Endotoxin activity trend and multi-organ dysfunction in critically ill patients with septic shock, who received Polymyxin-B hemadsorption: A multicenter, prospective, observational study.

BACKGROUND: The baseline endotoxin activity (EAT0) may predict the outcome of critically ill septic patients who receive Polymyxin-B hemadsorption (PMX-HA), however, the clinical implications of specific EA trends remain unknown. METHODS: Subgroup analysis of the prospective, multicenter, observational study EUPHAS2. We included 50 critically ill patients with septic shock and EAT0 ≥ 0.6, who received PMX-HA. The primary outcome of the study was the EA and SOFA score progression from T0 to 120 h afterwards (T120). Secondary outcomes included the EA and SOFA score progression in whom had EA at 48 h (EAT48) < 0.6 (EA responders, EA-R) versus who had not (EA non-responders, EA-NR). RESULTS: Septic shock was mainly caused by 27 abdominal (54%) and 17 pulmonary (34%) infections, predominantly due to Gram negative bacteria (39 patients, 78%). The SAPS II score was 67.5 [52.8-82.3] and predicted a mortality rate of 75%. Between T0 and T120, the EA decreased (p < 0.001), while the SOFA score and the Inotropic Score (IS) improved (p < 0.001). In comparison with EA-NR (18 patients, 47%), the EA-R group (23 patients, 53%) showed faster IS improvement and lower requirement of continuous renal replacement therapy (CRRT) during the ICU stay. Overall hospital mortality occurred in 18 patients (36%). CONCLUSIONS: In critically ill patients with septic shock and EAT0 ≥ 0.6 who received PMX-HA, EA decreased and SOFA score improved over 120 h. In whom high EA resolved within 48 h, IS improvement was faster and CRRT requirement was lower compared with patients with EAT48 ≥ 0.6.

Signal peptide and N-glycosylation of N-terminal-CD2v determine the hemadsorption of African swine fever virus.

IMPORTANCE: African swine fever virus (ASFV) is the cause of the current major animal epidemic worldwide. This disease affects domestic pigs and wild boars, has spread since 2007 through Russia, Eastern Europe, and more recently to Western European countries, and since 2018 emerged in China, from where it spread throughout Southeast Asia. Recently, outbreaks have appeared in the Caribbean, threatening the Americas. It is estimated that more than 900,000 animals have died directly or indirectly from ASFV since 2021 alone. One of the features of ASFV infection is hemoadsorption (HAD), which has been linked to virulence, although the molecular and pathological basis of this hypothesis remains largely unknown. In this study, we have analyzed and identified the key players responsible of HAD, contributing to the identification of new determinants of ASFV virulence, the understanding of ASFV pathogenesis, and the rational development of new vaccines.

Targeted therapy using polymyxin B hemadsorption in patients with sepsis: a post-hoc analysis of the JSEPTIC-DIC study and the EUPHRATES trial.

BACKGROUND: Polymyxin B hemadsorption (PMX-HA) reduces blood endotoxin levels, but characteristics of patients with sepsis likely to benefit from PMX-HA are not well known. We sought to identify patient subgroups likely to benefit from PMX-HA. METHODS: We retrospectively identified 1911 patients with sepsis from a retrospective observational study in Japan (the JSEPTIC-DIC study) and 286 patients with endotoxemic septic shock from a randomized controlled trial in North America that restricted patients to those with high endotoxin activity (the EUPHRATES trial). We applied the machine learning-based causal forest model to the JSEPTIC-DIC cohort to investigate heterogeneity in treatment effects of PMX-HA on 28-day survival after adjusting for potential confounders and ascertain the best criteria for PMX-HA use. The derived criteria for targeted therapy by PMX-HA were validated using the EUPHRATES trial cohort. RESULTS: The causal forest model revealed heterogeneity in treatment effects of PMX-HA. Since patients having higher treatment effects were more likely to have severe coagulopathy and hyperlactatemia, we identified the potential treatment targets of PMX-HA as patients with PT-INR > 1.4 or lactate > 3 mmol/L. In the EUPHRATES trial cohort, PMX-HA use on the targeted subpopulation (75% of all patients) was significantly associated with higher 28-day survival (PMX-HA vs. control, 68% vs. 52%; treatment effect of PMX-HA, + 16% [95% CI + 2.2% to + 30%], p = 0.02). CONCLUSIONS: Abnormal coagulation and hyperlactatemia in septic patients with high endotoxin activity appear to be helpful to identify patients who may benefit most from PMX-HA. Our findings will inform enrollment criteria for future interventional trials targeting patients with coagulopathy and hyperlactatemia.

