Cambridge University Hospitals NHS Foundation Trust

Scientists have grown 'mini-guts' in the lab to help understand Crohn's disease, showing that 'switches' that modify DNA in gut cells play an important role in the disease and how it presents in patients. The researchers say these mini-guts could in future be used to identify the best treatment for an individual patient, allowing for more precise and personalized treatments. Cambridge scientists have grown 'mini-guts' in the lab to help understand Crohn's disease, showing that 'switches' that modify DNA in gut cells play an important role in the disease and how it presents in patients. The researchers say these mini-guts could in future be used to identify the best treatment for an individual patient, allowing for more precise and personalised treatments. Crohn's disease is a form of inflammatory bowel disease (IBD). It is a life-long condition characterised by inflammation of the digestive tract that affects around one in 350 people in the UK, with one in four presenting before the age of 18. Even at its mildest, it can cause symptoms that have a major impact on quality of life including stomach pain, diarrhea, weight loss and fatigue, but it can also lead to extensive surgery, inpatient admissions, exposure to toxic drugs and have a major impact on patient and their families. While there is some evidence that an individual is at greater risk of developing the condition if a first-degree relative has Crohn's, there has been only limited success in identifying genetic risk factors. As a result, it's estimated that only 10% of inheritance is due to variations in our DNA. Matthias Zilbauer, Professor of Paediatric Gastroenterology at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust (CUH), said: "The number of cases of Crohn's disease and IBD are rising dramatically worldwide, particularly amongst younger children, but despite decades of research, no one knows what causes it. Part of the problem is that it's been difficult to model the disease. We've had to rely mainly on studies in mice, but these are limited in what they can tell us about the disease in people." In research published today in Gut, Professor Zilbauer and colleagues used cells from inflamed guts, donated by 160 patients, mainly patients and adolescents, at CUH to grow more than 300 mini-guts -- known as organoids -- in the lab to help them better understand the condition. Samples were donated by patients with Crohn's disease and ulcerative colitis, as well as by patients unaffected by IBD. "The organoids that we've generated are primarily from children and adolescents," said Professor Zilbauer. "They've essentially given us pieces of their bowel to help with our research. Crohn's can be a severe condition to have to deal with at any age, but without our volunteers' bravery and support, we would not be able to make such discoveries as this." Organoids are 3D cell cultures that mimic key functions of a particular organ, in this case the epithelium -- the lining of the gut. The researchers grew them from specific cells, known as stem cells, taken from the gut. Stem cells live forever in the gut, constantly dividing allowing the gut epithelium to regenerate. Using these organoids, they showed that the epithelia in the guts of Crohn's disease patients have different 'epigenetic' patterns on their DNA compared to those from healthy controls. Epigenetics is where our DNA is modified by 'switches' attached to our DNA that turn genes on and off -- or turn their activity up or down -- leaving the DNA itself intact, but changing the way a cell functions. Professor Zilbauer, a researcher at the Stem Cell Institute at the University of Cambridge, said: "What we saw was that not only were the epigenetic changes different in Crohn's disease, but there was a correlation between these changes and the severity of the disease. Every patient's disease course is different, and these changes help explain why -- not every organoid had the same epigenetic changes." The researchers say the organoids could be used to develop and test new treatments, to see how effective they are on the lining of the gut in Crohn's disease. It also opens up the possibility of tailoring treatments to individual patients. Co-author Dr Robert Heuschkel, Consultant Paediatric Gastroenterologist at CUH and Lead of the Paediatric IBD Service, said: "At the moment, we have no way of knowing which treatment will work best for a patient. Even those treatments we currently have only work in around half of our patients and become less effective over time. It's a huge problem. "In future, you could imagine taking cells from a particular patient, growing their organoid, testing different drugs on the organoid, and saying, 'OK, this is the drug that works for this person'." The research highlighted a specific pathway implicated in Crohn's, known as major histocompatibility