modern medicine, associated with profound morbidity and high mortality rates. As a clinical syndrome characterized by a dysregulated systemic response to infection, its progression toward life-threatening organ dysfunction is driven by an array of signaling molecules. Extracorporeal therapy has emerged as a key adjunctive strategy for the targeted elimination of these inflammatory mediators. While current modalities - including non-selective cytokine adsorption, selective LPS-adsorption, and therapeutic plasma exchange (TPE) - have shown clinical benefits in specific patient cohorts, research into more precise interventions continues.

A new frontier focuses on the extracorporeal removal of cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs), which recognized as pivotal drivers of systemic inflammation. This study evaluates the "Nucleocor" plasma adsorption column, a pioneering device designed for the selective removal of DNA-containing structures. By targeting septic shock patients with prognostically unfavorable cfDNA elevations, this research aims to establish standardized protocols and generate the evidence base necessary for integrating this novel therapy into national clinical guidelines.

Sepsis remains a critical problem with significant morbidity and mortality for a modern healthcare. According to the latest definitions, sepsis is a clinical syndrome defined by a systemic response to infection leading to organ failure. Recent breakthroughs in the pathophysiology of sepsis have identified key signaling molecules - including cytokines, toxins, and DAMPs - that initiate and perpetuate the dysregulated immune response. As an adjunctive treatment, extracorporeal therapy has emerged as an effective strategy for the targeted elimination of these mediators.

Current clinical and research methods include: non-selective hemoperfusion, which targets pro-inflammatory middle-molecular-weight proteins (10-60 kDa) such as s IL-1, TNF-α, IL-2, IL-6, IL-8, IL-10, IFN-γ and complement proteins (e.g., CytoSorb, HA330 hemadsorption cartridges); and selective hemoperfusion, designed to eliminate Gram-negative bacterial lipopolysaccharides (LPS) via affinity-binding fibers like Polymyxin B (e.g., Toraymyxin). A meta-analysis by Li et al. (2021), synthesizing data from 13 randomized controlled trials, demonstrated that LPS-selective hemoperfusion significantly reduces mortality and endotoxin levels while stabilizing hemodynamic parameters. The EUPHRATES trial, the largest RCT to date, demonstrated improvements in mean arterial pressure and 28-day survival exclusively within the subgroup of patients exhibiting endotoxin activity levels between 0.6 and 0.89.

Therapeutic Plasma Exchange (TPE) serves as an alternative adjunctive therapy that entails the complete separation and removal of the patient's plasma from cellular components, including cytokines and toxins. A recent EXCHANGE-1 study has demonstrated that TPE is associated with the reduction of acute-phase proteins and improved hemodynamics in patients with septic shock. The clinical potential of TPE in sepsis treatment remains a subject of active investigation.

A prominent frontier in sepsis research focuses on the novel approach extracorporeal removal of cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs), which are now recognized as one more critical drivers of systemic inflammation. Excessive cell-free DNA (cfDNA) acts as DAMP, further activating immune cells and the endothelium through the TLR-9 (Toll-like receptor) signaling pathway. This process leads to cellular damage and microvascular thrombosis. Consequently, cfDNA serves as a primary driver of 'immunothrombosis' - a state of inflammation-induced hypercoagulation. Furthermore, cfDNA is implicated in the pathogenesis of sepsis-associated acute kidney and lung injury. These mechanisms provide a robust hypothetical framework for therapies targeting the extracorporeal elimination of cfDNA in septic shock.

Some hemoadsorption cartridges like 'Nucleocor' bind circulating histones to prevent them from triggering NETosis and systemic inflammation. To date, there are no universally accepted guidelines for the extracorporeal elimination of DNA-containing structures-such as cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs)-from the systemic circulation in sepsis and septic shock. This study will evaluate the efficacy and safety of extracorporeal therapy using 'Nucleocor' plasma adsorption columns in patients with septic shock characterized by prognostically unfavorable elevations in cfDNA levels. The 'Nucleocor' adsorption columns represent a unique, world-first device designed for the selective removal of DNA-containing molecular structures from the bloodstream. The project aims to establish a standardized protocol for this extracorporeal therapy and generate the evidence base required for its inclusion in national clinical guidelines.

Inclusion Criteria:

• The age of patients is 18-65 years,
• Septic shock (Sepsis-3 criteria) with dependence on vasopressor and/ or sympathomimetic therapy (norepinephrine - more than 0.05 mcg / kg/min, adrenaline - more than 0.05 mcg / kg/min), persisting after correction of hypovolemia.
• concentration of cfDNA in the bloodstream is greater than its prognostically unfavorable level, determined by the fluorimetric method, or the presence of predictors of a prognostically unfavorable level of cfDNA: the concentration of mixed venous blood lactate is more than 1.9 mmol/l, the number of SOFA scores is more than 7

Exclusion Criteria:

• Clinical death after the onset of sepsis;
• An untreated surgical infection site;
• History of transfusion-related acute lung injury;
• Allergy to heparin, GIT in the anamnesis;
• Uncontrolled bleeding or a high risk of its occurrence,
• The presence of cardiovascular events within the last 2 months: AMI, stroke, PE, Severe congestive CHF;
• Severe chronic congestive heart failure;
• End-stage CKD;
• Chronic use of immunosuppressive therapy;
• HIV infection, Constant use of immunosuppressive therapy, severe granulocytopenia (WBC less than 500 cells /mm3),
• Development of acute cardiovascular insufficiency characterized by hypotension (BP system. less than 60 mmHg) and/or bradycardia (heart rate less than 40 min -1), refractory to adrenaline (bolus of more than 100 micrograms or infusion of more than 300 mcg/kg/min).