The latest list of publications from the Cambridge Biomedical Research Centre with a brief summary.
Publication: The Lancet
Prof Rebecca C Fitzgerald, Massimiliano di Pietro, Maria O’Donovan, Roberta Maroni, Beth Muldrew, Irene Debiram-Beecham, Marcel Gehrung, Judith Offman, Monika Tripathi, Samuel G Smith, Benoit Aigret, Fiona M Walter, Prof Greg Rubin, on behalf of theBEST3 Trial team † Prof Peter Sasieni
31 July 2020
Barrett’s oesophagus is a condition that can lead to oesophageal cancer in a small number of people. It’s usually diagnosed in hospital by endoscopy (passing a camera down into the stomach). Samples of cells from any areas that don’t look normal are then collected, but an endoscopy can be uncomfortable and does have some risks.
The Cytosponge test allows the patient to swallow a small capsule with a sponge inside, which is attached to a piece of string. The capsule dissolves after a few minutes, and the sponge inside is released. A nurse then gently pulls the string to remove the sponge. On the way out the sponge collects cells from the lining of the oesophagus. The sample is then taken for analysis using a new laboratory marker called TFF3.
Researchers studied 13,222 participants who were randomly allocated to being offered the sponge test or being looked after by the GP in the usual way. Over the course of a year, the odds of detecting Barrett’s were ten times higher in those who were offered the Cytosponge with 140 cases diagnosed compared to 13 in usual care. In addition, the Cytosponge diagnosed five cases of early cancer (stage 1 and 2), whereas only one case of early cancer was detected in the usual care group.
Alongside better detection, the test means cancer patients can benefit from kinder treatment options if their cancer is caught at a much earlier stage. Read the full news article.
Publication: Cell Reports
Michael C. Lee, Michael S. Nahorski, James R.F. Hockley, Frank Reimann, Ewan St. John Smith, C. Geoffrey Woods
21 July 2020; DOI: 10.1016/j.celrep.2020.107941
Women who don’t need pain relief during childbirth may have a key genetic variant that acts as a natural epidural. Supported by the NIHR Cambridge BRC, researchers investigated why some women experience different levels of pain during childbirth.
Women who did not require any pain relief during the birth of their first child took part in a study to understand their pain threshold. This included applying heat and pressure to their arms and putting their hands in icy water. They were then measured against a control group of women were who were given pain relief during childbirth.
They found the group the women who didn’t need any pain relief had a high pain threshold than those of the control group. Their genetic cold was then sequenced and found these women had a higher-than-expected prevalence of a rare variant of the gene KCNG4. This gene acts as a gate, controlling the electric signal that flows along our nerve cells. This could be the reason why these women did not require pain relief during childbirth. Read the full news articleView publication
Publication: Journal of Neurology, Neurosurgery and Psychiatry
Jonathan Tay, Robin G Morris, Anil M Tuladhar, Masud Husain, Frank-Erik de Leeuw, Hugh S Markus
Cerebral small vessel disease (SVD) is the leading vascular cause of dementia and plays a major role in cognitive decline and mortality.
This research aimed to determine whether apathy or depression predicts all-cause dementia in SVD patients.
Using two prospective cohort studies of SVD, the researchers looked at changes in apathy and depression in 104 patients to predict dementia.
The research indicated that while increasing apathy was associated with dementia, baseline depression and change in depression did not predict dementia.
The researchers concluded that apathy, but not depression, may be an early sign of dementia in SVD, and that this may be useful in identifying at-risk individuals.View publication
Dami A Collier, Sonny M Assennato, Nyarie Sithole, Katherine Sharrocks, Allyson Ritchie, Pooja Ravji, Matt Routledge, Dominic Sparkes, Jordan Skittrall, Ben Warne, Anna Smielewska, Isobel Ramsey, Neha Goel, Martin Curran, David Enoch, Rhys Tassell, Michelle Lineham, Devan Vaghela, Clare Leong, Hoi Ping Mok, John Bradley, Kenneth Gc Smith, Vivien Mendoza, Nikos Demiris, Martin Besser, Gordon Dougan, Paul J Lehner, Hongyi Zhang, Claire Waddington, Helen Lee, Ravindra K Gupta
03 June 2020
SAMBA II machines were deployed in the ED and holding wards at Addenbrooke’s hospital to help detect COVID-19 in patients as part of a research trial called COVIDx.
