Data scientists have used clinical data to help predict how the incurable neurological condition amyotrophic lateral sclerosis (ALS) will progress in individual patients, offering hope for better management and quicker trials of new treatments. Affecting up to 5,000 adults in the UK at any one time, ALS (also called motor neurone disease or Lou Gehrig’s disease) leaves patients unable to move, talk, swallow and eventually breathe. The latest research, led by Professor Joanna Holbrook from the NIHR Southampton Biomedical Research Centre and published in the journal PLOS one, could help to explain why this muscle wasting disease progresses much faster in some patients than others. Better prediction of disease progression could enable smaller and more targeted clinical trials, which focus on groups of patients with the same form of the disease. Predicting lifespan Most ALS patients only survive 3-5 years from the point of diagnosis, but this varies from person to person. Some people can live up to ten years and in a few rare cases, such as Professor Stephen Hawking, even longer. This study set out to use existing patients’ clinical data to predict how fast the disease would progress. Targeted treatments The research team analysed anonymous data from people with ALS in who had taken part in clinical trials, stored in the PROACT database, collected by the Prize4Life foundation. Using this data, they developed an algorithm based on four indicators (weight, alkaline phosphatase, albumin and creatine kinase) that could predict the rate of disease progression and likelihood of survival over the course of the two year period covered. The algorithm will aid the study of the role of these indicators and other factors in the slower and faster forms of the disease, opening the potential for targeted treatments for specific groups of patients.

For centuries the Sherpa peoples of the Himalayas have lived in air so thin in oxygen that lowlanders find every breath difficult – now our researchers have shown how, and how it could improve NHS critical care. On 23 May 2007 at the summit of Mount Everest a small team of exhausted Southampton doctors and scientists jabbed their own femoral arteries to take blood samples. A decade of groundbreaking research into low oxygen effects on the body followed, and ten years on, Professor Mike Grocott and the Xtreme Everest team returned to the Himalayas to share these with the Sherpa and Nepalese clinicians. Living with less oxygen One in five people in the UK end up in intensive care at some point and, of those, 25-30 per cent die, with lack of oxygen, or hypoxia, a major contributory factor. Yet the Sherpa have lived normally in similarly low oxygen at high altitude for generations. Renowned as expert mountaineers, many Sherpas have climbed Mount Everest, the most famous being Tenzing Norgay, part of the first ever successful ascent with Edmund Hillary. While lowlanders must acclimatise over days and weeks to low oxygen to avoid altitude sickness, the latest findings show that Sherpas have adapted genetically over the last 500-600 years, having a version of a key gene that enables their cells to use oxygen more efficiently. Better critical care The Xtreme Everest team returned to the Sherpa capital of Namche to share their findings and thank the Sherpa community. Among the crowd to hear theme was Edmund Hillary’s cook. “We have been extremely fortunate to work with the Sherpa community in Nepal,” said Prof Grocott. “Without them the expeditions could not have taken place, nor would we have made these findings.” They also held a two-day conference, KnO2wledge Kathmandu, sharing their wider findings with local medical professionals. Just one of many discoveries made by Xtreme Everest and our BRC, this result has identified new targets for drugs and care that improve oxygen uptake in critically ill and trauma patients.

Southampton researchers are working with the University of Cambridge to trial a revolutionary ‘artificial pancreas’ device that could transform the lives of type 1 diabetic children and possibly prevent the progression of type 1 diabetes. Type 1 diabetes develops in childhood when the body’s own defences attack cells in the pancreas responsible for safely controlling blood sugar levels. Without this control, people with type 1 diabetes rely on a daily routine of insulin delivered either by injections or a pump to avoid dangerous rises in blood sugar levels. Now Southampton researchers are part of a groundbreaking University of Cambridge study, to see if a new artificial pancreas device can take the strain and help protect their own pancreas. Protecting the pancreas The pancreas releases insulin, a hormone that tells the body to absorb sugar when it senses rising blood sugar levels. The new trial, led in Southampton by Dr Nicola Trevelyan, will test a closed loop insulin delivery system, or artificial pancreas. This works by monitoring the patient’s blood sugar and, when required, automatically releasing a precise dose of insulin, just as the pancreas of someone without diabetes would do. Over two years newly diagnosed children in the trial will be given either standard care or the artificial pancreas. This involves wearing both a glucose monitor and insulin pump, and carrying a wireless controller the size of a mobile phone. The researchers hope the device will not only control blood sugar, but also help reduce the ongoing damage to the patient’s pancreas, keeping some of its sugar control intact and making things easier long-term for patients with diabetes. No need for injections Type I diabetes is currently managed through daily injections of insulin, with top-up injections with food. Some patients later choose to switch to an insulin pump, which delivers a regular pre-set dose of insulin, but they still need to accurately estimate the carbohydrate in every meal or snack to get the right dose. The artificial pancreas removes the burden of injections, although patients will still need to calculate carbohydrate intake and insulin every time they eat. However, between meals the system will automatically deliver exact doses of insulin according to the person’s blood sugar so that blood sugar levels stay very stable. The children, their families and the clinical team can track changes in sugar and insulin on the hand-held device. “This is seen as the next massive step forward in diabetes treatment,” says Dr Trevelyan, “to have a device that takes you out of having to control your own blood sugar.”