complex (MHC)-I. This pathway allows immune cells to recognise antigens -- that is, a toxin or other foreign substance that induces an immune response in the body, and which could include molecules in our food, or our gut microbiota. The team showed that the cells forming the inner lining of the gut in Crohn's disease patients have an increased activity of MHC-I, which can lead to inflammation in specific parts of the gut. "This is the first time where anyone has been able to show that stable epigenetic changes can explain what is wrong in the gut epithelium in patients with Crohn's disease," said Professor Zilbauer. The epigenetic modifications were found to be very stable, which may explain why even after treatment, when a patient appears to be healed, their inflammation can return after several months -- the drugs are treating the symptoms, not the underlying cause. Epigenetic changes are programmed into our cells very early on during the development of the baby in the womb. They are influenced by environmental factors, which may include exposure to infections or antibiotics -- or even lack of exposure to infection, the so-called 'hygiene hypothesis' that says we are not exposed to sufficient microbes for our immune systems to properly develop. The researchers say this may offer one possible explanation for how the epigenetic changes that lead to Crohn's disease occur in the first place. The research was largely supported by the Medical Research Council. It was also supported through collaboration with the Milner Therapeutics Institute, University of Cambridge. Cambridge Enterprise is working with Professor Zilbauer and team and has recently filed a patent for this technology. They are seeking commercial partners to help with the development of this opportunity.

In Bristol, UK, attendees of the European Group Meeting focused on using technology to enable better care outcomes, patient experiences, and clinician happiness. BRISTOL, UK, June 4, 2024 /PRNewswire/ -- Experts from leading healthcare and medical research organisations came together at Epic's first European Group Meeting (EGM) in Bristol, UK. Participants showcased innovations that have delivered real-world improvements in areas such as quality of care, patient experience, clinician well-being, population health, and operational efficiency. "EGM goes a step beyond other industry conferences," said Dr. Ari Ercole, Interim Chief Clinical Information Officer, Cambridge University Hospitals NHS Foundation Trust (Cambridge, UK). "We discussed the challenges we're facing and how technology can help, and I left with concrete, actionable plans to improve the lives of the patients I serve. It's a must not only for hospital digital teams but also for decision makers who want to see opportunities for using the electronic health record for transformation." Healthcare organisations around the world are having to do more with less, as clinician shortages combine with an aging population and an increased demand for specialised services. At EGM, participants shared specific ways that they are meeting these challenges to help their peers in Europe and worldwide implement similar approaches. Example topics included: Making scheduling easier for patients and staff: Manchester University NHS Foundation Trust (MFT) (Manchester, UK) shared how they use patient self-scheduling capabilities to reduce administrative burden for Trust staff while delivering convenience to patients. For many specialties, patients can now schedule their own appointments through MyMFT (MFT's branding of Epic's MyChart Patient Experience Platform). In one specialty, 98% of surveyed patients said that they would recommend using MyMFT for self-scheduling. Seeing patients more quickly with FastPass: The Oy Apotti Ab (Helsinki, Finland) shared their experience with Epic's FastPass technology. When an appointment is cancelled, FastPass automatically finds waiting list patients who are a good match. It then offers the appointment to the patient directly—without the need for manual staff intervention. At Apotti, patients scheduled via FastPass can be seen an average of 20 days sooner than their original appointment times. Breaking ground with artificial intelligence to create better experiences for clinicians and patients: In May, Elisabeth-TweeSteden Ziekenhuis (Tilburg, Netherlands) and Universitair Medisch Centrum Groningen (Groningen, Netherlands) became two of the first organisations in the world to deploy Epic's AI-enabled Patient Summaries. This technology rapidly distills years' worth of clinical notes into a brief summary that clinicians can review, significantly reducing the amount of time needed to prepare for a high-quality patient visit. "This conference highlighted the value in working together at a global level, on a shared technological platform, to provide exemplary patient experiences while improving