Review
Cell Biology
Cheng-long Zhu, Ren-qi Yao, Lu-xi Li, Peng Li, Jian Xie, Jia-feng Wang, Xiao-ming Deng
Summary: Autophagy plays a vital role in maintaining cellular homeostasis by clearing damaged mitochondria to promote mitochondrial quality control and protect against organ dysfunction in sepsis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Alba Montero-Jodra, Miguel Angel de la Fuente, Dino Gobelli, Marta Martin-Fernandez, Jesus Villar, Eduardo Tamayo, Maria Simarro
Summary: Sepsis is the leading cause of infection-related death worldwide, and there is currently no specific treatment available. This review provides an overview of the important role of endothelial cell activation and dysfunction in sepsis development, as well as the involvement of mitochondria as potential targets in experimental models.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Caspar Mewes, Julius Runzheimer, Carolin Boehnke, Benedikt Buettner, Marcus Nemeth, Jose Hinz, Michael Quintel, Ashham Mansur
Summary: This study compared the mortality and sepsis-associated organ dysfunction between patients with sepsis following surgical intervention and those with sepsis without prior surgery. The results showed that non-surgical patients had a higher mortality rate and more severe organ dysfunction compared to surgical patients. These findings have important implications for clinical decision-making, patient management, and resource allocation in sepsis care.
Article
Critical Care Medicine
Hye Ju Yeo, Young Seok Lee, Tae Hwa Kim, Jin Ho Jang, Heung Bum Lee, Dong Kyu Oh, Mi Hyeon Park, Chae-Man Lim, Woo Hyun Cho
Summary: This prospective, multicenter, observational study aimed to investigate the effect of initiating vasopressor within 1 hour of fluid loading on mortality and organ dysfunction in patients with septic shock. The results showed that early vasopressor use was associated with higher 28-day mortality and higher Sequential Organ Failure Assessment score and lactate level on day 3 in the ICU.
CRITICAL CARE MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Shaymaa Ramzy Senousy, Mahmoud El-Daly, Ahmed R. N. Ibrahim, Mohamed Montaser A. Khalifa, Al-Shaimaa F. Ahmed
Summary: Infliximab (IFX) and celecoxib (CLX) have similar effects in ameliorating organ damage caused by sepsis, improving lung, kidney, and liver injuries, reducing oxidative stress, enhancing antioxidant defense, and reducing serum cytokines.
Review
Immunology
Ri Wen, Yong-Ping Liu, Xiao-Xu Tong, Tie-Ning Zhang, Ni Yang
Summary: This review summarizes the roles and regulatory mechanisms of pyroptosis in sepsis and sepsis-associated organ dysfunction (SAOD). Moderate pyroptosis promotes the clearance of pathogens, whereas excessive activation of pyroptosis leads to host immune response disorders and SAOD. Transcription factors, non-coding RNAs, epigenetic modifications, and post-translational modifications are involved in the regulation of pyroptosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Francesco Pallotti, Christian Bergamini, Costanza Lamperti, Romana Fato
Summary: Coenzyme Q (CoQ) is a crucial component of the respiratory chain in eukaryotic cells, functioning as an electron transporter in mitochondrial respiration. Its cellular functions are diverse, including limiting the harmful effect of free radicals and participating in the aging process. Recent studies also suggest that CoQ contributes to suppressing a type of iron-dependent programmed cell death characterized by lipid peroxidation. Understanding the multiple functions of CoQ is essential for its potential therapeutic use in diseases associated with primary or secondary CoQ deficiency.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yun-Seok Kim, Han A. Reum Lee, Min Ji Lee, Ye Jin Park, Sehwan Mun, Chang June Yune, Tae Nyoung Chung, Jinkun Bae, Mi Jin Kim, Yong-Soo Choi, Kyuseok Kim
Summary: Previous studies have shown that mitochondrial transplantation has immune modulatory effects in the sepsis model. The effects of mitochondrial transplantation on the sepsis model may vary depending on the cell type from which mitochondria are isolated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Matthew Kim, Azadeh Nikouee, Yuxiao Sun, Qing-Jun Zhang, Zhi-Ping Liu, Qun Sophia Zang
