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2. Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA)

Author

Rosas, Ivan O, Bräu, Norbert, Waters, Michael, Go, Ronaldo C, Malhotra, Atul, Hunter, Bradley D, Bhagani, Sanjay, Skiest, Daniel, Savic, Sinisa, Douglas, Ivor S, Garcia-Diaz, Julia, Aziz, Mariam S, Cooper, Nichola, Youngstein, Taryn, Del Sorbo, Lorenzo, De La Zerda, David J, Ustianowski, Andrew, Gracian, Antonio Cubillo, Blyth, Kevin G, Carratalà, Jordi, François, Bruno, Benfield, Thomas, Haslem, Derrick, Bonfanti, Paolo, van der Leest, Cor H, Rohatgi, Nidhi, Wiese, Lothar, Luyt, Charles Edouard, Bauer, Rebecca N, Cai, Fang, Lee, Ivan T, Matharu, Balpreet, Metcalf, Louis, Wildum, Steffen, Graham, Emily, Tsai, Larry, and Bao, Min

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Lung, Vaccine Related, Emerging Infectious Diseases, Pneumonia & Influenza, Infectious Diseases, Prevention, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Coronavirus disease 2019, Interleukin-6, Randomised controlled trial, Tocilizumab, Severe acute respiratory syndrome coronavirus-2, Viral load, Clinical sciences, Health services and systems, Public health
Abstract

BackgroundIn COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated.MethodsAdults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615.FindingsBy day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference -0·5% [95% CI -9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase-quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti-SARS-CoV-2 antibodies at day 60.InterpretationThere was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments.FundingF. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C.

Published
2022

4. Evaluating the clinical validity of genes related to hemostasis and thrombosis using the Clinical Genome Resource gene curation framework

Author

Ross, Justyne E., Mohan, Shruthi, Zhang, Jing, Sullivan, Mia J., Bury, Loredana, Lee, Kristy, Futchi, Isabella, Frantz, Annabelle, McDougal, Dara, Perez Botero, Juliana, Cattaneo, Marco, Cooper, Nichola, Downes, Kate, Gresele, Paolo, Keenan, Catriona, Lee, Alfred I., Megy, Karyn, Morange, Pierre-Emmanuel, Morgan, Neil V., Schulze, Harald, Zimowski, Karen, Freson, Kathleen, and Lambert, Michele P.

Published
2024
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5. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia

Author

Rosas, Ivan O, Bräu, Norbert, Waters, Michael, Go, Ronaldo C, Hunter, Bradley D, Bhagani, Sanjay, Skiest, Daniel, Aziz, Mariam S, Cooper, Nichola, Douglas, Ivor S, Savic, Sinisa, Youngstein, Taryn, Del Sorbo, Lorenzo, Cubillo Gracian, Antonio, De La Zerda, David J, Ustianowski, Andrew, Bao, Min, Dimonaco, Sophie, Graham, Emily, Matharu, Balpreet, Spotswood, Helen, Tsai, Larry, and Malhotra, Atul

Subjects
Clinical Research, Patient Safety, Infectious Diseases, Lung, Clinical Trials and Supportive Activities, Pneumonia, Pneumonia & Influenza, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Adult, Aged, Antibodies, Monoclonal, Humanized, COVID-19, Double-Blind Method, Female, Hospital Mortality, Hospitalization, Humans, Infusions, Intravenous, Intensive Care Units, Male, Middle Aged, Receptors, Interleukin-6, Respiration, Artificial, Treatment Failure, COVID-19 Drug Treatment, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundCoronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.MethodsIn this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo.ResultsOf the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P = 0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points; 95% CI, -7.6 to 8.2; nominal P = 0.94).ConclusionsIn this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann-La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.).

Published
2021

6. The role of CD8+ T-cell clones in immune thrombocytopenia

Author

Malik, Amna, Sayed, Anwar A., Han, Panpan, Tan, Michelle M. H., Watt, Eleanor, Constantinescu-Bercu, Adela, Cocker, Alexander T. H., Khoder, Ahmad, Saputil, Rocel C., Thorley, Emma, Teklemichael, Ariam, Ding, Yunchuan, Hart, Alice C. J., Zhang, Haiyu, Mitchell, Wayne A., Imami, Nesrina, Crawley, James T. B., Salles-Crawley, Isabelle I., Bussel, James B., Zehnder, James L., Adams, Stuart, Zhang, Bing M., and Cooper, Nichola

