Article
Cell Biology
Pei-Yao Liu, Chih-Yuan Chen, Yu-Lung Lin, Chien-Ming Lin, Wen-Chiuan Tsai, Yu-Ling Tsai, Gu-Jiun Lin, Yu-Guang Chen, Shih-Yun Wang, Rui-Nong Sun, Yu-Chuan Huang, Hung Chang, Ying-Chuan Chen
Summary: Acute lung injury (ALI) is a severe condition characterized by pulmonary inflammation, barrier disruption, and oedema. This study identifies RNF128 as a negative regulator of ALI by inhibiting neutrophil activation, reducing pro-inflammatory cytokines, and targeting TLR4 for degradation. Overexpression of RNF128 alleviates lung damage and reduces inflammatory cell infiltration, suggesting its potential as a therapeutic candidate for ALI.
CELL DEATH & DISEASE
(2023)
Article
Critical Care Medicine
Lindsay Rein, Karel Calero, Ronak Shah, Charles Ojielo, Kristin M. Hudock, Saba Lodhi, Farid Sadaka, Shashi Bellam, Christopher Palma, David N. Hager, Jeannie Daniel, Richard Schaub, Kevin O'Hayer, Nicole M. Theodoropoulos
Summary: This study evaluated the safety and efficacy of the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib in COVID-19-associated acute respiratory distress syndrome requiring mechanical ventilation. The results showed that ruxolitinib did not significantly reduce the 28-day mortality rate compared to placebo. However, there were numerical improvements with ruxolitinib in secondary outcomes.
CRITICAL CARE MEDICINE
(2022)
Article
Immunology
Jiarun Gu, Xufei Ran, Jin Deng, Anqiang Zhang, Guoxuan Peng, Juan Du, Dalin Wen, Baowei Jiang, Fei Xia
Summary: The study demonstrates that glycyrrhizin (GL) can improve sepsis-induced acute respiratory distress syndrome (ARDS), reduce the formation of neutrophil extracellular traps (NETs) in lung tissues, and may exert its effects by inhibiting the HMGB1/TLR9 pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiaoting Yang, Jing Wang, Wei Liu
Summary: In this study, molecular markers associated with type II alveolar epithelial cell injury in acute lung injury (ALI) were identified using bioinformatics methods. The results provide new insights for the diagnosis and treatment of ALI/ARDS.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Rachita Panda, Fernanda V. S. Castanheira, Jared M. Schlechte, Bas G. J. Surewaard, Hanjoo Brian Shim, Amanda Z. Zucoloto, Zdenka Slavikova, Bryan G. Yipp, Paul Kubes, Braedon McDonald
Summary: Acute respiratory distress syndrome (ARDS) is a life-threatening syndrome caused by immune activation and resulting lung damage. SARS-CoV-2 infection has become the main cause of ARDS worldwide, and neutrophils and their effector functions are believed to drive immune-mediated lung injury in COVID-19 ARDS. A study found that COVID-19 ARDS patients have a distinct functional landscape of neutrophils, providing a potential target for adjunctive immunotherapy.
Article
Pharmacology & Pharmacy
Ting- Kao, Po-Jen Chen, Yi-Hsuan Wang, Hsin-Hui Tseng, Shih-Hsin Chang, Tian-Shung Wu, Sien-Hung Yang, Yen-Tung Lee, Tsong-Long Hwang
Summary: Bletinib demonstrates therapeutic effects in human neutrophil inflammation and LPS-induced ALI in mice by regulating the SFK-Btk-Vav pathway and ameliorating prominent inflammatory changes in the lung tissue. Further optimization of bletinib may lead to the development of new therapeutic agents for inflammatory diseases.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Plant Sciences
JunMei Wang, Chunxiu Ren, WenHui Bi, Wuliji Batu
Summary: Glycyrrhiza glabra L. is a widely used traditional Chinese medicine with various therapeutic effects. This study found that its active ingredient, glycyrrhizin, has anti-inflammatory effects and can alleviate acute lung injury (ALI) by interfering with the NF-κB/NLRP3 signaling pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yen-Tung Lee, Yu-Li Chen, Yi-Hsuan Wu, Ih-Sheng Chen, Hsun-Shuo Chang, Yi-Hsuan Wang, Shih-Hsin Chang, Yi-Hsiu Wu, Ting- Kao, Huang-Ping Yu, Tsong-Long Hwang
Summary: A natural lignan called meso-dihydroguaiaretic acid (MDGA) has been found to inhibit inflammatory responses in human neutrophils and reduce lung damage associated with acute respiratory distress syndrome (ARDS) in mice. This study suggests that MDGA has anti-inflammatory effects and free-radical scavenging activity, making it a potential lead for developing new therapeutics for ARDS.