Hemadsorption in Critically Ill Children.

Application of extracorporeal blood purification in children is increasing with the improvement of technology and the broadening of indications in critically ill patients. Furthermore, novel devices are being made available with a miniaturized design to be applicable to pediatric machines and circuits. Current literature in the pediatric setting is essentially based on case series and observational studies. Novel prospective uncontrolled databases are underway, and the interest is growing in children, since the potential indications for pediatric sepsis and other inflammatory conditions might rely on the enhanced mediator clearance warranted by these techniques. This review will describe the application of hemadsorption in children, the available cartridges, the clinical results available in the pediatric setting, and the potential future uses.

Effects of cytokine hemadsorption as salvage therapy on common laboratory parameters in patients with life-threatening COVID-19.

BACKGROUND: The COVID-19 pandemic has led to emergency approval of treatment modalities unusual for viruses, such as therapeutic cytokine Hemadsorption(HA). This study aims to investigate the experience of salvage HA therapy and the effect of HA on routine laboratory tests. METHODS: Life-threatening COVID-19 patients followed up between April 2020 and October 2022 who underwent HA salvage therapy were retrospectively enrolled. Data derived from the medical records were evaluated to meet the assumptions of statistical tests, and those that met the relevant statistical rules were selected for further analysis. Tests of Wilcoxon, Paired-T, and repeated measures-ANOVA were used to analyse the laboratory tests performed before and after HA among the surviving and nonsurviving patients. P < 0.05 was selected for the statistical significance of the alpha. RESULTS: A total of 55 patients were enrolled in the study. Fibrinogen (p = 0.007), lactate dehydrogenase (LDH) (p = 0.021), C-reactive protein (CRP) (p < 0.0001), and platelet (PLT) (p = 0.046) levels showed a significant decrease with the HA effect. WBC (p = 0.209), lymphocyte (p = 0.135), procalcitonin (PCT) (p = 0.424), ferritin (p = 0.298), and D-dimer (p = 0.391) levels were not affected by HA. Ferritin level was significantly affected by survival status (p = 0.010). All patients tolerated HA well, and 16.4 % (n = 9) of the patients with life-threatening COVID-19 survived. CONCLUSION: HA is well tolerated even when used as a last option. However, HA may not affect WBC, lymphocyte, and D-dimer levels. In contrast, the effect of HA could limit the benefits of LDH, CRP, and fibrinogen in various clinical assessments. This study suggests that HA treatment could be beneficial even if selected as a salvage therapy.

Hemoadsorption as part of a multimodal therapy concept to treat Capnocytophaga sepsis with thrombocytopenia and multiple organ failure.

BACKGROUND: Capnocytophaga, a bacteria native to the oral flora of canines, in rare cases can lead to severe infections resulting in septic shock, respiratory tract infection, and multiple organ failure. In case of trauma following animal bites with rapidly progressing clinical courses, also adjunctive therapeutic measures such as extracorporeal blood purification therapies might be beneficial. CASE PRESENTATION: We report on a 68-year-old male who was hospitalized with fever, oliguria and repeated vomiting after suffering a minor bite by his dog. On admission, he was diagnosed with sepsis. In addition, his coagulation status was markedly deranged resulting in the administration of mass transfusions to stabilize his coagulative status. Following detection of Capnocytophaga canimorsus, anti-infective therapy was initiated. In the context of a progressive respiratory deterioration and an increasing vigilance disorder, he had to be intubated. Due to development of renal failure, dialysis was started in conjunction with CytoSorb hemoadsorption therapy to control the hyperinflammatory condition. All of the applied therapeutic measures led to a rapid clinical stabilization, a control of the hyperinflammatory situation, and an improvement in his neurological status. The therapy was well tolerated with no complications encountered. CONCLUSIONS: This case supports the clinical recognition of severe Capnocytophaga infection that can lead to critical conditions even in immunocompetent patients. Combined broad spectrum antibiotic therapy, mass transfusions, CRRT, and CytoSorb hemoadsorption therapy resulted in a control of the critical situation. However, further research is needed to fully elucidate the role of hemoadsorption in this rare but life-threatening setting.