Published
2023
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9. Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA)

Author

Rosas, Ivan O., Bräu, Norbert, Waters, Michael, Go, Ronaldo C., Malhotra, Atul, Hunter, Bradley D., Bhagani, Sanjay, Skiest, Daniel, Savic, Sinisa, Douglas, Ivor S., Garcia-Diaz, Julia, Aziz, Mariam S., Cooper, Nichola, Youngstein, Taryn, Sorbo, Lorenzo Del, Zerda, David J. De La, Ustianowski, Andrew, Gracian, Antonio Cubillo, Blyth, Kevin G., Carratalà, Jordi, François, Bruno, Benfield, Thomas, Haslem, Derrick, Bonfanti, Paolo, van der Leest, Cor H., Rohatgi, Nidhi, Wiese, Lothar, Luyt, Charles Edouard, Bauer, Rebecca N., Cai, Fang, Lee, Ivan T., Matharu, Balpreet, Metcalf, Louis, Wildum, Steffen, Graham, Emily, Tsai, Larry, and Bao, Min

Published
2022
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10. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells

Author

Chauss, Daniel, Freiwald, Tilo, McGregor, Reuben, Yan, Bingyu, Wang, Luopin, Nova-Lamperti, Estefania, Kumar, Dhaneshwar, Zhang, Zonghao, Teague, Heather, West, Erin E., Vannella, Kevin M., Ramos-Benitez, Marcos J., Bibby, Jack, Kelly, Audrey, Malik, Amna, Freeman, Alexandra F., Schwartz, Daniella M., Portilla, Didier, Chertow, Daniel S., John, Susan, Lavender, Paul, Kemper, Claudia, Lombardi, Giovanna, Mehta, Nehal N., Cooper, Nichola, Lionakis, Michail S., Laurence, Arian, Kazemian, Majid, and Afzali, Behdad

Published
2022
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12. Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19

Author

Maher, Allison K., Burnham, Katie L., Jones, Emma M., Tan, Michelle M. H., Saputil, Rocel C., Baillon, Laury, Selck, Claudia, Giang, Nicolas, Argüello, Rafael, Pillay, Clio, Thorley, Emma, Short, Charlotte-Eve, Quinlan, Rachael, Barclay, Wendy S., Cooper, Nichola, Taylor, Graham P., Davenport, Emma E., and Dominguez-Villar, Margarita

Published
2022
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16. Real‐world use of thrombopoietin receptor agonists for the management of immune thrombocytopenia in adult patients in the United Kingdom: Results from the TRAIT study

Author

Cooper, Nichola, primary, Scully, Marie, additional, Percy, Charles, additional, Nicolson, Phillip L. R., additional, Lowe, Gillian, additional, Bagot, Catherine N., additional, Thachil, Jecko, additional, Grech, Henri, additional, Nokes, Tim, additional, Hill, Quentin A., additional, Bradbury, Charlotte, additional, Talks, Kate, additional, Dutt, Tina, additional, Evans, Gillian, additional, Pavord, Sue, additional, Wexler, Sarah, additional, Charania, Asad, additional, Collington, Sarah J., additional, Ervin, Andrew, additional, Ramscar, Nicholas, additional, and Provan, Drew, additional

Published
2024
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19. Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration

Author

Arno, Gavin, Carss, Keren J, Hull, Sarah, Zihni, Ceniz, Robson, Anthony G, Fiorentino, Alessia, Hardcastle, Alison J, Holder, Graham E, Cheetham, Michael E, Plagnol, Vincent, Moore, Anthony, Raymond, F Lucy, Matter, Karl, Balda, Maria S, Webster, Andrew R, Black, Graeme, Hall, Georgina, Ingram, Stuart, Gillespie, Rachel, Manson, Forbes, Sergouniotis, Panagiotis, Inglehearn, Chris, Toomes, Carmel, Ali, Manir, McKibbin, Martin, Poulter, James, Khan, Kamron, Lord, Emma, Nemeth, Andrea, Downes, Susan, Halford, Stephanie, Yu, Jing, Lise, Stefano, Ponitkos, Nikos, Michaelides, Michel, Webster, Andrew, van Heyningen, Veronica, Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allen, Louise, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K, Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bitner-Glindzicz, Maria, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R, Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carmichael, Jenny, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Chitre, Manali, Church, Colin, Clement, Emma, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cooper, Nichola, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri VV, and Deshpande, Charu

