Therapeutic potential of mitochondrial transplantation in modulating immune responses post-cardiac arrest: a narrative review

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 3, 2024

Abstract Background Mitochondrial transplantation (MTx) has emerged as a novel therapeutic strategy, particularly effective in diseases characterized by mitochondrial dysfunction. This review synthesizes current knowledge on MTx, focusing its role modulating immune responses and explores potential treating post-cardiac arrest syndrome (PCAS). Methods We conducted comprehensive narrative of animal human studies that have investigated the effects MTx context immunomodulation. included following critical condition such ischemia reperfusion injury, impact these responses, various conditions. Results Recent indicate can modulate complex reduce ischemia–reperfusion injury post-CA, suggesting novel, potentially more approach. The highlights modulation, synergistic with existing treatments hypothermia, need for further research to optimize application PCAS. safety efficacy autologous versus allogeneic reactions, are areas future investigation. Conclusion represents promising frontier treatment PCAS, offering approach restore cellular energetics. Future should focus long-term effects, combination therapies, personalized medicine approaches fully harness improving patient outcomes

Language: Английский

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Inflammatory response after prehospital high-dose glucocorticoid to patients resuscitated from out-of-hospital cardiac arrest: a sub-study of the STEROHCA trial

Resuscitation, Journal Year: 2024, Volume and Issue: 202, P. 110340 - 110340

Published: July 31, 2024

BackgroundThe post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac (OHCA) is characterized by a series of pathological events, including inflammation. In the randomized "STERoid for OHCA" (STEROHCA) trial, prehospital high-dose glucocorticoid decreased interleukin (IL) 6 and C-reactive protein levels following resuscitated OHCA. The aim this predefined sub-study was to assess inflammatory response first three days admission.MethodsThe STEROHCA trial enrolled 137 OHCA patients either single injection methylprednisolone 250 mg or placebo. Inflammatory markers, pro- anti-inflammatory cytokines, were analyzed in plasma samples, from 0-, 24-, 48-, 72 h post-admission. Mixed-model analyses applied using log-transformed data group differences.ResultsThe included had median age 67 years (57 74), 180-day survival rates 75% (n = 51/68) 64% 44/69) placebo group, respectively. A total 130 (95%) at least one sample available. cytokine IL-10 increased hospital admission (ratio 2.74 (1.49–5.05), p 0.006), but intervention showed strongest effect 24 h, decreasing pro-inflammatory IL-6 0.06 (0.03–0.10), < 0.001), IL-8 0.53 (0.38–0.75), macrophage chemokine protein-1 (MCP-1, ratio 0.02 (0.13–0.31), protein-1-beta (MIP-1b, 0.28 (0.18–0.45), tumor necrosis factor-α (TNF-α, 0.6 (0.4–0.8), 0.01).ConclusionAdministering treatment promptly resuscitation influenced with reduction several systemic proinflammatory cytokines h.Trial registrationEudraCT number: 2020–000855-11; submitted March 30, 2020.URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04624776.

Language: Английский

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Ventilator-Associated Pneumonia After Cardiac Arrest and Prevention Strategies: A Narrative Review

Medicina, Journal Year: 2025, Volume and Issue: 61(1), P. 78 - 78

Published: Jan. 5, 2025

Background and Objectives: Ventilator-associated pneumonia (VAP) poses a significant threat to the clinical outcomes hospital stays of mechanically ventilated patients, particularly those recovering from cardiac arrest. Given already elevated mortality rates in arrest cases, addition VAP further diminishes chances survival. Consequently, paramount focus on prevention becomes imperative. This review endeavors comprehensively delve into nuances VAP, specifically patients requiring mechanical ventilation post-cardiac care. The overarching objectives encompass (I) exploring etiology, risk factors, pathophysiology (II) delving available diagnostic modalities, (III) providing insights management options recent treatment guidelines. Methods: A literature search was conducted using PubMed, MEDLINE, Google Scholar databases for articles about Cardiac We used MeSH terms "VAP", "Cardiac arrest", "postcardiac syndrome", syndrome". presentation, diagnostic, strategies were summarized, all authors reviewed selection decided which studies include. Key Content Findings: incidence exhibit variability, yet recurring pattern emerges, marked by prolonged hospitalization exacerbated outcomes. is attributed drug-resistant infections delayed initiation antimicrobial treatment. focuses aiming offer valuable efficient identification this fatal complication patients. Conclusion: prognosis survival after challenging, outlook even more daunting when complicated VAP. timely diagnosis antibiotics pose considerable challenges, primarily due invasive nature obtaining high-quality samples time required speciation sensitivity. controversy surrounding prophylactic persists, but promising new have been proposed; however, they are still awaiting well-designed trials.

