Targeting the host response in sepsis: current approaches and future evidence

Article Medicine, General & Internal

Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A mendelian randomisation study

Fergus W. Hamilton et al.

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.

PLOS MEDICINE (2023)

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Article Critical Care Medicine

Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial

Antoine Roquilly et al.

Summary: This study aimed to investigate whether interferon gamma-1b can prevent hospital-acquired pneumonia in mechanically ventilated patients. The results showed that compared to the placebo group, treatment with interferon gamma-1b did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28, and the trial was discontinued early due to safety concerns.

INTENSIVE CARE MEDICINE (2023)

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Editorial Material Critical Care Medicine

What's new in intensive care: disease tolerance

Rachel E. Powell et al.

INTENSIVE CARE MEDICINE (2023)

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Article Medicine, General & Internal

Hydrocortisone in Severe Community-Acquired Pneumonia

Pierre-Francois Dequin et al.

Summary: This study investigates the effects of glucocorticoids on mortality in patients with severe community-acquired pneumonia. The results show that patients who received hydrocortisone had a lower risk of death by day 28 compared to those who received placebo.

NEW ENGLAND JOURNAL OF MEDICINE (2023)

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Review Immunology

Endothelial dysfunction and immunothrombosis in sepsis

Eleni Maneta et al.

Summary: Sepsis is a dangerous clinical syndrome that occurs when the body has an excessive response to infection, resulting in dysfunction of multiple organs. In sepsis, the immune system cells like neutrophils and monocytes activate the coagulation cascade, leading to clot formation in the microcirculation, known as immunothrombosis. While this process aims to protect the host, it can also cause endothelial dysfunction and microthrombotic complications that lead to organ dysfunction. Developing treatments that target endothelial immune responses and immunothrombosis is important for reducing morbidity and mortality in sepsis. Medications that modify cell-specific immune responses or inhibit platelet-endothelial interaction or platelet activation have been proposed. In this article, we discuss the mechanisms of organ-specific endothelial dysfunction and immunothrombosis in sepsis, as well as recent advances in new therapeutic approaches to improve prognosis in sepsis.

FRONTIERS IN IMMUNOLOGY (2023)

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Review Critical Care Medicine

Survival Benefits of Therapeutic Plasma Exchane in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis

Olive P. E. Lee et al.

Summary: This study aimed to summarize the role of therapeutic plasma exchange (TPE) in critically ill adults and children with severe sepsis. The results showed that TPE significantly reduced mortality in adults with severe sepsis, but had no significant effect in children.

JOURNAL OF INTENSIVE CARE MEDICINE (2023)

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Article Multidisciplinary Sciences

Tissue-specific reprogramming of glutamine metabolism maintains tolerance to sepsis

Brooks Leitner et al.

Summary: Reprogramming metabolism is important for treating sepsis-induced critical illness. This study analyzed the metabolic response of different tissues during sepsis using transcriptomics and metabolomics, revealing tissue-specific mitochondrial reprogramming. The liver showed increased energetic demands and antioxidant synthesis, while skeletal muscle and spleen exhibited unique metabolic signatures. These findings suggest that sepsis leads to tissue-specific metabolic alterations rather than global mitochondrial dysfunction.

PLOS ONE (2023)

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Review Critical Care Medicine

Efficacy and safety of adjunctive corticosteroids in the treatment of severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials

Jheng-Yan Wu et al.

Summary: This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia (sCAP). The results showed that adjunctive corticosteroids can provide survival benefits and improve clinical outcomes without increasing adverse events in patients with sCAP. However, further studies are required to confirm these findings.

CRITICAL CARE (2023)

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Review Critical Care Medicine

Efficacy of CytoSorb®: a systematic review and meta-analysis

Soeren Becker et al.

Summary: This analysis examined the efficacy of the CytoSorb (R) adsorber in various clinical settings, including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery, or recovery after cardiac arrest. The results showed that there is no evidence to support the use of the CytoSorb (R) adsorber in reducing mortality across different diagnoses in intensive care medicine.

CRITICAL CARE (2023)

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Article Critical Care Medicine

Inflammatory biomarkers to predict the prognosis of acute bacterial and viral infections

Aline H. de Nooijer et al.

Summary: Mortality in acute infections, especially sepsis, is a result of the dysregulated host response to infection. Identifying patients with increased mortality risk is challenging due to the heterogeneity in the host immune response and disease progression. Biomarkers reflecting different pathways involved in the inflammatory response can improve prediction of mortality risk by reducing heterogeneity and suggest novel strategies for patient stratification and treatment. This review provides an overview of the value of inflammatory biomarkers in predicting mortality in bacterial and viral infections.