Summary: The study suggests that the Parkin/PINK1 mitophagy pathway is involved in the regulation of cardiac mitochondria-associated membranes (MAMs) during endotoxemia. However, the W402A point mutation is not sufficient to alleviate endotoxemia-induced cardiomyopathy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Yuichi Hattori, Kohshi Hattori, Takuji Machida, Naoyuki Matsuda
Summary: Vascular endotheliitis plays a crucial role in immune responses, inflammation, and infectious pathologies. It is strongly associated with the pathogenesis of diseases such as COVID-19 and sepsis. Protecting endothelial cells and reversing vascular endotheliitis can be the main therapeutic goal for these diseases.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Yi-Feng Wang, Jia-Wei Li, Da-Peng Wang, Ke Jin, Jiao-Jie Hui, Hong-Yang Xu
Summary: Intestinal barrier injury and hyperglycemia are common in patients with sepsis. Hyperglycemia is an independent risk factor for intestinal barrier injury. Some anti-hyperglycemic agents can improve intestinal barrier function and are beneficial in managing sepsis-induced organ dysfunction.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Multidisciplinary Sciences
Lisa Mellhammar, Louise Thelaus, Sixten Elen, Jane Fisher, Adam Linder
Summary: This study found that in severe COVID-19 patients, Heparin binding protein (HBP) is elevated before the onset of organ dysfunction. The analysis of HBP concentration using a point-of-care test can be used as a prognostic marker in COVID-19 patients in clinical settings.
Review
Critical Care Medicine
Sebastien Preau, Dominique Vodovar, Boris Jung, Steve Lancel, Lara Zafrani, Aurelien Flatres, Mehdi Oualha, Guillaume Voiriot, Youenn Jouan, Jeremie Joffre, Fabrice Huel, Nicolas De Prost, Stein Silva, Eric Azabou, Peter Radermacher
Summary: Organ dysfunction in sepsis is associated with impaired metabolism and mitochondrial dysfunction, which could lead to new diagnostic and therapeutic approaches. These findings may help identify distinct subgroups of sepsis and develop personalized treatment strategies, while also serving as bioenergetic targets for metabolism- and mitochondria-targeted treatments in the future.
ANNALS OF INTENSIVE CARE
(2021)
Review
Critical Care Medicine
Kusum Menon, Luregn J. Schlapbach, Samuel Akech, Andrew Argent, Paolo Biban, Enitan D. Carrol, Kathleen Chiotos, Mohammod Jobayer Chisti, Idris V. R. Evans, David P. Inwald, Paul Ishimine, Niranjan Kissoon, Rakesh Lodha, Simon Nadel, Claudio Flauzino Oliveira, Mark Peters, Benham Sadeghirad, Halden F. Scott, Daniela C. de Souza, Pierre Tissieres, R. Scott Watson, Matthew O. Wiens, James L. Wynn, Jerry J. Zimmerman, Lauren R. Sorce
Summary: The study aimed to determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with sepsis, severe sepsis, or septic shock in children with infection, as well as multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. The findings revealed significant associations between multiple markers of organ dysfunction and the outcomes of interest.
CRITICAL CARE MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Franz-Simon Centner, Jochen J. Schoettler, Kathrin Brohm, Sonani Mindt, Evelyn Jaeger, Bianka Hahn, Tanja Fuderer, Holger A. Lindner, Verena Schneider-Lindner, Joerg Krebs, Michael Neumaier, Manfred Thiel
Summary: A common final pathway of pathogenetic mechanisms in septic organ dysfunction and death is a lack or non-utilization of oxygen. Plasma concentrations of lactate serve as surrogates for the oxygen-deficiency-induced imbalance between energy supply and demand. S-adenosylhomocysteine (SAH) appears to be a better contributor to the prediction of septic organ dysfunction and death than lactate in critically ill patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Health Care Sciences & Services
Alyssa M. Pandolfo, Robert Horne, Yogini Jani, Tom W. Reader, Natalie Bidad, David Brealey, Virve Enne, David M. Livermore, Vanya Gant, Stephen J. Brett
Summary: ICU clinicians' antibiotic decisions are influenced by their judgement of necessity for prescribing/not prescribing and their concerns about potential adverse consequences. Beliefs and perceptions strongly influence clinicians' views on antibiotic necessity, with clinicians often erring on the side of caution in uncertain situations.
