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Most patients admitted to intensive care after severe trauma, high-risk surgery, or acute respiratory distress are frequently characterized by significant initial inflammation accompanied by a compensatory anti-inflammatory response, which can lead to profound post-aggressive immunosuppression. This immunosuppression is associated with an increased risk of nosocomial infections, viral reactivations, prolonged ICU stays, and ultimately, increased mortality. Consequently, immunostimulation with agents such as interferon gamma (IFN-γ) has been proposed as a means to restore immune defense in the most severe patients. However, in a recent study conducted on mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared to placebo did not significantly reduce the incidence of nosocomial pneumonia or 28-day mortality and was even associated with an increase in severe side effects, leading to the premature termination of the trial. These results, along with previous studies, suggest that for IFN-γ to be effective, it must be targeted at patients who have reached the immunosuppressive phase. In the absence of evident clinical signs, the use of biomarkers could guide clinicians in identifying the appropriate patients and the optimal timing for this therapy.
In a recent monocentric study, they evaluated a new automated IFN-γ assay on a cohort of 22 septic patients to monitor T lymphocyte functionality independently of antigen. As expected, the results showed a marked decrease in IFN-γ release, which correlated with altered classical cellular parameters (CD8+ T cells, mHLA-DR). Since the test is performed using whole blood, requires no technician intervention, and provides results within four hours, this project propose to characterize the evolution of the immune status of a large cohort of ICU patients, including those with severe trauma, high-risk surgery, or acute respiratory distress syndrome.
Most patients admitted to intensive care after severe trauma, high-risk surgery, or acute respiratory distress are frequently characterized by significant initial inflammation accompanied by a compensatory anti-inflammatory response, which can lead to profound post-aggressive immunosuppression. This immunosuppression is associated with an increased risk of nosocomial infections, viral reactivations, prolonged ICU stays, and ultimately, increased mortality. Consequently, immunostimulation with agents such as interferon gamma (IFN-γ) has been proposed as a means to restore immune defense in the most severe patients. However, in a recent study conducted on mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared to placebo did not significantly reduce the incidence of nosocomial pneumonia or 28-day mortality and was even associated with an increase in severe side effects, leading to the premature termination of the trial. These results, along with previous studies, suggest that for IFN-γ to be effective, it must be targeted at patients who have reached the immunosuppressive phase. In the absence of evident clinical signs, the use of biomarkers could guide clinicians in identifying the appropriate patients and the optimal timing for this therapy.
Among the described immune alterations and associated biomarkers in critically ill patients, the decrease in Human Leukocyte Antigen (HLA-DR) expression on monocytes (mHLA-DR) has been studied more extensively and is now considered a reliable biomarker for guiding myeloid-targeted immunotherapies. While functional tests are the best means to explore acquired immunosuppression in the ICU, as they directly measure the capacity of a given cell population to respond to an in vitro stimulus, they present analytical obstacles to their deployment. Most protocols are "homemade" and lack standardization, which is a major obstacle to large-scale trials and their use in clinical practice.
In a recent monocentric study, they evaluated a new automated IFN-γ assay on a cohort of 22 septic patients to monitor T lymphocyte functionality independently of antigen. As expected, the results showed a marked decrease in IFN-γ release, which correlated with altered classical cellular parameters (CD8+ T cells, mHLA-DR). Since the test is performed using whole blood, requires no technician intervention, and provides results within four hours, this project propose to characterize the evolution of the immune status of a large cohort of ICU patients, including those with severe trauma, high-risk surgery, or acute respiratory distress syndrome.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adults in Intensive care | Patient included will be adult patients admitted to intensive care after severe trauma, high-risk surgery, or presenting with acute respiratory distress |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| blood sampling | Other | After informing eligible patients (or their trusted support person, relative/guardian/curator where applicable) and in the absence of any opposition, they are included in the research. Blood samples from an arterial catheter already in place will be taken every day from D1 to D7, then every 72 hours until discharge from intensive care, or until D28. For each of these samples, a maximum volume of 4 ml will be collected in a heparinized tube. Samples will not be taken if the hemoglobin level is below 7g/dl. For patients undergoing controlled surgery, the D1 sample will be taken as soon as possible after induction of anaesthesia. Patients will be monitored until discharge from intensive care, or until D28 at the latest. Apart from the blood samples included in this study, all other examinations will be carried out as part of routine management. Data will be collected exclusively from medical records. |
| Measure | Description | Time Frame |
|---|---|---|
| INF-γ production in patients admitted to intensive care after severe trauma, high-risk surgery, or acute respiratory distress | The measurement of INF-γ production will be conducted using a fully automated Interferon Gamma Realease Assay (IGRA) test. | Daily value from day 1 to day 7, then every 72 hours until discharge from intensive care (assessed up to day 28). |
| Measure | Description | Time Frame |
|---|---|---|
| ICU discharge Vital status | Vital status at discharge from ICU | at ICU discharge, and at the latest Day 28 |
| Incidence of nosocomial infections | Incidence of nosocomial infections occurring in the ICU : number, type, and duration of antibiotic therapy |
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Inclusion Criteria:
Exclusion Criteria:
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Patient included will be adult patients admitted to intensive care after severe trauma, high-risk surgery, or presenting with acute respiratory distress
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jean-michel Constantin, MD, PhD | Contact | 33142161936 | jean-michel.constantin@aphp.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Reanimation department, Annecy Genevois hospital | Not yet recruiting | Annecy | 74370 | France |
The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.
Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations
Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor.
Researchers who provide a methodologically sound proposal.
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| ID | Term |
|---|---|
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Blood
|
| From ICU-admission to ICU-discharge, and at the latest Day 28 |
| Incidence of viral reactivations for CMV and HSV | Incidence of viral reactivations as detected by PCR for CMV (Cytomegalovirus) and HSV (Herpes Simplex Virus) in the ICU | From ICU-admission to ICU-discharge, and at the latest Day 28 |
| Length of mechanical ventilation | Duration of mechanical ventilation in ICU | From ICU-admission to ICU-discharge, and at the latest Day 28 |
| Presence of septic shock | Presence of septic shock in the ICU | From ICU-admission to ICU-discharge, and at the latest Day 28 |
| Renal impairment | Renal impairment defined by a Kidney Disease Improving Global Outcomes (KDIGO) score > 1. Scale of 1 to 3, with 3 corresponding to severe acute kidney damage. | From ICU-admission to ICU-discharge, and at the latest Day 28 |
| mHLA-DR expression | mHLA-DR expression by flow cytometry | Daily value from day 1 to day 7, then every 72 hours until discharge from intensive care (assessed up to day 28). |
| Length of ICU stay | Length of stay in intensive care | at ICU discharge, and at the latest day 28 |
| Reanimation department, Clermont-Ferrand Hospital | Not yet recruiting | Clermont-Ferrand | 63000 | France |
|
| Reanimation department, Lyon hospital | Not yet recruiting | Lyon | 69003 | France |
|
| Réanimation cardio-chirurgicale - Pitié-Salpêtrière hospital | Recruiting | Paris | Île-de-France Region | 75013 | France |
|
| Réanimation chirurgicale Gaston Cordier - Pitié-Salpêtrière hospital | Recruiting | Paris | Île-de-France Region | 75013 | France |
|
| Réanimation chirurgicale Husson Mourrier - Pitié-Salpêtrière hospital | Not yet recruiting | Paris | Île-de-France Region | 75013 | France |
|
| Réanimation neuro-chirurgicale - Pitié-Salpêtrière hospital | Not yet recruiting | Paris | Île-de-France Region | 75013 | France |
|
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |