A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn’s disease (PROFILE): a multicentre, open-label randomised controlled trial

Publication: The Lancet

Nurulamin M Noor, James C Lee, Simon Bond, Francis Dowling, Biljana Brezina, Kamal V Patel, Tariq Ahmad, Paul J Banim, James W Berrill, Rachel Cooney, Juan De La Revilla Negro, Shanika de Silva, Shahida Din, Dharmaraj Durai, John N Gordon, Prof Peter M Irving, Matthew Johnson, Alexandra J Kent, Klaartje B Kok, Prof Gordon W Moran, Craig Mowat, Pritash Patel, Prof Chris S Probert, Tim Raine, Rebecca Saich, Abigail Seward, Dan Sharpstone, Melissa A Smith, Sreedhar Subramanian, Sara S Upponi, Alan Wiles, Horace R T Williams, Prof Gijs R van den Brink, Prof Séverine Vermeire, Prof Vipul Jairath, Prof Geert R D’Haens, Prof Eoin F McKinney, Paul A Lyons, Prof James O Lindsay, Nicholas A Kennedy, Prof Kenneth G C Smith, Prof Miles Parkes,  

22 February 24

Summary

A large-scale clinical trial of treatment strategies for Crohn’s disease has shown that offering early advanced therapy to all patients straight after diagnosis can drastically improve outcomes, including by reducing the number of people requiring urgent abdominal surgery for treatment of their disease by ten-fold. Read the full news story.

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Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study

Publication: The Lancet

Tommy Nyberg, Prof Neil M Ferguson, Sophie G Nash, Harriet H Webster, Seth Flaxman, Nick Andrews, Wes Hinsley, Jamie Lopez Bernal, Meaghan Kall, Prof Samir Bhatt, Paula Blomquist,
Asad Zaidi, Erik Volz, Nurin Abdul Aziz, Katie Harman, Prof Sebastian Funk, Sam Abbott, COVID-19 Genomics UK (COG-UK) consortium, Russell Hope, Andre Charlett, Meera Chand, Prof Azra C Ghani, Shaun R Seaman,

17 March 2022


Summary

The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.

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Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study

Publication: MedRxiv

Kamen A Tsvetanov, Lennart R B Spindler, Emmanuel A Stamatakis, Virginia FJ Newcombe, Victoria C Lupson, Doris A Chatfield, Anne E Manktelow, Joanne G Outtrim, Anne Elmer, Nathalie Kingston, John R Bradley, Edward T Bullmore, James B Rowe, David K Menon

02 February 2022


Summary

COVID-19 have seen multi-system effects that include neurological, vascular and neurovascular injury. Acute neurological sequelae are common, ranging from mild dizziness, headaches and anosmia to severe encephalitis, stroke and delirium. Researchers assessed the impact of COVID-19 on chronic cerebrovascular reactivity after hospitalisation.

Patients were recruited through the NIHR COVID-19 BioResource. Eligibility was based on admission to Addenbrookes Hospital with COVID-19 between 10th March 2020 and 31st July 2020, aged 18 years or older, survived the acute illness, and attended for a follow up visit, and no contradictions to MRI.

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SARS-CoV-2 Omicron spike mediated immune escape, infectivity and cell-cell fusion

Publication: bioRxiv

Bo Meng, Isabella A.T.M Ferreira, Adam Abdullahi, Steven A. Kemp, Niluka Goonawardane, Guido Papa, Saman Fatihi, Oscar J. Charles, Dami A. Collier, CITIID-NIHR BioResource COVID-19 Collaboration, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Jinwook Choi, Joo Hyeon Lee, Petra Mlcochova, Leo James, Rainer Doffinger, Lipi Thukral, Kei Sato,  View ORCID ProfileRavindra K. Gupta

21 December 2021


Summary

As the SARS-CoV-2 virus replicates and spreads, errors in its genetic code can lead to changes in the virus. Working in secure conditions, researchers created synthetic viruses – known as ‘pseudoviruses’ – that carried key mutations found in the Delta and Omicron strains. They used these to study the virus’s behaviour.

They tested the pseudoviruses against blood samples donated to the NIHR COVID-19 BioResource. The blood samples were from vaccinated individuals who had received two doses of either the AstraZeneca (ChAdOx-1) or Pfizer (BNT162b2) vaccines. Read the full story.

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Characterization of disease course and remission in early seropositive rheumatoid arthritis: results from the TACERA longitudinal cohort study

Publication: Therapeutic Advances in Musculoskeletal Disease

Michael Barnes, Sarah Brockbank, Ian N Bruce, Coziana Ciurtin, Andrew P. Cop, Michael R. Ehrenstein, Paul Emery, Benjamin A. Fisher, John Isaacs, Ruth Matthews, Iain B. McInnes, Hayley Noble, Ayako Wakatsuki Pedersen, Costantino Pitzalis, Karim Raza, Anthony Rowe, Gemma Simpson, Dominic Stringer, Peter C. Taylor, Brian Tom, Yujie Zhong

21 October 2021


Summary
Researchers carried out a longitudinal observational study of newly diagnosed, seropositive rheumatoid arthritis patients from 28 UK centres. Every 3 months over a total of 18 months, clinical and laboratory measures were collected. To understand the progression of the disease it was measured against the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI). Researchers found that collecting biological markers early after diagnosis could help manage the disease.