BMJ QUALITY & SAFETY
(2022)
Review
Critical Care Medicine
Daniel A. Hofmaenner, Mervyn Singer
Summary: Medical practice is often guided by dogma without sufficient evidence. Clinicians rely on engrained treatment strategies, even though the supporting evidence may be distorted or overlooked. Critical reflection and prospective studies are necessary to improve current practices.
INTENSIVE CARE MEDICINE
(2022)
Review
Infectious Diseases
Muska Miller, Mervyn Singer
Summary: While antibiotics play a crucial role in treating infections, their modulation of the immune system can have harmful effects on pathogen clearance and immune functionality, increasing the risk of secondary infection. These adverse consequences may be mediated, in part, through effects on the compromised functioning of mitochondria, which is already affected by the underlying septic process.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Review
Infectious Diseases
Prashant Nasa, Elie Azoulay, Arunaloke Chakrabarti, Jigeeshu Divatia, Ravi Jain, Camilla Rodrigues, Victor Rosenthal, Waleed Alhazzani, Yaseen M. Arabi, Jan Bakker, Matteo Bassetti, Jan De Waele, George Dimopoulos, Bin Du, Sharon Einav, Laura Evans, Simon Finfer, Claude Guerin, Naomi E. Hammond, Samir Jaber, Ruth M. Kleinpell, Younsuck Koh, Marin Kollef, Mitchell M. Levy, Flavia R. Machado, Jordi Mancebo, Ignacio Martin-Loeches, Mervyn Mer, Michael S. Niederman, Paolo Pelosi, Anders Perner, John Peter, Jason Phua, Lise Piquilloud, Mathias W. Pletz, Andrew Rhodes, Marcus J. Schultz, Mervyn Singer, Jean-Francois Timsit, Balasubramanian Venkatesh, Jean-Louis Vincent, Tobias Welte, Sheila Myatra
Summary: There is a wide variation in the clinical practice of infection control and prevention for SARS-CoV-2 in ICU. International experts have developed consensus statements on infection control, including 25 clinical practice statements. However, consensus has not been reached on the optimal return to work criteria for healthcare workers infected with SARS-CoV-2 or the acceptable disinfection strategy for heat-sensitive instruments used for airway management of patients with SARS-CoV-2 infection. Further research is needed to address these uncertainties.
LANCET INFECTIOUS DISEASES
(2022)
Article
Critical Care Medicine
Pietro Arina, Matteo Sorge, Andrea Gallo, Vittoria Di Mauro, Nicoletta Vitale, Paola Cappello, Luca Brazzi, Maria Barandalla-Sobrados, James Cimino, V. Marco Ranieri, Fiorella Altruda, Mervyn Singer, Daniele Catalucci, Mara Brancaccio, Vito Fanelli
Summary: This study identifies the AKT/Melusin pathway as a key player in preserving cardiac function in sepsis-induced cardiomyopathy. The cell-permeable mimetic peptide (R7W-MP) represents a potential therapeutic option for this condition.