clinician wellbeing," said Pippa Kassam, Chief Nursing Officer at Royal Devon University Healthcare NHS Foundation Trust (Exeter, UK). "It was particularly special and exciting being part of the first-ever EGM. The event was organised with such precision and thought for Epic's Europe-based customers." EGM will be held annually to bring together providers, technology experts, and industry leaders in advancing healthcare in Europe and around the world. Epic is a global healthcare software company that helps people get well, helps people stay well, and helps future generations be healthier. Founded in a basement in 1979 with three half-time employees, Epic is now a leading EHR software developer. Epic supports healthcare organizations in 16 countries, with more than 2,700 hospitals using Epic and over 190 million patients using Epic's MyChart patient portal to manage their care online. For more information contact: [email protected]. Visit . Logo -

One in 200 newborns is admitted to a neonatal unit with sepsis caused by a bacteria commonly carried by their mothers -- much greater than the previous estimate, say researchers. The team has developed an ultra-sensitive test capable of better detecting the bacteria, as it is missed in the vast majority of cases. Streptococcus agalactiae (known as Group B Streptococcus, or GBS) is present in the genital tract in around one in five women. Previous research by the team at the University of Cambridge and Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, identified GBS in the placenta of around 5% of women prior to the onset of labour. Although it can be treated with antibiotics, unless screened, women will not know they are carriers. GBS can cause sepsis, a life-threatening reaction to an infection, in the newborn. Worldwide, GBS accounts for around 50,000 stillbirths and as many as 100,000 infant deaths per year. In a study published today in Nature Microbiology, the team looked at the link between the presence of GBS in the placenta and the risk of admission of the baby to a neonatal unit. The researchers re-analysed data available from their previous study of 436 infants born at term, confirming their findings in a second cohort of 925 pregnancies. From their analysis, the researchers estimate that placental GBS was associated with a two- to three-fold increased risk of neonatal unit admission, with one in 200 babies admitted with sepsis associated with GBS -- almost 10 times the previous estimate. The clinical assessment of these babies using the current diagnostic testing identified GBS in less than one in five of these cases. In the USA, all pregnant women are routinely screened for GBS and treated with antibiotics if found to be positive. In the UK, women who test positive for GBS are also treated with antibiotics -- however, only a minority of pregnant women are tested for GBS, as the approach in the UK is to obtain samples only from women experiencing complications, or with other risk factors. There are a number of reasons why women in the UK are not screened, including the fact that detecting GBS in the mother is not always straightforward and only a small minority of babies exposed to the bacteria were thought to become ill. A randomised controlled trial of screening for GBS for treatment with antibiotics is currently underway in the UK. Dr Francesca Gaccioli from the Department of Obstetrics & Gynaecology at the University of Cambridge said: "In the UK, we've traditionally not screened mothers for GBS, but our findings -- that significantly more newborns are admitted to the neonatal unit as a result of GBS-related sepsis than was previously thought -- profoundly changes the risk/benefit balance of universal screening." To improve detection, the researchers have developed an ultrasensitive PCR test, which amplifies tiny amounts of DNA or RNA from a suspected sample to check for the presence of GBS. They have filed a patent with Cambridge Enterprise, the University of Cambridge's technology transfer arm, for this test. Professor Gordon Smith, Head of Obstetrics & Gynaecology at the University of Cambridge, said: "Using this new test, we now realise that the clinically detected cases of GBS may represent the tip of the iceberg of complications arising from this infection. We hope that the ultra-sensitive test developed by our team might lead to viable point-of-care testing to inform immediate neonatal care." When the researchers analysed serum from the babies' umbilical cords, they found that over a third showed greatly increased levels of several cytokines -- protein messengers release by the immune system. This suggests that a so-called 'cytokine storm' -- an extreme immune response that causes collateral damage to the host -- was behind the increased risk of disease. The research was funded by the Medical Research Council and supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.