Article
Cardiac & Cardiovascular Systems
Thomas S. Metkus, Lori J. Sokoll, Andreas S. Barth, Matthew J. Czarny, Allison G. Hays, Charles J. Lowenstein, Erin D. Michos, Eric P. Nolley, Wendy S. Post, Jon R. Resar, David R. Thiemann, Jeffrey C. Trost, Rani K. Hasan
Summary: The study found that over 50% of intubated patients with severe COVID-19 had myocardial injury, which was associated with a higher mortality rate. Myocardial injury in COVID-19 was closely related to baseline comorbidities, age, and multisystem organ dysfunction. Compared with ARDS patients without COVID-19, COVID-19 patients were older and had poorer cardiac function, but had a lower incidence of myocardial injury.
Article
Immunology
Jian Xie, Cheng-long Zhu, Xiao-jian Wan, Zhen-zhen Zhao, Yan Meng, Peng Li, Yu Guo, Qiang Liu, Jin-jun Bian, Xiao-ming Deng, Jia-feng Wang
Summary: The cleavage of GSDMD in neutrophils is crucial for NET release during ARDS. Inhibition of GSDMD reduces NET production and attenuates lung injury, while extrinsic NETs may reverse the protective effect of GSDMD inhibition.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Maria Gabriella Matera, Paola Rogliani, Josuel Ora, Luigino Calzetta, Mario Cazzola
Summary: Preclinical research on NE inhibitors has shown promising results, but sivelestat is currently the only approved treatment for ALI/ARDS. Further studies are needed to identify specific patient subsets who may benefit from NE inhibitor treatment and to develop more advanced NE inhibitors.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2023)
Article
Critical Care Medicine
Nadir Yehya, Hossein Fazelinia, Gladys G. Lawrence, Lynn A. Spruce, Mark Mai, G. Scott Worthen, Jason D. Christie
Summary: This study found that plasma nucleosomes are associated with the severity of acute respiratory distress syndrome (ARDS) in children, as well as with nonpulmonary organ failures. Nucleosomes were also linked to higher mortality rates and fewer ventilator-free days in the pediatric ARDS patients. Proteomic analysis further showed elevated levels of core nucleosome histones in septic children with ARDS.
CRITICAL CARE MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jie Zhao, Ningxin Zhen, Qichao Zhou, Jian Lou, Wei Cui, Gensheng Zhang, Baoping Tian
Summary: Acute respiratory distress syndrome (ARDS) is a life-threatening condition in critically ill patients with unclear mechanisms. Neutrophil extracellular traps (NETs) released by activated neutrophils have a critical role in inflammatory injury. This study investigated the role of NETs and the underlying mechanism in acute lung injury (ALI). The findings suggest that targeting cGAS-STING may be a potential therapeutic approach for ARDS/ALI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Qianqian Li, Rui Li, Hanlin Yin, Suli Wang, Bei Liu, Jun Li, Mi Zhou, Qingran Yan, Liangjing Lu
Summary: This study evaluated the potential of IRAK4 inhibitors as a treatment for ARDS-cytokine release syndrome (CRS). The results showed that BAY-1834845 effectively prevented lung injury and improved existing ARDS when combined with dexamethasone. Compared to other drugs, BAY-1834845 reduced inflammatory cell infiltration and neutrophil count. Interestingly, BAY-1834845 preserved the signatures of naive lymphocytes and stromal cells.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Allergy
Jessica Oh, Elizabeth Garabedian, Ramsay Fuleihan, Charlotte Cunningham-Rundles
Summary: Activated phosphoinositide 3-kinase delta syndrome is a combined primary immunodeficiency characterized by various manifestations such as respiratory infections, lymphadenopathy, and developmental delay. Clinical features differ between PIK3CD and PIK3R1 patients, with a higher frequency of asthma observed in the PIK3CD cohort.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Article
Biochemistry & Molecular Biology
