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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
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2. The ‘omics of obesity in B-cell acute lymphoblastic leukemia

Author

Delaney K Geitgey, Miyoung Lee, Kirsten A Cottrill, Maya Jaffe, William Pilcher, Swati Bhasin, Jessica Randall, Anthony J Ross, Michelle Salemi, Marisol Castillo-Castrejon, Matthew B Kilgore, Ayjha C Brown, Jeremy M Boss, Rich Johnston, Anne M Fitzpatrick, Melissa L Kemp, Robert English, Eric Weaver, Pritha Bagchi, Ryan Walsh, Christopher D Scharer, Manoj Bhasin, Joshua D Chandler, Karmella A Haynes, Elizabeth A Wellberg, and Curtis J Henry

Subjects
Cancer Research, Oncology
Abstract

The obesity pandemic currently affects more than 70 million Americans and more than 650 million individuals worldwide. In addition to increasing susceptibility to pathogenic infections (eg, SARS-CoV-2), obesity promotes the development of many cancer subtypes and increases mortality rates in most cases. We and others have demonstrated that, in the context of B-cell acute lymphoblastic leukemia (B-ALL), adipocytes promote multidrug chemoresistance. Furthermore, others have demonstrated that B-ALL cells exposed to the adipocyte secretome alter their metabolic states to circumvent chemotherapy-mediated cytotoxicity. To better understand how adipocytes impact the function of human B-ALL cells, we used a multi-omic RNA-sequencing (single-cell and bulk transcriptomic) and mass spectroscopy (metabolomic and proteomic) approaches to define adipocyte-induced changes in normal and malignant B cells. These analyses revealed that the adipocyte secretome directly modulates programs in human B-ALL cells associated with metabolism, protection from oxidative stress, increased survival, B-cell development, and drivers of chemoresistance. Single-cell RNA sequencing analysis of mice on low- and high-fat diets revealed that obesity suppresses an immunologically active B-cell subpopulation and that the loss of this transcriptomic signature in patients with B-ALL is associated with poor survival outcomes. Analyses of sera and plasma samples from healthy donors and those with B-ALL revealed that obesity is associated with higher circulating levels of immunoglobulin-associated proteins, which support observations in obese mice of altered immunological homeostasis. In all, our multi-omics approach increases our understanding of pathways that may promote chemoresistance in human B-ALL and highlight a novel B-cell–specific signature in patients associated with survival outcomes.

Published
2023
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5. Spatial and temporal variation of late summer ichthyoplankton assemblage structure in the eastern Chukchi Sea: 2010–2015

Author

Adam Spear, Kathryn L. Mier, Morgan S. Busby, and Jessica Randall

Subjects
0106 biological sciences, Water mass, biology, Boreogadus saida, 010604 marine biology & hydrobiology, Sand lance, Ichthyoplankton, biology.organism_classification, 010603 evolutionary biology, 01 natural sciences, Eleginus, Bottom water, Oceanography, Arctic, Limanda proboscidea, General Agricultural and Biological Sciences
Abstract

The survival of the planktonic stages of marine fishes is widely considered to be a bottleneck in recruitment success and is a period when fishes are highly sensitive to changes in their environment. In high latitude areas that are forecasted to experience warming temperatures, it is critical to determine a baseline of ichthyoplankton assemblages to detect how the ecosystem may change in response to shifting conditions. This study used ichthyoplankton data from the eastern Chukchi Sea in the summers of 2010–2015 to assess temporal and spatial variation in assemblage structure. Larval densities were examined in relation to oceanographic conditions at depth and corresponding water masses. Additionally, the standard lengths of polar cod (Boreogadus saida), a key trophic link in Arctic food webs, were assessed for size-at-catch relationships. In 2010 and 2011, years of widespread presence of warm, low salinity bottom water masses such as Alaska Coastal Water, yellowfin sole (Limanda aspera) and longhead dab (Limanda proboscidea) dominated the assemblages. In 2012 and 2013, the increased presence of colder, more saline Winter Water coincided with a shift to polar cod-dominated assemblages. In 2014 and 2015, water masses were less spatially defined and different assemblages, characterized by Arctic sand lance (Ammodytes hexapterus) and saffron cod (Eleginus gracilis), were detected than previous years. The greatest range in sizes of polar cod was observed in 2014, as well as the highest number of juveniles and age-1 individuals were collected. The biophysical patterns identified here support the strong connection between interannual oceanographic conditions and ichthyoplankton assemblages which reflect the importance of continuous, multi-year surveys to document assemblage changes in the Arctic.

