Publications

The latest list of publications from the NIHR Cambridge Biomedical Research Centre with a brief summary. 

If you are publishing research which has had funding and / or support from the NIHR Cambridge Biomedical Research Centre, please complete this form

Publication: Journal of Clinical Urology

Vincent J Gnanapragasam, Kelly Leonard, Michal Sut, Cristian Ilie, Jonathan Ord, Jacques Roux, Maria Consuelo Hart Prieto, Anne Warren, Priya Tamer

June 2020


Prostate cancer is the commonest male cancer and more than one million rectal biopsies for suspected prostate cancer are carried out each year. However, a significant number of men undergoing rectal biopsies develop infection and sepsis.

This study showed that the CamPROBE, a device developed by Cambridge researchers that can be used under local anaesthetic, is just as good at diagnosing prostate cancer as rectal biopsies – with less infection risk.

Led by Cambridge University Hospitals (CUH), the study recruited 40 patients across six sites. CUH developed a user training course and disseminated the method to the other sites, which then offered the Cambridge Prostate Biopsy Device (CamPROBE), as an alternative to transrectal ultrasound guided biopsy to men due for a biopsy as part of their clinical management.

There were no infections, device deficiencies or safety issues reported, and the CamPROBE appears non-inferior in terms of cancer detection rates. The study also showed that the procedure is well tolerated by patients, suited to the local anaesthetic outpatient setting and can be readily disseminated and adopted.

Future clinical investigation trials will aim at confirming the veracity of the findings, develop head-to-head comparisons with other biopsy methods and explore comparative health economic and cost benefit analysis.

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Publication: Brain

Maura Malpetti, Rogier A Kievit, Luca Passamonti, P Simon Jones, Kamen A Tsvetanov, Timothy Rittman, Elijah Mak, Nicolas Nicastro, W Richard Bevan-Jones, Li Su, Young T Hong, Tim D Fryer, Franklin I Aigbirhio, John T O’Brien, James B Rowe

07 May 2020


Summary:

Alzheimer’s disease is a condition associated with an ongoing decline of the brain functioning correctly. It can affect loss of memory, language and completing everyday tasks.

Researchers having been investigating the brains functionality, and whether they could help clinicians calculate how a patient will progress with their dementia.

Using an imaging machine called PET (positron emission tomography) they were able to take brain scans and detect the build-up of ‘junk proteins’ in the brain alongside brain inflammation and shrinkage. It could help predict how fast or slow and individual will progress with their dementia.

The PET scans could predict faster cognitive decline in patients and they were more accurate predictors than MRI measures of brain shrinkage.

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Publication: medRxiv

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


Summary:

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.

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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


Summary:

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.

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Publication: eLife

Lucy Rivett, Sushmita Sridhar, Dominic Sparkes, Matthew Routledge, Nick K. Jones, et al

12 May 2020


Summary:

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.

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Publication: Nature

James E. D. Thaventhiran, Hana Lango Allen, Kenneth G. C. Smith 

06 May 2020


Summary:

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 here

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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


Summary: 

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.

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Publication: Nature

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


Summary: 

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.

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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


Summary: 

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.

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Publication: Scientific Reports

T. D. Turmezei, G. M. Treece, A. H. Gee, S. Sigurdsson, H. Jonsson, T. Aspelund, V. Gudnason & K. E. S. Poole

March 2020


Summary

Hip osteoarthritis is a very common condition that will affect up to 25% of the population in their lifetime. There is no cure for this painful and debilitating disease, with the mainstay of treatment currently being surgical replacement of the joint once it has become too stiff or painful to use. Research trials trying to find effective therapies for osteoarthritis currently rely on x-ray radiograph imaging to test if there have been any meaningful changes in the structure of the joint for a new therapy, but this method suffers from being unable to detect small changes reliably and from only being able to see the joint in 2D.

We developed the joint space mapping (JSM) technique in a collaboration between the Departments of Medicine and Engineering at the University of Cambridge and have since taken it to test on patient data from the widely regarded AGES-Reykjavik patient cohort of healthy older Icelandic adults.

Our research showed that JSM can identify structurally relevant disease features related to the important outcome of joint replacement in hip osteoarthritis better than the current clinical trial 2D imaging gold standards. This means that JSM could be a significantly better way of identifying who might be at high risk from getting hip osteoarthritis, those in whom the disease might be progressing rapidly, and whether any new therapy is effective at stopping the joint destruction that ultimately leads to joint failure. These results have been achieved by using an existing and readily available clinical imaging technique to look at the hip joint in 3D.

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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


Summary: 

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.

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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


Summary:

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.

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