Wanwisa Dejnirattisai, Jiandong Huo, Daming Zhou, Jiri Zahradnik, Piyada Supasa, Chang Liu, Helen M. E. Duyvesteyn, Helen M. Ginn, Alexander J. Mentzer, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Aiste Dijokaite, Suman Khan, Ori Avinoam, Mohammad Bahar, Donal Skelly, Sandra Adele, Sile Ann Johnson, Ali Amini, Thomas G. Ritter, Chris Mason, Christina Dold, Daniel Pan, Sara Assadi, Adam Bellass, Nicola Omo-Dare, David Koeckerling, Amy Flaxman, Daniel Jenkin, Parvinder K. Aley, Merryn Voysey, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid-Correa, Marilda M. Siqueira, Vicky Baillie, Natali Serafin, Gaurav Kwatra, Kelly Da Silva, Shabir A. Madhi, Marta C. Nunes, Tariq Malik, Peter J. M. Openshaw, J. Kenneth Baillie, Malcolm G. Semple, Alain R. Townsend, Kuan-Ying A. Huang, Tiong Kit Tan, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Bede Constantinides, Hermione Webster, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, Gideon Schreiber, David Stuart, Gavin R. Screaton
Summary: On November 24, 2021, the sequence of a new SARS-CoV-2 variant, Omicron-B.1.1.529, was announced. Compared to previous variants, Omicron has a higher number of mutations in the Spike (S) protein. Serum neutralization of Omicron by individuals vaccinated or previously infected with Alpha, Beta, Gamma, or Delta variants is significantly reduced or ineffective. Third vaccine doses can boost neutralization titers against Omicron, and high titers are observed in both vaccinated individuals and those infected with the Delta variant. Most potent monoclonal antibodies and antibodies under development are unable to effectively neutralize Omicron due to mutations in its Spike protein. Omicron has structural changes compared to earlier viruses and utilizes mutations that enhance its binding to ACE2, allowing for immune escape. This results in a large number of mutations in the ACE2 binding site and a rebalancing of receptor affinity similar to earlier pandemic viruses.
Article
Cardiac & Cardiovascular Systems
Tom Norris, Cameron Razieh, Francesco Zaccardi, Thomas Yates, Nazrul Islam, Clare L. Gillies, Yogini Chudasama, Alex Rowlands, Melanie J. Davies, Gerry P. McCann, Amitava Banerjee, Carolyn S. P. Lam, Annemarie B. Docherty, Peter J. M. Openshaw, J. Kenneth Baillie, Malcolm Gracie Semple, Claire Alexandra Lawson, Kamlesh Khunti
Summary: In hospitalized patients with COVID-19, cardiovascular complications or death impacts nearly half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidity.
Article
Genetics & Heredity
Chiara Fallerini, Nicola Picchiotti, Margherita Baldassarri, Kristina Zguro, Sergio Daga, Francesca Fava, Elisa Benetti, Sara Amitrano, Mirella Bruttini, Maria Palmieril, Susanna Croci, Mirjam Lista, Giada Beligni, Floriana Valentino, Ilaria Meloni, Marco Tanfoni, Francesca Minnai, Francesca Colombo, Enrico Cabri, Maddalena Fratelli, Chiara Gabbi, Stefania Mantovani, Elisa Frullanti, Marco Gori, Francis P. Crawley, Guillaume Butler-Laporte, Brent Richards, Hugo Zeberg, Miklos Lipcsey, Michael Hultstrom, Kerstin U. Ludwig, Eva C. Schulte, Erola Pairo-Castineira, John Kenneth Baillie, Axel Schmidt, Robert Frithiof, Francesca Mari, Alessandra Renieri, Simone Furini
Summary: The study developed a machine-learning model using common and rare exonic variants to predict COVID-19 severity. By selecting key Boolean features and combining them into an Integrated PolyGenic Score, the model offers insights into the genetic contribution to disease severity. A quarter of the selected genes are sex-specific, and pathway analysis highlighted the multi-organ nature of COVID-19 severity. This model could potentially aid in diagnostics, therapeutics, and disease management at the bedside.
Article
Critical Care Medicine
G. Bellingan, F. Jacono, J. Bannard-Smith, D. Brealey, N. Meyer, D. Thickett, D. Young, A. Bentley, B. J. McVerry, R. G. Wunderink, K. C. Doerschug, C. Summers, M. Rojas, A. Ting, E. D. Jenkins
Summary: Bone marrow-derived, allogeneic, multipotent adult progenitor cells showed safety and tolerability in patients with ARDS, improving clinical outcomes and quality of life. Larger trials are needed to evaluate the therapeutic efficacy and optimal patient population based on the promising results from this trial.