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Ophthalmology and Optometry, Human Genome, Rare Diseases, Neurosciences, Eye Disease and Disorders of Vision, Aetiology, 2.1 Biological and endogenous factors, Eye, Adult, Alleles, Amino Acid Sequence, Cell Polarity, Epithelial Cells, Exome, Eye Proteins, Female, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Missense, Nerve Tissue Proteins, Pedigree, Phenotype, Retina, Retinal Degeneration, Retinal Dystrophies, Rho Guanine Nucleotide Exchange Factors, rhoA GTP-Binding Protein, UK Inherited Retinal Disease Consortium, NIHR Bioresource - Rare Diseases Consortium, ARHGEF18, apicobasal polarity, inherited retinal dystrophy, p114RhoGEF, retinal degeneration, retinitis pigmentosa, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that further genes remain to be identified. Whole-exome and -genome sequencing studies employed here in large cohorts of affected individuals revealed biallelic mutations in ARHGEF18 in three such individuals. ARHGEF18 encodes ARHGEF18, a guanine nucleotide exchange factor that activates RHOA, a small GTPase protein that is a key component of tight junctions and adherens junctions. This biological pathway is known to be important for retinal development and function, as mutation of CRB1, encoding another component, causes retinal dystrophy. The retinal structure in individuals with ARHGEF18 mutations resembled that seen in subjects with CRB1 mutations. Five mutations were found on six alleles in the three individuals: c.808A>G (p.Thr270Ala), c.1617+5G>A (p.Asp540Glyfs∗63), c.1996C>T (p.Arg666∗), c.2632G>T (p.Glu878∗), and c.2738_2761del (p.Arg913_Glu920del). Functional tests suggest that each disease genotype might retain some ARHGEF18 activity, such that the phenotype described here is not the consequence of nullizygosity. In particular, the p.Thr270Ala missense variant affects a highly conserved residue in the DBL homology domain, which is required for the interaction and activation of RHOA. Previously, knock-out of Arhgef18 in the medaka fish has been shown to cause larval lethality which is preceded by retinal defects that resemble those seen in zebrafish Crumbs complex knock-outs. The findings described here emphasize the peculiar sensitivity of the retina to perturbations of this pathway, which is highlighted as a target for potential therapeutic strategies.

Published
2017

20. Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Author

Carss, Keren J, Arno, Gavin, Erwood, Marie, Stephens, Jonathan, Sanchis-Juan, Alba, Hull, Sarah, Megy, Karyn, Grozeva, Detelina, Dewhurst, Eleanor, Malka, Samantha, Plagnol, Vincent, Penkett, Christopher, Stirrups, Kathleen, Rizzo, Roberta, Wright, Genevieve, Josifova, Dragana, Bitner-Glindzicz, Maria, Scott, Richard H, Clement, Emma, Allen, Louise, Armstrong, Ruth, Brady, Angela F, Carmichael, Jenny, Chitre, Manali, Henderson, Robert HH, Hurst, Jane, MacLaren, Robert E, Murphy, Elaine, Paterson, Joan, Rosser, Elisabeth, Thompson, Dorothy A, Wakeling, Emma, Ouwehand, Willem H, Michaelides, Michel, Moore, Anthony T, Consortium, NIHR-BioResource Rare Diseases, Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K, Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R, Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Church, Colin, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cooper, Nichola, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri VV, Deshpande, Charu, Devlin, Lisa, Doffinger, Rainer, Dormand, Natalie, Drewe, Elizabeth, and Edgar, David

Subjects
Genetics, Neurosciences, Eye Disease and Disorders of Vision, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Eye, Good Health and Well Being, Adaptor Proteins, Signal Transducing, Alleles, Base Sequence, Choroideremia, DNA Mutational Analysis, Ethnicity, Exome, Female, Genes, Recessive, Genetic Variation, Genome, Human, Humans, Introns, Male, Mutation, Rare Diseases, Retinal Diseases, NIHR-BioResource Rare Diseases Consortium, copy-number variants, rare sequence variant, retinal dystrophy, whole-genome sequence, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.