JOURNAL OF CRITICAL CARE (2023)

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Article Critical Care Medicine

Granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients presenting sepsis-induced immunosuppression: The GRID randomized controlled trial

Charles-Herve Vacheron et al.

Summary: This study aimed to evaluate the effects of GM-CSF on ICU-acquired infections in immunosuppressed septic patients. The results showed that GM-CSF had no effect on preventing ICU-acquired infections.

JOURNAL OF CRITICAL CARE (2023)

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Article Critical Care Medicine

The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials

Baofang Liang et al.

Summary: This meta-analysis found that intravenous vitamin C (IVVC) administration can effectively improve the SOFA score and reduce the duration of vasopressor use in sepsis or septic shock patients. However, its effect on reducing short-term mortality is uncertain, and it may increase the risk of adverse events.

CRITICAL CARE (2023)

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Article Critical Care Medicine

Embracing complexity in sepsis

Alex R. R. Schuurman et al.

Summary: "Sepsis through the lens of complexity theory" is an article that discusses the importance of understanding the complexity of sepsis and highlights the role of computational modeling and network-based analysis in this regard. The article also identifies barriers in measurement, research approaches, and clinical applications and advocates for more continuous biological data collection in sepsis. The authors emphasize the importance of interdisciplinary collaboration and provide an example of an immunological predictive model that could inform personalized treatments.

CRITICAL CARE (2023)

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Article Surgery

Molecular Patterns in Acute Pancreatitis Reflect Generalizable Endotypes of the Host Response to Systemic Injury in Humans

Lucile P. A. Neyton et al.

Summary: This study identified four distinct and stable molecular endotypes in acute pancreatitis (AP), with some endotypes sharing similarities with endotypes in acute respiratory distress syndrome (ARDS). This finding suggests the presence of generalizable molecular patterns in diverse presentations of critical illness.

ANNALS OF SURGERY (2022)

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Article Immunology

Effect of Bone Marrow Mesenchymal Stromal Cell Therapies in Rodent Models of Sepsis: A Meta-Analysis

Lite Ge et al.

Summary: This meta-analysis study found that naive MSC(M) therapy can decrease mortality in rodent models of sepsis. However, there is significant heterogeneity among the studies and several knowledge gaps, including the lack of large animal studies and uncertainty regarding the optimal dose of MSC(M) transplantation in sepsis.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Medicine, General & Internal

ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol

Antigone Kotsaki et al.

Summary: This study aims to investigate the efficacy of precision immunotherapy on sepsis patients, focusing on the phenotypes of MALS and immunoparalysis. The study utilizes a randomized placebo-controlled double-blind design and stratifies patients using biomarkers. The results will be published in peer-reviewed journals.

BMJ OPEN (2022)

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Article Cell Biology

Sepsis, pyruvate, and mitochondria energy supply chain shortage

Charles E. McCall et al.

Summary: This study reveals that phosphorylation and deactivation of mitochondrial pyruvate dehydrogenase complex contribute to the disruption of the tricarboxylic cycle during sepsis. By inhibiting pyruvate dehydrogenase kinases, the use of dichloroacetate can stimulate mitochondrial energetics and improve disease tolerance and survival rate.

JOURNAL OF LEUKOCYTE BIOLOGY (2022)

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Review Medicine, General & Internal

Immunopathophysiology of human sepsis

W. Joost Wiersinga et al.

Summary: Sepsis is a poorly defined syndrome that is a major cause of morbidity and mortality worldwide. This review discusses the immunopathogenesis of sepsis, highlighting recent pathophysiological findings and the role of the gut microbiome in sepsis immunity.

EBIOMEDICINE (2022)

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Article Multidisciplinary Sciences

Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19

Fotios Karagiannis et al.

Summary: This study found that impaired production of beta-hydroxybutyrate (BHB) is associated with severe COVID-19 respiratory distress syndrome. BHB promotes the survival and interferon-gamma production of CD4(+) T cells. BHB acts as an alternative carbon source, fueling oxidative phosphorylation and maintaining the redox balance.

NATURE (2022)

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Article Medicine, General & Internal

Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit

Francois Lamontagne et al.