Editorial Material
Respiratory System
Bin Du, Chunting Wang, Mervyn Singer
JOURNAL OF THORACIC DISEASE
(2022)
Review
Immunology
Sang Ho Choi, Antoni Cesar, Timothy Arthur Chandos Snow, Naveed Saleem, Nishkantha Arulkumaran, Mervyn Singer
Summary: This study found that the efficacy of doxycycline is comparable to macrolides or fluoroquinolones in adult patients with mild-to-moderate community-acquired pneumonia (CAP), suggesting that it is a viable treatment option. However, larger trials are needed to confirm these findings due to the lack of recent studies.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Critical Care Medicine
Bruno A. M. P. Besen, Otavio T. Ranzani, Mervyn Singer
INTENSIVE CARE MEDICINE
(2023)
Review
Anesthesiology
W. Pisciotta, P. Arina, D. Hofmaenner, M. Singer
Summary: Dealing with uncertain or missed diagnoses in the intensive care unit is common. It can lead to a decrease in quality of care and increase the risk of poor outcomes for affected patients. The diagnostic process is complex, especially in critically ill patients where history may be unclear and clinical features may not be specific. This review aims to analyze common causes of diagnostic errors and suggest a diagnostic framework, emphasizing the importance of debiasing strategies and multidisciplinary teamwork to improve patient care and outcomes.
Review
Critical Care Medicine
Pedro Povoa, Luis Coelho, Felipe Dal-Pizzol, Ricard Ferrer, Angela Huttner, Andrew Conway Morris, Vandack Nobre, Paula Ramirez, Anahita Rouze, Jorge Salluh, Mervyn Singer, Daniel A. Sweeney, Antoni Torres, Grant Waterer, Andre C. Kalil
Summary: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Biomarkers can be used as indicators for infection, dysregulated host response, treatment response, and can aid in prognosticating patient risk. Over 250 biomarkers have been identified and evaluated, but none can accurately differentiate between sepsis and sepsis-like syndrome.
INTENSIVE CARE MEDICINE
(2023)
Editorial Material
Medicine, General & Internal
Michael Klompas, Chanu Rhee, Mervyn Singer
Summary: This viewpoint discusses the failure of SEP-1 sepsis outcome improvement initiative by Centers for Medicare & Medicaid Services in improving patients' sepsis outcomes, and suggests shifting the focus of sepsis quality metrics from processes to outcomes.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Review
Medicine, Research & Experimental
Miranda J. Melis, Muska Miller, Vera B. M. Peters, Mervyn Singer
Summary: Sepsis is a life-threatening condition caused by an uncontrolled host response to infection, leading to organ dysfunction. It affects various body systems with fluctuations in gene transcription and downstream pathways. However, the complex nature of sepsis pathophysiology has hindered the development of new therapeutic approaches. This review highlights the impact of altered endocrine system on mitochondrial dysfunction and immune suppression, important aspects of sepsis pathophysiology.
Article
Multidisciplinary Sciences
Nishkantha Arulkumaran, Mervyn Singer, Stefan Howorka, Jonathan R. R. Burns
Summary: In this study, the authors assemble DNA subunits into structural frameworks to support the formation of membrane-based protocells and prototissues, harnessing simplicity to create complexity.
NATURE COMMUNICATIONS
(2023)
Article
Critical Care Medicine
Matthew Fish, Kate Arkless, Aislinn Jennings, Julie Wilson, Michael J. Carter, Gill Arbane, Sara Campos, Neus Novellas, Rianne Wester, Nedyalko Petrov, Umar Niazi, Barney Sanderson, Richard Ellis, Mansoor Saqi, Jo Spencer, Mervyn Singer, Rocio T. Martinez-Nunez, Simon Pitchford, Chad M. Swanson, Manu Shankar-Hari
Summary: The study aims to provide information for immunomodulation in sepsis-related critical illness by characterizing the immune trajectory of sepsis patients.
JOURNAL OF THE INTENSIVE CARE SOCIETY
(2022)
Article
Critical Care Medicine
John P. R. Moore, Yahya Shehabi, Michael C. Reade, Michael Bailey, John F. Fraser, Lauren Murray, Christopher Anstey, Mervyn Singer
Summary: This study aimed to compare the impact of early sedation with dexmedetomidine and usual sedatives on the stress response in critically ill patients on mechanical ventilation. The results showed that early sedation with dexmedetomidine had comparable effects on physiological and blood-borne parameters associated with the stress response compared to usual-care sedation.