The goal of this observational study is to evaluate whether whole blood H3.1 nucleosome levels can predict 30-day mortality in adult critically ill patients admitted to the ICU with conditions such as sepsis, septic shock, cardiogenic shock, severe trauma, post-cardiac arrest, acute brain injury, or severe acute pancreatitis.

The main questions it aims to answer are:

Do initial whole blood H3.1 nucleosome levels predict 30-day mortality in critically ill patients?

Are whole blood nucleosome measurements using a novel point-of-care device correlated with traditional plasma chemiluminescence immunoassays (ChLIA)?

If there is a comparison group: Researchers will compare point-of-care whole blood nucleosome results with plasma ChLIA assays to see if the device provides reliable and feasible bedside measurements.

Participants will:

Provide blood samples at admission, 6h, Day 1, Day 3, and Day 7 for nucleosome analysis.

Undergo point-of-care H3.1 nucleosome measurement and parallel plasma storage for ChLIA testing.

(If applicable, in acute brain injury patients with external ventricular drains) provide daily cerebrospinal fluid samples until Day 5, only if otherwise discarded.

Have standard ICU data (SOFA, SAPS II, etc.) collected as part of routine care.

The NuROPI study is a prospective, observational, non-interventional, monocentric study conducted in the Intensive Care Unit (ICU) of Erasme Hospital, Brussels. It aims to evaluate the association between initial levels of H3.1 nucleosomes in whole blood and 30-day mortality in critically ill patients, and to validate a novel point-of-care device for nucleosome measurement against standard chemiluminescence immunoassay (ChLIA) performed on plasma.

Inclusion requires the presence of an arterial or central venous catheter for blood sampling. Exclusion criteria include age <18, life expectancy <24 hours, therapeutic limitations, active cancer, absence of vascular access, ICU stay >24h before screening, or prior inclusion. Blood will be sampled at five predefined timepoints: admission (H0), 6 hours (H6), Day 1 (D1), Day 3 (D3), and Day 7 (D7). At each timepoint, four 5 mL blood tubes will be collected during routine care, and a 20 µL aliquot will be used for immediate point-of-care H3.1 measurement. Plasma will be extracted and stored for delayed ChLIA analysis. In patients with acute brain injury and an external ventricular drain (EVD), cerebrospinal fluid (CSF) will be sampled daily until Day 5, but only if the fluid is otherwise intended to be discarded. The study seeks to establish whether nucleosome levels can serve as a biomarker for prognosis and patient stratification in critical illness.

Standard ICU data such as SOFA scores and SAPS II will be recorded, as is already routinely done in some registries like Epimed.

Data will be entered into RedCap by the research team and the investigators.

The study population will consist of 130 adult critically ill patients admitted to the Intensive Care Unit (ICU) of Erasme Hospital. Eligible participants must be 18 years or older and admitted to the ICU within the past 24 hours. All patients must have arterial or central venous access for blood sampling. The population will include a diverse group of critically ill individuals representing various acute conditions commonly encountered in intensive care:

• Sepsis, as defined by SEPSIS-3 criteria (approximately 30 patients)
• Septic shock, per SEPSIS-3 (approximately 30 patients)
• Cardiogenic shock, classified as at least SCAI stage C (approximately 10 patients)
• Severe trauma, requiring at least 4 units of red blood cells within 6 hours post-admission (approximately 10 patients)
• Acute brain injury, requiring invasive neuromonitoring (approximately 20 patients)
• Post-cardiac arrest, with at least 15 minutes of no or low perfusion (approximately 20 patients)
• Severe acute pancreatitis, requiring ICU management (approximately 10 patients) This heterogeneous ICU population is specifically chosen to evaluate the relevance of H3.1 nucleosome levels across multiple critical illness etiologies.

Objectives

Primary

- To evaluate the association between initial levels of H3.1 nucleosomes in whole blood and 30-day mortality in a cohort of critically ill patients.

Secondary

• To assess the correlation between nucleosome levels measured in whole blood at the point of care and traditional chemiluminescence immunoassays performed on plasma.
• To validate the feasibility and reliability of a novel point-of-care device for rapid nucleosome quantification.
• To determine whether nucleosome measurement is relevant across a variety of critical conditions (e.g., sepsis, septic shock, cardiogenic shock, severe trauma, cardiac arrest, acute brain injury, severe acute pancreatitis)

Inclusion Criteria:

• Admission to the intensive care unit (ICU) within the past 24 hours.
• Patient must meet one of the following conditions:

Sepsis, defined according to SEPSIS-3 criteria.

Septic shock, defined according to SEPSIS-3 criteria.

Cardiogenic shock, classified as Stage C according to the Society for Cardiovascular Angiography and Interventions (SCAI).

Severe trauma requiring transfusion of four or more units of red blood cells within six hours.

Acute brain injury requiring invasive neuromonitoring.

Post-cardiac arrest with at least 15 minutes of no or low perfusion.

Severe acute pancreatitis requiring ICU-level care.

- Presence of an arterial or central venous catheter to allow blood sampling.

Exclusion Criteria

• Patient who has expressed opposition to participate.
• Age younger than 18 years.
• Imminent death with an expected survival of less than 24 hours.
• Presence of therapeutic limitations (e.g., no indication for intubation).
• Active cancer.
• Absence of the required vascular access.
• ICU admission longer than 24 hours prior to screening.
• Readmission of a previously enrolled patient.

The study population will consist of 130 adult critically ill patients admitted to the Intensive Care Unit (ICU) of Erasme Hospital. Eligible participants must be 18 years or older and admitted to the ICU within the past 24 hours. All patients must have arterial or central venous access for blood sampling. The population will include a diverse group of critically ill individuals representing various acute conditions commonly encountered in intensive care:

Sepsis Septic shock Cardiogenic shock Severe trauma Acute brain injury Severe trauma Post-cardiac arrest shock Severe pancreatitis