2 D I G I TA L PAT H O LO G Y Going digital New frontiers for nephrology ence hospital for three other hos- pitals from the group, with all the slides from the various scanners uploaded to the same cloud. Other hurdles in the transition to digital pathology, he said, were the high initial cost, revision of the pre- analytical phase, and integration with the Laboratory Information System (LIS). Digital technology solutions are creating new opportunities for pathologists in diagnosis and assessment of renal conditions. With the opportunity for whole slide imaging (WSI), improved workflow and better visualization, hospitals and laboratories are already seeing a return on the investment in such technology. Artificial intelligence is also offer- ing a new dimension and forging new frontiers in nephrology and, whilst it may still have limitations, clinicians are starting to understand and recognise the potential AI offers. Advantages and hurdles The challenges laboratories and hos- pital systems face in adopting digital solutions for nephrology were out- lined during the ‘Nephrology; New frontiers – nephrology goes digi- tal’ session during the online 33rd European Congress of Pathology. Delegates also heard about advan- tages and benefits detailed by five expert speakers. from Dr Pablo Cannata the Hospital Universitario Fundación Jiménez Díaz (FJD) in Madrid, Spain, described advantages and hurdles of going digital, reflecting on the experience of the FJD pathol- ogy department, which introduced digital pathology in 2018 for renal pathology and uropathology. Within However, he said, ‘There have been clear and wide-ranging advan- tages from going digital. These are the ability to offer telepathology in small pathology labs where there is no renal pathologist, it has delivered improvements in workflow, and supported annotation and quantifi- cation of pathologic findings.’ It also allows better and faster visualisation of serial sections, ena- bles a global vision at different lev- els for more accurate diagnosis, and ‘opens the door for computational pathology.’ Global application Dr Vijaya B Kolachalama, Assistant Professor in the Department of Medicine at Boston University School of Medicine and the Department of Computer Science at Boston University, highlighted various aspects related to the role of AI in pathology. Machine learning, he said, can perform various tasks, such as diagnosis and staging of disease, biomedical segmentation, prognosis, and biomarker develop- ment (omics and drug discovery). However, Kolachalama added, there are limitations to its glob- al application, which depend on the location. ‘For developed coun- tries, or places with good clini- o t o h P _ t i b b a R / k c o t s r e t t u h s © a year, almost all slides – except for cytopathology – were scanned digitally, though he acknowledged that some pathologists were initially reluctant to use digital pathology as the only solution for diagnosis. ‘Some were still using microscopes,’ he explained. ‘But, by 2020, all our pathologists were using digital Digital solutions are creating new opportunities in nephrology pathology as their most important diagnostic tool.’ Workflow improvements Cannata explained that the main university hospital works as a refer- Advancing personalised health and genomics cal resources, the argument is that AI can assist the pathologist. For developing countries, or for places with limited clinical resources, the argument is that AI can serve as a tool to perform diagnosis/screening of patients. The sobering reality is that none of these tools are fully deployed in clinical settings. Tools are still largely under development.’ The reality gap The ‘exciting aspect’: the field is open for researchers and entrepre- neurs to build these technologies, and there is huge potential for tele- pathology. Kolachalama said more publicly available kidney pathology datasets are needed that are representa- tive of clinical practices globally to accelerate research in computational pathology. He also underlined the impor- tance of validation of computational algorithms to ensure that models developed on a single cohort of data are generalisable across other populations. There also remains a gap between reality and hype surround- ing explainable AI, and questions remain over demonstrating clinical and workflow benefits and who is going to pay for these AI-driven systems. The session also covered hav- ing a Central Repository for Digital Pathology, which was discussed in a presentation by Renate Kain from the Department of Pathology at the Medical University of Vienna; Dr Peter Boor, from the Pathology and Nephrology Department at RWTH Aachen in Germany, looked at pathomics as a novel tool for min- ing histology data; and Dr Romain Bulow, from the same unit, looked at deep learning-based classification of kidney allograft pathology. (MN) Biosafety measures There was also a lower number of patients being included in clini- cal trials and Hofman highlighted challenges and issues surrounding the use for translational research of human samples obtained during the Covid-19 pandemic from lung cancer patients. Issues of biosafety measures and biospecimen handling resulted in a, decrease of specimens for diag- nosis, and fewer collected samples also disrupted translational and basic non-Covid-19 research. A shortage of personnel also impaired routine work and research. However, on the plus side there was a contribution to research on Covid-19 pathogenesis/pathology and a better understanding of the disease. In addition, the biologi- cal safety for personnel working in the pathology lab during Covid-19 had to be carefully assessed and managed with correct training and protocols. The role of pathologists Lung pathologists were particularly able to observe the changes taking place in the lung over the pandemic waves. Professor Fiorella Calabrese, from the Department of Cardiothoracic and Vascular Sciences and Public Health (University of Padova, Italy), spoke of current knowledge of path- ological lung lesions of Covid-19 and how to recognise and describe the Left: Covid-19 pneumonia: acute lung injury. Right: Covid-19 pneumonia: vascular injury – microthrombosis Continued from page 1 major pathological lung differences through pandemic waves. Pathologists, she said, had made an important contribution in this respect and had shown that from the first wave, there were three main phenotypes: with prevalent Alveolar Injury (AI); with prevalent Vascular Injury (VI); and with both (mixed type). The second wave During this, the most significant dif- ference was a higher frequency of fungal infection, and in particular aspergillus, Calabrese explained. ‘In terms of the important contribution of pathology, and the impact on clinical management, it had deliv- ered clear-cut evidence of differ- ent injuries: e. g. vascular lesions. This has increased awareness about Professor Paul Hofman from the Laboratory of Clinical and Experimental Pathology at the Louis Pasteur Hospital in Nice, France, is Full Professor, Head of Human Biobank Unit at the University of Nice and of the FHU OncoAge. He obtained an MD at the University of Nice Sophia Antipolis and a PhD at the University of Montpellier and has pub- lished more than 500 articles in peer- reviewed journals. some therapeutic strategies (throm- boprophylaxis).’ There had been identification of different pathological phenotypes in patients with severe disease and this led to the development of math- ematic algorithms to predict different phenotypes. There were also extensive tissue analyses from full autopsies, which increased a broader understanding of causes of death, because not all patients died due to severe Covid- 19 pneumonia. ‘With more superim- posed infections – particularly fungal Professor Fiorella Calabrese is a Full Professor in the Department of Cardio- thoracic and Vascular Sciences at the University of Padova, Pathology Section. Her research includes pulmonary patholo- gies, transplant pathologies, molecular pathology, infectious and immunological diseases, and cardiomyopathies. She has authored 280 publications in peer-reviewed journals and is past chair of the European Society of Pathology (ESP) Pulmonary Pathology Working Group. infections (CAPA) – this helped to enable the development of a diag- nostic procedure for a more sensi- tive detection of proven CAPA,’ she added. Zsuzsanna The session also heard from Professor Varga (University Hospital Zurich), who discussed viral detection in the lung specimens, and Professor Ines Testoni from the University of Padova, who discussed how patholo- gists had reacted to the pandemic. EUROPEAN HOSPITAL Vol 30 Issue 4/21

