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The purpose of blood purification therapy is to remove uremic toxins, and middle molecules (MMs) are a specific target. An MM is defined as a solute that passes through the glomerulus with a molecular weight in the range of 0.5–58 kDa, and new classifications of "small-middle 0.5–15 kDa," "medium-middle 15–25 kDa," and "large-middle 25–58 kDa" were proposed. In Japan, the removal of α1-microglobulin (αMG) in the large-middle range has been the focus, but a new theory of removal has been developed, emphasizing the antioxidant effect of αMG as a physiological function. Clinical proof of this mechanism will lead to further development of blood purification therapies. [ABSTRACT FROM AUTHOR]

(1) Background: Cardiac surgery may evoke a generalized inflammatory response, typically magnified in complex, combined, redo, and emergency procedures with long aortic cross-clamp times. Various treatment options have been introduced to help regain control over post-cardiac surgery hyper-inflammation, including hemoadsorptive immunomodulation with CytoSorb®. (2) Methods: We conducted a single-center retrospective observational study of patients undergoing complex cardiac surgery. Patients intra-operatively treated with CytoSorb® were compared to a control group. The primary outcome was the change in the vasoactive-inotropic score (VIS) from pre-operatively to post-operatively. (3) Results: A total of 52 patients were included in the analysis, where 23 were treated with CytoSorb® (CS) and 29 without (controls). The mean VIS increase from pre-operative to post-operative values was significantly lower in the CS group compared to the control group (3.5 vs. 5.5, respectively, p = 0.05). In-hospital mortality in the control group was 20.7% (6 patients) and 9.1% (2 patients) in the CS group (p = 0.26). Lactate level changes were comparable, and the median intensive care unit and hospital lengths of stay were similar between groups. (4) Conclusions: Despite notable imbalances between the groups, the signals revealed point toward better hemodynamic stability with CytoSorb® hemoadsorption in complex cardiac surgery and a trend of lower mortality. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb® and four Oxiris® hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45–85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb® blood flow [mL/min] = 4.226 × MAP [mmHg] − 3.496 (R-square 0.8133) and Oxiris® blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb® and Oxiris® devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes. [ABSTRACT FROM AUTHOR]

Background: Patients on direct oral anticoagulants are at high risk of perioperative bleeding complications. We analyzed the results of intraoperative hemoadsorption (HA) in patients undergoing cardiac surgery who were also on concurrent therapy with apixaban. Methods: we included 25 consecutive patients on apixaban who underwent cardiac surgery with the use of cardio-pulmonary bypass (CPB) at three sites. The first 12 patients underwent surgery without hemoadsorption (controls), while the next 13 consecutive patients were operated with the Cytosorb® (Princeton, NJ, USA) device integrated into the CPB circuit (HA group). The primary outcome was perioperative bleeding assessed by the Bleeding Academic Research Consortium (BARC) definition and secondary outcomes included 24 h chest-tube-drainage (CTD) and need for 1-deamino-8-d-arginine-vasopressin (desmopressin (DDAVP)) administration to achieve hemostasis. Results: Preoperative mean daily dose of apixaban was higher in the HA group (8.5 ± 2.4 vs. 5.6 ± 2.2 mg, p = 0.005), while time since last apixaban dose was longer in the controls (1.3 ± 0.9 vs. 0.6 ± 1.2 days, p < 0.001). No BARC-4 bleeding events and no repeat-thoracotomies occurred in the HA group compared with 3 and 1, respectively, in the controls. Postoperative 24 h CTD volume was significantly lower in the HA group (510 ± 152 vs. 893 ± 579 mL, p = 0.03) and there was no need for DDAVP compared to controls, who received an average of 10 ± 13.6 mg (p = 0.01). Conclusions: In patients on apixaban undergoing emergent cardiac surgery, the intraoperative use of hemoadsorption was feasible and safe. Compared to patients operated on without hemoadsorption, BARC-4 bleeding complications did not occur and the need for 24 h CTD and DDAVP was significantly lower. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide, the main component of the outer membrane of Gram-negative bacteria is a highly potent endotoxin responsible for organ dysfunction in sepsis. It is present in the blood stream not only in Gram-negative infections, but also in Gram-positive and fungal infections, presumably due to sepsis-related disruption of the intestinal barrier. Various pathways, both extra- and intracellular, are involved in sensing endotoxin and non-canonical activation of caspase-mediated pyroptosis is considered to have a major role in sepsis pathophysiology. Endotoxin induces specific pathological alterations in several organs, which contributes to poor outcomes. The adverse consequences of endotoxin in the circulation support the use of anti-endotoxin therapies, yet more than 30 years of experience with endotoxin adsorption therapies have not provided clear evidence in favor of this treatment modality. The results of small studies support timely endotoxin removal guided by measuring the levels of endotoxin; unfortunately, this has not been proven in large, randomized studies. The presence of endotoxemia can be demonstrated in the majority of patients with COVID-19, yet only case reports and case series describing the effects of endotoxin removal in these patients have been published to date. The place of blood purification therapies in the treatment of septic shock has not yet been determined. [ABSTRACT FROM AUTHOR]

Background: Aim of this study was to evaluate the outcomes of endocarditis patients undergoing valve surgery with the Cytosorb® hemoadsorption (HA) device during cardiopulmonary bypass. Methods: From 2009 until 2019, 241 patients had undergone valve surgery due to endocarditis at the Department of Cardiac Surgery, University Hospital of Basel. We compared patients who received HA during surgery (n = 41) versus patients without HA (n = 200), after applying inverse probability of treatment weighting. Results: In-hospital mortality, major adverse cardiac and cerebrovascular events and postoperative renal failure were similar in both groups. Demand for norepinephrine (88.4 vs. 52.8%; p = 0.001), milrinone (42.2 vs. 17.2%; p = 0.046), red blood cell concentrates (65.2 vs. 30.6%; p = 0.003), and platelets (HA vs. Control: 36.7 vs. 9.8%; p = 0.013) were higher in the HA group. In addition, a higher incidence of reoperation for bleeding (34.0 vs. 7.7 %; p = 0.011), and a prolonged length of in-hospital stay (15.2 (11.8 to 19.6) vs. 9.0 (7.1 to 11.3) days; p = 0.017) were observed in the HA group. Conclusions: No benefits of HA-therapy were observed in patients with infective endocarditis undergoing valve surgery. [ABSTRACT FROM AUTHOR]

Nafamostat mesylate (NM) is a synthetic serine protease inhibitor that can be used as an anticoagulant during blood purification in critically ill patients, as well as a treatment for disseminated intravascular coagulation. Although NM has been reported to reduce the risk of bleeding during blood purification, its effect on survival outcomes of patients who received blood purification treatments is unclear. We hypothesized that administration of NM during blood purification can reduce mortality in patients with sepsis. A post hoc analysis was conducted on a nationwide retrospective registry that included data from 3195 sepsis patients registered at 42 intensive care units throughout Japan. We evaluated the effect of NM on hospital mortality and bleeding complications using propensity score matching in 1216 sepsis patients who underwent blood purification in the intensive care unit (ICU). Two-hundred-and-sixty-eight pairs of propensity score-matched patients who received NM and conventional therapy were compared. Hospital and ICU mortality rates in the NM group were significantly lower than those in the conventional therapy group. However, rates of bleeding complications did not differ significantly between the two groups. These data suggest that administration of NM improved the survival outcomes of sepsis patients who underwent blood purification in the ICU. [ABSTRACT FROM AUTHOR]