Researchers from the NIHR Southampton Respiratory Biomedical Research Unit have seen promising results from a new treatment for the incurable, fatal lung disease idiopathic pulmonary fibrosis (IPF). Preventing lung damage Each year over 5,000 new cases of IPF are diagnosed in the UK, with an average life expectancy of only three years. The condition, which usually affects elderly people, causes steadily expanding inflammation and scarring of the lungs, making it increasingly difficult to breathe. The latest research, led by Prof Donna Davies and published in the journal Oncotarget, has shown that the drug romidepsin can stop the spread of damaged, scarred tissue in the lungs. If given to newly diagnosed IPF patients, it might help prevent their condition from getting worse. Switching genes on and off Genes can be turned on or off by modifying the histone protein balls that DNA is wrapped around. Romidepsin works by preventing chemical changes to histones, influencing which genes are active in fibroblast cells involved in the scarring of lungs in IPF patients. By allowing chemical structures called acetyl groups to build up on certain parts of the histone proteins, Romidepsin stopped fibroblast cells taken from IPF patients and grown in the lab from growing and multiplying. Although this research is still at an early stage, it shows that Romidepsin is a promising new drug for trials aimed at improving survival and quality of life for IPF patients.

A quick-acting test for flu and other viral infections could help fight the rise in antibiotic resistant ‘superbugs’ and ensure patients with respiratory conditions get the right treatment faster. New research, led by Dr Tristan Clark from the NIHR Biomedical Research Centre, has shown a quick-acting test for respiratory viruses like flu could improve care for patients. Patients with asthma and chronic obstructive pulmonary disease (COPD) who had the test received the right treatment faster, with shorter courses of antibiotics and shorter stays in hospital. Personalised treatment The study results, published in Lancet Respiratory Medicine, are an early example of personalised medicine – where the treatment is tailored to cater for each individual patient. The test, known as a point-of-care test, avoids the need for samples to be sent off to a laboratory, allowing patients to get a diagnosis within an hour rather than a couple of days. Overall, the study involved 720 patients with acute respiratory illness, including pneumonia and exacerbation of asthma and COPD at University Hospital Southampton’s emergency department and acute medical department during the winter months of 2015 and 2016. Half the patients had the point-of-care test, in which case a swab was analysed on the device and the results given to their doctor, while the other half received standard care. Patients who had the point-of-care test got the right treatment for their condition faster. Patients who tested positive for flu in the point-of-care testing group were appropriately isolated in a side room and given antiviral medication more often and sooner than those in the standard care group. “My vision is that anyone who comes in with an acute respiratory condition would receive a point-of-care test as routine, as they came through the hospital door,” explains Tristan. “That would tell us immediately what they had, so for example if they had flu, they could be isolated in a side room and given antiviral drugs.” Fighting antibiotic resistance Overuse of antibiotics is fuelling a rise in ‘superbugs’ – resistant strains of bacteria that can’t be treated with antibiotics – a threat which could take medicine back to a time when bacterial infections were untreatable and deadly. Lung infections in asthma and COPD patients are a common cause of antibiotic overuse, as infections can be very serious in these patients and cause their symptoms to get much worse. Antibiotics are only effective at treating bacterial infections, and cannot be used to treat infections caused by a virus, like a cold or flu. Yet they are often given to patients when the cause of the infection is not immediately apparent. Armed with the results from this point-of-care test, doctors were reassured that that it was safe to give patients shorter courses of antibiotics. If it became incorporated into standard practice, this test could therefore be a useful tool in the fight to prevent this rise in antibiotic resistant infections.

