{"paper_id":"98675d78-09f2-49ff-bb8e-e3b3ba23ee55","body_text":"The role of hemoadsorption in cardiac surgery – a systematic review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The role of hemoadsorption in cardiac surgery – a systematic review Marijana Matejic-Spasic, Sandra Lindstedt, Guillaume Lebreton, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3805383/v3 This work is licensed under a CC BY 4.0 License Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Abstract Background Despite advancements, cardiopulmonary bypass-assisted cardiac surgery still carries a significant risk for morbidity and mortality, often related to postoperative hyperinflammation. Hemoadsorption of cytokines and various exogenous and endogenous inflammation triggers has been increasingly used in cardiac surgery to mitigate the risk of inflammation-mediated complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to assess the role of perioperative hemoadsorption in cardiac surgery critically. Methods A comprehensive literature search with predefined criteria was conducted. The screening and selection process followed rigorous scientific principles (PRISMA statement). The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search and retrieve all available data. Results The search resulted in 29 publications that were grouped and descriptively analyzed due to the remarkable variability in study designs, however, they all reported exclusively on CytoSorb â therapy. CytoSorb â use was proven feasible and safe with no unanticipated device-related adverse events reported in the retrieved articles. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability. Conclusions The role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery of patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Current evidence suggests limited value from CytoSorb ® use in routine elective surgery and low-risk patients. Further evaluation in more extensive prospective trials is required concerning proper patient selection and postoperative timing and administration. cardiac surgery hemoadsorption hyperinflammation blood purification CytoSorb infective endocarditis aortic surgery heart transplantation ECMO Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Major surgery-related trauma and cardiopulmonary bypass (CPB) itself, are associated with hyperinflammation, formerly described in the literature as SIRS – Systemic Inflammatory Response Syndrome. Despite recent advancements in surgical and anesthetic techniques, open cardiac surgery per se still carries a significant risk for morbidity and mortality [1]. Even with recent developments towards minimally invasive techniques, cardiac surgery using CPB is still the current “gold standard”. Moreover, the complexity of cardiac surgery will further increase due to the aging population, frailty, and many comorbidities. Despite recent advantages in myocardial protection for several hours, systemic pathological inflammation derived from extracorporeal circulation might still occur [2]. Various measures have been introduced to prevent or treat dysregulated inflammatory response in cardiac surgery and reduce its serious harm. However, a single approach cannot block multiple (severe) inflammation pathways. Extracorporeal blood purification techniques have been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or for postoperative complications [2]. This review aims to critically assess the role of hemoadsorption in cardiac surgery, by summarizing the results of published studies conducted in this clinical setting in the last decade. 2. Methods The scope of the current literature search was to identify all relevant studies to summarize the current level of evidence concerning the use of hemoadsorption in the field of cardiac surgery. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search and retrieve all available data. Literature search strategy A comprehensive literature search was conducted of the online database of the United States National Library of Medicine (PubMed) and Cochrane Library. In the literature screening and selection process, we followed the principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [3], to preserve an objective approach (Additional file 1: PRISMA 2020 Checklist). A search of both databases was made on June 1 st , 2023, using the following key search words: “cardiac surgery” OR “cardiothoracic surgery” AND “hemoadsorption” OR “hemoadsorbtion” OR “hemadsorption” OR “hemadsorbtion” OR “haemoadsorption” OR “haemoadsorbtion” OR “haemadsorption” OR “haemadsorbtion”. Abstracts were considered for inclusion if they were written in English and published within the last ten years. Eligibility criteria Publications were eligible for assessment if reporting on original data from comparative studies in which hemoadsorptive device was investigated during or after cardiac surgery. Data extraction and critical appraisal The most important details about all the studies are presented in a tabular view (Additional file 2: Evidence table ). Outcomes related to the intervention were deemed eligible to be included if statistically significant differences were found. For defined primary outcomes, statistically non-significant findings were also included. Considering secondary outcomes, if the difference was not statistically significant but still striking, or the observed trend was evident, such results were added and described as “notable”. Three researchers (P.S., M.T., C.B.) independently assessed these results and the final agreement on the inclusion of notable differences in the analysis was reached by consensus. Primary outcomes were highlighted if defined as such in the respective study. In studies without statistical analysis, findings highlighted in respective articles were copied. 