanted lungs have a limited life time. Patients gain five Urte Sommerwerck Dr Urte Sommerwerck is Medical the Department of Director of Pulmonology, Allergology, Sleep and Ventilation Medicine at the Augustinerinnen Hospital in Cologne, Germany. The former transplant pul- monologist at University Hospital Essen, is an expert for lung transplan- tation with the audit committee of the German Medical Association. Transplanted lungs in Germany. Percentage change compared to the previous year O S D © AI for an eye: Performance of corneal Many consider our eyes to be the windows to the soul. Yet the cornea, the panes of these windows, sometimes need sig- nificant repair. Friso Heslinga, PhD, created artificial intelli- gence models to support sur- geons in one of the oldest and most common transplantation procedures. Our eye has several layers. The cornea is the transparent, dome- shaped outer layer that helps focus light, so we can see clearly. The light passes through the cornea and is then focused by the lens onto the retina, where it interacts with photoreceptor cells to gene- rate signals for the brain to process. A damaged or diseased cornea can become less transparent, which can prevent light reaching the reti- na and cause the transmitted image to be distorted or unclear. When this happens, the patient might need corneal transplant surgery, in which the surgeon removes all or part of the dam- aged cornea and replaces it with a healthy layer of tissue. The type of keratoplasty, or corneal graft transplantation, depends on which part is damaged or how much of the cornea needs replacing. ‘Over the years, corneal transplan- tation surgery has improved a lot. Surgeons started by replacing the whole layer. Now, it only compris- es the endothelial cells. For the cornea it’s only a monolayer, a sin- gle layer of cells,‘ Friso Heslinga, from the Eindhoven University of Technology, said. ‘It's an immac- ulate procedure. They scrape it away from the donor, roll it up, make a small hole in the patient’s cornea. Then they put the roll through that hole and roll it out again and use a small bubble, e.g., air, to push it on the cornea.‘ Deep learning research Heslinga and his collaborators did four projects on the corneal transplantation surgery. First, they developed an AI model to deter- mine intraoperatively whether or not the donor graft is orientated correctly. ‘An expert can look at the images and figure it out, but it takes time. And it’s not that easy,‘ the expert said. ‘We used intraoperative opti- cal coherence tomography (OCT) imaging to take images intra-op- eratively. So, the quality is very often suboptimal. It’s very hard to see the graft, very often you see only part of it,‘ he said. With col- laborators from the ophthalmology department at University Medical Center (UMC) Utrecht, Heslinga trained an AI segmentation model to automatically assess the orienta- tion of the new layer of tissue. This is important because if it is upside- down, then it cannot be attached to the existing cornea. Two post-operation projects Furthermore, they did two post- operative projects: first, to assess the level of attachment of the graft after transplantation surgery. ‘We collaborated with corneal special- ists from Copenhagen to design a method that finds any spots where the donor tissue is detaching from the underlying tissue.‘ For the second post-operation project, Heslinga and his col- laborators developed AI models, which were trained using super- vised deep learning, to automat- ically measure corneal thickness at every point in the eye and con- struct a detailed thickness map. Abnormal corneal thickness is linked to various corneal disor- ders. ‘Corneal thickness is some- thing you could measure by hand; you could draw the lines on the monitor. You still would need a software to do a thickness profile. Again, that takes time doctors rarely have in clinical practice. That is where the AI models come in: to save time,‘ he said. For the fourth project, Heslinga developed a model for assess- ing specular microscopy images. Looking at the individual cells, the technique gives the physician an idea about the state of the cornea. When they zoom in, they can see the number of cells in a square millimetre or differences in cell size. Similar to the corneal thickness maps, these results can then be provided to an ophthal- mologist to establish the success of the transplantation procedure and help determine if further treatment is needed. ‘For an assessment of these types of images, much depends on the experience of the surgeon. There is quite some information being lost, and that’s the part where we think our models will help: by bringing this extra information, we can do measurements and relate these measurements to outcome,‘ Heslinga is convinced. m o c . e r u t a n . w w w © Optical Coherence Tomography (OCT) cross-sectional image of the front part of the eye. Visible are the cornea and anterior chamber. Some non-attached parts of the corneal donor tissue are also visible, floating in the anterior chamber (just below the cornea). The red lines indicate the borders of the cornea. The blue lines indicate how the corneal thickness is measured. EUROPEAN HOSPITAL Vol 31 Issue 3/22