Southampton researchers have compared two types of defibrillator and identified the best at resetting the heart’s natural rhythm in patients with disrupted heartbeat. Affecting millions of people each year, atrial fibrillation is the most common form of abnormal heartbeat, or cardiac arrhythmia. Defibrillators, which give out a momentary electrical impulse, are often used to reset the heart’s rhythm. There are many different types available, but little guidance on which work best for atrial fibrillation. Now researchers in Southampton and Denmark have identified the best defibrillator for treating atrial fibrillation. Their findings are published in the Journal of the American Heart Association. Resetting the heart’s rhythm Defibrillators work by sending an electrical shock through the heart to reset its natural rhythm. The electric current passes between two pads placed on the chest either side of the heart. Most defibrillators have the same ‘biphasic’ way of working, sending shocks back and forth across the heart in both directions, but they vary in the nature and frequency of these shocks. Informing best practice The latest study compared the effectiveness and safety of two types of defibrillator – pulsed biphasic (PB) and biphasic truncated exponential (BTE), finding BTE defibrillators more effective for resetting the heartbeat of patients with atrial fibrillation. Over 130 patients took part in the study, which was conducted at the Regional Hospital of Randers in Denmark. Patients were told about the study prior to treatment, with those who decided to take part randomly assigned to receive either PB or BTE treatment. Both devices were found to be safe, but the BTE treatment saw more patients’ heartbeats return to normal within four hours. The study team aims to use the results to change standard practice, ensuring those with atrial fibrillation get the best possible treatment.

Asian women with a lower vitamin B12 status have been found to be more at risk of gestational diabetes, raising the possibility that changes or supplements to their diet could help prevent the condition. New findings from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study have revealed that vitamin B12, found in meat, fish and dairy foods, could play a key role in preventing pregnant mothers developing diabetes. The collaborative research between the team at the Singapore Institute for Clinical Sciences and Professor Keith Godfrey at the NIHR Southampton BRC is reported in the journal Clinical Nutrition. Gestational diabetes Insulin is a hormone critical to controlling blood sugar levels and during pregnancy some women will develop diabetes, when the body cannot produce or use insulin effectively. This gestational diabetes usually goes away after birth, but increases the risk of pre-eclampsia, premature birth, high birth weight and low blood sugar or jaundice in the baby. Reducing the risk Asian women are particularly at risk, with around 1 in 5 affected during their pregnancy. The latest study analysed blood test results from 913 pregnant Chinese, Malay and Indian women participating in the GUSTO study. Blood tests to measure blood sugar and vitamin B12 levels were taken at their hospital visits at 26-28 weeks of pregnancy. In total, 48% of the women who took part had vitamin B12 insufficiency, and those who had low vitamin B12 and high folate levels were most likely to go on to develop gestational diabetes. The link was particularly strong in Indian women. While this study did not investigate the reason for this,the higher rates of vegetarianism amongst Indian women may be a possible cause, as meat, fish and dairy foods are the primary sources of vitamin B12. These findings, if supported by further research, could have important implications for the advice given to pregnant women to lessen the likelihood of getting gestational diabetes.

