Revolution in sepsis: a symptoms-based to a systems-based approach?

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: May 30, 2024

Abstract Severe infection and sepsis are medical emergencies. High morbidity mortality linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy multiple organ dysfunction. Males appear have a higher risk of than females. Currently, there few or no effective drug therapies protect the brain, maintain blood brain barrier, resolve inflammation reduce secondary injury in other vital organs. We propose major reason for lack progress is consequence treat-as-you-go, single-nodal target approach, rather more integrated, systems-based approach. A new revolution required better understand how body responds an infection, identify markers detect its progression discover system-acting drugs treat it. In this review, we present brief history followed by pathophysiology from systems’ perspective future opportunities. argue that targeting body’s early immune-driven CNS-response may improve patient outcomes. If barrage PAMPs DAMPs can be reduced early, CNS-organ circuits (or axes) will preserved reduced. been developing systems-based, small-volume, fluid therapy comprising adenosine, lidocaine magnesium (ALM) endotoxemia. Our studies indicate ALM shifts sympathetic parasympathetic dominance, maintains cardiovascular-endothelial glycocalyx coupling, reduces corrects coagulopathy, tissue O 2 supply. Future research investigate potential translation humans.

Language: Английский

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NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 7, 2024

Abstract Increased recruitment of transitional and non-classical monocytes in the lung during SARS-CoV-2 infection is associated with COVID-19 severity. However, whether specific innate sensors mediate activation or differentiation response to different proteins remain poorly characterized. Here, we show that Spike 1 but not nucleoprotein induce into subsets from both peripheral blood bronchoalveolar lavage samples a NFκB-dependent manner, this process does require inflammasome activation. NLRP3 NLRC4 differentially regulated CD86 expression Nucleoprotein, respectively. Moreover, exposed significantly higher proportions Th1 Th17 CD4 + T cells. In contrast, Nucleoprotein reduce degranulation CD8 cells severe patients. Our study provides insights differential impact regulating proteins, which might be useful better understand immunopathology identify therapeutic targets.

Language: Английский

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Evolving Paradigms in Sepsis Management: A Narrative Review

Cells, Journal Year: 2024, Volume and Issue: 13(14), P. 1172 - 1172

Published: July 9, 2024

Sepsis, a condition characterized by life-threatening organ dysfunction due to dysregulated host response infection, significantly impacts global health, with mortality rates varying widely across regions. Traditional therapeutic strategies that target hyperinflammation and immunosuppression have largely failed improve outcomes, underscoring the need for innovative approaches. This review examines development of agents sepsis, focus on clinical trials addressing immunosuppression. It highlights frequent failures these trials, explores underlying reasons, outlines current research efforts aimed at bridging gap between theoretical advancements applications. Although personalized medicine phenotypic categorization present promising directions, this emphasizes importance understanding complex pathogenesis sepsis developing targeted, effective therapies enhance patient outcomes. By multifaceted nature future can pave way more precise individualized treatment strategies, ultimately improving management prognosis patients.

Language: Английский

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Sepsis: the evolution of molecular pathogenesis concepts and clinical management

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: Feb. 23, 2025

Abstract The mortality rate of sepsis is approximately 22.5%, accounting for 19.7% the total global mortality. Since Lewis Thomas proposed in 1972 that “it our response makes disease (sepsis)” rather than invading microorganisms, numerous drugs have been developed to suppress “overwhelming” inflammatory response, but none them has achieved desired effect. Continued failure led investigators question whether deaths septic patients are indeed caused by uncontrolled inflammation. Here, we review history clinical trials based on evolving concepts pathogenesis over past half century, summarize factors these historical and prerequisites success future drugs, propose basic principles preclinical research ensure successful translation. strategy targeting like attempting eliminate invaders suppressing host's armed forces, which logically untenable. Sepsis may not be complex; rather, result a fight microbes when force an pathogen overwhelms defenses. Thus, strengthening body's defense forces instead correct overcome sepsis.