4 L A B O R AT O RY Meeting the needs of laboratories of every size Molecular scaleable solutions One size does not fit all when it comes to diagnostics. Different diagnostic locations need solutions that meet their needs, whether for on-demand testing in a healthcare setting or a laboratory managing population screening. Finding the right solution can be a challenge especially when the future may change what a labora- tory needs, Hologic Inc. reports. Hologic Molecular Scalable Solutions are well placed to meet the growing diagnostics testing needs of labora- tories of all shapes and sizes, from a single patient rapid result in about an hour to population level screen- ing, meeting the molecular diagnostic needs of laboratories today and in the future. The portfolio of systems has recently expanded with the addition of the on-demand, molecular-testing Novodiag® sys- tem, Hologic’s Molecular Scalable Solutions portfolio. This system offers a simple fast way to pinpoint patients most at risk with targeted, multiplex and syndromic on-demand testing. Novodiag’s high multiplex technology is precision engi- neered for simplicity, accu- racy and affordability across a broad and growing menu of high- and lowplex assays to detect infectious diseases and for antibiotic resistance manage- ment. It is a small, quiet, stackable, fully auto- mated platform that combines easy to use functionality with molecular performance. With a just a few simple steps the Novodiag system enables fast, life-saving diagnoses, delivering precise, easy-to-read results in an hour, so improving efficiency and bringing clinical confidence closer to the patient. Infectious diseases are detected from a single use cartridge in about one hour and a comprehen- sive menu of assays for screening of antibiotic resistances, gastrointestinal, respiratory (including Covid-19) hos- pital acquired infections is available. Each Novodiag assay can detect mul- tiple targets simultaneously, for exam- ple, the Novodiag Bacterial GE+ assay has 14 targets, while the Novodiag Stool Parasites assay detects 26. For settings that need a larger on-demand capacity, Novodiag PLUS links up to four instruments. These can be stacked and controlled by a single computer and offer a total of four independent slots per instru- ment, adding flexibility and conveni- ence. For laboratories requiring systems with a higher throughput, Hologic’s Panther Scalable Solutions offer a range of options with a broad menu of high performing assays, allowing laboratories to expand their testing menu while adding on flexibility, capacity and walkaway time. The portfolio’s foundation is the Panther system, which was launched in Europe in 2010. This offers ran- dom access and full automation for molecular testing with a broad assay menu including tests for women’s health, sexually transmitted infections (STIs), respiratory health, and viral load, as well as Open Access func- tionality for laboratory developed tests (LDTs). This menu enables laboratories to consolidate molecular testing onto a single platform. The Panther system has additional add-ons including Panther Fusion, which launched in 2016 and provides additional IVD menu and the Open Access functionality, the Panther Plus, Panther Link and Panther Trax*. The Panther Fusion module adds the ability to run real-time PCR, TMA and RT-TMA assays on a single, fully automated platform. This enables laboratories to consolidate testing, increase walkaway time and enhance flexibility. With Panther Plus, laboratories can load more consumables directly on the instrument, allowing even greater walkaway time (up to 13.5 consecu- tive hours). Both fluids and waste can be changed while tests are in process, and an option for automatic liquid waste disposal is available. These features allow an additional 210 tests to be run in 24 hours, providing a total throughput of greater than 1,200 patient samples in that time. Laboratories can gain additional efficiencies by using Panther Link, a software solution that creates a Body-on-a-chip technology A boost for drug development Integrating laboratory functions on a microchip circuit is helping to improve the cost-effectiveness of drug development. at Cornell and CEO & president of Hesperos, Inc. in Orlando, Florida. The technology integrates multiple analytic steps (such as measuring the time-dependent concentrations of drug and metabolites as well as cellular activities) on a single chip with the physiological-based pharmacokinetic models mimicking the integrated responses of organs such as the liver, colon, heart or lung to predict outcomes and reac- tions of proposed new therapeutical approaches. Weeding out the drug candidates The body-on-a-chip technology can also be used for rapid analysis or screening, and while Professor Shuler believes the main application is within pharmacology, the technol- So-called ‘lab-on-a-chip’ or ‘human- on-a-chip’ technology can highlight which treatments may, or may not, work before advancing along the clinical trial process. It can also have benefits for chronic and rare diseases, as well as helping shape personalised medicine. Professor Michael Shuler, who is one of the pioneers of this technol- ogy, outlined how it has evolved. Over the past two decades his group at Cornell University in New York has applied chemical reaction engi- neering principles to biological sys- tems to develop conceptual tools to test hypotheses about cellular mechanisms. This work combines mathematical models of subcellular and cellular mechanisms with mod- els of the whole body as a means to relate the rapidly increasing insight from molecular toxicology and pharmacology with human and ani- mal physiology via body-on-a-chip devices constructed on a microscale using the techniques of nanotechnol- ogy. ‘My work has focused primarily on micro-physiological systems, or body-on-a-chip, where we try to emulate what happens in the body and use it in terms of drug develop- ment to determine which drugs may most likely be successful in clinical trials,’ said Professor Shuler, who is Professor of Engineering Emeritus ogy can be applied to toxicology and even to determine the safety of cosmetics. Professor Shuler said: ‘At present, it is generally associated with pharmaceuticals and develop- ing new drugs in clinical trials. A key question is how to decide which drug is best to take into clinical tri- als. About 10% of drugs in clinical trials are approved as useful. The rest are not, but it still costs a lot of money to go into clinical trials, particularly with those candidates that get to Phase III trials. So, if you could have a device which tells you which drugs in the human body are likely to fail and which are likely to succeed, there could be savings of hundreds of millions of dollars. ‘The idea is to divide the body into different organ compartments and use the physiologically based pharmacokinetic model, in con- junction with a physical microscale model with organs represented by . c n I , s o r e p s e H © living cell constructs, to predict the efficacy of a drug (i.e.: ‘does it work on a critical organ?’) and determine the potential side effects. A whole- body model is needed because many drugs fail due to side effects even if they work on the primary target. The ultimate idea would be to have a system to improve the success rate of drugs in clinical trials.’ He said it is a fast-evolving field with major opportunities to improve the success rate for pharmaceu- tical companies in clinical trials. Professor Shuler, who was the first to demonstrate the feasibil- ity of such body-on-a-chip systems, explained that while he focussed on the whole body on a chip looking at multiple organ systems and their behaviour, others have developed more specific systems for a single organ-on-a-chip, such as a detailed liver model for liver response, for example. ‘Our model is a physiologi- cal model which predicts what will happen in the human, and is being applied to different diseases – some chronic and rare diseases, although cancer is a big area of application,’ he added. Finding the right diseases and target groups With drug development, the technol- ogy can examine complications from drugs and how they may be affected by other medications patients are taking, before they are advanced to the clinical trial stage. ‘It may be helpful for some chronic diseases where it could take the cells from a body and expand or use them directly to test multiple potential treatments and see which of those treatments work best,’ he continued. While a drug may work well in the majority of the population, there may be a proportion of the popula- tion in which they do not, so a clini- virtual connection allowing multiple Panther instruments to communi- cate with one another and func- tion within a singular, streamlined workflow. Linked instruments can share information such as reagent kits and reflex test orders, enabling more efficient reagent utilisation and improved turn-around time. A dashboard command feature allows technicians to monitor instrument inventories, maintenance tasks and test results on a single screen from a centralised location. Finally, the upcoming Panther Trax* will offer the ultimate in lab automation by physically and elec- tronically linking multiple Panther instruments together into a single, powerful workcell that allows labs to increase testing volumes without increasing staff. Taken together, these configur- able options address the needs of today’s laboratories, allowing them to increase operational capacity and testing volumes at their own pace, while building on the flexibility and streamlined user experience they require. To find out more about how Hologic’s Molecular Scalable Solutions can meet the growing pres- sure and demands of today and tomorrow visit https://www.hologic. com/hologic-products/diagnostic- solutions. *Not CE-IVD, not for sale. www.hologic.com Michael Shuler is Professor of Engineering Emeritus at Cornell University in New York, having been the Samuel B. Eckert Professor of Chemical Engineering at the Meinig School of Biomedical Engineering. He maintains a funded research program at Cornell, which focus- es on applying chemical reaction engi- neering principles to biological systems. cal trial can be designed to select a subpopulation in which the drug should be tested. ‘You can also build a system where you have represen- tation of different types of pheno- types, people from different back- grounds and groups and see how the treatments will work,’ he added. Future applications Professor Shuler suggests an addi- tional area where the technology may be applied is the support of regulatory approval. In the future, he believes a strong application for the technology will be in personalised medicine, rare diseases, and immu- nological disorders where there are no robust animal models at present. ‘Having a human-based model is better for predictions than animal models. In some cases, for example for rare disease where there are no animal models, it becomes essential,’ said Professor Shuler. ‘This kind of technology will have a major, or more immediate, impact because there is not a good alternative.” (MN) EUROPEAN HOSPITAL Vol 30 Issue 4/21

6 M A S S S P E C T R O M E T RY NEW: The MasSpec pen Pinning down the fringes of cancer Mass spectrometry – a powerful tool for analysing the molecular composition of a tissue sample – is invaluable during cancer surgery. However, mass spectrometers are complex and unwieldy, and cer- tainly a poor fit for an operating room (OR). To create a bridge between the lab and OR, Professor Livia S Eberlin, from Baylor College of Medicine, has developed a very promising ‘pen’. Report: Wolfgang Behrends Surgical removal of cancerous tissue is a formidable tightrope walk: remove too little and a tumour could return; cut out too much and damage to the surrounding tissue becomes an issue – especially in vital organs. Where to draw the line when the border between cancer and healthy tissue is invisible to the naked eye? Mass spectrometry is the answer. ‘Mass spec is an amazing tool to quickly measure and analyse molecules in a sample,’ surgeon Livia Eberlin explains. ‘The molecular makeup is highly reflective of our biological system – when we become diseased, its composition will change in a characteristic way, which can then be detected via mass spectrometry.’ Put simply: when applied to a tissue sample, mass spectrometry can tell the difference between can- cerous and non-cancerous cells. However, due to its complexity, the technology has largely been used in research and development labora- tories, but has seen limited use in Dr James Suliburk, head of endocrine surgery at Baylor College of Medicine, using the MasSpec Pen during thyroid surgery. hospitals and operating rooms. The MasSpec Pen, a new tool developed by Eberlin’s team, aims to change this. ‘We envisioned and designed the MasSpec Pen to be an easy-to- use, handheld interface between the surgeon and the mass spectrometer.’ How it works During surgery, the pen-size device is held against the tissue in ques- tion. ‘The tip of the pen holds a droplet of water, which acts as a solvent to extract molecules from a sample. After three to five seconds of direct contact with the tissue, a vacuum transports the droplet to the mass spectrometer, where the molecules in the droplet are read.’ Using machine learning technol- ogy, the device has been trained to identify molecular patterns of differ- ent cancers, such as breast, ovarian, pancreatic or thyroid cancer. The system can translate this complex information into easy-to-read visual or auditory cues, Eberlin says. ‘This might be a low pitch signal for healthy tissue, and high pitch for cancer, so that the surgeon could act upon this feedback immedi- ately, while remaining focused on the patient.’ To ensure hygiene and prevent infections, the contact areas e n i c i d e M f o e g e l l o C r o l y a B , k r u b i l u S J r D © Early detection – new diagnostic possibilities with MS qPCR Newborn screening improve over In some cases, the therapeutic opportunities the course of time, meaning that screen- ing of newborns still makes sense. Currently, this includes spinal mus- cular atrophy (SMA), which can be safely diagnosed via PCR, but which cannot be cured. Zolgensma (AVXS- 101), a new medication introduced only this year, has brought a cure for muscular atrophy within tangible reach. ‘Newborn screening for SMA started on 1 October 2021,’ Ceglarek reports. ‘The screening community is now observing with great inter- est how successful pre-symptomatic gene therapy will be.’ New legislation threatens diagnostic options The new version of the EU In Since its introduction around 60 years ago, the screening of newborns for immune, hormone and meta- bolic disorders has prevented many children from experiencing severe disease progression. The scope of systematic early testing has been significantly enhanced through mass spectrometry (MS). In our inter- view, Professor Uta Ceglarek, one of the driving forces behind the introduction of MS procedures in new- born screening, outlines new diagnostic possibilities offered by MS and qPCR procedures for screening – and also the ethical limits and possible dangers of new regulations for their implementation. The prerequisite for screening inclusion is the existence of a reli- able diagnostic procedure and the respective disorder being treatable. Although curative care is not pos- sible in all cases, such as in the case of mucoviscidosis, early detection helps to delay the progression of the disease and to increase the quality of life for those affected. 3-mm blood spot test for newborn screening Report: Daniela Zimmermann The foundations for using drops of blood from newborn babies to make predictions about the development and prevention of diseases later in life were laid in the 1960s with the systematic screening of babies for phenylketonuria (PKU). Professor Ceglarek deems this a success story, confirming, ‘It has allowed us to diagnose diseases before symptoms develop.’ the The expert views the inherited metabolic disorder PKU as a prime example of importance of screening: Those affected lack an important enzyme which results in the amino acid phenylalanine not being converted into tyrosine. When phenylalanine is ingested through food it accumulates in the body – with serious consequences. ‘Once these diseases take hold, the damage they cause is often irreversible.’ Due to the lack of tyrosine, untreated PKU can lead to severe impact on brain development, with resulting intellectual disabilities. Prior to the introduction of newborn screening, those affected required lifelong care and, in the most severe cases, had to be looked after in spe- cialist care facilities. However, when PKU is detected early, the disorder can be managed well, with strict dietary measures, and specifically through the reduction of protein in the diet. ‘The first patients who had PKU diagnosed during newborn screening are now aged over 40 and, due to early detection of the disease, lead normal lives,’ Ceglarek points out. MS/MS covers the lion’s share The range of diseases diagnosed through screening has increased significantly through the use of mass-spectrometry, and specifically through the tandem procedure MS/ MS. The so-called enhanced new- born screening (funded by the statu- tory health insurers in Germany since 2005), currently includes 19 inherited diseases, nine of which are diagnosed via MS/MS [source: https://www.screening-dgns.de/ richtlinien.php]. Additionally, PCR diagnosis, a procedure which has become more widely known to the public during the Corona pandemic, is used to diagnose severe combined immunodeficiency and spinal mus- cular atrophy. of the pen are disposable but can also be sterilised with an autoclave for re-use. While the information gathered from the molecular readout is not quite as specific as, for example, genetic analysis, the expression of the molecules offers a robust disease indication with accuracies ranging from 92 to 99 percent, depending on the cancer type. ‘Still,’ Eberlin warns, ‘we need to be aware Jialing Zhang demonstrates the use of the MasSpec Pen on a human tissue sample. n i t s u A t a s a x e T f o . v i n U / u i g a b A n a i v i V © Vitro Diagnostic Medical Devices Regulation (IVDR), which will finally come into force in 2022, will make the use of new, but also of already established, self-developed proce- dures much more difficult, Ceglarek says. This also affects mass spectrome- try. On the one hand, all procedures developed in the laboratory must be newly revalidated before they can be used on patients. ‘This means large, additional overheads for all para- meters which need to be reviewed,’ Ceglarek points out. On the other hand, the regulation prescribes the use of CE marked, commercially available laboratory tests. Even self- developed ‘in-house’ solutions, so- called LDTs, can only be used when there is no equivalent product avail- able in the market, and only if they can prove full CE conformity. ‘The IVDR is not about economic effi- ciency, meaning that the use of a different procedure must always be justified with reasons other than cost efficiency. This means that in case of comparable analytical character- istics, the commercial method must always be used. This also has devastating effects on molecular diagnostics, which, to a large part, works with self-devel- oped reagents. ‘In our laboratory we are currently having to evalu- ate which LDTs we can realistically still offer,’ Ceglarek explains, add- ing: ‘If adherence to the IVDR had been compulsory at the start of the Corona pandemic, the initial supply of Covid LDTs would have taken a lot longer, because each procedure would have needed extensive valida- tion before being used on patients.’ The new regulation could there- fore turn into a nail in the coffin for EUROPEAN HOSPITAL Vol 30 Issue 4/21

8 L A B O R AT O RY Outlook: Lab automation in 2021 4,000+ laboratories worldwide have installed automated systems Innovations in technology continue to improve clinical laboratory productivity. Total lab automation systems are responding to dramatic growth in internet-driven streamlined processes. Report: Bernard Banga In 2021, around the world, microbi- ology labs in commercial and uni- versity teaching hospitals have been processing more files and data then ever and systems are constantly reorganising to reach a critical mass for profitability. Objectives: to reduce the time need- ed for reports, speed up workflow and improve overall sensitivity of results. This year, a dozen major operators have business units in this sector, including the world’s top five in vitro diagnostics (IVD) companies: Roche Holdings, Thermo Fisher Scientific, Abbott Laboratories, Becton Dickinson Life Sciences and Siemens Healthineers. Covid-19: Increased testing volumes is unprecedented The world still grapples with the impact of the ongoing Covid-19 pandemic, which has intensified research as well as added pres- sure on pharma and clinical labs. Ensuring quicker turnarounds has become the priority, which leads to greater demand for automated liquid handling, microplate readers and robotic systems. Immunology and serology testing have gained importance during this pandemic, now in its third year. There has been significant deployment of polymer- ase chain reaction (PCR) and quan- titative polymerase chain reaction (qPCR) techniques in laboratories and hospitals, to improve Covid-19 testing capacity. This unprecedented increase in testing volumes presented a great opportunity to ramp up automation in immunology diagnostics, clinical chemistry and haematology labs. Mass spectrometry and TLA According to Professor Gian Luca Salvagno, in the department of clinical biochemistry at the University of Verona, Italy, ‘The spread of laboratory automation is also embracing mass spectrometry.’ The new generation of pre-analytics workstations, which can be con- nected directly to mass spectrometer systems, will allow the auto- mation of manual extraction and the elimination of time-consum- ing activities, such as tube labelling, capping and de-capping. ‘The use of automated liquid-handling platforms for pipetting sam- ples and protein precipitation reduces turnaround time and increas- es throughput in mass spectrometry testing,’ Salvagno added. The development and integration of different technologies into auto- mated mass spectrometry (MS) analysers will also generate techni- cal and practical advantages, such as pre-packaged, ready-to-use reagents, automated dispensing, incubation and measurement, automated sample processing, multiplex testing and automated validation and interpretation. v o h z y R y e g r e S / k c o t s r e t t u h s © Total lab automation embeds in biochemistry labs Today, total lab automation enters a new phase. Laboratories are invest- ing heavily in Total Lab Automation (TLA) systems supplied by in vitro diagnostics companies. These sys- tems combine to form an integrated system for total automation of pre- analytics, processing, clinical chem- istry and post-analytics immuno- chemistry workstations. The aim is for specimens to be processed, ana- lysed, and even stored with minimal user intervention. According to the American Association for Clinical Chemistry (AACC), 4,000+ laborato- ries worldwide have now installed automated systems. Robotic systems or centralised hubs in Europe On the one hand, mid-sized facili- ties (1.5 to 6 million tests annually) Cyber attack: Be prepared! Will your system beat ransomware? and any other individuals or ven- dors who have access to lab’s opera- tions that appear to be coming from a trusted sender, to identify who responds. Paul Caron, senior director of incident response at Arete, a global cybersecurity consulting compa- ny, emphasised the importance of assessing emails to learn the vol- ume of potential spam and phish- ing. ‘Phishing allows an attacker to distribute a weaponised payload or spoofed website to many recipients. Credentials are compromised or tro- jans added to establish a foothold within the environment, allowing