A new study aims to improve heart attack test accuracy, by analysing routine blood tests from 20,000 patients at University Hospital Southampton. The CHARIOT study, led by Southampton cardiologist and researcher Professor Nick Curzen, aims to improve the standard test for a heart attack to ensure patients get the right treatment. To do this, his team will analyse blood test results from 20,000 patients admitted to University Hospital Southampton, taken as a routine part of their care. Detecting heart damage Heart damage during a heart attack releases the protein troponin into the bloodstream, and it is this that the standard heart attack test detects. However, raised troponin isn’t always the result of a heart attack, and can indicate other problems with the heart. “Troponin can be raised in conditions that are not a heart attack,” explains Dr Mark Mariathas, who is involved in the study. “This is to do with the balance between supply and demand of oxygen to the heart - if this balance is compromised, with the oxygen demand of the heart outweighing the supply, you will get a rise in the troponin.” Because of this, many patients who are not affected by a heart attack, but show raised troponin, undergo a series of unnecessary and sometimes risky procedures for treating heart attacks. Putting patients first A key challenge is that the level of troponin indicating a heart attack was originally determined by measuring troponin in the blood of healthy people between the ages of 18 and 40 years old. Those in the highest 1% are considered to have abnormally high levels. However, patients treated for a heart attack in the hospital are generally older and suffer with significant medical conditions. Both old age and health problems such as heart failure, hypertension or sepsis can cause an increase in their troponin level, even if they haven’t suffered a heart attack. “The problem comes when someone comes in to the hospital who hasn’t had symptoms of a heart attack, and we decide to check the troponin,” says Dr Mariathas. “We don’t really know what a raised troponin level in these patients means when the underlying cause is not a heart attack.” To address this, the researchers aim to build as complete a picture as possible of troponin levels across patient ages and conditions. They will do this by including troponin testing in all routine blood tests at University Hospital Southampton, and use that data to set new test limits better aligned to age and accounting for other factors that contribute to high troponin. For example, they expect patients with limited oxygen supply to the heart to have chronically high troponin levels, such as patients in the intensive care unit, having major surgery or those with the lung condition chronic obstructive pulmonary disease (COPD). “We’re expecting the results from the study to change the way clinicians look at the troponin blood test,” says Dr Mariathas, “and show that patients in hospital tend to have higher troponin levels than a healthy population.” Through this study, they hope to improve the detection of heart attacks and ensure the often life-saving treatment is targeted to those who truly need it. Should you wish to withdraw your data from the study or for more information about the study, please call the Coronary Research Group on 023 8120 8538, or email Zoe at zoe.nicholas@uhs.nhs.uk or Mark at mark.mariathas@uhs.nhs.uk. Alternatively, you can write to: Coronary Research Group, Cardiovascular & Thoracic Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD.

10 years on from the first Xtreme Everest expedition, Southampton’s Prof Mike Grocott and colleagues from University College London and Duke University in the USA have returned to Nepal to share the findings of their research. Tackling lack of oxygen One in five of us enter critical care at some point in our lives, with 40% - nearly half – dying, often due to a lack of oxygen when our bodies need it most. Over 10 years and two major expeditions, the Xtreme Everest team has used the oxygen-thin air of the Himalayas to simulate that hypoxia (lack of oxygen) experienced by many critical care patients. Now in their 10th anniversary year, they’re back in Nepal performing more experiments in the mountains, and sharing their research findings with Nepalese clinicians, and the Sherpa community. The 4,500 mile knowledge exchange The two-day KnO2wledge Kathmandu: Oxygen conference in Kathmandu will present the knowledge and research findings around the Xtreme Everest expeditions, covering physiology and illness at altitude, better clinical oxygen care and infectious diseases. A collaboration with the Nepal Mountain Medicine Society, it will involve clinicians and healthcare professionals from across Nepal. University hospital Southampton critical care consultant Max Jonas will also present experiences from Southampton’s Intensive Care Unit, distributing 40 copies of the latest ICU clinical textbooks to Nepalese hospitals and medical centres. A week later, on 7 April 2017 the team will head to the Sherpa city of Namche to share the findings of their research into how Sherpas have adapted, and respond to altitude better than lowlanders. “Both events are a great way to celebrate the last ten years, and the work that’s advanced our understanding of low-oxygen effects, physiological adaptation and targets for better oxygen therapy” Comments Prof Grocott, critical care research lead for the NIHR Southampton Respiratory Biomedical Research Unit. “The event in Namche is particularly important to us however. We work closely with our participants and families across our critical care research, and the Sherpa community have been a central part of that through the Xtreme Everest studies.” Celebrating 10 years on Everest The expedition and meetings are part of several events celebrating Xtreme Everest’s 10th anniversary, culminating in a conference at the Royal Society of Medicine on 23 and 24 May - the exact dates the 2007 expedition summited on Everest - and a public event looking back at 60 years of research on Everest at the Royal geographic Society on the evening of 24 May. More information is available on the Xtreme Everest website, here.