Language: Английский

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Chronic Obstructive Pulmonary Disease and COVID-19: The Impact of Hematological Biomarkers on Disease Severity and Outcomes

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(8), P. 2765 - 2765

Published: April 17, 2025

Background/Objectives: Chronic obstructive pulmonary disease (COPD) patients are at heightened risk of severe COVID-19 due to underlying respiratory impairment, systemic inflammation, and immune dysregulation. This review explores the hematological changes that occur in COPD with their implications for progression, prognosis, clinical management. Methods: We conducted a comprehensive analysis recent peer-reviewed studies from medical databases including Clarivate Analytics, PubMed, Google Scholar. Results: Hematological alterations, such as lymphopenia, elevated neutrophil-to-lymphocyte ratio (NLR), increased D-dimer fibrinogen levels, inflammatory anemia, erythrocyte dysfunction, commonly observed COVID-19. These linked suppression, hyperinflammation, oxidative stress, thromboembolic complications. Conclusions: biomarkers valuable tools early assessments guiding treatment strategies this high-risk population. The regular monitoring D-dimer, fibrinogen, NLR is advisable. Prophylactic anticoagulation immunomodulatory therapies, corticosteroids IL-6 IL-1 inhibitors, may improve outcomes. Further needed validate personalized approaches explore antioxidant-based interventions.

Language: Английский

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Impact of Treatment with Antioxidants as an Adjuvant to Standard Therapy in Patients with Septic Shock: Analysis of the Correlation between Cytokine Storm and Oxidative Stress and Therapeutic Effects

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16610 - 16610

Published: Nov. 22, 2023

Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of inflammatory response and deregulation oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this homeostasis. We included 131 patients with who were treated vitamin C (Vit C), E E), N-acetylcysteine (NAC), melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Failure Assessment (SOFA) score, we determined levels Interleukins (IL) IL1β, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth B (TGFβ), IL-4, IL-10, IL-12, Interferon-γ (IFNγ). The SOFA score decreased Vit C, NAC, MT. Patients MT had statistically significantly reduced IL-8, MCP-1, IL-10 levels. Lipid peroxidation, Nitrates nitrites (NO3− NO2−), glutathione reductase, superoxide dismutase after E, thiols recovered use all antioxidants maintained their selenium levels, contrast controls (p = 0.04). findings regarding stress markers cytokines allow us consider future combined clinical trial larger sample demonstrate reproducibility these beneficial effects.

Language: Английский

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COVID-19-Associated Sepsis: Potential Role of Phytochemicals as Functional Foods and Nutraceuticals

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8481 - 8481

Published: Aug. 3, 2024

The acute manifestations of coronavirus disease 2019 (COVID-19) exhibit the hallmarks sepsis-associated complications that reflect multiple organ failure. inflammatory cytokine storm accompanied by an imbalance in pro-inflammatory and anti-inflammatory host response to severe respiratory syndrome 2 (SARS-CoV-2) infection leads critical septic shock. sepsis signature severely afflicted COVID-19 patients includes cellular reprogramming dysfunction high mortality rates, emphasizing importance improved clinical care advanced therapeutic interventions for associated with COVID-19. Phytochemicals functional foods nutraceutical have incredible impact on healthcare system, which prevention and/or treatment chronic diseases. Hence, present review, we aim explore pathogenesis disrupts physiological homeostasis body, resulting damage. Furthermore, summarized diverse pharmacological properties some potent phytochemicals, can be used as well nutraceuticals against SARS-CoV-2 infection. phytochemicals explored this article include quercetin, curcumin, luteolin, apigenin, resveratrol, naringenin, are major phytoconstituents our daily food intake. We compiled findings from various studies, including trials humans, more into potential each phytochemical COVID-19, highlights their possible pathogenesis. conclude review will open a new research avenue exploring phytochemical-derived agents preventing or treating life-threatening

Language: Английский

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ANAKINRA EFFICACY IN COVID-19 PNEUMONIA GUIDED BY SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR: ASSOCIATION WITH THE INFLAMMATORY BURDEN OF THE HOST

