Search

Your search keyword '"Charlotte Killick"' showing total 8 results
Start Over Author "Charlotte Killick"
8 results on '"Charlotte Killick"'

1. The Use of Different Sepsis Risk Stratification Tools on the Wards and in Emergency Departments Uncovers Different Mortality Risks: Results of the Three Welsh National Multicenter Point-Prevalence Studies

Author

Harry J. A. Unwin, MBBCh, BSc, Maja Kopczynska, MBBCh, BSc, Richard Pugh, FRCA, Laura J. P. Tan, MBBS, BSc, Christian P. Subbe, MD, Gemma Ellis, MSc, Paul Morgan, FRCA, Peter Havalda, MD, Ben Sharif, MBBCh, John Burke, MSc, Tamas Szakmany, MD, PhD, FCCM, on behalf of Welsh Digital Data Collection Platform (WDDCP) Collaborators, Maria Hobrok, Moriah Thomas, Annie Burden, Nadia Youssef, Katherine Carnegie, Helena Colling-Sylvester, Natasha Logier, Meshari Alsaeed, Hannah Williams, Arfa Ayob, Nor Farzana, Sweta Parida, David Lawson, Emily Evans, Laura Jane Davis, Billie Atkins, Llywela Wyn Davies, Lee Sanders-Crook, Steffan Treharne Seal, Alice Cains, Richard Pugh, Katy Crisp, Sarah Venning, Ella Sykes, Stephanie Narine, Georgia Parry, Emily Angela Dillon, Qi Zhuang Siah, Ting Yang, Tyler Jones, Parvathi Thara, Emma Wood, Lara Wirt, Georgina St Pier, Richard Betts, Kyriaki Mitsaki, Mari Tachweed Pierce, Sioned Davies, Yakeen Hafouda, Erin Ifan, Grace Lacey, Francesca Mitchell, John Lynch, Michal Mazur, Lezia D’Souza, Bethan Ponting, Terrance Lau, Ruairidh Kerrigan, Lucy Morgan, Roshan Vindla, Claudia Zeicu, Becky James, Amirah Amin Ariff, Wan Binti Wan Azzlan, Charlotte Collins, Elizabeth Wickens, Alisa Norbee, Aliya Zulkefli, Thomas Haddock, Megan Thomas, Matthew Lee, Miriam Cynan, Nik-Syakirah Nik Azis, Imogen Hay, Catherine Russell, Margriet Vreugdenhil, Mustafa Abdimalik, Joseph Davies, Peter Havalda, Angharad Evans, Kate Robertson, Grace Gitau, Mei-yin Gruber, Thomas Telford, Anas Qarout, Naomi Nandra, Hannah Garrard, James Cutler, Rhiannon Tammy Jones, Amy Prideaux, Timothy Spence, Sarah Hardie, Harriet Seymour, Sam Willis, Matthew Warlow, Shanali Thanthilla, Thomas Downs, Nina Foley, Chad McKeown, Akshita Dandawate, Holleh Shayan-Arani, Ellie Taylor, Oliver Kyriakides, Rachel Price, Ffion Haf Mackey, Emily Haines, Samuel Chun, Nilarnti Vignarajah, Tessa Chamberlain, Dongying Zhao, Nayanatara Nadeesha T Tantirige, Naomi Dennehey, Georgina Evans, John Watts, Ceri Battle, Ryan Jones, Selina Jones, Charlotte James, James O’Hanlon, Isabella Bridges, Bethany Hughes, Leo Polchar, Elise Bisson, Charlotte Mykura, Lara Money, Joshua McKenna, Sarah Kinsman, Demiana Hanna, Emily Baker, Harrison Sprague, Liam Sharma, Tom Pontin, Emma Shore, Tamara Hughes, Sam Nightingale, Philby Baby, Matthew Shield, Alice Cross, Jenna Boss, Olivia Ross, George Ashton, Kimaya Pandit, Daniel Davies, Cameron Garbutt, Charlotte Johnston, Marcus Cox, Chantal Roberts, Alessia Waller, Laura Heekin, Kathy Wang, Rhianna Church, Shrina Patel, Marianne Broderick, Hannah Whillis, Daniel Craig Hathaway, Emel Yildirim, Caitlin Atkins, Elin Walters, Carys Durie, Robert James Hamilton Sinnerton, Benjamin Tanner, Julimar Abreu, Kiran Bashir, Vincent Hamlyn, Amelia Tee, Zoe Ann Hinchcliffe, Rita Otto, Georgie Covell, Megan Stone, Victoria Maidman, Katherine Godfray, Rhidian Caradine, Hannah Beetham, Adanna