Published
2019
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6. Physical and biological drivers of zooplankton communities in the Chukchi Sea

Author

David G. Kimmel, Jeffrey M. Napp, Adam Spear, Jessica Randall, Phyllis J. Stabeno, and Janet T. Duffy-Anderson

Subjects
0106 biological sciences, Water mass, Advection, 010604 marine biology & hydrobiology, Community structure, Forcing (mathematics), Biology, biology.organism_classification, 010603 evolutionary biology, 01 natural sciences, Zooplankton, Current (stream), Oceanography, Abundance (ecology), General Agricultural and Biological Sciences, Copepod
Abstract

The physical environments of high-latitude systems are rapidly changing. For example, the Chukchi Sea has experienced increased water temperatures, advection from the Bering Sea, declines in sea-ice concentration, earlier spring ice retreat, and delayed fall ice formation. This physical restructuring is expected to impact ecosystem structure and function. In this study, a series of bio-oceanographic research surveys were conducted in the summers of 2010, 2011, and 2012 to characterize the physical environment and to examine the influence of physical forcing on zooplankton community distribution and abundance. Results revealed yearly advection from the Bering Sea influenced zooplankton community structure, but this influence became less apparent in the northeastern Chukchi due to changes in current speeds and patterns. Decreased advection and later ice retreat in colder years resulted in zooplankton communities that exhibited more diversity, had higher abundances of the lipid-rich copepod Calanus glacialis, and were less closely related to water masses advected from the south. These findings suggest more localized processes are influencing zooplankton community structure in the Chukchi Sea. Increased inflow of water into the Chukchi is predicted with increased warming in the Arctic and changes in food-web structure and function are likely to result.

Published
2019
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7. Mediastinitis after pediatric cardiac surgery: a 15-year experience at a single institution

Author

Timothy F. Feltes, Jessica Randall, Jeffrey D. Friedman, Tia A. Tortoriello, Antonio R. Mott, Charles D. Fraser, and E. Dean McKenzie

Subjects
Pulmonary and Respiratory Medicine, Heart Defects, Congenital, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Risk Assessment, Severity of Illness Index, Surgical Flaps, Cohort Studies, Pharmacotherapy, medicine.artery, Severity of illness, Medicine, Humans, Surgical Wound Infection, Cardiac Surgical Procedures, Child, Retrospective Studies, Heart transplantation, Wound Healing, business.industry, Infant, Newborn, Infant, Retrospective cohort study, medicine.disease, Mediastinitis, Combined Modality Therapy, Surgery, Cardiac surgery, Anti-Bacterial Agents, Treatment Outcome, Debridement, Anesthesia, Bacteremia, Child, Preschool, Pulmonary artery, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

The spectrum of sternal wound infections after cardiac surgery ranges from superficial infections to a deep sternal infection known as mediastinitis. Mediastinitis is a rare but clinically relevant source of postoperative morbidity and mortality in adult and pediatric patients after cardiac surgery.We retrospectively identified all patients diagnosed with mediastinitis after cardiac surgery from January 1987 to December 2002 (17 patients/7,616 surgeries = 0.2%). Demographic data, cardiac diagnosis, cardiac surgery, hospital length of stay, associated medical diagnosis, and surgical treatment for mediastinitis were collected.Fifteen pediatric patients (age18 years) were diagnosed with mediastinitis (mean age at diagnosis 37.5 months, range 21 days to 17 years. The median postoperative day of diagnosis was 14 days (6 to 50 days). The most common organism was Staphylococcus species (n = 9). Six patients had an associated bacteremia. The median hospital length of stay for all patients was 42.5 days (range 16 to 163 days). The hospital mortality was 1 of 15 (6%). Each patient was treated with intravenous antibiotics; sternal debridement; and rectus abdominus flap reconstruction (n = 7), pectoralis muscle flap reconstruction (n = 3), omentum reconstruction (n = 1), or primary sternal closure (n = 4). Three patients have undergone redo-sternotomy with orthotopic heart transplantation, bidirectional cavopulmonary anastomosis, and replacement of a right ventricle to pulmonary artery homograft.Timely diagnosis, aggressive sternal debridement, and liberal use of rotational muscle flaps can potentially minimize the morbidity and mortality in pediatric postoperative cardiac patients. Subsequent redo-sternotomy has not been problematic.

Published
2003

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