Language: Английский

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Correlation between the white blood cell/platelet ratio and 28-day all-cause mortality in cardiac arrest patients: a retrospective cohort study based on machine learning

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

This study aims to evaluate the association between white blood cell-to-platelet ratio (WPR) and 28-day all-cause mortality among patients experiencing cardiac arrest. Utilizing data from 748 arrest in Medical Information Mart for Intensive Care-IV (MIMIC-IV) 2.2 database, machine learning algorithms, including Boruta feature selection method, random forest modeling, SHAP value analysis, were applied identify significant prognostic biomarkers. Key patient characteristics, encompassing demographic data, comorbidities, hematological biochemical indices, vital signs, extracted using PostgreSQL Administration Tool (pgAdmin) software. The Cox proportional hazards model assessed impact of WPR on outcomes, while Kaplan-Meier survival curves restricted cubic spline (RCS) analysis further validated findings. Subgroup analyses stratified by clinical factors. demonstrated highest significance variables studied, showing a strong with mortality. In unadjusted Model 1, hazard ratios (HRs) quartiles ranged 1.88 (95% CI: 1.22-2.90) Q2 3.02 2.04-4.47) Q4 (Ptrend <0.05). Adjusted models (Models 2-4) confirmed robustness these associations, even after accounting covariates. RCS revealed U-shaped relationship risk. indicated that elevated was particularly associated increased males, elderly patients, married individuals, those chronic pulmonary disease. serves as an independent reliable biomarker patients. Its integration into decision-making may enhance early identification high-risk guide tailored therapeutic interventions.

Language: Английский

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Suppression of PCK1 attenuates neuronal injury and improves post-resuscitation outcomes

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167674 - 167674

Published: Jan. 1, 2025

Language: Английский

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Mechanisms and strategies for organ recovery

Nature Reviews Bioengineering, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Language: Английский

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Glucocorticoid signaling mediates lymphopoiesis impairment after cardiac arrest in mice

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Cardiac arrest (CA) is a life-threatening condition that requires immediate medical attention. Considerable advances in resuscitation have led to an increasing number of patients who survive the initial event. However, among this growing patient population, morbidity and mortality rates remain strikingly high. This has been attributed post-CA syndrome which imbalanced immune response crucial component. Using murine CA model, we shown profound immunosuppressive phase, characterized by severe lymphopenia, ensues following pro-inflammatory after CA. In current study, found T B lymphopoiesis was greatly impaired, as evidenced rapid marked depletion double-positive cells pre-B thymus bone marrow, respectively. Our data then demonstrated pharmacologic suppression glucocorticoid signaling significantly attenuated impairment, thereby mitigating lymphopenia. Lastly, showed specific deletion receptor or largely prevented CA-induced immature lymphocyte populations Together, our findings indicate mediates impairment lymphopoiesis, key contributor immunosuppression.

Language: Английский

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Acute Kidney Injury in Patients After Cardiac Arrest: Effects of Targeted Temperature Management

Life, Journal Year: 2025, Volume and Issue: 15(2), P. 265 - 265

Published: Feb. 10, 2025

Background: Cardiac arrest (CA) is a leading cause of mortality and morbidity, with survivors often developing post-cardiac syndrome (PCAS), characterized by systemic inflammation, ischemia–reperfusion injury (IRI), multiorgan dysfunction. Acute kidney (AKI), frequent complication, associated increased prolonged intensive care unit (ICU) stays. This study evaluates AKI incidence progression in cardiac patients managed different temperature protocols explores urinary biomarkers’ predictive value for risk. Methods: A prospective, single-center observational was conducted, including Return Spontaneous Circulation (ROSC) arrest. Patients were stratified into three groups: therapeutic hypothermia (TH) at 33 °C, Targeted Temperature Management (TTM) 35 no management (No TTM). defined using KDIGO criteria, serum creatinine biomarkers (TIMP-2 IGFBP7) measured regular intervals during ICU stay. Results: 72 h 31%, varying across protocols. It higher the No TTM group 24 TH groups rewarming. Persistent elevation fluid imbalance notable group. Biomarkers indicated moderate tubular stress groups. Conclusions: complication arrest, rewarming phase identified as critical renal vulnerability. Tailored monitoring, biomarker-guided risk assessment, precise are essential to improve outcomes.

Language: Английский

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The Protective Effect of JANEX-1 on Cerebral Ischemia-Reperfusion Injury in Post-Cardiac Arrest Brain Injury

Published: Jan. 1, 2025

Language: Английский

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Regulated cell death and DAMPs as biomarkers and therapeutic targets in normothermic perfusion of transplant organs. Part 1: their emergence from injuries to the donor organ

Frontiers in Transplantation, Journal Year: 2025, Volume and Issue: 4

Published: April 24, 2025

This Part 1 of a bipartite review commences with succinct exposition innate alloimmunity in light the danger/injury hypothesis Immunology. The model posits that an alloimmune response, along presentation alloantigens, is driven by DAMPs released from various forms regulated cell death (RCD) induced any severe injury to donor or organ, respectively. To provide strong foundation for this review, which examines RCD and as biomarkers therapeutic targets normothermic regional perfusion (NRP) machine (NMP) improve outcomes organ transplantation, key insights are presented on nature, classification, functions DAMPs, well signaling mechanisms pathways, including ferroptosis, necroptosis, pyroptosis, NETosis. Subsequently, comprehensive discussion provided major periods injuries organs associated induction precede onset response recipients. These include conditions donation after brain (DBD) circulatory (DCD). Particular emphasis placed different origins RCD-associated DBD DCD routes they use within system reach potential allografts. ends addressing another particularly critical period organs: their postischemic reperfusion following implantation into recipient-a decisive factor determining transplantation outcome. Here, focuses ischemia-induced oxidative causes generates initiate robust response.

Language: Английский

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