Researchers investigated whether using the new machines could accurately provide a faster diagnosis than standard testing practices and review how it would affect patient waiting times.
After collecting nose and throat swabs from over 140 patients, the samples were processed using the SAMBA II machine. Researchers found they were able to provide an accurate diagnostic result within 90 minutes, compared to the standard 24-48-hour lab waiting time. Read the full story.View publication
Publication: Journal of Clinical Endocrinology & Metabolism
Katherine Lawler, Isabel Huang-Doran, Takuhiro Sonoyama, Tinh-Hai Collet, Julia M Keogh, Elana Henning, Stephen O’Rahilly, Leonardo Bottolo, I Sadaf Farooqi
11 May 2020
The hormone leptin is a key regulator of weight. Children who lack leptin (due to changes in the leptin gene) have a very large appetite and rapidly gain weight. After treatment with leptin injections, they can lose weight.
The researchers know that leptin works by reducing their appetite, but they wanted to find out if leptin can affect other metabolic processes around the body too.
They used a cutting-edge technique called metabolomics to simultaneously measure more than 600 metabolic reactions in a single blood sample taken from children and young adults before and after a short period of leptin treatment.
They found that leptin not only caused big shifts in how the body processes fats, but it affected amino acids (which make proteins), bile acids (which can act as cell signals) and steroids (involved in making hormones). These changes overlapped with the changes discovered previously in healthy adults after a period of fasting.
The research findings show that as well as affecting how much food we eat, leptin affects other aspects of our metabolism. This research paves the way for further research into leptin’s action on different cells in the human body.View publication
Lucy Rivett, Sushmita Sridhar, Dominic Sparkes, Matthew Routledge, Nick K. Jones, et al
12 May 2020
Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3-week period (April 2020), 1,032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19) >7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.View publication
James E. D. Thaventhiran, Hana Lango Allen, Kenneth G. C. Smith
06 May 2020
Cambridge researchers sequenced the entire genetic code of 974 people with PID. The team were able to identify variations in genes already known to cause PID. To help identify genetic causes for the remaining participants and other patients with PID, the team used a statistical program known as BeviMed. BeviMed can be used to predict genes that may cause PID, by comparing the genomes of cases and controls. Using this technique, the team were able to identify new genes that cause PID. Full press release hereView publication
Publication: Nature Microbiology
Francesca Gaccioli, Susanne Lager, Marcus C. de Goffau, Ulla Sovio, Justyna Dopierala, Sungsam Gong, Emma Cook, Andrew Sharkey, Ashley Moffett, Wai Kwong Lee, Christian Delles, Cristina Venturini, Judith Breuer, Julian Parkhill, Sharon J. Peacock, D. Stephen Charnock-Jones & Gordon C. S. Smith
4 May 2020
The placenta is the interface between the mum and the fetus and supports the growth of the baby in the womb. Abnormal function of the placenta is associated with poor pregnancy outcome, including maternal and infant diseases and deaths. In turn, placental dysfunction could be due to viral infections, which are known to cause organ failure. We investigated whether viral infection of the placenta is associated with diseases of human pregnancy related to poor placental function, such as pre-eclampsia (hypertensive disorder in the mother) and fetal growth restriction (impaired growth of the fetus during pregnancy).
Using samples from more than 5,000 pregnancies and data available in the literature, we demonstrated that the presence of inherited human herpesvirus 6 (HHV-6) DNA in the feto-placental unit is associated with an increased risk of the mother to develop pre-eclampsia. The virus can be passed to the fetus and the placenta from both the mother and the father. Importantly, our study did not identify any other viral associations with the 2 studied conditions. HHV-6 was the only clear viral signal observed in a large number of placental samples from pathological and normal pregnancies.