Summary: A study on the use of intravenous vitamin C in adult sepsis patients receiving vasopressor therapy in the ICU showed that there is a higher risk of death or persistent organ dysfunction compared to placebo.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Medicine, General & Internal

Effects of enrichment strategies on outcome of adrecizumab treatment in septic shock: Post-hoc analyses of the phase II adrenomedullin and outcome in septic shock 2 trial

Dirk van Lier et al.

Summary: In septic shock patients with high ADM levels, a further post-hoc analysis based on cDPP3 may indicate that therapeutic efficacy is more pronounced in patients with lower cDPP3 levels.

FRONTIERS IN MEDICINE (2022)

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Article Cell Biology

Toward personalized immunotherapy in sepsis: The PROVIDE randomized clinical trial

Konstantinos Leventogiannis et al.

Summary: This study investigates the role of immune activation in guiding targeted immunotherapy for sepsis. Using biomarkers such as ferritin and HLA-DR/CD14, sepsis patients were classified into three immune classifications: macrophage activation-like syndrome (MALS), immunoparalysis, and intermediate. The results show that MALS and immunoparalysis are associated with higher mortality rates, while immunotherapy can improve patient survival.

CELL REPORTS MEDICINE (2022)

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Article Critical Care Medicine

Renaissance of glucocorticoids in critical care in the era of COVID-19: ten urging questions

Martin S. Winkler et al.

Summary: A clear indication for the use of glucocorticosteroids (GCs) in severe COVID-19 has been established, potentially leading to a wider use of GCs in critical illnesses. To better understand the heterogeneity of critical illness and optimize the use of GCs within the precision medicine approach, this study formulates ten major questions that need to be answered.

CRITICAL CARE (2022)

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Article Critical Care Medicine

Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial

Eleni Karakike et al.

Summary: Clarithromycin did not reduce mortality in patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration.

CRITICAL CARE (2022)

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Article Critical Care Medicine

Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial

Klaus Stahl et al.

Summary: This study demonstrates that therapeutic plasma exchange (TPE) can rapidly improve hemodynamics and preserve stability in patients with septic shock by removing injurious mediators and replenishing protective factors. Baseline lactate concentration shows potential as a predictor for response to TPE treatment.

CRITICAL CARE (2022)

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Review Critical Care Medicine

Immunomodulation by Tetracyclines in the Critically Ill: An Emerging Treatment Option?

Andrea Sauer et al.

Summary: This article is one of the selected reviews from the Annual Update in Intensive Care and Emergency Medicine 2022, providing the latest research in the field. Additional selected articles can be found online, offering further information about the Annual Update in Intensive Care and Emergency Medicine.

CRITICAL CARE (2022)

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Article Critical Care Medicine

Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial

Antoine Monsel et al.

Summary: The efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS was assessed in this study. The results showed no significant difference in respiratory indicators between the UC-MSCs and placebo groups. The repeated UC-MSCs infusions did not lead to any serious adverse events during treatment or thereafter.

CRITICAL CARE (2022)

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Article Immunology

Tetracycline Antibiotics Induce Host-Dependent Disease Tolerance to Infection

Henrique G. Colaco et al.

Summary: Tetracycline antibiotics targeting the mitoribosome were found to protect against sepsis by perturbing the electron transport chain and reducing tissue damage in the lung, while increasing fatty acid oxidation and glucocorticoid sensitivity in the liver. This study demonstrates that mitochondrial protein synthesis inhibition leading to ETC perturbation is a mechanism for inducing disease tolerance beyond the antibacterial activity of these antibiotics.

IMMUNITY (2021)

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Article Critical Care Medicine

A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction in Murine Polymicrobial Sepsis

Timothy W. Phares et al.

Summary: In a study using LD01 to treat CLP-induced sepsis in mice, it was found that LD01 significantly improved survival rates, reduced bacterial burden, and enhanced macrophage phagocytic activity and T-cell production of interferon-gamma. These results suggest that LD01 modulates host immunity and could be a viable therapeutic candidate for alleviating immunosuppression in sepsis and other infectious diseases.

SHOCK (2021)

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Letter Critical Care Medicine

Adjuvant therapeutic plasma exchange in septic shock

Sascha David et al.

INTENSIVE CARE MEDICINE (2021)

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Review Immunology

The immunology of sepsis

Tom van der Poll et al.

Summary: Sepsis is a life-threatening condition caused by infection-induced organ dysfunction, characterized by unbalanced hyperinflammation and immune suppression. Current research aims to stratify sepsis patients into more similar subgroups to better identify those who are likely to benefit from specific immune interventions.

IMMUNITY (2021)

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Article Critical Care Medicine

Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial

Pierre-Francois Laterre et al.