1 4 C A R D I O L O G Y / E S C - S P E C I A L Algorithms support diagnostics AI in cardiology: so much is feasible – but is everything useful? It might sound like science fic- tion but it is reality in cardi- ology: with the help of artifi- cial intelligence (AI) physicians can recognize from a patient’s headshot whether the person is suffering from coronary artery disease and is therefore at risk of myocardial infarction. But is that knowledge really use- ful? Professor Dr David Duncker calls for a differentiated and careful assessment of the pos- sibilities and risks associated with AI. He thus recommends the careful selection of the tar- get group in order to recognize at-risk patients early. AI, he says, can help analyse larg- er data volumes but he cautions that ‘An algorithm is always only as good as the person who trained it. Biases and wrong decisions cannot be avoided. This ethical dimension has to be taken into consideration by all means. ‘Atrial fibrillation is the most frequent type of arrhythmia,’ says Professor Duncker, Head of Rhythmology and Electrophysiology at the Department of Cardiology and Angiology at Hannover Medical School, and adds that “it often causes sequelae such as strokes that can be avoided with early prophylaxis.’ He does acknowl- edge though the potential of AI, particularly when human resources are scarce and patient numbers increase. Algorithms can pre-scan huge data volumes in the back- ground so the physicians have to Detecting heart diseases y t e i c o S c a i d r a C n a m r e G © ECG curves recorded on Smartwatches: a Sinus rhythm, Apple Watch (Apple, Cupertino, CA, USA). b Sinus rhythm with ventricular extrasystoles, ScanWatch (Withings, Issy- les-Moulineaux, France). c Atrial fibrillation, Apple Watch. d Regular narrow-complex tachycardia, Apple Watch younger than 65 years with risk factors should be screened dur- ing their next doctor’s appointment. Germany is facing the problem that there are too many people in that age bracket, Professor Duncker points out: ‘The physicians simply don’t have the resources to review all ECGs. AI would have to preselect deal only with suspicious findings. But proper selection of the target group is crucial. ‘Today, we can record ECGs with smartwatches and specifically look for arrhyth- mia,’ Professor Duncker explains and adds that ‘the users of such smartwatches however, are usually much younger than the group at risk for arrhythmia. Therefore we have to make sure the algorithms are applied to the correct target population.’ Screening recommendations for arrhythmia Recently, the European Heart Rhythm Association (EHRA) issued new recommendations, co-authored by Professor Duncker, regarding the use of digital devices for arrhythmia screening. Systematic screening is recommended for persons over 75 years and those above 65 years who are at risk. Persons over 75 years without risk factors and those personalised therapies, e.g. by calculating the effects of medica- tion and optimally planning sur- gical interventions. But Professor Duncker warns that ‘we should not lower our scientific standards. New pharmaceuticals that are being tested must not be administered to each and every patient. We have to continue scientific studies. These standards also have to apply to AI and randomised studies have to be conducted to assess the effects.’ Report: Sonja Buske a smaller group that needs attention. Specialized apps on the smartphone would be a good alternative to smartwatches for that target group.’ Therapy differences caused by incor- rectly trained AI Professor Duncker, however, underlines that AI does not neces- sarily make better decisions than human beings: ‘Humans make mistakes and are biased. Studies have shown that not every patient receives equal treatment. Factors such as gender, ethnic background or religion play a role. When biases enter AI unchecked, differences in treatment will result which, in the worst case, may harm the patient. This is something we have to be aware of. We have to try to avoid training the algorithms incorrectly.’ Personalised therapies with the help of AI In a few years, the cardiologist hopes, AI will be able to design David Duncker Professor Dr David Duncker is Director of the Hannover Heart Rhythm Centre and Managing Senior Consultant and Head of Rhythmology and Electrophysiology at the Department of Cardiology and Angiology at Hannover Medical School. He is a member of the EHRA board and chair of the EHRA commit- tee for digital communication. m o c . k c o t S e b o d A – n i d o b _ y e x e l a l © AI supported vector cardiography to enhance scr Cardisiography is a precise screening method for detecting structural, rhythmical, or vascu- lar heart disease. Neuronal net- works assess and analyse vector cardiography data. The attending physician receives a report that describes a patient’s individual risk. Cardisiography is a deci- sion support tool that guides the targeted follow up for the patient. Meik Baumeister, CEO of Cardisio, gave insight into the development and the operating principle of the method. cal excitation in multiple dimen- sions. However, interpretation of the multidimensional mapping of the heart is very complex. The mathematical analysis is barely pos- sible with the human brain. Now, in the age of super computers and artificial intelligence (AI), we got a new chance to revive the dormant method using vector cardiography. Cardisiography unites neuronal networks with vector cardiography.’ Many parameters are calculated and analysed EH: What is the idea behind Cardisiography? Baumeister: ‘In the summer of 2015, we had the idea to breathe new life into vector cardiography and find a way to apply it in clinical practice. The vector cardiography is a 70-year-old idea, with a lot of research on the technique show- ing great potential. Put simply, the method aims to map the heart and the propagation of the electri- How do vector cardiography and AI work together? ‘We measure normal medical parameters, such as the spacing or width of the QRS complexes. The two-dimensional ECG contains information about three angles. The three-dimensional VCG has information about four angles, a volume, and the sheathing surface of the measured loop. All these parameters are calculated and then analysed by the neuronal network. The calculation is followed by sta- tistical evaluation, correlations are ruled out and significant results are identified. We use a big data- set to train the neural network in a supervised learning approach. Each patient is assigned their own set of parameters, which are com- pared to match the trained results for healthy or sick patients. This way, we can always reconstruct why the algorithm decided the way it did.’ What was crucial for the devel- opment? ‘Good data. We, as computer sci- entists, love code, math, and sta- tistics, but without medical know how and good data we are lost. We needed time to get the data and to interpret the data success- fully. We also needed – and still need – innovative cardiologists and open-minded medical doctors who declare their interest in the meth- od and the willingness to use it. The cardiologists need to show that they trust the Cardisiography reports.’ How does Cardisiography work? ‘Three electrodes are applied to the front of a patient’s chest and anoth- y t e i c o S c a i d r a C n a m r e G © Functional principle of cardisiography: measurement on the patient, data forwarding to the cloud, evaluation of the data by the algorithm in the cloud. EUROPEAN HOSPITAL Vol 31 Issue 3/22

1 6 Women’s heart health C A R D I O L O G Y / E S C - S P E C I A L The impact of pregnancy and menopause The critical times in a woman’s life of pregnancy and the men- opause – and their relation to heart health – was explored in a special session at the European Society of Cardiology congress (ESC). With recognition that heart health treatment and care need to take into account gen- der-specific factors, the defined field of women’s cardiology is becoming an increasingly important area of focus. ‘Menopause is an important phase in women’s life, affecting changes in cardiovascular disease (CVD) risk factors, the immune system, thrombotic system and several others. The decline in Estrogens start from 30 years onwards and has a huge impact on fertility, CVD risk and many co-morbidi- ties. These appear when women enter their forties, such as thyroid disorders and rheumatic diseas- es. Women with severe vasomotor symptoms are at higher CVD risk and often develop (early) hyper- tension. Menopause is therefore an important turning point in life and a good moment to assess an indi- vidual’s CVD risk,’ said Professor Angela Maas. Female-specific risk factors Clinical cardiologist Maas, who is the author of “A Woman’s Heart – why female heart health really mat- ters” and Chair in Cardiology for Women at the Radboud University Medical Center in Nijmegen, The Netherlands, said there are a number of key considerations Non-invasive method als who engage with women of reproductive age with CVD have a role in reducing adverse pregnancy outcomes,’ she said. ‘Women of reproductive age can have pre-existing CVD, risk factors for CVD, and present with new CVD in pregnancy.’ She points out that adverse pregnancy outcomes, such as hypertensive disorders of pregnancy and gestational diabe- tes, are associated with CVD later in life. Escalation of care She said awareness of CVD in pregnancy among healthcare pro- fessionals is crucial and by recog- nising their pivotal role in provi- sion of preconception care across a women’s reproductive years can lead to better outcomes. Simpson, who is also Advanced Clinical Nurse Specialist at the NHS Golden Jubilee centre in Glasgow, said recognition of women with CVD can help identify those who may require preconception coun- selling from experts in CVD in pregnancy, facilitate access to con- traception, and refer for follow-up with the Pregnancy Heart Team during pregnancy. Following recognition of signs and symptoms of CVD presenting in pregnancy/postpartum, healthcare professionals can assess, investi- gate, make a diagnosis, and esca- late care to senior members of the multi-disciplinary team. Report: Mark Nicholls Angela Maas Professor Angela Maas has been a clinical cardiologist since 1988. She has been Chair in Cardiology for Women at the Radboud University Medical Center in Nijmegen, The Netherlands, since 2012, where she focuses on the early identification of women at increased cardiovascular risk and stable and unstable ischem- ic heart disease in women at mid- dle-age. As one of the most influential female doctors in Dutch healthcare, she was the 2020/21 Women’s repre- sentative of the Dutch Government to the United Nations. Maggie Simpson Maggie Simpson is Lead Clinician with the Scottish Obstetric Cardiology Network and Advanced Clinical Nurse Specialist at the NHS Golden Jubilee University Hospital in Glasgow. m o c . k c o t S e b o d A – s w o d d e © Women should pay special attention to their heart health during pregnancy and menopause for women during the menopause when it comes to heart health. ‘The shift in CVD risk factors is very important and also the consider- ation of other female-specific risk factors,’ she explained. ‘Migraine from puberty onwards and high blood pressure in pregnancy are other important female-specific risk factors that are often present in women with early menopause and many vasomotor symptoms.