International Journal of Antimicrobial Agents, Journal Year: 2024, Volume and Issue: unknown, P. 107405 - 107405

Published: Dec. 1, 2024

Anakinra was approved by the European Medicines Agency and received Emergency Use Authorization Food Drug Administration of United States for patients with COVID-19 pneumonia at risk severe respiratory failure (SRF) blood levels suPAR (soluble urokinase plasminogen activator receptor) ≥ 6 ng/ml. We report final results phase II open-label single-arm SAVE trial in a large population. Patients ≥6 ng/ml subcutaneously anakinra 100mg once daily 10 days. The primary outcome incidence SRF day 14. Secondary outcomes were 30-day mortality, according to time delay start treatment, safety associations inflammatory burden host. From March 2020 2022, 992 enrolled. 18.8% similar III pivotal trial. overall mortality 9.5%. Participants divided into four subgroups between symptoms onset anakinra. all subgroups. Serious adverse events reported 15.4%; only 3 possibly related most common event increased liver function tests. A post-hoc comparison showed among patients' mediators D-dimers. Results support efficacy registrational pneumonia. lack comparator group is limitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04357366.

Language: Английский

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Covid-19 A Comprehensive Review of Signs, Symptoms, Diagnosis, and Treatment Strategies

International Journal of Advanced Research in Science Communication and Technology, Journal Year: 2024, Volume and Issue: unknown, P. 51 - 68

Published: May 8, 2024

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has significantly impacted global health. This review aims to provide a comprehensive overview of the signs, symptoms, diagnosis, and treatment modalities COVID-19. clinical presentation COVID-19 varies widely, ranging from asymptomatic or mild symptoms distress multiorgan failure. Common include fever, cough, fatigue, dyspnea, with less frequent such as anosmia, ageusia, gastrointestinal symptoms. Diagnosis primarily relies on reverse transcription-polymerase chain reaction (RT-PCR) testing specimens. However, imaging chest X-ray Antibody Test Antigen test in especially cases atypical presentations. Treatment strategies supportive care, antiviral therapy, and, cases, other intensive care measures. development distribution vaccines have been pivotal controlling spread virus. Despite significant progress understanding managing COVID-19, ongoing research is crucial refine diagnostic strategies, develop effective therapies, improve patient outcomes. Antiviral drugs, remdesivir, poxolovid, molonupiravir, widely used inhibit viral replication reduce severity duration Immunomodulators, including tocilizumab target specific pathways involved hyperinflammatory response seen Monoclonal antibodies, casirivimab/imdevimab sotrovimab, employed for passive immunization neutralize virus risk progression

Language: Английский

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Legionella pneumophila—Klebsiella pneumoniae Pulmonary Coinfection in a COVID-19 Patient: Case Report

Infectious Disease Reports, Journal Year: 2024, Volume and Issue: 16(6), P. 1055 - 1063

Published: Nov. 11, 2024

Background. Pulmonary superinfections increase the mortality risk among COVID-19 patients, highlighting need for enhanced understanding to enable early and accurate diagnosis. Methods. We present case of a patient, 76-year-old man, hospitalized severe form COVID-19, with ground-glass pneumonia, involving 40–45% lung surfaces. Results. In evolution, clinical condition worsened, presenting leukocytosis neutrophilia, imaging towards resorption, computer tomography images showing appearance pulmonary condensations in right lower lobe, posterior portion left lobe pleural collections. Carbapenemase-producing Klebsiella pneumoniae was isolated from tracheal aspirate, real-time polymerase chain reaction test positive Legionella pneumophila. The investigations that were carried out allowed us establish coinfections as probable Legionnaire’s disease ventilator-associated pneumonia pneumoniae. Conclusions. analysis revealed rare pneumonias may remain undiagnosed, be conditioned by pathophysiological factors or components critical treatment. Enhanced these aspects practice contribute reducing patients.

Language: Английский

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