Summary: The study aimed to investigate the safety and tolerability of adrecizumab in septic shock patients with high adrenomedullin levels. The results showed that adrecizumab was well tolerated and did not significantly impact safety endpoints or efficacy endpoints. However, further randomized controlled trials are needed to confirm the efficacy and safety of adrecizumab in septic shock patients.

INTENSIVE CARE MEDICINE (2021)

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Article Critical Care Medicine

High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial

Elena Garbero et al.

Summary: The study evaluated the efficacy and safety of high-dose CPFA in treating patients with septic shock, with a higher mortality rate observed in the CPFA group compared to the control group. The harmful effects were more pronounced in the early phase of septic shock and patients without severe renal failure were more at risk, showing a dose-response relationship. The COMPACT-2 trial was stopped due to the potential harm of CPFA in these patients, and until further research is conducted, the use of CPFA for septic shock is not recommended.

INTENSIVE CARE MEDICINE (2021)

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Article Critical Care Medicine

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021

Laura Evans et al.

INTENSIVE CARE MEDICINE (2021)

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Review Respiratory System

Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential

Ellen Gorman et al.

Summary: Mesenchymal stromal (stem) cell (MSC) therapies show promising potential for the treatment of Acute Respiratory Distress Syndrome (ARDS) and sepsis due to their reparative, immunomodulatory, and antimicrobial properties. Both preclinical and clinical evidence support the use of MSC therapy in these conditions, with further optimization strategies such as altered gene expression and cell-free MSC-derived products offering additional benefits. Overall, MSC products hold considerable therapeutic promise for ARDS and sepsis treatment, with ongoing research aiming to enhance their efficacy in clinical settings.

EXPERT REVIEW OF RESPIRATORY MEDICINE (2021)

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Review Immunology

Immune Checkpoints: Novel Therapeutic Targets to Attenuate Sepsis-Induced Immunosuppression

Margaret A. McBride et al.

Summary: Sepsis is a leading cause of death in intensive care units, with survivors often experiencing immunosuppression and recurrent infections. Current treatment relies on supportive care and with the increasing incidence of antibiotic-resistant microbes, there is a need to discover novel therapeutics. Studies have shown that specific cell surface inhibitory immune checkpoint receptors and ligands play crucial roles in mediating the balance between host immune competency and immunosuppression in sepsis. Targeting these immune checkpoints may improve host resistance to infection and serve as a means of individualized therapy for septic patients.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Critical Care Medicine

Inhibition of Caspase-1 with Tetracycline Ameliorates Acute Lung Injury

Konrad Peukert et al.

Summary: The study found that tetracycline may be effective in treating direct ARDS patients by reducing lung injury and inflammation through inhibiting the production of IL-1β and IL-18, thereby improving survival rates.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2021)

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Article Critical Care Medicine

Identifying High-Risk Subphenotypes and Associated Harms From Delayed Antibiotic Orders and Delivery*

Xuan Han et al.

Summary: Early antibiotic administration is crucial in sepsis treatment, and delays in antibiotic ordering and delivery are both associated with increased mortality. Identifying high-risk patients for targeted timely therapy is important in reducing the risk of harm from delays.

CRITICAL CARE MEDICINE (2021)

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Article Immunology

Case Report: Interferon- γ Rescues Monocytic Human Leukocyte Antigen Receptor (mHLA-DR) Function in a COVID-19 Patient With ARDS and Superinfection With Multiple MDR 4MRGN Bacterial Strains

Clemens Grimm et al.

Summary: This study reported a case of multidrug-resistant superinfected COVID-19 acute respiratory distress syndrome. The immune system was successfully reactivated using IFN gamma therapy, leading to rapid resolution of infection and discharge of the patient.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Respiratory System

Antibiotics as immunomodulators: a potential pharmacologic approach for ARDS treatment

Andrea Sauer et al.

Summary: Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure with no proven pharmacologic therapy. Some antibiotics have been found to have immunomodulatory effects that could potentially help rectify the dysregulated inflammatory response in ARDS patients. Further studies are needed to explore the full therapeutic potential of antibiotics in treating ARDS.

EUROPEAN RESPIRATORY REVIEW (2021)

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Article Hematology

The promise and perils of immunotherapy

Stefanie Lesch et al.

Blood Advances (2021)

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Article Critical Care Medicine

Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock

Klaus Stahl et al.