Hemadsorption in patients requiring V-A ECMO support: Comparison of Cytosorb versus Jafron HA330.

BACKGROUND: ECMO support is associated with the development of a systemic hyper-inflammatory response, which may become quite significant and extreme in some cases. We hypothesize that Cytosorb or Jafron therapy may benefit patients on V-A ECMO in terms of levels of inflammatory markers such as IL-6, complications, and overall outcomes. METHODS: We conducted a retrospective study of prospectively collected data in a single tertiary care center between January 2021 and April 2022. At the time of the analysis of this article, 20 patients on V-A ECMO had cytokine adsorption while on ECMO support: Cytosorb group (n = 10), Jafron group (n = 10). In 10 ECMO-supported patients cytokine adsorption was not used, this group served as a control group, which may be quite significant in some cases. Evaluation of the level of inflammatory markers (IL-1, 6, 8; CRP, Leukocyte, Lactate, PCT, NT-proBNP, TNF-α) was performed. RESULTS: There was statistically significant longer CPB time, aortic cross-clamp time and ICU stay in cytokine adsorption groups than in the control group, but there were no differences between subgroups with different types of haemoadsorption used. Moreover, in the control group mortality rate was higher than in the cytokine adsorption groups (60% vs. 20%, p = 0.02). All patients had an elevation of inflammatory markers in the perioperative and immediate postoperative periods. After 72 h of intensive care, blood inflammation markers had a tendency to decline. CONCLUSION: At the time of writing, hemadsorption in patients requiring V-A ECMO support represents a good therapeutic effect. This effect is permanent for the whole period of extracorporeal cytokine hemadsorption application for both CytoSorb and Jafron HA330 devices.

Effect of Hemadsorption Therapy in Critically Ill Patients with COVID-19 (CYTOCOV-19): A Prospective Randomized Controlled Pilot Trial.

INTRODUCTION: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from the removal of inflammatory mediators via hemadsorption. METHODS: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 µg/kg/min to maintain a mean arterial pressure ≥65 mm Hg), interleukin-6 (IL-6) ≥500 ng/L, and an indication for renal replacement therapy or extracorporeal membrane oxygenation were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18-24 h. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min ≥24 h). RESULTS: Of 242 screened patients, 24 were randomized and assigned to either HT (N = 12) or SMT (N = 12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p = 0.590) and SOFA (17 vs. 16, p = 0.551). Median IL-6 levels were 2,269 (IQR 948-3,679) and 3,747 (1,301-5,415) ng/L in the HT and SMT groups at baseline, respectively (p = 0.378). Shock resolution (primary endpoint) was reached in 33% (4/12) versus 17% (2/12) in the HT and SMT groups, respectively (p = 0.640). Twenty-eight-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p = 1.0). During the treatment period of 5 days, 6/12 (50%) of the SMT patients died, in contrast to 1/12 (8%) in the HT group. CONCLUSION: HT was associated with a non-significant trend toward clinical improvement within the intervention period. In selected patients, HT might be an option for stabilization before transfer and further therapeutic decisions. This finding warrants further investigation in larger trials.

Comparison of Cytokine Hemadsorption as an Immunomodulator Therapy in COVID-19 Patients with and without Bacterial Sepsis.