INTENSIVE CARE MEDICINE
(2022)
Article
Immunology
Katharine A. Relph, Clark D. Russell, Cameron J. Fairfield, Lance Turtle, Thushan de Silva, Matthew K. Siggins, Thomas M. Drake, Ryan S. Thwaites, Simon Abrams, Shona C. Moore, Hayley E. Hardwick, Wilna Oosthuyzen, Ewen M. Harrison, Annemarie B. Docherty, Peter J. M. Openshaw, J. Kenneth Baillie, Malcolm G. Semple, Antonia Ho
Summary: Procalcitonin measurements and microbiology results were not clinically significant or diagnostically useful for bacterial coinfection in hospitalized adults with coronavirus disease 2019.
OPEN FORUM INFECTIOUS DISEASES
(2022)
Review
Critical Care Medicine
Lieuwe D. J. Bos, John G. Laffey, Lorraine B. Ware, Nanon F. L. Heijnen, Pratik Sinha, Brijesh Patel, Matthieu Jabaudon, Julie A. Bastarache, Daniel F. McAuley, Charlotte Summers, Carolyn S. Calfee, Manu Shankar-Hari
Summary: The pathophysiology of acute respiratory distress syndrome (ARDS) leads to biological heterogeneity, making it difficult for pharmacological interventions to improve patient outcomes. This manuscript provides an overview of potential methods to capture the underlying biological heterogeneity of ARDS and discusses how this information could be used to redefine ARDS.
INTENSIVE CARE MEDICINE EXPERIMENTAL
(2022)
Correction
Multidisciplinary Sciences
Steven A. Kemp, Dami A. Collier, Rawlings P. Datir, Isabella A. T. M. Ferreira, Salma Gayed, Aminu Jahun, Myra Hosmillo, Chloe Rees-Spear, Petra Mlcochova, Ines Ushiro Lumb, David J. Roberts, Anita Chandra, Nigel Temperton, Katherine Sharrocks, Elizabeth Blane, Yorgo Modis, Kendra E. Leigh, John A. G. Briggs, Marit J. van Gils, Kenneth G. C. Smith, John R. Bradley, Chris Smith, Rainer Doffinger, Lourdes Ceron-Gutierrez, Gabriela Barcenas-Morales, David D. Pollock, Richard A. Goldstein, Anna Smielewska, Jordan P. Skittrall, Theodore Gouliouris, Ian G. Goodfellow, Effrossyni Gkrania-Klotsas, Christopher J. R. Illingworth, Laura E. Mccoy, Ravindra K. Gupta
Article
Respiratory System
Jatin Patel, Damon Bass, Albertus Beishuizen, Xavier Bocca Ruiz, Hatem Boughanmi, Anthony Cahn, Hugo Colombo, Gerard J. Criner, Katherine Davy, Javier de-Miguel-Diez, Pablo A. Doreski, Sofia Fernandes, Bruno Francois, Anubha Gupta, Kate Hanrott, Timothy Hatlen, Dave Inman, John D. Isaacs, Emily Jarvis, Natalia Kostina, Tatiana Kropotina, Jean-Claude Lacherade, Divya Lakshminarayanan, Pedro Martinez-Ayala, Charlen McEvoy, Ferhat Meziani, Mehran Monchi, Sumanta Mukherjee, Rosana Munoz-Bermudez, Jessica Neisen, Ciara O'Shea, Gaetan Plantefeve, Lorrie Schifano, Lee E. Schwab, Zainab Shahid, Michinori Shirano, Julia E. Smith, Eduardo Sprinz, Charlotte Summers, Nicolas Terzi, Mark A. Tidswell, Yuliya Trefilova, Russell Williamson, Duncan Wyncoll, Mark Layton
Summary: Treatment with anti-interleukin-6 did not significantly reduce mortality or respiratory failure in COVID-19 patients, but showed a reduction in inflammatory markers and had an acceptable safety profile.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Review
Immunology
Emily Naish, Alexander J. T. Wood, Andrew P. Stewart, Matthew Routledge, Andrew Conway Morris, Edwin R. Chilvers, Katharine M. Lodge
Summary: Neutrophils, the most abundant circulating leukocytes, play a crucial role in the initial innate immune response to infection. They eliminate pathogens through phagocytosis and a complex interplay of multiple systems and mechanisms within the phagosome creates an antimicrobial environment. However, gaps in knowledge and controversies exist regarding how neutrophil phagosomes optimize pathogen killing.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Medicine, General & Internal
Fergus W. Hamilton, Matt J. Thomas, David Arnold, Tom Palmer, Ed Moran, Alexander J. Mentzer, Nick Maskell, Kenneth M. Baillie, Charlotte Summers, Aroon Hingorani, Alasdair MacGowan, Golam M. J. Khandaker, Ruth Mitchell, George Davey Smith, Peter Ghazal, Nicholas J. Timpson
Summary: IL6R blockade is associated with a decreased risk of sepsis and improved survival, similar to its effect in severe COVID-19. Randomized controlled trials of IL-6 receptor antagonists in sepsis should be considered.