Published
2017

22. Sustained response off‐treatment in eltrombopag‐treated adult patients with ITP who are refractory or relapsed after first‐line steroids: Primary, final, and ad‐hoc analyses of the Phase II TAPER trial

Author

Cooper, Nichola, primary, Ghanima, Waleed, additional, Vianelli, Nicola, additional, Valcárcel, David, additional, Yavaşoğlu, İrfan, additional, Melikyan, Anait, additional, Ruiz, Eduardo Yañez, additional, Haenig, Jens, additional, Somenzi, Olivier, additional, Lee, James, additional, Clark, Joan, additional, Zhang, Yifan, additional, and Zaja, Francesco, additional

Published
2023
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23. Treatment of Critical Bleeding Events in Patients with Immune Thrombocytopenia: A Systematic Review

Author

Sirotich, Emily, primary, Chowdhury, Saifur, additional, Guyatt, Gordon, additional, Gill, Daya, additional, Modi, Dimpy, additional, Venier, Laura, additional, Eisa, Kerolos, additional, Beck, Carolyn E, additional, Breakey, Vicky R., additional, de Wit, Kerstin, additional, Porter, Stephen, additional, Webert, Kathryn Elizabeth, additional, Cuker, Adam, additional, O'Connor, Clare, additional, MacWhirter - DiRaimo, Jennifer, additional, Yan, Justin, additional, Manski, Charles, additional, Kelton, John G., additional, Kang, Matthew, additional, Strachan, Gail, additional, Hassan, Ziauddin, additional, Pruitt, Barbara, additional, Pai, Menaka, additional, Grace, Rachael F., additional, Paynter, Dale, additional, Charness, Jay, additional, Cooper, Nichola, additional, Fein, Steven, additional, Nazaryan, Hasmik, additional, Agarwal, Arnav, additional, Siddiqui, Ishaq, additional, Leong, Russell, additional, Pallapothu, Sushmitha, additional, Wen, Aaron, additional, Xu, Emily, additional, Liu, Bonnie, additional, Rathod, Preksha, additional, Kwon, Henry, additional, Dookie, Jared, additional, Shafiee, Amirmohammad, additional, Couban, Rachel, additional, and Arnold, Donald, additional

Published
2023
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25. Evaluating the clinical validity of genes related to hemostasis and thrombosis using the ClinGen gene curation framework

Author

Ross, Justyne E., primary, Mohan, Shruthi, additional, Zhang, Jing, additional, Sullivan, Mia J., additional, Bury, Loredana, additional, Lee, Kristy, additional, Futchi, Isabella, additional, Frantz, Annabelle, additional, McDougal, Dara, additional, Botero, Juliana Perez, additional, Cattaneo, Marco, additional, Cooper, Nichola, additional, Downes, Kate, additional, Gresele, Paolo, additional, Keenan, Catriona, additional, Lee, Alfred, additional, Megy, Karyn, additional, Morange, Pierre-Emmanuel, additional, Morgan, Neil V., additional, Schulze, Harald, additional, Zimowski, Karen, additional, Freson, Kathleen, additional, and Lambert, Michele P., additional

Published
2023
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26. Multi-arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate COVID-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial

Author

Vergis, Nikhil, Phillips, Rachel, Cornelius, Victoria, Katsarou, Alexia, Youngstein, Taryn, Cook, Lucy, Willicombe, Michelle, Pilay, Clio, Shturova, Tina, Almonte, Melanie, Charania, Asad, Turner, Richard, Kon, Onn Min, Cooke, Graham, Thursz, Mark, Cherlin, Svetlana, Wason, James, Milojkovic, Dragana, Innes, Andew J., and Cooper, Nichola

Published
2021
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28. Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders

Author

Downes, Kate, Megy, Karyn, Duarte, Daniel, Vries, Minka, Gebhart, Johanna, Hofer, Stefanie, Shamardina, Olga, Deevi, Sri V.V., Stephens, Jonathan, Mapeta, Rutendo, Tuna, Salih, Al Hasso, Namir, Besser, Martin W., Cooper, Nichola, Daugherty, Louise, Gleadall, Nick, Greene, Daniel, Haimel, Matthias, Martin, Howard, Papadia, Sofia, Revel-Vilk, Shoshana, Sivapalaratnam, Suthesh, Symington, Emily, Thomas, Will, Thys, Chantal, Tolios, Alexander, Penkett, Christopher J., Ouwehand, Willem H., Abbs, Stephen, Laffan, Michael A., Turro, Ernest, Simeoni, Ilenia, Mumford, Andrew D., Henskens, Yvonne M.C., Pabinger, Ingrid, Gomez, Keith, and Freson, Kathleen

Published
2019
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29. Updated international consensus report on the investigation and management of primary immune thrombocytopenia

Author

Provan, Drew, Arnold, Donald M., Bussel, James B., Chong, Beng H., Cooper, Nichola, Gernsheimer, Terry, Ghanima, Waleed, Godeau, Bertrand, González-López, Tomás José, Grainger, John, Hou, Ming, Kruse, Caroline, McDonald, Vickie, Michel, Marc, Newland, Adrian C., Pavord, Sue, Rodeghiero, Francesco, Scully, Marie, Tomiyama, Yoshiaki, Wong, Raymond S., Zaja, Francesco, and Kuter, David J.