BACKGROUND: In this retrospective study, we aimed to compare the laboratory and clinical results of cytokine hem-adsorption as an immunomodulation therapy in COVID-19 ICU patients with or without sepsis. METHODS: The levels of PCT, CRP, and ferritin were determined as indicators of infection/sepsis; the levels of in-terleukins (IL-6, IL-8 and IL-10, and TNF-α) were determined as indicators of cytokine storm were compared. APACHE score, SOFA score, and mortality rates were compared for the progression of the disease in 23 COVID-19 patients. RESULTS: The therapy was generally successful in reducing the levels of IL-6, IL-8, IL-10, and TNF-α but the levels measured after the procedure did not differ among the patients with or without sepsis, suggesting that the presence of sepsis did not affect the efficacy and function of the cytokine hemadsorption procedure in COVID-19 patients. All parameters were reduced after the procedure except the levels of PCT and ferritin and mortality rates of patients diagnosed with sepsis. The level of PCT was significantly higher in these patients compared with the patients without sepsis while the ferritin and mortality did not show any significant difference between the two groups, suggesting that the cytokine hemadsorption may be safe in the treatment of critical COVID-19 patients. CONCLUSIONS: As a result, the progression of sepsis in COVID-19 may be avoided with cytokine hemadsorption applied as an immunomodulator therapy. However, this therapy should be further explored and validated prior to its introduction to everyday clinical practice when the epidemic conditions end.

African Swine Fever Virus Hemadsorption Inhibition Assay.

Adsorption of red blood cells (hemadsorption) on the surface of macrophages infected with African swine fever virus (ASFV) is a unique phenomenon allowing to determine virus infectious titer in hemadsorption unit (HAU) and differentiate virus strains phenotypically. In the meantime, hemadsorption of particular ASFV strain can by inhibited by homologous anti-ASFV serum containing antibody to the serogroup-specific virus protein (CD2v). Here, we describe a hemadsorption inhibition assay (HADIA) to phenotype ASFV strains to one of the known nine serogroups using blood-derived swine macrophages. The HADIA is a powerful method in the ASFV immunopathology and vaccine research since it provides additional antigenic and phenotypic characteristics of virus strains that can't be defined by other assays.

Hemadsorption for removal of ticagrelor and direct oral anticoagulants in cardiac surgery.

INTRODUCTION: Cardiac patients on antiplatelets or oral anticoagulation undergoing emergent cardiac surgery without appropriate washout periods are at increased risk for developing perioperative bleeding. CytoSorb is a commercially available hemadsorption adsorber that can simultaneously remove a wide range of substances including ticagrelor, and direct oral anticoagulants (DOACs). AREAS COVERED: Although CytoSorb has been used to remove various protein-bound substances, this review will specifically evaluate and review current evidence for applying CytoSorb in removing ticagrelor and DOACs using four in vitro studies, three case reports, one retrospective study and two cost analysis studies. Based on limited evidence, CytoSorb may be effective in reducing perioperative bleeding by reducing chest tube output, blood product transfusions, and re-thoracotomy rates. CytoSorb can also reduce length of intensive care unit (ICU) and hospital stay. Although, CytoSorb has an initial upfront cost, it was proven to be cost-effective due to potential health resource savings on both short- and long-term projections. EXPERT COMMENTARY: CytoSorb provides a novel strategy to remove ticagrelor and DOACs in patients requiring emergency cardiac surgery. Although promising results, more solid evidence is required to establish its clinical effectiveness in reducing perioperative bleeding, bleeding-related complications, mortality, and finally, its overall safety.

Literature Review of Hemadsorption Therapy in Severe COVID-19 Cases: a Narrative Review.

