Monitoring Mitophagy In Myeloid Cells Upon Intensive Care

Study Overview
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Brief Summary
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Severe infections (sepsis) are a frequent cause of admission to the intensive care unit. Sepsis represent a significant risk for the health of patients in the short and medium term. Sepsis are notably linked to a change in the function of immune cells. In some patients, a state of pseudo-dormancy of monocyte and macrophage immune cells, called myeloid cell immunosuppression, is observed. This situation, which leads to a worsening of the infection, must be avoided because it represents a danger for the patient, even during antibiotic therapy. At present, these events are still very poorly understood. Research is needed to understand how the immunosuppression of myeloid cells occurs in order to adapt existing treatments or to find new ones. Laboratory work on animal models of sepsis has shown that this state of myeloid cell immunosuppression is closely linked to a modification of energy production by myeloid cells (monocytes and macrophages). The function of the mitochondria (energy factory of the cells) in these cells is impaired. Thus, restoring mitochondrial function in myeloid cells could be a therapeutic solution against the immunosuppression of myeloid cells during severe sepsis. The aim of this study is to verify whether alterations in mitochondrial function in myeloid cells occur in both patients with and without bacterial infection.

Official Title
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Monitoring Mitophagy In Myeloid Cells Upon Intensive Care

Conditions
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Septicemia

Intervention / Treatment
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* Biological: Blood sampling at inclusion
* Biological: Blood sampling at 24 hours
* Other: Data collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Criteria common to all 4 groups: Patient (and/or trusted person/health care proxy or relative) or volunteer who provided oral consent after receiving information about the study, or patient included in emergency situation Age ≥ 18 years Common criteria for patients - Admission to the Intensive Care Unit or the Anesthesia and Intensive Care Unit of the Dijon University Hospital Exclusion Criteria: Person not affiliated to national health insurance Person subject to a measure of legal protection (curatorship, guardianship) Person subject to limited judicial protection Pregnancy or breastfeeding Known primary or secondary immune deficiency (radiotherapy, chemotherapy, immunosuppressive treatment or systemic corticosteroid therapy in the 3 months preceding inclusion (> 0.15 mg/kg/d of prednisone equivalent for more than 2 weeks or bolus greater than 2mg/kg/d of prednisone equivalent), HIV infection, primary cellular immune deficiency) Patients hospitalized within 3 months prior to inclusion for sepsis. Patients receiving therapy known to modulate mitochondrial function, mitochondrial biogenesis or mitophagy (chloroquine, hydroxychloroquine, rapamycin, carbamazepine, resveratrol, sildenafil) Patients with COVID-19

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients without sepsis<br>patient without sepsis admitted to the Intensive Care Unit or the Anesthesia and Intensive Care Unit of the Dijon University Hospital | Biological: Blood sampling at inclusion<br>* Sampling of 2 tubes of 3 ml: patient: H0: 0-6h post-admission healthy volunteer: at inclusion<br>Biological: Blood sampling at 24 hours<br>* Collection of 2 tubes of 3 ml (H24: 24-30h post-admission)<br>Other: Data collection<br>* clinical and biological medical data for patients and general health data for healthy volunteers<br>|
| Experimental: Patients with sepsis<br>Patients with sepsis admitted to the Intensive Care Unit or the Anesthesia and Intensive Care Unit of the Dijon University Hospital | Biological: Blood sampling at inclusion<br>* Sampling of 2 tubes of 3 ml: patient: H0: 0-6h post-admission healthy volunteer: at inclusion<br>Biological: Blood sampling at 24 hours<br>* Collection of 2 tubes of 3 ml (H24: 24-30h post-admission)<br>Other: Data collection<br>* clinical and biological medical data for patients and general health data for healthy volunteers<br>|
| Experimental: Patients with septic shock<br>Patients with septic shock admitted to the Intensive Care Unit or the Anesthesia and Intensive Care Unit of the Dijon University Hospital | Biological: Blood sampling at inclusion<br>* Sampling of 2 tubes of 3 ml: patient: H0: 0-6h post-admission healthy volunteer: at inclusion<br>Biological: Blood sampling at 24 hours<br>* Collection of 2 tubes of 3 ml (H24: 24-30h post-admission)<br>Other: Data collection<br>* clinical and biological medical data for patients and general health data for healthy volunteers<br>|
| Active Comparator: Healthy volunteers<br> | Biological: Blood sampling at inclusion<br>* Sampling of 2 tubes of 3 ml: patient: H0: 0-6h post-admission healthy volunteer: at inclusion<br>Other: Data collection<br>* clinical and biological medical data for patients and general health data for healthy volunteers<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of mitophagy |  | at admission and at 24 hours post-admission |