Challenges and opportunities for conducting a vaccine trial during the COVID-19 pandemic in the United Kingdom

Publication: Clinical Trials

Estée Török, Benjamin R Underwood, Mark Toshner, Claire Waddington, Emad Sidhom, Katherine Sharrocks, Rachel Bousfield, Charlotte Summers, Caroline Saunders, Zoe McIntyre, Helen Morris, Jo Piper, Gloria Calderon, Sarah Dennis, Tracy Assari, Anita Marguerie de Rotrou, Ashley Shaw, John Bradley, John O’Brien, Robert C Rintoul, Ian Smith, Ed Bullmore, Krishna Chatterjee

22 June 2021


Summary

Researchers describe their experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom.

Researchers encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. These were overcome by setting up a project team that included key members from all three organisations that met at least daily by teleconference.

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Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

Publication: Cell Reports

Bo Meng, Steven A. Kemp, Guido Papa, Rawlings Datir, Isabella A.T.M. Ferreira, Sara Marelli, William T. Harvey, Spyros Lytras, Ahmed Mohamed, Giulia Gallo, Nazia Thakur, Dami A. Collier, Petra Mlcochova

29 June 2021


One of the key mutations seen in the ‘Alpha variant’ of SARS-CoV-2 – the deletion of two amino acids, H69/V70 – enables the virus to overcome chinks in its armour as it evolves, say an international team of scientists.

SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

As SARS-CoV-2 divides and replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect.

Towards the end of 2020, Cambridge scientists observed SARS-CoV-2 mutating in the case of an immunocompromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation – the deletion of two amino acids, H69/V70, in the spike protein. This deletion was later found in B1.1.7, the variant that led to the UK being forced once again into strict lockdown in December (now referred to as the ‘Alpha variant’).

Researchers led by scientists at the University of Cambridge show that the deletion H69/V70 is present in more than 600,000 SARS-CoV-2 genome sequences worldwide, and has seen global expansion, particularly across much of Europe, Africa and Asia.

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FFP3 respirators protect healthcare workers against infection with SARS-CoV-2

Publication: Authorea (pre-print)

Mark Ferris, Rebecca Ferris, Chris Workman, Eoin O’Connor, David A Enoch, Emma Goldesgeyme, Natalie Quinnell, Parth Patel, Jo Wright, Geraldine Martell, Christine Moody, Ashley Shaw, Christopher J.R. Illingworth, Nicholas J. Matheson, Michael P. Weekes

24 June 2021


When Addenbrooke’s Hospital in Cambridge upgraded its face masks for staff working on COVID-19 wards to filtering face piece 3 (FFP3) respirators, it saw a dramatic fall – up to 100% – in hospital-acquired SARS-CoV-2 infections among these staff.

The findings are reported by a team at the University of Cambridge and Cambridge University Hospitals (CUH) NHS Foundation Trust. The research has not yet been peer-reviewed, but is being released early because of the urgent need to share information relating to the pandemic.

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Cross-tissue immune cell analysis reveals tissue-specific a daptations and clonal architecture 2 across the human body

Publication: bioRxiv

Conde C Domínguez, T Gomes, LB Jarvis, C Xu, SK Howlett, DB Rainbow, O Suchanek, HW King, L Mamanova, K Polanski, N Huang, E Fasouli, KT Mahbubani, M Prete, L Campos, HS Mousa, EJ Needham, S Pritchard, T Li, R Elmentaite, J Park, DK Menon, OA Bayraktar, LK James, KB Meyer, MR Clatworthy, K Saeb-Parsy, JL Jones, SA Teichmann

28 April 2021


Summary

Despite their crucial role in health and disease, researchers knowledge of immune cells within human tissues, in contrast to those circulating in the blood, remains limited. Researchers surveyed the immune compartment of lymphoid and non-lymphoid tissues of six adult donors by single-cell RNA sequencing, including alpha beta T-cell receptor, gamma delta TCR and B-cell receptor variable regions.

To aid systematic cell type identification researchers developed CellTypist, a tool for automated and accurate cell type annotation. Using this approach combined with manual curation, researchers determined the tissue distribution of finely phenotyped immune cell types and cell states.

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Stepwise pathogenic evolution of Mycobacterium abscessus.

Publication: Science

Josephine M. Bryant,  Karen P. Brown,  Sophie Burbaud,  Isobel Everall,  Juan M. Belardinelli, Daniela Rodriguez-Rincon,  Dorothy M. Grogono,  Chelsea M. Peterson,  Deepshikha Verma,  Ieuan E. Evans,  Christopher Ruis,  Aaron Weimann,  Divya Arora,  Sony Malhotra,  Bridget Bannerman, Charlotte Passemar,  Kerra Templeton,  Gordon MacGregor, Kasim Jiwa,  Andrew J. Fisher,  Tom L. Blundell,  Diane J. Ordway,  Mary Jackson, Julian Parkhill, R. Andres Floto

30 April 2021


Summary:

Researchers have been able to track how a multi-drug resistant organism is able to evolve and spread widely among cystic fibrosis patients – showing that it can evolve rapidly within an individual during chronic infection. The researchers say their findings highlight the need to treat patients with Mycobacterium abscessus infection immediately, counter to current medical practice.

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