Article
Biochemistry & Molecular Biology
Varsha Ramineni, Philip Millroth, Lalitha Iyadurai, Thomas Jaki, Jonathan Kingslake, Julie Highfield, Charlotte Summers, Michael B. Bonsall, Emily A. Holmes
Summary: ICU staff who have experienced work-related traumatic events during the COVID-19 pandemic often suffer from intrusive memories (IMs). In this study, a novel behavioral intervention was developed to reduce the number of IMs for ICU staff experiencing post-traumatic symptoms. Using Bayesian statistical approaches, a digitized version of the intervention was evaluated for remote delivery and showed a significant positive treatment effect in reducing IMs.
MOLECULAR PSYCHIATRY
(2023)
Article
Pharmacology & Pharmacy
Malcolm Begg, Augustin Amour, Emily Jarvis, Teresa Tang, Sara Santos Franco, Andrew Want, Misba Beerahee, Disala Fernando, Yakshitha Karkera, Clare Sander, Thomas Southworth, Dave Singh, Jonathan Clark, Sergey Nejentsev, Klaus Okkenhaug, Alison Condliffe, Anita Chandra, Anthony Cahn, Edward Banham Hall
Summary: Activated PI3K8 Syndrome (APDS) is a rare genetic disorder that causes recurring pulmonary infections due to mutations in the p110 delta isoform of phosphoinositide 3-kinase (PI3K8). An open-label trial was conducted to evaluate the safety and efficacy of the inhaled inhibitor nemiralisib in APDS patients. Despite an acceptable safety profile, nemiralisib did not show significant effects on lung or systemic biomarkers, indicating that inhaled treatment with nemiralisib may not benefit APDS patients.
PULMONARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Respiratory System
Rohit Saha, Tai Pham, Pratik Sinha, Manoj Maddali, Giacomo Bellani, Eddy Fan, Charlotte Summers, Abdel Douiri, Gordon D. Rubenfeld, Carolyn S. Calfee, John Gerard Laffey, Daniel Francis McAuley, Manu Shankar-Hari, LUNG SAFE Investigators
Summary: This study estimated the mortality rate of acute respiratory distress syndrome (ARDS) using a case-control matching method and analyzed it in different patient subgroups. The results showed that there were variations in the mortality rate of ARDS among different subgroups. Depending on the severity of hypoxemia, the number of lung quadrants involved, and the inflammatory phenotype, the mortality rate of ARDS ranged from 20.9% to 38.0%.
Article
Psychiatry
Lalitha Iyadurai, Julie Highfield, Marie Kanstrup, Alfred Markham, Varsha Ramineni, Boliang Guo, Thomas Jaki, Jonathan Kingslake, Guy M. Goodwin, Charlotte Summers, Michael B. Bonsall, Emily A. Holmes
Summary: We evaluated the impact of a brief remotely-delivered digital imagery-competing task intervention on reducing intrusive memories and improving mental health and functioning for ICU staff during the COVID-19 pandemic.
TRANSLATIONAL PSYCHIATRY
(2023)
Meeting Abstract
Rheumatology
Noelle Pisacano, Stephen P. McAdoo, Jochen Guck, Charles D. Pusey, Edwin R. Chilvers, Andrew S. Cowburn, Katharine M. Lodge, Maria F. Prendecki
ARTHRITIS & RHEUMATOLOGY
(2022)