Nicole Anomneze-Collins, Jeanette Tan, Yasmina Abdelrazik, Azizah Khan, Nabihah Malik, Aidan Clack, Lewis Oliva, Tyler Thomas, Adam George Mounce, Anoopama Ramjeeawon, Ndaba Mtunzi, Duncan Soppitt, Jay Hale, Jack Wellington, Robert Buchanan Ross, Danielle Lis, Rebecca Parsonson, Jude Joseph-Gubra, Ajitha Arunthavarajah, Jessica Nicholas, Aaron Harris, Henry Atkinson, Jessica Webster, Tim Burnett, Josephine Raffan Gowar, Sam DeFriend, Jasmine Whitaker, Elizabeth Beasant, Luis Macchiavello, Danyal Usman, Abdullah Mahdi, Tiffany Ye Tze Shan, Nick Savill, Jennifer Gee, Lizzie Hodges, Ami Desai, Hannah Rossiter, Matthew Taylor, Kevin Pinto, Eleanor Hartley, Oscar Emanuel, Rhiannon Long, Megan Selby, Elilis Wardle, Alexandra Urquhart, Jack Barrington, Matthew Ashman, Elizabeth Adcock, Amelia Dickinson, Rebecca Jordache, Rym Chafai El Alaoui, Sophie Stovold, Sam Vickery, Nia Jones, Alice O’Donnell, Monty Cuthbert, Osa Eghosa, Muhammad Karim, Lowri Williams, Louise Tucker, Tom Downs, Rebecca Walford, Annabelle Hook, Adam Mounce, Emily Eccles, Ross Edwards, Kirtika Ramesh, Charlie Hall, Maria Lazarou, Rhidian Jones, Katy McGillian, Hari Singh Bhachoo, Zoe The, Vithusha Inpahas, Ruchi Desai, Yusuf Cheema, Andrew Hughes, Olivia Cranage, Felicity Bee, Khalid Osman, Humza Khan, Jennifer Pitt, Charlotte Pickwick, Jorge Carter, Fiona Andrew, Naseera Seedat, Roshni Patel, Megan Walker, Alicia Boam, Jessica Randall, Beth Bowyer, Josh Edwards, Natasha Jones, Emma Walker, Ailsa MacNaught, Swagath Balachandran, Abbie Shipley, Jennifer Louise Kent, Samuel Tilley, Bethany Davies, Emma Withers, Krishna Parmar, Lucie Webber, Angelica Sharma, Amy Handley, Alexandra Gordon, Lucy Allen, Rebecca Paddock, Harriet Penney, Lopa Banerjee, Chloe Victoria Vanderpump, Kate Harding, John Burke, Orsolya Minik, Nia Jarrett, Ellie Rowe, Adanna Anomneze-Collins, Harry Griffiths, Sarah Pengelly, Ffion Bennett, Ahmed Bilal, Abdullah El-badawey, Bethan Ellis, Luke Cook, Harriet Elizabeth Valentine Maine, Kiri Armstrong, Hannah Beresford, Timia Raven-Gregg, Tom Liddell-Lowe, Caitlin Ong, Harriet Reed, Frederika Alice St John, Weronika Julia Kozuch, Isabelle Ray, Irukshi Anuprabha Silva, Sin Ting Natalie Cheng, Umme-Laila Ali, Noreena Syed, Luke Murphy, Thomas Grother, Harry Smith, Rachel Watson, Omar Marei, Emma Kirby, Anna Gilfedder, Lydia Maw, Sarah O’Connor, Charlotte Maden, Helena Jones, Hazel Preston, Nur Amirah Binti Maliki, Mark Zimmerman, Jessica Webber, Llewelyn Jones, Rebecca Phillips, Lauren McCarthy, Emily Hubbard, Leo Duffy, Abigail Guerrier Sadler, Tamas Szakmany, Owen Richards, Charles King, Charlotte Killick, Yusuf Chema, Kavita Shergill, Yi Huen, Lillian Lau, Hannah Mustafa Ali, Lucas Wilcock, Molly Timlin, Ayeesha Rela, Daniel Smith, Sarah Ireland, Jennifer Evans, Nayanatara Poobalan, Jessica Pearce, Thivya V Vadiveloo, Zoe Black, Daniel Elis Samuel, Humaira Hussain, Joanna Hawkins, Zeid Atiyah, Rebecca Creamer, Maham Zafar, Ahmad Almazeedi, Hannah Brunnock, Zain Nasser, Mekha Jeyanthi, Poorya Moghbel, Katie Kwan, Isobel Sutherland, Frank Davis, Abigail Rogers, Zhao Xuan Tan, Clare Chantrill, Amal Robertson, Jonathan Foulkes, Rahana Khanam, Jomcy John, Sarah Hannah Meehan, Huria Metezai, Hannah Dawson, Navrhinaa Vadivale, Camilla Lee, Amrit Dhadda, Sian Cleaver, Genna Logue, Joy Inns, Isabel Jones, Robyn Howcroft, Carys Gilbert, Matthew Bradley, Louise Pike, Rachel Keeling, Charldré Banks, Eleanor Cochrane, James McFadyen, Matthew Mo, Emily Ireland, Esme Brittain, Ihssen Laid, Charlotte Green, Adriel Mcforrester, Xuong Michelle Ly, Mariana Nalbanti, Raven Joseph, Jack Tagg, David Purchase, Pan Myat, Ayako Niina, Tyler Joshua Jones, Lowri Hughes Thomas, Natalie Hoyle, Patrick Benc, Ellen Davies, Meng-Chieh Wu, David Fellows, Sam Tilley, Eloise Baxendale, Karishma Khan, Andrew Forrester, Oliver Moore, Hse Juinn Lim, Aimee Owen, Faris Hussain, Nima-banu Allybocus, Maneha Sethi, Harry Waring, Adeel Khan, Claire Smith, Nicholas Doyle, Mohammad Yahya Amjad, Luke Galloway, Paul Morgan, Gemma Ellis, Robert Lundin, Haamed Al Hassan, Bethan Markall, Namratha Kaur, Emmanuel Onyango, Heather Beard, Elliot Field, Ellen Nelson-Rowe, Lizzie Adcock, Amelia Stoddart, Frederika St John, Mathoorika Sivananthan, Rhys Jones, Sung Yeon Kwak, Lily Farakish, Holly Rhys-Ellis, Kate Moss, Tallulah Ray, Tessa David, Talea Roberts, Annie Quy, Aniket Paranjape, Nutchanun Poolworaluk, Mary Keast, Si Liang Yao, Dion Manning, Isobel Irwin, Umair Asim, Emelia Boggon, Ibrahim Alkurd, Genevieve Lawerece, Jade Brown, Emily Murphy, Evie Lambert, Jeremy Guilford, Beth Payne, Mariam Almulaifi, Arwel Poacher, Sashiananthan Ganesananthan, Berenice Cunningham-Walker, Chloe Spooner, Akanksha Kiran, Nabeegh Nadeem, Vidhi Unadkat, Esme Sparey, David Li, Jessica Smith, India Corrin, Amit Kurani, Paul McNulty, Ceri Brown, Wojciech Groblewski, Szilvia Szoke, Amelia Redman, Esther McKeag, Anastasia Donnir, Gaautham Ravishangar, Emanuela Howard, Charlotte Salmon, Sara Tanatova, Jasmine Kew, Megan Eilis Clark, Ellen Hannay, Olesya Godsafe, Christina Houghton, Francesca Lavric, Rachel Mallinson, Chris Littler, Harsha Reddy, Andrew Campbell, Benedict Soo, Rachel Evans, Georgina Donowho, Alexandra Cawthra, Maddison Davies, Matthew Lawrence Ashman, Jamie Scriven, James Vautrey, Shannon Seet, Imogen Britton, Abigail Hodgson, Emma Twohey, Joseph Robbins, Vanessa Yeo Yung Ling, Kimiya Asjadi, Carven Chin Yee Shean, Zoe McCarroll, Oritseweyimi Amatotsero, Hei Man Priscilla Chan, John Ng Cho Hui, Antonia Ashaye, Josephine Acheampong, Ayowade Adeleye, Saber Ahmed, Alexandra Chrysostomou, Harry Unwin, Eshen Ang, Niamh McSwiney, Yin Yin Lim, Zong Xuan Lee, Svetlana Kulikouskaya, Nur Zulkifili, Sheryl Lim, Lim Xin, Adiya Urazbayeva, Nur Haslina Ahmad Hanif, Yau Ke Ying, Alice Coleclough, Eilis Higgins, Naomi Spencer, Tze Gee Ng, Sam Booth, Stephanie Wai Yee Ng, Christian P Subbe, Isabella Patterson, Wen Li Chia, Abdullah Mukit, Hei Yi Vivian Pak, Felicity Lock, Mariana Nalmpanti, Shôn Alun Thomas, Tanisha Burgher, Alfred Wei Zhen Yeo, Siwan Powell Jones, Charlie Miles, Millicent Perry, Holly Burton, Katharine Powell, Luthfun Nessa, Aalaa Fadlalla, Rhian Morgan, Elizabeth Hodges, Amelia Heal, Chloe Scott, Alice Tayler, Thomas Chandy, Abduahad Taufik, James Cochrane, Samuel Willis, Sieh Yen Heng, Alex Cooper, Henrik Graf von der Pahlen, Isabella Talbot, Robin Gwyn Roberts, Jessica Sharma Smith, Aisling Sweeney, Cerian Roberts, Laura Bausor, Chania, Daniah Thomas, Elen Wyn Puw, Ronan A Lyons, and Judith E Hall

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN:. Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING:. The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS:. We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS:. We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS:. Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

Published
2021
Full Text
View/download PDF

2. Procalcitonin Increase Is Associated with the Development of Critical Care-Acquired Infections in COVID-19 ARDS

Author

Owen Richards, Philip Pallmann, Charles King, Yusuf Cheema, Charlotte Killick, Emma Thomas-Jones, Jessica Harris, Catherine Bailey, and Tamas Szakmany

Subjects
COVID-19, procalcitonin, C-reactive protein, secondary infection, Therapeutics. Pharmacology, RM1-950
Abstract

Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study. For daily biomarker and secondary infection, laboratory-confirmed bloodstream infection (LCBI) and ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) data were collected. We observed a PCT rise in 53 (81.5%) of the patients, a C-reactive protein (CRP) rise in 55 (84.6%) and a white blood cell count (WBC) rise in 61 (93.8%). Secondary infection was confirmed in 33 (50.8%) of the patients. A PCT rise was present in 97.0% of patients with at least one confirmed VAP/VAT and/or LCBI event. CRP and WBC rises occurred in 93.9% and 97.0% of patients with confirmed VAP/VAT and/or LCBI, respectively. Logistic regression analysis found that, when including all biomarkers in the same model, there was a significant association between PCT rise and the occurrence of LCBI and/or VAP/VAT (OR = 14.86 95%CI: 2.20, 342.53; p = 0.021). Conversely, no statistically significant relationship was found between either a CRP rise (p = 0.167) or a WBC rise (p = 0.855) and the occurrence of VAP/VAT and/or LCBI. These findings provide a promising insight into the usefulness of PCT measurement in predicting the emergence of secondary bacterial infection in ICU.

Published
2021
Full Text
View/download PDF

3. Sex Hormone-regulated CMG2 Is Involved in Breast and Prostate Cancer Progression

Author

ZIQIAN FANG, CHARLOTTE KILLICK, CERITH HALFPENNY, NATASHA FREWER, KATHRYN A. FREWER, FIONA RUGE, WEN G. JIANG, and LIN YE

Subjects
Male, Cancer Research, Estradiol, Receptors, Peptide, Prostate, Prostatic Neoplasms, Breast Neoplasms, Biochemistry, Receptors, Estrogen, Genetics, Humans, Female, Breast, Molecular Biology, Research Article
Abstract

Background/Aim: Capillary morphogenesis gene 2 (CMG2) is involved in prostate and breast cancer progression. This study aimed to investigate sex hormone receptor-mediated regulation of CMG2 in breast and prostate cancer, and its implication in disease progression. Materials and Methods: Expression of CMG2, oestrogen receptor (ER) and androgen receptor (AR) was determined in breast and prostate cancer cell lines, respectively, using real-time quantitative PCR (QPCR) and western blot. Association between CMG2 and sex hormone receptors was analysed in a number of transcriptome datasets. Immunochemical staining was performed in tissue microarrays of breast cancer (BR1505D) and prostate cancer (PR8011A). CMG2 expression was determined in 17β-oestradiol treated breast cancer cells and AR over-expressing prostate cancer cells. Results: CMG2 was found to be inversely correlated with sex hormone receptors in breast and prostate cancer. Lower expression of CMG2 was associated with a poor prognosis in ER (+) breast cancer but not ER (–) tumours. Both ER (+) breast cancer cell lines and AR (+) prostate cancer cell lines presented lower expression of CMG2, which was increased following sex hormone deprivation. Exposure to 17-β-oestradiol and AR over-expression repressed CMG2 expression in breast cancer and prostate cancer cell lines, respectively. Conclusion: CMG2 is inversely correlated with ER and AR status in breast and prostate cancer, respectively. ER and AR mediate repression of CMG2 expression in corresponding cancerous cells.

Published
2022

4. Procalcitonin Increase Is Associated with the Development of Critical Care-Acquired Infections in COVID-19 ARDS

Author

Charlotte Killick, Catherine Bailey, Philip Pallmann, Yusuf Cheema, Emma Thomas-Jones, Jessica Harris, Owen Richards, Tamas Szakmany, and Charles King

Subjects
Microbiology (medical), medicine.medical_specialty, ARDS, Secondary infection, RM1-950, Biochemistry, Microbiology, Article, Procalcitonin, law.invention, C-reactive protein, law, Internal medicine, secondary infection, parasitic diseases, medicine, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, biology, business.industry, COVID-19, procalcitonin, Retrospective cohort study, medicine.disease, bacterial infections and mycoses, Intensive care unit, Pneumonia, Infectious Diseases, biology.protein, Biomarker (medicine), Therapeutics. Pharmacology, business
Abstract

Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study. For daily biomarker and secondary infection, laboratory-confirmed bloodstream infection (LCBI) and ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) data were collected. We observed a PCT rise in 53 (81.5%) of the patients, a C-reactive protein (CRP) rise in 55 (84.6%) and a white blood cell count (WBC) rise in 61 (93.8%). Secondary infection was confirmed in 33 (50.8%) of the patients. A PCT rise was present in 97.0% of patients with at least one confirmed VAP/VAT and/or LCBI event. CRP and WBC rises occurred in 93.9% and 97.0% of patients with confirmed VAP/VAT and/or LCBI, respectively. Logistic regression analysis found that, when including all biomarkers in the same model, there was a significant association between PCT rise and the occurrence of LCBI and/or VAP/VAT (OR = 14.86 95%CI: 2.20, 342.53; p = 0.021). Conversely, no statistically significant relationship was found between either a CRP rise (p = 0.167) or a WBC rise (p = 0.855) and the occurrence of VAP/VAT and/or LCBI. These findings provide a promising insight into the usefulness of PCT measurement in predicting the emergence of secondary bacterial infection in ICU.

Published
2021

5. Differences in inflammatory marker kinetics between the first and second wave of COVID-19 patients admitted to the ICU: a retrospective, single-center study

Author

Yusuf Cheema, Nick Wetherall, Charles King, Tamas Szakmany, Elsa Harte, Saraswathi Ramachandran, Charlotte Killick, Henry Breen, William Tuckwell, Owen Richards, and Shannon Price

Subjects
corticosteroid, medicine.medical_specialty, medicine.drug_class, immunomodulation, Single Center, Article, Procalcitonin, C-reactive protein, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, White blood cell, Medicine, 030212 general & internal medicine, biology, business.industry, Organ dysfunction, COVID-19, Retrospective cohort study, General Medicine, medicine.anatomical_structure, 030228 respiratory system, biology.protein, Corticosteroid, SOFA score, medicine.symptom, business, procalcitonin
Abstract

Background: We sought to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels between the first and the second COVID-19 wave of ICU patients. Methods: In a single-center retrospective observational study, ICU patients were enrolled during the first and second waves of the COVID-19 pandemic. Data were collected on patient demographics, comorbidities, laboratory results, management strategies, and complications during the ICU stay. The inflammatory response was evaluated using WBC count, CRP, PCT, and Ferritin levels on the day of admission until Day 28, respectively. Organ dysfunction was measured by the SOFA score. Results: 65 patients were admitted during the first and 113 patients during the second wave. WBC and ferritin levels were higher in the second wave. CRP and PCT showed markedly different longitudinal kinetics up until day 28 of ICU stay between the first and second wave, with significantly lower levels in the second wave. Steroid and immunomodulatory therapy use was significantly greater in the second wave. Mortality was similar in both waves. Conclusions: We found that there was a significantly reduced inflammatory response in the second wave, which is likely to be attributable to the more widespread use of immunomodulatory therapies.