BACKGROUND: A novel therapy for reducing the cytokines in the circulatory system used for severe COVID-19 cases was hemoperfusion or hemadsorption method. Although the hemoperfusion methods have been shown to be beneficial in the cytokine storm during influenza infection, it is not known to what extent it is successful for COVID-19 patients. Therefore, the purpose of this study is to review the studies on severe COVID-19 treated with the hemoperfusion methods. METHODS: A literature search was conducted using the databases PubMed, Science Direct, and Springer databases. Since the included articles consisted of case reports, case series, and one controlled trial, only the mean of the analyzed data could be calculated. RESULTS: Sixteen studies were included in the narrative review, including 86 patients with severe COVID-19. All the patients had hemoperfusion therapy with following cartridges: CytoSorb®, oXiris®, Biosky filter, SeaStar® CLR filter, HA280, HA330 Jafron©, and resin directed hemadsorption cartridges. Mortality rate, the mean of intubation time, duration in intensive care unit and hospital were 29%, 14.93 days, 17.21 days, and 31.7 days, respectively. The mean values of C-reactive protein and interleukin-6 decreased after hemoperfusion sessions (131.7 to 66.0, 527.5 to 334.7, respectively). CONCLUSIONS: In this narrative review, it is demonstrated that hemadsorption therapy is an alternative salvage treatment method in critically ill COVID-19 patients, but the data must be supported by strong evidence.

Hemoperfusion with CytoSorb® in Critically Ill COVID-19 Patients.

INTRODUCTION: Systematic inflammatory response occurred in some critically ill patients with COVID-19. Cytokine reduction by hemadsorption is a mechanism of treatment. However, whether CytoSorb hemoperfusion works for critically ill COVID-19 patients remains unknown. MATERIALS AND METHODS: We observed case series of critically ill COVID-19 patients receiving CytoSorb hemoperfusion as rescue therapy from 3 hospitals in Hubei, China from February 28, 2020, to April 7, 2020. Their demographic, laboratory, and clinical data were collected. The parameters for organ function and IL-6 levels were compared before and after treatments. RESULTS: A total of 10 cases were included. The median age of the patients was 67.7 years (range = 50-85) with APACHE II (23.5) and SOFA (11.4). Patients received a median of 3 attempts of hemoperfusion (range = 1-6). The median CytoSorb perfusion time was 47 h (12-92 h). The level of IL-6 significantly decreased after treatments (712.6 [145-5,000] vs. 136.7 [46.3-1,054] pg/mL, p = 0.005). Significant improvement was found in PaO2/FiO2 (118 [81-220] vs. 163 [41-340] mm Hg, p = 0.04) and lactate levels (2.5 [1-18] vs. 1.7 [1.1-10] mmol/L, p = 0.009). The hemodynamics measured by norepinephrine/MAP slightly improved after treatment (17 [0-68] vs. 8 [0-39], p = 0.09). Albumin mildly decreased after CytoSorb. No significant changes were found in red blood cell counts, white cell counts, and platelets. CONCLUSION: Treatment with CytoSorb in critically ill COVID-19 patients was associated with decreased IL-6 improvement in oxygenation. However, these effects cannot be confirmed as the direct effects of CytoSorb owing to lack of controls. Establishing causality requires large-scale randomized clinical trials.

Clinical profile and outcomes of Coronavirus Disease 19 (COVID-19) patients who underwent Hemoperfusion (HP) in a tertiary COVID-19 referral hospital: A descriptive study

Introduction@#As of February 4, 2021, a total of 530,118 COVID-19 cases were recorded in the Philippines with a fatality rate of 2.1%. Significant morbidity from COVID-19 is caused by hyperinflammation. Hemoperfusion (HP), which adsorbs inflammatory cytokines, has been performed in the Philippine General Hospital (PGH) as an adjunct to management given to COVID-19 patients. @*Objectives@#This study aimed to describe the clinical and laboratory profile, ventilatory support, therapeutic regimens, and outcomes of COVID-19 patients who underwent hemoperfusion in PGH. @*Methods@#The COVID-19 patient electronic database (April to September 2020) of the Division of Nephrology was reviewed and we included patients with COVID-19 who underwent hemoperfusion. Demographic, clinical, and laboratory data as well as therapeutics and outcomes were described. @*Results@#Sixty-six patients with COVID-19 underwent hemoperfusion. The majority were male (59.1%) with an average age of 61.3 years (SD 15). Hypertension was the most common comorbidity (62.1%). Acute kidney injury (AKI) requiring dialysis comprised 28.8% while 33.3% had diagnosed chronic kidney disease (CKD). The majority were critical COVID-19 cases who had acute respiratory distress syndrome (ARDS) (56.1%). The mean baseline inflammatory marker levels (Il-6, CRP, LDH, ferritin) were elevated. Post-HP inflammatory markers decreased except for IL-6 among patients who died. Most patients were mechanically ventilated (54.5%). Steroids were the most common medications administered (71.2%). Mortality occurred in 62.1% of the patients. The average length of hospital stay was 20.8 days (SD 19.5), duration from admission to first HP 5.9 days (SD 5.8), and 15.3 days (SD 17.4) from first HP to death or discharge. @*Conclusion@#Our study showed the characteristics of patients with COVID-19 who underwent HP. Majority were hypertensive men in their early 60s with critical COVID-19 disease. The mean inflammatory markers were elevated with a decrease in most markers post-hemoperfusion (except for IL-6 among those who died). Despite this, mortality was still high and the average length of hospital stay was long.

