Risultati per: Il “grasso cattivo” impedisce alle cellule T killer di attaccare il cancro

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Abstract Or107: Sulfatide-specific natural killer T cells regulate early inflammation and ameliorate post-cardiac arrest brain injury

Circulation

Circulation, Volume 150, Issue Suppl_1, Page AOr107-AOr107, November 12, 2024. Background:Innate T cells have both deleterious and protective roles in a range of diseases. Natural killer T (NKT) cells are a major type of innate T cell, but their role and clinical relevance after cardiac arrest (CA) are undefined.Hypothesis:In patients after CA, an early increase in diverse NKT (dNKT) cells correlates with good neurological outcomes. dNKT cells improve outcomes after CA by reducing inflammatory responses in the brain.Aims:To investigate the clinical relevance of dNKT cells after out-of-hospital CA (OHCA) and their roles in a murine CA model.Methods:A clinical retrospective cohort study of complete blood cell counts with differentials after OHCA. Single-cell RNA-seq and flow cytometry of circulating T cells in OHCA patients. Good neurological outcomes were defined as a Cerebral Performance Category of 1 or 2 at 30 days post-CA. Single-nucleus RNA-sequencing(-seq) of hippocampal cells (50,332 nuclei), RT-PCR, and flow cytometry of the brain 24 hours post-CA in mice.Results:In a large OHCA patient cohort (N=1,955), the percentage of lymphocytes early (less than 12 hours) after CA was independently associated with good neurological outcomes (adjusted odds ratio [95%CI], 1.08 [1.03-1.14], P=0.005). Transcriptional profiling of T cells in OHCA patients at single-cell resolution showed an increase in an innate T cell-like NCAM1+subset in patients with good neurological outcomes. This subset expressed cytotoxic, cytokine, and chemokine genes. Flow cytometry identified an early increase in circulating dNKT cells in patients with good neurological outcomes post-CA. In a murine model of CA, type II dNKT cells migrated to the brain after CA. NKT cell-deficient mice (Cd1d-/-) had increased neuronal injury and mortality after CA. Cd1d-/-mice had increased molecular and cellular inflammation compared to wild-type mice 24 hours post-CA. Global transcriptomic analysis of murine brain at single-nucleus resolution indicated NKT cells suppressed inflammatory axes post-CA in multiple cell types, including astrocytes, microglia, and inhibitory neurons. Treatment with sulfatide (a lipid antigen for dNKT cells) improved neurological function after CA.Conclusions:Early abundance of dNKT cells was associated with good neurological outcomes after OHCA. dNKT cells are neuroprotective after CA by suppressing inflammatory axes in the brain. Immunomodulation of dNKT cells via endogenous lipids is a potential treatment approach after CA.

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Novembre 2024

Abstract 4138570: The Hidden Killer in Patients with Sepsis Spectra Disorders: Systolic Heart Failure

Circulation

Circulation, Volume 150, Issue Suppl_1, Page A4138570-A4138570, November 12, 2024. Introduction:Sepsis and systolic heart failure (sHF) often prompt hospitalization and require near diametrically opposite treatment strategies. We, therefore, studied whether sHF would impact outcomes in patients with sepsis spectra.Methods:We examined the National Inpatient Sample 2021 for adults admitted with sepsis spectra (sepsis, severe sepsis, and septic shock). We compared patients with sHF vs those without. STATA 18thedition was used for analyses. Age, gender, race, hypertension, diabetes, obesity, dyslipidemia, and Elixhauser comorbidity index were identified as confounders by univariate analyses and tested further with multivariate logistic regression models. The primary outcome was mortality. Secondary outcomes were the need for intubation, cardiac arrest, length of stay (LOS), and total hospital charges.Results:In 2021, nationwide, 3,030,351 adults were admitted for sepsis spectra, and 209,134 (6.9%) had concomitant sHF. Patients with sHF and sepsis spectra (as compared to those without sHF) were less likely female (35.5% vs. 48%), had a substantially higher likelihood of a prior MI, and nearly 50% were diabetic and hyperlipidemic with a higher comorbidity index. Baseline characteristics are in the Table.Sepsis and sHF resulted in substantially higher mortality (22.7%) as compared to patients with sepsis alone (14.9%) adjusted odds ratio (aOR) of 1.11 (CI 1.08-1.14; p-value < 0.001). Patients with sepsis and sHF were more likely to require intubation 22.2% vs. 14.0% aOR 1.21 (CI 1.18-1.25; p-value < 0.001), had more cardiac arrest 7.7% vs. 4.0% aOR 1.38 (CI 1.32-1.44; p-value < 0.001), and a longer LOS (11.9 vs 9.4 days adjusted incidence rate ratio (aIRR) 1.06; CI 1.05 – 1.08; p-value < 0.001). Consequently, total hospital charges were also higher, $189,415 vs $133,720, aIRR 1.15 (CI 1.13-1.18; p-value < 0.001).Conclusion:In 2021, nationwide, sepsis spectra remain a major cause of in-patient mortality. We demonstrate that the coexistence of systolic heart failure and sepsis dramatically worsens complications, mortality, and total hospital costs. This study is a call to action for the in-depth analyses of this very high-risk group of patients.

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Novembre 2024
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