Published
2019
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30. Blockchain Introduced

Author

Thomason, Jane, primary, Bernhardt, Sonja, additional, Kansara, Tia, additional, and Cooper, Nichola, additional

Published
2021
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31. Emerging Markets

Author

Thomason, Jane, primary, Bernhardt, Sonja, additional, Kansara, Tia, additional, and Cooper, Nichola, additional

Published
2021
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34. Transforming Cities

Author

Thomason, Jane, primary, Bernhardt, Sonja, additional, Kansara, Tia, additional, and Cooper, Nichola, additional

Published
2021
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38. The role of Protein Kinase Cα in the skin and cutaneous wound healing

Author

Cooper, Nichola, Hardman, Matthew, and Travis, Mark

Subjects
617.1, Desmosome, Wound healing, Collagen, Extracellular matrix
Abstract

Chronic wounds represent a severe socio-economic burden and a key area of unmet clinical need. PKCα is ubiquitous in the skin, particularly the epidermis and functions in numerous pathways that are fundamental to wound repair. By utilising a global PKCα-/- mouse we have identified PKCα-regulated processes both in unwounded skin and during wound healing. PKCα-/- mice display considerably delayed wound healing with a dramatic reduction in re-epithelialisation. By analysing the ultrastructure of the epidermis, I have shown that this delay directly correlates with a failure of wound edge desmosomes to switch to a their adhesive properties. A major risk factor for the development of chronic wounds is age. Crucially, this delay in modulating cell adhesion is conserved in human chronic wounds and aged murine skin. Furthermore, manipulation of PKCα using an inducible bitransgenic mouse containing epidermal specific constitutively active PKCα can accelerate the modulation of desmosome adhesion and subsequently improve re-epithelialisation. Global gene expression analysis of PKCα-/- skin and wounds revealed further defects. Upon wounding, we observed a failure to correctly regulate expression of key collagen and Wnt signalling genes that are essential for correct and timely wound healing. Finally, intrinsic gene expression changes were identified in the skin of PKCα-/- mice, specifically a downregulation of multiple extracellular matrix genes. Of note was the downregulation of small leucine-rich proteoglycans which led to alterations to dermal collagen structure and skin tensile strength. These changes render the PKCα-/- skin susceptible to breaking and wound development. To conclude, we have identified multiple roles for PKCα intrinsically in the skin and also during cutaneous wound healing. Importantly, these intrinsic changes appear to predispose PKCα-/- skin to the development of cutaneous wounds and altered wound-specific processes that manifest in a delayed healing phenotype.

Published
2014

41. Safety and efficacy of SARS‐CoV‐2 vaccination in patients with immune thrombocytopenia: A two‐centre review.

Author

Stefani, Sara, Buti, Noora, Hart, Alice C. J., Paul, Deena, Rizvi, Naghma, Ragoonanan, Vashti, Vladescu, Camelia, Szydlo, Richard, Ademokun, Christine, Jansen, A. J. Gerard, and Cooper, Nichola

Subjects
IDIOPATHIC thrombocytopenic purpura, SARS-CoV-2, VACCINATION, ANTIBODY formation, PATIENT safety
Abstract

Summary: Multiple studies have reported immune thrombocytopenia (ITP) relapse following SARS‐CoV‐2 vaccination, however baseline ITP relapse rate and antibody response to vaccination are not known. Patients with ITP who received at least one of the first three SARS‐CoV‐2 vaccination doses were included in the study. One hundred and twenty‐four patients met the inclusion criteria. Relapse rate was 4.2% following a first vaccine dose, 9.1% after a second and 2.9% after a third; baseline relapse rate was 7.6%. Ninety‐four per cent of patients who received three vaccine doses developed a clinical antibody response. SARS‐CoV‐2 vaccination appears to be safe and effective in patients with ITP. [ABSTRACT FROM AUTHOR]

