ObjectiveSepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system.Measurements and main resultsPurified proteins were added to whole blood at clinically relevant concentrations and recirculated through a device filled with CytoSorb® hemoadsorbent polymer beads (CytoSorbents Corporation, USA) or control (no bead) device in vitro. Except for the TNF-α trimer, hemoadsorption through porous polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS, PAMPS and mycotoxins by more than 50 percent.ConclusionsThis study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive SIRS response, organ dysfunction and death in patients with a broad range of life-threatening inflammatory conditions such as sepsis, toxic shock syndrome, necrotizing fasciitis, and other severe inflammatory conditions.

Mycotoxins, such as aflatoxin B 1 (AFB 1), pose a serious threat as biological weapons due to their high toxicity, environmental stability, easy accessibility and lack of effective therapeutics. This study investigated if blood purification therapy with CytoSorb (CS) porous polymer beads could improve survival after a lethal aflatoxin dose (LD 90). The effective treatment window and potential therapeutic mechanisms were also investigated. Sprague Dawley rats received a lethal dose of AFB 1 (0.5-1.0 mg/ kg) intravenously and hemoperfusion with a cS or control device was initiated immediately, or after 30, 90, or 240-minute delays and conducted for 4 hours. The CS device removes AFB 1 from circulation and significantly improves survival when initiated within 90 minutes of toxin administration. Treated subjects exhibited improved liver morphology and health scores. changes in the levels of cytokines, leukocytes and platelets indicate a moderately-severe inflammatory response to acute toxin exposure. Quantitative proteomic analysis showed significant changes in the level of a broad spectrum of plasma proteins including serine protease/endopeptidase inhibitors, coagulation factors, complement proteins, carbonic anhydrases, and redox enzymes that ostensibly contribute to the therapeutic effect. Together, these results suggest that hemoadsorption with cS could be a viable countermeasure against acute mycotoxin exposure. Aflatoxins are toxic secondary fungal metabolites (mycotoxins) produced by fungus from the genus Aspergillus that cause severe acute reactions that can be lethal. Aspergillus species are important human pathogens and the toxic metabolites appear to act as virulence factors to suppress the immune system in invasive aspergillosis 1. Aflatoxins cause damage to the liver resulting in hemorrhagic liver necrosis, steatosis, bile duct proliferation and subsequent organ failure and have been detected in pulmonary lesions of immune-compromised patients with systemic aspergillosis 2. Aflatoxin B 1 (AFB 1), the most potent toxin of the 14 naturally occurring aflatoxin variants, is extremely cytotoxic, genotoxic, and carcinogenic 3,4. In the liver, cytochrome P450-modified AFB 1 forms DNA adducts that lead to impaired cellular function, carcinogenesis and/or cell death and organ failure 5,6. Acute aflatoxin poisoning from mold contaminated foods has been linked with numerous deaths in several instances 7,8. Importantly, mycotoxins pose a serious threat as potential biowarfare agents due to their inherent stability and ease of manufacture. The toxins can be readily weaponized into aerosol form and dispersed over a wide area to elicit mass casualties through both inhalation and dermal exposure 9. There have been several reported incidents of use of mycotoxins as bioweapons in Southeast Asia and the Gulf States 10,11. Early symptoms of mycotoxin exposure in bio-warfare manifest rapidly in minutes to hours and can include burning, pain, wheezing, nausea, vomiting, tearing, weakness, bleeding and a host of other symptoms...

Background Patients with kidney failure are at risk for lethal complications from hyperkalemia. Resuscitation, medications, and hemodialysis are used to mitigate increased potassium (K+) levels in circulating blood; however, these approaches may not always be readily available or effective, especially in a resource limited environment. We tested a sorbent cartridge (KC, K+ontrol CytoSorbents Medical Inc., Monmouth Junction, New Jersey) which contains a resin adsorber for K+. The objective of this study was to test the utility of KC in an ex vivo circulation system. We hypothesized that KC reduces K+ levels in extracorporeal circulation of donor swine whole blood infused with KCl. Methods A six-hour circulation study was carried out using KC, a NxStage (NxStage Medical, Inc., Lawrence, MA) membrane, blood bag containing heparinized whole blood with KCl infusion, 3/16-inch ID tubing, a peristaltic pump, and flow sensors. The NxStage permeate line was connected back to the main circuit in the Control group ( n = 6), creating a recirculation loop. For KC group ( n = 6), KC was added to the recirculation loop, and a continuous infusion of KCl at 10 mEq/hour was administered for two hours. Blood samples were acquired at baseline and every hour for 6 h. Results In the control group, K+ levels remained at ∼9 mmol/L; 9.1 ± 0.4 mmol/L at 6 h. In the KC group, significant decreases in K+ at hour 1 (4.3 ± 0.3 mmol/L) and were sustained for the experiment duration equilibrating at 4.6 ± 0.4 mmol/L after 6 h ( p = 0.042). Main loop blood flow was maintained under 400 mL/min; recirculation loop flow varied between 60 and 70 mL/min in the control group and 45–55 mL/min in the KC group. Decreases in recirculation loop flow in KC group required 7% increase of pump RPM. Conclusions During ex-vivo extracorporeal circulation using donor swine blood, KC removed approximately 50% of K+, normalizing circulating levels.