Summary: Therapeutic plasma exchange using fresh frozen plasma may play a role in mitigating endothelial glycocalyx damage in patients with septic shock, reducing injurious degradation products and partially restoring protective factors.

INTENSIVE CARE MEDICINE EXPERIMENTAL (2021)

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Article Cell Biology

Combined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis

Jolien Vandewalle et al.

Summary: Defects in the glucocorticoid receptor signaling pathway exacerbate sepsis pathophysiology by reducing lactate clearance and sensitizing mice to lactate-induced toxicity, ultimately leading to lethal vascular collapse.

CELL METABOLISM (2021)

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Review Critical Care Medicine

Effect of IV High-Dose Vitamin C on Mortality in Patients With Sepsis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials*

Ryota Sato et al.

Summary: In patients with sepsis, the use of IV high-dose vitamin C was not associated with lower short-term mortality but was linked to significantly shorter vasopressor duration and greater decline in Sequential Organ Failure Assessment score at 72-96 hours.

CRITICAL CARE MEDICINE (2021)

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Letter Critical Care Medicine

Cytokine adsorption in severe, refractory septic shock

Pedro David Wendel Garcia et al.

INTENSIVE CARE MEDICINE (2021)

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Article Medicine, General & Internal

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19 AMeta-analysis

Manu Shankar-Hari et al.

Summary: This study identified 27 clinical trials and found that the use of IL-6 antagonists was associated with lower 28-day all-cause mortality in patients hospitalized for COVID-19 compared to usual care or placebo. Different risk effects were observed between tocilizumab and sarilumab, increasing understanding of the treatment with these drugs.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

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Article Multidisciplinary Sciences

Swarm Learning for decentralized and confidential clinical machine learning

Stefanie Warnat-Herresthal et al.

Summary: The study introduces Swarm Learning, a decentralized machine-learning approach that integrates medical data globally while complying with local privacy regulations. Using over 16,400 blood transcriptomes and more than 95,000 chest X-ray images, the research shows that Swarm Learning classifiers outperform those developed at individual sites.

NATURE (2021)

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Article Biochemistry & Molecular Biology

Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial

Evdoxia Kyriazopoulou et al.

Summary: The SAVE-MORE phase 3 study demonstrated the efficacy of anakinra, an IL-1 alpha/beta inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor, showing significant reduction in clinical deterioration and decreased 28-day mortality.

NATURE MEDICINE (2021)

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Article Multidisciplinary Sciences

Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons

Ravi Shankar Keshari et al.

Summary: Late-stage anthrax infections involve dysregulated immune responses and hematogenous spread of Bacillus anthracis, leading to severe bacteremia, sepsis, organ failure, and death. Some fulminant anthrax patients develop a secondary atypical hemolytic uremic syndrome (aHUS). By studying baboons challenged with PGN, a pathogen-associated molecular pattern responsible for hemostatic dysregulation in anthrax sepsis, researchers found that C5 neutralization can prevent hemolysis and kidney injury induced by PGN. This study identifies PGN-driven complement activation as the pathologic mechanism underlying hemolytic anemia in anthrax and other gram-positive infections.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Critical Care Medicine

Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies

Daisuke Kudo et al.

Summary: We identified four sepsis phenotypes based on coagulation markers. The treatment effects of thrombomodulin varied across different sepsis phenotypes. This discovery will facilitate future trials of thrombomodulin targeting specific sepsis phenotypes with high FDP and D-dimer levels.

CRITICAL CARE (2021)

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Article Critical Care Medicine

Pharmacokinetics, Pharmacodynamics, and Safety of Nivolumab in Patients With Sepsis-Induced Immunosuppression: A Multicenter, Open-Label Phase 1/2 Study

Eizo Watanabe et al.

SHOCK (2020)

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Article Medicine, General & Internal

Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock The VITAMINS Randomized Clinical Trial

Tomoko Fujii et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

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Article Medicine, General & Internal

Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study

Kristina E. Rudd et al.

LANCET (2020)

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Review Pharmacology & Pharmacy

Immunotherapy in sepsis - brake or accelerate?

Folkert Steinhagen et al.

PHARMACOLOGY & THERAPEUTICS (2020)

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Article Medicine, Research & Experimental

Post-sepsis immunosuppression depends on NKT cell regulation of mTOR/IFN-γ in NK cells

Edy Y. Kim et al.

JOURNAL OF CLINICAL INVESTIGATION (2020)

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Review Hematology

Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis-associated coagulopathy: A systematic review and meta-analysis

Emanuele Valeriani et al.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2020)

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Article Cell & Tissue Engineering

Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies

Xue-Yi Sun et al.