Published
2021

6. Prevalence of phenotypes of acute respiratory distress syndrome in critically ill patients with COVID-19: a prospective observational study

Author

Shiney Cherian, Charlotte Killick, Daniel F. McAuley, Sean Cutler, David Brealey, Yusuf Cheema, Kevin L. Delucchi, Murali Shyamsundar, Kiran Reddy, Charles H. King, Cecilia O'Kane, Carolyn S. Calfee, Owen Richards, Pratik Sinha, Catherine Bailey, Anthony C. Gordon, Tamas Szakmany, and Manu Shankar-Hari

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, ARDS, Clinical Sciences, Type I, Systemic inflammation, law.invention, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, Randomized controlled trial, law, Internal medicine, Intensive care, Receptors, medicine, Humans, 2.1 Biological and endogenous factors, 030212 general & internal medicine, Prospective Studies, Aetiology, Prospective cohort study, Lung, APACHE, Respiratory Distress Syndrome, Other Medical and Health Sciences, business.industry, Case-control study, COVID-19, Articles, Middle Aged, medicine.disease, Phenotype, Good Health and Well Being, 030228 respiratory system, Simvastatin, Case-Control Studies, Cohort, Respiratory, Public Health and Health Services, Female, medicine.symptom, business, Tumor Necrosis Factor, Cytokine Release Syndrome, medicine.drug
Abstract

BACKGROUND: In acute respiratory distress syndrome (ARDS) unrelated to COVID-19, two phenotypes, based on the severity of systemic inflammation (hyperinflammatory and hypoinflammatory), have been described. The hyperinflammatory phenotype is known to be associated with increased multiorgan failure and mortality. In this study, we aimed to identify these phenotypes in COVID-19-related ARDS.METHODS: In this prospective observational study done at two UK intensive care units, we recruited patients with ARDS due to COVID-19. Demographic, clinical, and laboratory data were collected at baseline. Plasma samples were analysed for interleukin-6 (IL-6) and soluble tumour necrosis factor receptor superfamily member 1A (TNFR1) using a novel point-of-care assay. A parsimonious regression classifier model was used to calculate the probability for the hyperinflammatory phenotype in COVID-19 using IL-6, soluble TNFR1, and bicarbonate levels. Data from this cohort was compared with patients with ARDS due to causes other than COVID-19 recruited to a previous UK multicentre, randomised controlled trial of simvastatin (HARP-2).FINDINGS: Between March 17 and April 25, 2020, 39 patients were recruited to the study. Median ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO2/FiO2) was 18 kpa (IQR 15-21) and acute physiology and chronic health evaluation II score was 12 (10-16). 17 (44%) of 39 patients had died by day 28 of the study. Compared with survivors, patients who died were older and had lower PaO2/FiO2. The median probability for the hyperinflammatory phenotype was 0·03 (IQR 0·01-0·2). Depending on the probability cutoff used to assign class, the prevalence of the hyperinflammatory phenotype was between four (10%) and eight (21%) of 39, which is lower than the proportion of patients with the hyperinflammatory phenotype in HARP-2 (186 [35%] of 539). Using the Youden index cutoff (0·274) to classify phenotype, five (63%) of eight patients with the hyperinflammatory phenotype and 12 (39%) of 31 with the hypoinflammatory phenotype died. Compared with matched patients recruited to HARP-2, levels of IL-6 were similar in our cohort, whereas soluble TNFR1 was significantly lower in patients with COVID-19-associated ARDS.INTERPRETATION: In this exploratory analysis of 39 patients, ARDS due to COVID-19 was not associated with higher systemic inflammation and was associated with a lower prevalence of the hyperinflammatory phenotype than that observed in historical ARDS data. This finding suggests that the excess mortality observed in COVID-19-related ARDS is unlikely to be due to the upregulation of inflammatory pathways described by the parsimonious model.FUNDING: US National Institutes of Health, Innovate UK, and Randox.

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results