remote access into the environment Ransomware attacks are a highly profitable and flourishing business in the 21st century. They can have a drastic impact on hospitals, clini- cal laboratories, and patients, Cynthia E Keen reports. Prepare employees Ongoing training is essential. In addition to enhancing awareness and knowledge about security risks and to reduce the risk of acciden- tal human error, employees need to know how to identify, report, and respond to a possible security incident. Labs should regularly perform data privacy reviews and penetra- tion testing. Johnson recommends the use of internal phishing mis- sions, sending emails to employees The Sophos Group, a British secu- rity hard/software company, has reported survey responses from 328 healthcare IT managers in 30 coun- tries. These reveal that 34% experi- enced a ransomware attack in 2020. Of these, about 40% could stop the attack before data was encrypted, but 34% paid unspecified ransoms to restore only 69% of their data. The average cost to attacked facili- ties was $1.27 million, represent- ing downtime, staff/device/network costs, and ransom paid. In a recent seminar, two experts in prevention and mitigation of ran- somware attacks provided practical advice to clinical laboratories on how to prevent attacks and what to do if an attack occurs. Emily Johnson, a Chicago-based health- care attorney specialising in data breach mitigation, discussed the components of a proactive ransom- ware data breach mitigation plan for clinical laboratories. Based on a comprehensive, writ- ten information security program, it should include annual risk assess- ments, a detailed basic cyber inci- dent response plan, a resiliency plan, and a plan for internal and external communications. Labs should have confidentiality agree- ments for employees and vendors and should conduct due diligence to confirm that people or companies they are doing business with also deploy breach prevention measures. and harvesting of legitimate creden- tials of employees.’ Be wary of remote desktops Remote desktops available to the internet can pose major security concerns. ‘Attackers will use brute force or compromised credentials to log into the specific system that is openly available externally. After gaining access to the system, the threat will compromise further cre- dentials or begin to move laterally throughout the IT environment.’ Endpoint detection and response (EDR) technology can facilitate the process. EDR security systems use behavioural analysis to analyse the activity of unusual behaviour attributed to individual users. They monitor and collect activity from endpoints that could be a threat, analyse this data to identify threat patterns, automatically respond to identify threats to remove or con- tain them, and immediately notify security personnel.New guidance released by the U.S. Cybersecurity and Infrastructure Security Agency (CISA) emphasises the importance of maintaining offline, current, and encrypted backups of data and reg- ularly testing them. When internet- facing vulnerabilities and miscon- figurations are identified, they need to be immediately mitigated. Recommendations in case of a cyberattack When a hacking incident occurs, it is critical to identify what data has been exposed and to determine the scope of the attack. Caron recom- mends the following actions when a security incident is identified: • Immediately retain digital foren- sics and incident response spe- cialists, who have expertise on ransomware attacks and can expedite internal assessment. • Leave all systems on; do not power down or reboot systems. Many ransomware variants do more damage or further encrypt systems upon reboot. • Disconnect inbound and out- bound network activity, network interface cards and internet LAN cables to prevent any connection to the Internet. • Obtain snapshots or full disk images of critical systems and servers, and potential ‘Patient Zero’ systems to facilitate a forensic team. If real-time backups exist, a lab needs to determine if the amount of time to restore via backup is acceptable. If negotiations seem necessary to restore operations rapidly, a key element that labs need to consider is whether it would be appropriate to negotiate for specific hacked sys- tems at a lower payment rate. Caron suggests that demands from the hacker be carefully assessed, and that a plethora of data be acquired to aid in negotiations. He recommends g n i y m u k l i o m p u s / k c o t s r e t t u h s © EUROPEAN HOSPITAL Vol 30 Issue 4/21

1 0 A I & I T Early detection AI technologies advancing cancer care Cancer care and the treatment clinicians can offer patients is being increasingly enhanced by artificial intelligence. Report: Mark Nicholls AI technology has a role in diagnosis, with algorithms trained to design and deliver patient care. It can match patients to clinical trials they may benefit from, and even help to predict outcomes and people who are at greatest risk. The session, ‘New Frontiers of AI and Data Analytics in Oncology’ at the online HIMSS21 European Health Conference explored where AI and data analytics is having the greatest impact today: screening and early detection, auto-planning for radiotherapy, treatment optimisa- tion, identification of new biomark- ers and more. Innovative technologies Clinicians are constantly seeking new ways of developing and imple- menting innovative technologies to support transformation of cancer care delivery, with AI pivotal to that, said Dr Tufia Haddad. But while new drugs and treat- ments are being approved on a weekly basis, she emphasised that they are only relevant if oncologists and their teams are up-to-date with the advances to ensure the right drugs reach the right patients. ‘With this in mind,’ she said, ‘we aim to develop clinical decision sup- port tools for our oncologists to help them select the best care, whether it is a standard care treatment option, or a clinical trial opportunity.’ Her presentation Patient Health ‘Improving and Provider Efficiency with Advanced Clinical Decision Support Systems’ high- lighted how the Mayo Clinic in the United States is working with commercial partners to develop a clinical trial matching system that extracts information from electronic health records to ensure patients match the trial’s inclusion and exclu- sion criteria. ‘We use natural language pro- cessing and machine learning to train the system to identify patient tumour attributes in order to match inclusion and exclusion criteria in individual clinical trials,’ said Dr Haddad, who is an Associate Professor of Oncology at the Mayo Clinic College of Medicine and Science, and a Consultant in the Department of Oncology. Sustained impact Once brought into practice, there was an immediate and sustained impact in how the system allowed the providers to better understand the clinical trial opportunities. ‘Because they were doing it more efficiently,’ she continued, ‘they had more time to spend counselling the patient about the potential benefits of participating in a clinical trial. We also saw a dramatic increase in our clinical trial accrual, both to our cancer-specific study as well as our broad Phase I experimental cancer therapeutics programme.’ Another priority is to develop a model to better assess breast cancer risk. ‘I really believe that having AI-enabled advance clinical deci- sion support systems can improve provider efficiency, engagement and effectiveness,’ she said. ‘For can- cer risk assessment, it can help us Professor Matteo Pepa is a Biomedical Engineer in the Division of Radiation Oncology and at the Radiomic Group of the IEO European Institute of Oncology IRCCS in Milan, Italy. He is also adjunct professor at the University of Milan. His fields of expertise include medical imaging, artificial intelligence, radiomics and radia- tion oncology. Professor Barbara Alicja Jereczek-Fossa is an Associate Professor of Radiation Oncology at the University of Milan and Head of the Department of Radiation Oncology at the IEO European Institute of Oncology IRCCS in Milan, Italy. Her main research and clini- cal interests include urological malignancies, breast cancer, combined modality approach, and high precision radiotherapy. Dr Tufia Haddad is an Associate Professor of Oncology at the Mayo Clinic College of Medicine and Science, Chair of Digital Health for the Department of Oncology, and serves as the Mayo Clinic Cancer Center Associate Director for Practice Innovation Platform. Her clini- cal practice and research are dedicated to breast cancer. individualise risk with increased accuracy and, overall, this has the potential to allow us to better tai- lor our screening and prevention recommendations to patients and reduce morbidity and the cost of care as well.’ at Decision support tool Professor Barbara Alicja Jereczek- Fossa, Associate Professor of Radiation Oncology the University of Milan, Italy, and Head of the Radiotherapy Division at the European Institute of Oncology, Milan, outlined how radiation oncol- ogy has an essential role in cancer management, contributing to cure in about 40% of all cancer patients. But with a huge amount of data to study to gain more knowledge on prognostic and predictive factors, AI is increasing in importance. in Her colleague, Professor Matteo Pepa, a bioengineer working on AI Jereczek-Fossa’s depart- ment, highlighted how AI plays a role in the radiotherapy workflow steps of patient consultation, plan- ning, image acquisition, segmen- tation, radiotherapy delivery and follow-up. ‘AI can be used as a decision support tool for radiation oncology,’ Pepa said. ‘The radia- tion oncologists can put their mind to the best course of treatment before expending resources on a lengthy treatment planning process.’ With image acquisition, AI is utilised in synthetic image generation, CT artefacts reduction, and image qual- ity improvement. Deep learning can help deter- mine optimal radiation parameters, Pepa said, and reduce planning time while improving the quality of images. ‘The last step is radiotherapy fol- low-up and artificial intelligence and machine learning models have been proven to be successful in pre- dicting outcome,’ he added. Radiology workflow The session also heard from Mathias Goyen, GE Healthcare’s Chief Medical Officer for Europe, who outlined examples of where artifi- cial intelligence is streamlining radi- ology workflow, automating repeti- tive and tedious tasks to allow the radiologist time to focus on their core roles. He gave examples in breast and prostate cancer, where technology is offering support. ‘One challenge for clinicians regarding breast cancer is how to increase detection rates, how to reduce false positives and how to avoid unnecessary patient recalls,’ Goyen said. He outlined how a GE Healthcare workflow solution used deep learn- ing that allows for advanced cancer detection, a significant improvement in workflow and delivered reading time reduction of almost 30 percent. an AI-powered advance visualisation review and reporting tool for pros- tate MRI. example was Another ‘AI can be deployed to stream- line workflows and support the radiologist in creating richer and more definitive reports, which can translate into more informed clinical decisions with a higher diagnostic confidence,’ Profesor Goyen pointed out. Every operating theatre is different - and we are prepared for it. In addition to technically and hygieni- cally high-quality wall-mounted consoles, operating theatre field monitors and all-in-one computers, we offer a scalable software suite that allows us to implement customized solutions for the medical IT sector. Our team integrates research and development, production and sales, project planning and service under one roof. With over 20 years of experience in the medical market, we stand for quality, innovation and reliable service. reinmedical.com The whole workflow in radiotherapy is based on medical images, a potential source of information on tumour biology, on- and post-treatment tumour remission. AI will help to analyse these images and create decision support tools. CT: computed tomography; EPID: electronic portal imaging device; CBCT: cone beam computer tomography; MRI-linac - magnetic resonance imaging-based linear accelerator. EUROPEAN HOSPITAL Vol 30 Issue 4/21

1 2 R A D I O LO G Y Saving lives Mobile stroke units Speed in treatment of ischemic stroke can mean the difference between successful recovery versus permanent disability or death caused by brain tissue damage. ) s e d n a l r a a S s e d t ä t i s r e v i n U © ( Professor Klaus Fassbender MD is Director of the Neurology Clinic in Homburg, Germany. blood clot-busting medication more frequently and sooner than patients who received initial care from emergency medical technicians in a standard ambulance. James C Grotta MD, director of the Houston Mobile Stroke Unity Consortium, called MSUs ‘a stroke centre on wheels’. Grotta reported that 53% of patients treated on an MSU in his study made a complete recovery, com- pared to 43% who were not treated on an MSU. Memorial Hermann Health System is sponsoring an ongoing randomised interventional clinical trial, the BEST-MSU Study, which began in August 2014 with an estimated enrolment of 1,038 patients. The completed study will provide data on outcomes and cost of MSUs compared to standard ambulances, and will help determine the value of integrating MSUs into hospital stroke programs in the USA. ‘This study will provide critical information that will be needed to determine if and how a subsequent more definitive study should be conducted. It is a necessary first step in a process which may dra- matically modify the way that acute stroke patients are managed in the United States,’ Grotta pointed out. Currently there are fewer than 30 MSU programs in operation in the USA. Major roadblocks to imple- mentation include cost, staffing, and the ability to identify individuals who have had a stroke by emer- gency telephone call dispatchers. Clinical trials performed in Europe A number of clinical trials have been conducted in Europe, all of which produced data supporting the benefits of MSUs to stroke vic- tims. A randomised clinical trial per- formed in Homburg between 2008 and 2011 showed that MSU-based stroke management significantly reduced time to treatment from 153 minutes for ischemic stroke patients receiving standard care to 72 min- utes with an MSU. Nearly 60% of patients in an MSU had therapy decisions for or against thromboly- sis based on diagnostic work-up, including laboratory and imaging studies, made within 60 minutes, compared to only 4% who received standard care. A newly published study in the Journal of the American Medical Association ( JAMA) conducted in Berlin between February 2017 and November 2019 also produced impressive results, with stroke vic- tims who received MSU care having less disability after 90 days. The objective of this non-randomized controlled intervention study of 1,543 patients was to evaluate the functional outcomes at three months among patients with acute ischemic stroke who received pre- hospital care by a conventional ambulance or by an MSU. Heinich J Audebert MD from the Centre for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, and co-researchers reported that 80.3% of MSU-dispatched patients had none-to-moderate disability at 90 days compared to 78.0% of the conventional ambulance-dispatched group, 12.6% compared to 13.3% had severe disability, and 7.1% com- pared to 8.8% died. James C Grotta MD is director of the Houston Mobile Stroke Unity Consortium, called MSUs ‘a stroke centre on wheels’ ) n o i t a i c o s s A t r a e H n a c i r e m A © ( Heinich J Audebert MD works at the Centre for Stroke Research Berlin, Charité- Universitätsmedizin Neurologie, Erik Freitag MD and colleagues at the Klinik und Hochschulambulanz für Charité– Universitätsmedizin Berlin, provides useful recommendations in a newly published article in Stroke ‘How to set up a successfully running mobile stroke unit program’. In addition to technical, staffing, and logistical requirements, they discuss if an MSU program makes sense in the area a hospital serves. One million people catchment area for one mobile stroke unit ‘We estimate a one million people catchment area to be a proper pop- ulation covered by one MSU,’ they advise. ‘In health systems with hos- pitals competing for stroke cases, it’s vital to start with intensive communications. MSU services can work smoothly if they are operated in close collaboration with the dis- patch centre and EMS.’ Allies, such as politicians, will be needed to support the system if it is to be paid by public funds. Legal issues also need to be investigated in advance. ‘Organising an MSU service is not an easy task,’ Freitag observes. ‘But enjoy the pleasure of thrombolys- ing patients in the ‘Golden Hour’ of stroke, with many patients experi- encing rapid recovery.’ EUROPEAN HOSPITAL Vol 30 Issue 4/21 Report: Cynthia E. Keen Time is of the essence to perform thrombolysis with a tissue plasmi- nogen activate (tPA), a protein that can dissolve blood clots causing the stroke or intra-arterial thrombolytic therapy (IAT) because of large-ves- sel occlusion. CT imaging to rule out intracrani- al haemorrhage is essential to deter- mine if this treatment is appropriate. In 2003, Professor Klaus Fassbender MD, director of the Neurology Clinic at Saarland University Medical Center in Homburg, Germany, pro- posed the idea of expediting CT imaging by bringing a CT scanner to the stroke victim in a specially configured ‘stroke ambulance’. His idea to shift acute stroke examina- tion, including brain imaging, to a prehospital setting became reality with the 2008 launch of the world’s More than just MRI accessories www.allmri.com h t l a e H T U © first mobile stroke unit (MSU) at his hospital, which serves mixed urban and rural communities in a 20 km radius. MSUs incorporate a compact CT scanner, a complex point-of- care laboratory equipped with small, commercially available portable laboratory devices to quantify haematological, clini- cal chemistry, coagulation mark- ers, and renal function markers; real-time bidirectional audio- video communications, and a PACS workstation. Clinical staff onboard typically include a par- amedic, CT technician, and phy- sician plus a registered nurse trained in stroke medicine. A The Houston Mobile Stroke Unit. neuroradiologist should be accessi- ble via PACS, and telemedicine con- nects with a hospital’s laboratory staff, emergency physicians, neu- rologists, and/or neurosurgeons. Blood clot-busting medica- tion: Sooner in MSUs MSUs shorten time to treatment, improve prehospital triage, and can increase thrombolysis rates. 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1 4 R A D I O LO G Y ‘We need to drive standardisation in scanning’ Hybrid imaging is the future During our interview with Professor Regina Beets-Tan, President of the European Society of Radiology (ESR), jour- nalist Michael Krassnitzer asked about possible future develop- ments in cancer imaging. Beets-Tan unhesitatingly pointed out that screening exams are ever- increasing and thus more and more tumours are and will be detected at an earlier stage. ‘The earlier a tumour is detected,’ she added, ‘the better it can be treated: by resection, minimally invasive sur- gery, or by interventional radiology. This means we need very sensi- tive imaging techniques that can identify very small tumours, and also tumour growth. So we need high-resolution anatomical imaging combined with biological imaging that visualises how the tumour is behaving. ‘Treatment of malignancies where the tumour has already spread to other parts of the body has also become more effective – the key- words are immunotherapy and targeted therapy. To evaluate the response of these therapies, we also need special imaging techniques that can visualise not only the mor- phology, but also the biology of the tumour. In addition, we want to extract as much information as pos- sible from these images by using artificial intelligence (AI).’ Future imaging techniques ‘Hybrid imaging. That’s the future. It involves the combination of sev- eral techniques: First, magnetic resonance imaging (MRI), which provides high-resolution images of morphology; second, perfusion r e v i l O d e v S / k c o t s r e t t u h s © imaging, which can quantify blood flow to the tumour; third, diffusion imaging that can map the cellular architecture, which is quite differ- ent in cancer cells than in healthy cells; and fourth, positron emission tomography (PET), which can map the metabolic activity of a tumour. Combining all these methods gives the highest possible sensitivity.’ The role of imaging in immunotherapy ‘Currently, imaging capabilities in immunotherapy are very limited. Computed tomography (CT) is used in follow-up scans, but this morpho- logic imaging alone is insufficient. Sometimes the tumour becomes larger during treatment, but this is not tumour growth but swelling due to the immune response. Therefore, biopsies have to be done regularly to find out what the response of the Screening exams are ever-increasing. The earlier a tumour is detected, the better it can be treated tumour to immunotherapy actually looks like. ‘In other words, we also need imaging here to visualise the behav- iour of the tumour. Specifically, we need to visualise the tumour micro- environment, that is, the immedi- ate environment of the tumour, down to the level of the individual immune cell.’ How far developed is this kind of imaging? ‘We are still at the very beginning. First, it’s important to get fund- ing for the relevant research. I’m a member of the Mission Board for cancer, an expert body that advises the EU Commission on can- cer. We have recommended that the Commission invest in research into modern hybrid technologies to better evaluate the response to the new, very expensive therapies – such as immunotherapy.’ Has the initial euphoria faded about AI’s potential to reveal tumours? ‘AI is still a pretty promising thing. However, it has proven to be a problem that the data with which the artificial intelligence system is fed must be very homogeneous. At my clinic, a study has just been completed in which 800 MRI imag- es of a particular tumour from all over the Netherlands have been fingerprinted by AI. The results are little better than a coin toss. That’s precisely because the scans are all so different. So we need to drive standardisation. Once the underly- ing data is standardised, the results Professor Regina Beets-Tan is President of the European Society of Radiology (ESR) and Chair of the Department of Radiology at the Netherlands Cancer Institute. obtained using AI will also be more reliable.’ Alongside future cancer imaging, what might arrive to advance radiology in general? ‘Radiologists will play a greater role in the clinic in the future. Currently, radiologists are busy with a lot of routine tasks, which in the future can be taken over by AI, and also by less specialised and less expen- sive staff. The time radiologists gain when relieved of routine tasks can be put into other tasks. Why shouldn’t radiologists explain their image findings to patients? ‘Now that malignant diseases are being detected earlier and earlier, the need for interventional radiol- ogy will also increase. In any case, radiology must continue to evolve. We need to combine our technology with clinical expertise. If we don’t, we run the risk that our specialty could one day become superfluous.’ D O N ’ T M I S S ! European Congress of Radiology (ECR) 2-6 March 2022, Vienna, Austria www.myesr.org/congress 1 TESLA IS GREAT. 