Pre-eclampsia is a condition characterized by high maternal blood pressure and protein levels in the urine in the second half of pregnancy. It represents a major determinant of the global burden of disease. Although pre-eclamspia is known to be associated with poor development and function of the placenta, the causes of placental insufficiency are not fully understood. Identifying those will help us to understand and treat this condition, which affects 5-8% of all pregnant women and is responsible for over 75,000 maternal deaths and 500,000 fetal deaths worldwide every year. Our work demonstates that viral infection of the placenta is not a major cause of pre-eclampsia and that a small proportion of cases is likely to be due to the presence of HHV-6 in the feto-placental unit.View publication
Luiza Moore, Daniel Leongamornlert, Tim H. H. Coorens, Mathijs A. Sanders, Peter Ellis, Stefan Dentro, Kevin Dawson, Tim Butler, Raheleh Rahbari, Thomas J Mitchell, Francesco Maura, Jyoti Nangalia, Patrick S. Tarpey, Simon F. Brunner, Henry Lee-Six, Yvette Hooks, Sarah Moody, Krishnaa Mahbubani, Mercedes Jimenez-Linan, Jan J. Brosens, Christine A. Iacobuzio-Donahue, Inigo Martincorena, Kourosh Saeb-Parsy, Peter J. Campbell, Michael R. Stratton
22 April 2020
This paper looks at somatic mutation (changes in the DNA) in healthy human tissue in the endometrium (womb lining) and provides insights into the earliest stages of uterine cancer development, which is the fourth most common cancer in women in the UK.
Many cells in the inner lining of the uterus carry ‘cancer-driving’ mutations that frequently arise early in life. Using whole-genome sequencing to better understand the genetic changes in healthy endometrial tissue, the researchers found that a high proportion of cells carry driver mutations, even though they appear completely normal under the microscope. Furthermore the team found that many of these driver mutations appear to have arisen early in life, in many cases during childhood.View publication
Publication: BMC Medicine
Lois Kim, Nicholas Boxall, Anne George, Keith Burling, Pete Acher, Jonathan Aning, Stuart McCracken, Toby Page and Vincent J. Gnanapragasam
17 April 2020
At the moment if a man is referred for suspected prostate cancer he has to undergo an MRI scan and perhaps a prostate biopsy to find out if he has the disease. This costs a lot of money and means many hospital visits and potentially dangerous side effects (bleeding or infections from the biopsy). In this study researchers wanted to test if using a new biomarker blood test called PHI (Prostate Health Index) could reduce the number of unnecessary investigations for suspected prostate cancer. To do this they measured the PHI levels in over 500 men from 5 hospitals and tested how effective it was at selecting men for further investigations.
They found that if the PHI test was used to decide who should go onto have MRI and biopsies, doctors would reduce the number of scans needed by 25% and the number of biopsies needed by 40%, but still find the same number of prostate cancers. Moreover, using this test and pathway would save the NHS a lot of money as it is much cheaper than the current pathway.
Hospital visits and appointments could also be drastically reduced, which is particularly important in these days of shielding and social distancing to help with the COVID crisis.View publication
Publication: European Heart Journal
Tammy Y N Tong, Paul N Appleby, Timothy J Key, Christina C Dahm, Kim Overvad, Anja Olsen, Anne Tjønneland, Verena Katzke, Tilman Kühn, Heiner Boeing, Anna Karakatsani, Eleni Peppa, Antonia Trichopoulou, Elisabete Weiderpass, Giovanna Masala, Sara Grioni, Salvatore Panico, Rosario Tumino, Jolanda M A Boer, W M Monique Verschuren, J Ramón Quirós, Antonio Agudo, Miguel Rodríguez-Barranco, Liher Imaz, María-Dolores Chirlaque, Conchi Moreno-Iribas, Gunnar Engström, Emily Sonestedt, Marcus Lind, Julia Otten, Kay-Tee Khaw, Dagfinn Aune, Elio Riboli, Nicholas J Wareham, Fumiaki Imamura, Nita G Forouhi, Emanuele di Angelantonio, Angela M Wood, Adam S Butterworth, Aurora Perez-Cornago
24 February 2020
This research looked at more than 418,000 people in nine European countries who were recruited to the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1992 and 2000. Researchers found that while higher intakes of fruit, vegetables, fibre, milk, cheese or yoghurt were each linked to a lower risk of ischaemic stroke, there was no significant association with a lower risk of haemorrhagic stroke.
As the study is observational, it cannot show that the foods studied cause an increase or decrease in risk of ischaemic or haemorrhagic stroke, only that they are associated with different risks.View publication
Publication: Clinical Transplantation
John O. O. Ayorinde, Mazin Hamed, Mingzheng Aaron Goh, Dominic M. Summers, Anna Dare, Yining Chen, Kourosh Saeb‐Parsy
20 January 2020
This research recorded donor and recipient data of kidney transplants and matched them with clinical outcomes, helping to build the Cambridge Kidney Assessment Tool (CKAT).
CKAT will assist surgeons to define macroscopic features of donor kidneys to help them better predict clinical outcome and help reduce unecessary discarding of donor kidneys offered for transplantion.View publication