Published
2024
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42. PB2612: UNITED KINGDOM RETROSPECTIVE OBSERVATIONAL STUDY OF ROMIPLOSTIM AND OTHER TREATMENTS IN EARLY IMMUNE THROMBOCYTOPENIA

Author

Mcdonald, Vickie, primary, Bradbury, Charlotte, additional, Talks, Kate, additional, Lowe, Gillian, additional, Pavord, Sue, additional, Evans, Gillian, additional, Andiappan, Mano, additional, Sandschafer, Darcie, additional, Barbosa, Vitor Jose De Sousa, additional, Stephens, Lorraine, additional, and Cooper, Nichola, additional

Published
2023
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43. PB2625: VAYHIT2: A RANDOMIZED, DOUBLE-BLIND, PHASE III TRIAL OF IANALUMAB VS PLACEBO IN ADDITION TO ELTROMBOPAG IN PATIENTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) WHO FAILED FIRST-LINE STEROID TREATMENT

Author

Zaja, Francesco, primary, Al-Samkari, Hanny, additional, Michel, Marc, additional, Ghanima, Waleed, additional, Cooper, Nichola, additional, Wong, Raymond, additional, Barcellini, Wilma, additional, Zhang, Fengkui, additional, Marturano, Emerenziana, additional, Peyrard, Severine, additional, and Cuker, Adam, additional

Published
2023
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45. P1589: PATIENT (PT) AND PHYSICIAN (MD) PERCEPTIONS OF THE BURDEN OF IMMUNE THROMBOCYTOPENIA (ITP) AND ITS MANAGEMENT: RESULTS FROM THE ITP WORLD IMPACT SURVEY (I-WISH) 2.0

Author

Cooper, Nichola, primary, Kruse, Caroline, additional, Ghanima, Waleed, additional, Provan, Drew, additional, Tomiyama, Yoshiaka, additional, Hou, Ming, additional, Arnold, Donald, additional, Santoro, Cristina, additional, Zaja, Francesco, additional, Lovrencic, Barbara, additional, Morgan, Mervyn, additional, Lahav, Leron, additional, Winograd, Michal, additional, Bailey, Tom, additional, Haenig, Jens, additional, Georget, Mahnouch, additional, and Bussel, James, additional

Published
2023
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46. PB2552: VAYHIA: A RANDOMIZED, DOUBLE-BLIND, PHASE III TRIAL TO ASSESS THE EFFICACY AND SAFETY OF IANALUMAB VS PLACEBO IN PATIENTS WITH WARM AUTOIMMUNE HEMOLYTIC ANEMIA THAT FAILED ≥1 LINE OF TREATMENT

Author

Barcellini, Wilma, primary, Michel, Marc, additional, Cuker, Adam, additional, Cooper, Nichola, additional, Ghanima, Waleed, additional, Wong, Raymond, additional, Zaja, Francesco, additional, Zhang, Fengkui, additional, Bezlyak, Vladimir, additional, Nguyen, Thu Thuy, additional, and Al-Samkari, Hanny, additional

Published
2023
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47. PB2636: VAYHIT1: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PHASE III TRIAL OF IANALUMAB VERSUS PLACEBO IN ADDITION TO FIRST-LINE CORTICOSTEROIDS IN PATIENTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA (ITP)

Author

Cooper, Nichola, primary, Cuker, Adam, additional, Michel, Marc, additional, Wong, Raymond, additional, Ghanima, Waleed, additional, Zaja, Francesco, additional, Barcellini, Wilma, additional, Zhang, Fengkui, additional, Lawniczek, Tomasz, additional, Weill, Marine, additional, and Al-Samkari, Hanny, additional

Published
2023
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50. Human retinoic acid–regulated CD161+ regulatory T cells support wound repair in intestinal mucosa

Author

Povoleri, Giovanni A. M., Nova-Lamperti, Estefania, Scottà, Cristiano, Fanelli, Giorgia, Chen, Yun-Ching, Becker, Pablo D., Boardman, Dominic, Costantini, Benedetta, Romano, Marco, Pavlidis, Polychronis, McGregor, Reuben, Pantazi, Eirini, Chauss, Daniel, Sun, Hong-Wei, Shih, Han-Yu, Cousins, David J., Cooper, Nichola, Powell, Nick, Kemper, Claudia, Pirooznia, Mehdi, Laurence, Arian, Kordasti, Shahram, Kazemian, Majid, Lombardi, Giovanna, and Afzali, Behdad

Published
2018
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