7 TESLA IS EVEN BETTER. Accutron® MR – the mobile MRI specialist. Quick configuration, versatile use and compatible with up to 7 teslas. Accutron® MR allows a high patient throughput. Next, please. IT system raises secur Monitors and digital door signs Pharmaceutical research companies espouse very high security stand- ards because they are potential vic- tims of cyberattacks and espionage. The biopharmaceutical company Boehringer Ingelheim, for example, ensures systems are or high stand- ards and particularly secure. The company runs regular secu- rity checks. One way to ensure this is to separate the systems from the office network. Each monitor is assigned a separate port, which is checked via IT security. This has helped to survive attacks without, so far, any damage. Monitors, as essential work aids, must be secure The IT service provider Rein Medical has been supplying these moni- tors since 2019. Before installation the company and its solutions also underwent a security check. In its labs and work areas, Boehringer Ingelheim relies on eight OPERION monitors with a screen diagonal of 24 inches and two monitors with a screen diagonal of 55 inches. The monitors are only used to display information. With the 24” displays, the employees also have access to the Manufacturing Management Software (MMS), i.e., the integrated software for automat- ic production planning and control. They use this to centrally enter data, and to operate and control worksta- tions and systems. In the selection process, Boehringer Ingelheim’s managers looked at a whole range of monitors from different manufacturers and assessed them based on predefined criteria. Finally they chose the solu- tions from Rein Medical because this company presents a broad port- folio and offers many different sizes. ‘The monitors also fulfilled other essential requirements: They can be treated with commercially available cleaning agents, have a retractable keyboard and meet all fire protec- tion requirements and other specifi- cations of the pharmaceutical com- pany,’ the IT specialist firm reports. ‘The introduction of the monitors went as smoothly as the choice of system. The displays run efficiently. Since the terminals are connected to the room information system via a ter- minal server, there is only one point that needs to be maintained. The electronic door signs also perform reliably.’ EUROPEAN HOSPITAL Vol 30 Issue 4/21

1 6 I N F E C T I O N P R E V E N T I O N A potentially devasting impact on non-Covid patients Covid-19 alters antibiotic use The long-term impact of the coronavirus pandemic on antimicrobial resistance (AMR) remains difficult to predict, Mark Nicholls reports. particularly how it could support antibiotic prescribing. diseases consultant Infectious Professor Alison Holmes said Covid- 19 has impacted on antibiotic use in hospitals and across the wider community, but more research is needed to fully assess the extent and implications. said: ‘There were many consequenc- es that could impact on infection that could fuel antimicrobial resist- ance, or indeed reduce it signifi- cantly, and it is important that we consider this across multiple lev- els.’ Further considerations included Initial research Low levels of coinfection in Covid- 19 patients (8%), but high rates of antimicrobial use (70%), were sug- gested in initial research, but there were research limitations: studies often did not differentiate whether the Holmes discussed sub- ject in detail in her presentation ‘Healthcare associated infection, antibiotic use, drug resistance and Covid-19’, to the 73rd annual con- gress of the German Society for Hygiene and Microbiology, with a focus on bacterial infections, antibi- otic use, hospital-onset Covid infec- tion and how that should be tackled, and healthcare associated infections (HCAI) in individuals with and with- out Covid-19. only in suspected or confirmed serious infections and with regular review, short duration and the need to maintain strong antimicrobial stewardship programmes, although more recent evidence has ‘expanded the level of understanding of co- infection’. Critical care has been highlighted as the main focus for coinfection, with organisms linked predominantly to local epidemiol- ogy. However, while the majority of coinfections were hospital-acquired pneumonia or ventilator-associated pneumonia, there was a need for these risk factors to be collected in a standardised way to ‘understand risk of Covid in terms of coinfection’. Non-Covid patients More recent study findings, how- ever, were not dissimilar to the ‘Bacterial infection and Covid- 19 were a major concern, particu- larly at the beginning of the pan- demic in terms of driving antibi- otic use and potential AMR,’ said Holmes, Professor of Infectious Diseases and Director of the NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, as well as and the Centre for Antimicrobial Optimisation (CAMO) at Imperial College London. Antibiotic prescribing Emphasising the importance of looking at the effect, directly and indirectly, of other clinical activ- ity related to infections on Covid and non-Covid populations, Holmes i a r k a t n O n u r a J / k c o t s r e t t u h s © the potential for bacterial infection risk on new therapies, particularly immunological; the pressures on different healthcare systems, and patient backlogs. Holmes, who has contributed to the national Covid-19 response in the UK, noted that early in the pandemic, experts were keen to conduct a rapid review in terms of bacterial and fungal infections, but Covid-19 has impacted on antibiotic use in hospitals patient populations were in critical care or not; there was limited micro- biology, risk factors such as whether patients were being ventilated were not reported; and complications of excessive prescribing were not iden- tified. She said the evidence at the time supported use of antibiotics early research, with 8.6% of bacte- rial infections seen versus 74.6% of patients on antibiotics. But she added: ‘We are not doing well enough in terms of understand- ing what is going on in low resource settings and we need to do much better around that to understand the potential devasting impact this is having on our non-Covid patients.’ Holmes also discussed the impact g a a H n e D , s i u h s t i r u a M © S H N / e r a c h t l a e H e g e l l o C l a i r e p m I © ( Alison Holmes is Professor of Infectious Diseases and Director of the NIHR Health Protection Research Unit in Healthcare Associated Infections and AMR, as well as the Centre for Antimicrobial Optimisation (CAMO) at Imperial College London. She leads an international, multidisci- plinary infectious disease research pro- gramme focusing on optimising anti- microbial use by developing innovative approaches and technologies to manage and prevent infections. of Covid on bacteremias, notably a major drop across the two waves of Covid and particularly in e.coli bac- teremia, though this was tempered by the change in the patient mix. In the USA, she noted, there was a rise in hospital-acquired infections in 2020 compared to 2019, after years of reductions, mainly catheter- associated urinary tract infections, ventilator associated events, and MRSA, but notably no increase in surgical site infections (with surgery being cancelled), and no increase in C.diff rates. Community prescribing With concerns about AMR in acute care, the implications of a fall in antibiotic use in the community – traditionally an area of higher usage – remain uncertain. ‘That’s a major concern because we don’t know if people could access treat- ment appropriately, or if patients with infections are going untreated. There is a need for better evidence on this,’ Holmes said and empha- sised the need for ‘strong, robust surveillance’ of hospital-onset Covid for future pandemic preparedness, and recovery of healthcare resil- ience and safety. Health systems need to understand that non-Covid patients can be well looked after and health systems be run effec- tively and safely with the appropri- ate level of capacity in terms of beds and staffing, she underlined. Local epidemiology While bacterial infection in Covid patients is relatively low, with the majority in acute care due to HCAIs, she said understanding the local epidemiology is critical and that a strong foundation of effective pre- vention and control practice is vital. Antibiotic stewardship is also cru- cial given the high rates of prescrib- ing, and there is a need for a better framework for prospective reporting to inform clinicians in providing safe healthcare for HCAIs associated with Covid, for hospital-onset Covid infections, and for antibiotic use within the Covid pandemic. ‘By recognising that the AMR pan- demic is happening already, we need to be able to understand and make the most of the information, so that we can learn from the Covid pandemic,’ the professor said. ‘The long-term impact of the pan- demic on AMR is still difficult to predict and it’s important to have a whole health system perspective, looking at what is happening in the community and in acute settings at the same time.’ EUROPEAN HOSPITAL Vol 30 Issue 4/21