Hemadsorption as rescue therapy for patients with multisystem organ failure in pediatric intensive care-Report of two cases reports and review of the literature.

Hemadsorption via the cytokine-adsorber CytoSorb (CytoSorbents Europe, Berlin, Germany) has successfully been used as an adjunctive method in adults, mainly for the purpose of immunomodulation under acute inflammatory conditions such as sepsis and cardiac surgery. In recent years, there has been growing interest in its use in pediatric intensive care to improve outcomes in patients with multiple organ failure following an inflammatory illness. Literature on the application of CytoSorb in neonatal and pediatric patients is scarce, though the implication is that it could be an effective last-resort treatment option in critically ill pediatric patients. Herein we present the clinical cases of two pediatric patients successfully treated with a combination of the CytoSorb hemadsorber, continuous renal replacement therapy, and extracorporeal membrane oxygenation due to multiple organ failure following different underlying medical conditions. Patient 1 was a 7-month-old male child with Down's syndrome admitted to the Pediatric Intensive Care Unit (PICU) after congenital heart surgery, who developed antimicrobial-resistant septic shock and severe acute respiratory distress syndrome. Patient 2 was a 2-year-old male child admitted to the PICU with influenza A-associated acute liver failure resulting in hyperammonemia, lactate acidosis, hemodynamic instability, and acute kidney failure. In both patients, hemadsorption with CytoSorb was initiated as an adjunctive rescue therapy to treat refractory multisystem organ failure. Improvement of laboratory and clinical parameters was observed within hours of treatment initiation. The application of the hemadsorber-developed for use in adults-proved simple and safe for use in both of our low-weight pediatric patients.

Blood purification with CytoSorb in critically ill COVID-19 patients: A case series of 26 patients.

Severe forms of the coronavirus disease 2019 (COVID-19) can progress to sepsis-like complications accompanied by "cytokine storm" for which the most effective treatment has not yet been established. Our study describes the results of CytoSorb hemoadsorption in COVID-19 patients treated on the intensive care unit (ICU). In this retrospective study, 26 patients with COVID-19 and acute respiratory distress syndrome (ARDS) were treated with hemoadsorption therapy. Pre-, and post-treatment values (clinical and laboratory) were compared. Data are expressed as mean (confidence intervals, CI), or median [interquartile ranges, IQR], as appropriate. Patients received 2 hemoadsorption treatments. This resulted in a significant decrease in norepinephrine requirements, and inflammatory marker plasma concentrations (procalcitonin, C-reactive protein, ferritin) when comparing pre versus post treatment levels. The PaO2 /FiO2 and overall organ function (ie, Sequential Organ Failure Assessment-SOFA score) also improved significantly. Patients stayed on the ICU for 9 days and 21 of them survived. To the best of our knowledge, this is one of the largest case series to date reporting early experiences on extracorporeal hemoadsorption therapy in SARS-CoV-2 positive patients with hyperinflammation and moderate ARDS. Treatment proved to be effective, technically feasible and well-tolerated.