‘ She also points out that anginal symptoms in women at middle age are importantly caused by coro- nary spasm and not by stenoses. Dedicated centres ‘The diagnosis is now easy in the cath lab, but still quite rarely done in too few centers,’ said Maas. ‘Many women walk around without a clear diagnosis and lack of treat- ment. This needs to change.’ With stress increasingly being a crucial risk factor in women, she said that nurses are important co-workers in the outpatient clinic to help women to learn to live with their symptoms. She advocates dedicat- ed centres for women’s cardiovas- cular health to support better diag- nosis and prognosis and believes women specific symptoms must be taken seriously, particularly for prevention. Maas emphasised that any comparisons of women’s symptoms with those of men is now an outdated approach. In her presentation on pregnancy and heart health, Maggie Simpson, Lead Clinician with the Scottish Obstetric Cardiology Network, highlighted how CVD is a leading cause of maternal death and mor- bidity. ‘All healthcare profession- Pressure-strain loop to assess myocardial work dial work in a way that is reliable and not invasive.’ Not completely precise, but very useful nonetheless Assessment of myocardial work remains ‘a pillar of assessment of myocardial function in terms of mechanics and energy demand,’ added Galli. First introduced in the late 1970s when researchers used pressure volume loops to calculate myocardial work, it became the gold standard, but as an invasive measure it is not applicable to patients in everyday clinical practice, whereas PSL offers a non-invasive option. The non-invasive assessment of myocardial work relies on the measure of blood pressure by an arm cuff sphygmomanometer to estimate LV pressure, and on the measure of LV strain curves by echocardiography. Pressure- strain curves are then obtained (see figure), which allow the esti- mation of regional and global LV work. LV myocardial work is then assessed. ‘It is not a completely precise calculation, but it is a good estimation of myocardial work, and the regional assessment of myocardial work is shown to be directly associated with myocardial oxygen consumption assessed at FDG-PET.’ Since PSL emerged in 2012, it has been validated by various research groups for estimating myocardi- al work in a reliable fashion in several different pathologies, she added, and most widely shown as beneficial in CRT candidates. ‘Studies also show applicability of the method to other clinical condi- tions; for instance, in patients with hypertension, systolic heart failure, diastolic heart failure, and valvular heart disease, particularly aortic stenosis,’ said Galli. ‘Also, there are some pioneer studies that have started for the non-invasive assess- ment of the myocardial work of the right ventricle by the analysis of pressure-strain loops.’ Ready for clinical practice Other approaches to assess left ventricular function and perfor- mance – such as left ventricle ejec- tion fraction and strain – have lim- itations, she continued, because they simply measure LV fiber shortening and do not take into account the effect of afterload on LV function. As such, PSL seems to provide a more precise and phys- iological assessment of LV func- tion. ‘This is one of the main points of the technique, together with its non-invasive nature,’ she said. Galli believes cardiologists can use PSL to highlight local differences in myocardial work to enable selec- tion of patients receiving CRT and, in the future, it may offer patho- physiological insight into other dis- ease states, such as heart failure and valvular heart disease. The technique is only slowly enter- ing clinical practice and not being widely applied to patients despite the increasing numbers of stud- ies being conducted in the field. ‘We can see that the evidence in research, and interest on param- eters derived by PSL analysis, is increasing,’ Galli added. ‘I think that in the future it could replace some of the parameters that we use now, for instance LV strain, but we need wider evidence to prove it, so we are still at the starting point of the method.’ Report: Mark Nicholls EUROPEAN HOSPITAL Vol 31 Issue 3/22 Illustration of LV pressure-strain loop The value of using left ven- tricular pressure-strain loops as a non-invasive way to assess myocardial work was outlined in a session on cutting edge echocardiography at ESC 2022 in Barcelona. Delegates heard how the tech- nique has benefits for cardiolo- gists in terms of diagnosis and prognostic stratification for condi- tions such as heart failure, ischem- ic cardiomyopathy, valvular heart disease, or selecting patients for CRT (Cardiac Resynchronization Therapy). The session provided new insights into pressure-strain loops (PSL) analysis for the non-in- vasive assessment of left ventricu- lar (LV) myocardial work and its potential clinical applications. Dr Elena Galli from Rennes University Hospital in France said the objec- tive is to present the benefits of PSL analysis as a new technique for assessment of left ventricular performance. She said: ‘The main aspect of this technique is that it allows an assessment of myocar-