STEM CELL RESEARCH & THERAPY (2020)

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Article Medicine, General & Internal

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19 The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial

Derek C. Angus et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

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Article Biology

Spectral clustering of risk score trajectories stratifies sepsis patients by clinical outcome and interventions received

Ran Liu et al.

ELIFE (2020)

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Article Critical Care Medicine

The therapeutic efficacy of adjunct therapeutic plasma exchange for septic shock with multiple organ failure: a single-center experience

Philip D. Keith et al.

CRITICAL CARE (2020)

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Article Critical Care Medicine

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

Guus P. Leijte et al.

CRITICAL CARE (2020)

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Article Critical Care Medicine

Effects of Mesenchymal Stem Cell Treatment on Systemic Cytokine Levels in a Phase 1 Dose Escalation Safety Trial of Septic Shock Patients

Kenny Schlosser et al.

CRITICAL CARE MEDICINE (2019)

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Article Critical Care Medicine

Cardiovascular clusters in septic shock combining clinical and echocardiographic parameters: a post hoc analysis

Guillaume Geri et al.

INTENSIVE CARE MEDICINE (2019)

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Article Critical Care Medicine

The clinical efficacy of intravenous IgM-enriched immunoglobulin (pentaglobin) in sepsis or septic shock: a meta-analysis with trial sequential analysis

Jie Cui et al.

ANNALS OF INTENSIVE CARE (2019)

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Article Medicine, General & Internal

Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis

Christopher W. Seymour et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2019)

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Article Medicine, General & Internal

Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy The SCARLET Randomized Clinical Trial

Jean-Louis Vincent et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2019)

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Review Immunology

IFN-γ: A cytokine at the right time, is in the right place

J. Daniel Burke et al.

SEMINARS IN IMMUNOLOGY (2019)

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Article Medicine, General & Internal

Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial

Alpha A. Fowler et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2019)

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Article Infectious Diseases

Multicentric experience with interferon gamma therapy in sepsis induced immunosuppression. A case series

Didier Payen et al.

BMC INFECTIOUS DISEASES (2019)

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Article Critical Care Medicine

Immune checkpoint inhibition in sepsis: a Phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab

Richard S. Hotchkiss et al.

INTENSIVE CARE MEDICINE (2019)

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Article Critical Care Medicine

Transcriptomic Signatures in Sepsis and a Differential Response to Steroids From the VANISH Randomized Trial

David B. Antcliffe et al.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2019)

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Article Critical Care Medicine

Identifying Novel Sepsis Subphenotypes Using Temperature Trajectories

Sivasubramanium Bhavani et al.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2019)

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Review Critical Care Medicine

Thrombomodulin in disseminated intravascular coagulation and other critical conditions-a multi-faceted anticoagulant protein with therapeutic potential

Takashi Ito et al.

CRITICAL CARE (2019)

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Review Immunology

Overview of the IL-1 family in innate inflammation and acquired immunity

Charles A. Dinarello

IMMUNOLOGICAL REVIEWS (2018)

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Article Critical Care Medicine

Cellular Immunotherapy for Septic Shock A Phase I Clinical Trial

Lauralyn A. McIntyre et al.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2018)

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Article Critical Care Medicine

Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration

Nuala J. Meyer et al.

CRITICAL CARE MEDICINE (2018)

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Article Critical Care Medicine

Unsupervised Analysis of Transcriptomics in Bacterial Sepsis Across Multiple Datasets Reveals Three Robust Clusters

Timothy E. Sweeney et al.

CRITICAL CARE MEDICINE (2018)

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Article Oncology

FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome

Robert Q. Le et al.

ONCOLOGIST (2018)

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Article Medical Laboratory Technology

Umbilical cord-derived mesenchymal stem (stromal) cells for treatment of severe sepsis: a phase 1 clinical trial

Xiao He et al.

TRANSLATIONAL RESEARCH (2018)

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Article Critical Care Medicine

Identification of subclasses of sepsis that showed different clinical outcomes and responses to amount of fluid resuscitation: a latent profile analysis

Zhongheng Zhang et al.

CRITICAL CARE (2018)

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Letter Infectious Diseases

Nivolumab plus interferon-γ in the treatment of intractable mucormycosis

David Grimaldi et al.

LANCET INFECTIOUS DISEASES (2017)

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Article Multidisciplinary Sciences

Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli sepsis

Ravi Shankar Keshari et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017)

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Article Critical Care Medicine

Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial

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