A pregnancy health programme for obese mothers has seen the body fat of their babies at 6 months, indicating with potential benefits for their children’s lifelong health and risk of obesity. New research involving Prof Keith Godfrey from the NIHR Biomedical Research Centre, published in the international journal of obesity, has shown that a health programme for obese pregnant women could help tackle the growing issue of childhood obesity. Breaking the cycle Mothers who are obese during their pregnancy are more likely to have children who are obese, who in turn are more likely to grow up to be obese in adulthood and go on to have obese children themselves. This study aimed to see if a health programme could help obese mothers to improve their diet and do more exercise during pregnancy and after giving birth, and so reduce their child’s risk of obesity. Starting as you mean to go on Known as the UK Pregnancies Better Eating and Activity Trial (UPBEAT), it involved over 1500 obese pregnant women from eight different hospitals across the UK, led by Professor Lucilla Poston at the NIHR Biomedical Research at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London. The women were split into two groups – one that just received standard antenatal care and a second that also took part in the health programme. They completed a questionnaire about their lifestyle and at six months old their baby’s body fat was assessed. Women who took part in the health programme had a better diet, less weight gain during pregnancy and a slight increase in physical activity. And at six months old, their babies had a lower body fat content. “This study underlines the potential benefit of simple, effective interventions like this,” comments Prof Godfrey. “If rolled out on a larger scale, health programmes during pregnancy like this could make a significant contribution to preventing childhood obesity across generations.”

New research by NIHR Southampton Respiratory Biomedical Research Unit has discovered that asthmatics have a weaker immune system, explaining why they are more likely to get flu. A study led by Dr Ben Nicholas and Professor Ratko Djukanović, working closely with the University of Southampton spin-out company Synairgen, has discovered that an asthmatic’s immune system can’t fight the flu virus as well as a person who doesn’t have asthma. These results help researchers better understand why asthmatics are more affected by influenza. They could also help find new treatments for common lung infections, which often make asthma symptoms worse. The study formed part of U-BIOPRED, a large-scale European project using information and samples from adults and children to learn more about different types of asthma. A decade of research Over the course of ten years, Dr Nicholas has developed and improved a method of growing lung samples taken from asthmatics and healthy volunteers in the laboratory. Unlike other techniques, which separate and grow a single layer of cells in a dish, Dr Nicholas keeps the whole sample intact. This lets him study a pin-head sized piece of lung, as it would be found in the body, in the lab. He then infects these lung samples with the flu virus to see how they react. By using this method, he can study the effects of viruses on lung cells in conditions similar to those in the body, without affecting participants’ health. Weaker immune system This study looked into whether immune system differences explain why asthmatics are more likely to get flu than the general population. This is important, as flu can cause a person’s asthma symptoms to get worse. Samples from healthy people showed a strong immune system-triggering reaction to the flu virus. But in lung samples from asthma patients, this reaction was much weaker. While the team can’t say this difference is due to the asthma itself, or the steroids used by participating asthmatics, it does provide an explanation why asthmatics are affected more. These findings could inform the search for new treatments to prevent and better manage lung infections in asthma.

Eating too much fructose - a common type of sugar - puts children at greater risk of fatty liver disease, shows new research from the NIHR Southampton Biomedical Research Centre. This new study, led by Professor Christopher Byrne, has shown that excessive consumption of the sugar fructose is not only fuelling childhood obesity, but may also be damaging their livers. Sugar overload Fructose is a natural sugar found in many foods, especially in fruits but also in vegetables and flour used for pasta, bread and pizza. In a balanced diet, eating fructose contained naturally in foods such as fruit does not cause any harm. However, high fructose syrups and sweeteners that are widely used in sugary drinks, fruit juices, jams and sweets have an artificially high sugar content. Just one 500ml bottle of cola can contain 14 sugar cubes worth, double the recommended daily amount for children. Given these high levels and the popularity of these drinks and snacks, many of children are eating an excess of fructose each day. Unfortunately, for every gram over the daily requirement, the risk of developing serious liver disease increases one and a half times. Liver disease and fructose Over 271 children and teenagers with fatty liver disease at the Bambino Gesù Children’s Hospital in Rome took part in the five year study, with almost 40% having advanced liver disease. Children who ate and drank more fructose had high levels of uric acid in their blood, and were more likely to have the serious and advanced form of fatty liver disease. A build up of uric acid occurs when excess fructose is broken down by the liver. Too much uric acid can be toxic to the body, contributing to diseases such as gout and kidney disease. The study results, published in the Journal of Hepatology, show that high levels of uric acid may also contribute to liver damage and the development of a serious form of fatty liver disease in children. “Several studies have shown that high consumption of sugar (containing fructose) is associated with a number of conditions in childhood such as obesity and type 2 diabetes. However, little was known of its effect on the liver until now,” explains Professor Byrne. “Our results suggest that too much sugar consumption may be harmful for the child’s liver because of the link between high fructose consumption and serious liver disease. The data emphasise the importance of parents ensuring that their children consume sugary drinks, snacks and sweets in moderation.”