3. Results The search resulted in 186 hits in total. After duplicates were removed (n=71), the remaining abstracts were screened and an additional seven were excluded (details given within the flowchart, Figure 1 ). Furthermore, 108 reports were assessed out of which 79 were deemed ineligible—29 included the wrong patient population (26 studies not associated with cardiac surgery and 3 publications reporting on hemoadsorption utilized for the removal of antithrombotic drugs – a topic already comprehensively covered elsewhere [4]), 33 articles contained no original data, and 17 were case reports or conference papers. Figure 1. Systematic literature search flowchart. Quantity of evidence The literature search resulted in a total of 29 publications that investigated hemoadsorption in cardiac surgery. The technology described in all of them was exclusively the CytoSorb â device (CytoSorbents Inc., Princeton, NJ, USA). The summary of retrieved articles in chronological order, and intervention-reported outcomes, are given in the Evidence table (Additional file 2). This review included a total of 1.057 patients who were treated with hemoadsorption and 988 control patients (subjects from post hoc analyses excluded). Considering the fact that several studies were conducted in the same centers and during overlapping periods, a portion of the above patients may be duplicates, however, it was impossible to identify them and exclude them from the present analysis. Appropriate notes are, therefore, included in respective sections. Assessment of endpoints The variability in study design, patient population, and reported endpoints was vast. Therefore, we decided to report the results of this search in systematic subgroups according to the underlying clinical indication or main surgical procedure. A separate subgroup for patients treated with hemoadsorption in the postoperative cardio-surgical period was also created. The most significant proportion of publications reported on intraoperative hemoadsorption utilization (25/29, 86.2%), including surgery for infective endocarditis (10/29, 34.5%), complex elective cardiothoracic surgery with prolonged CPB time (10/29, 34.5%), aortic surgery (3/29, 10.3%), left ventricular assist device implantation (1/29, 3.4%), and heart transplantation (1/29, 3.4%). The remaining four publications (4/29, 13.8%) reported on the postoperative use of hemoadsorption therapy adjacent to other extracorporeal blood purification techniques such as continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO). The most critical details from the grouped publications are given in the respective sections below. Finally, we assessed the safety of this technique by analyzing device-related adverse events outlined within the obtained literature. 3.1. Infective endocarditis Between 2017 and 2023, 10 published studies investigated the use of hemoadsorption in infective endocarditis surgery ( Table 1 ). Three were randomized controlled trials (RCTs), one case series, and six were comparative retrospective case-controlled studies with three employing dedicated statistical methods for case/control matching. The total cohort of this subgroup comprised 497 patients treated with hemoadsorption and 608 controls (a portion of subjects are likely duplicates, however, the identification and exclusion could not be performed). Indicator for Table 1 (as per instructions, table placed at the end of the document text file) In all studies, CytoSorb â was used intraoperatively by integration into the CPB-circuit, but in the Kühne et al . case series [5] and the small RCT from Asch et al . [6], hemoadsorption therapy was additionally continued postoperatively during the intensive care unit (ICU) period. The most frequently reported outcome was vasopressor requirements and in all but two studies [7, 8], a significant reduction (where statistical analysis was performed) in vasopressor drug demand was observed with intraoperative hemoadsorption. Cytokine reductions with CytoSorb â were confirmed in two studies [8, 9], while significantly lower postoperative sepsis-related mortality with hemoadsorption was observed in four studies [7, 10-12]. Out of these four, one recent study showed a significantly reduced 30- and 90-day mortality in selected patients suffering from Staphylococcus aureus -derived infective endocarditis [12]. Other reported outcomes varied according to each study and are discussed in more detail in the Discussion part of this review. 3.2. Elective complex cardiac surgery The search yielded 10 articles reporting on studies that enrolled patients undergoing elective, but complex, cardiac surgical procedures ( Table 2 ). Eight of the 10 studies were RCTs, six original and two post hoc subgroup analyses from the oldest RCT in this group from Bernardi et al . [13], while the remaining two studies were a prospective case series [14], and a retrospective comparative study [15]. The total cohort of this subgroup comprised 109 patients treated with hemoadsorption and 131 controls (subjects from post hoc analyses excluded) in the period 2016-2022. Indicator for Table 2 (as per instructions, table placed at the end of the document text file) Procedures included open valve surgery, coronary artery bypass grafting (CABG) - isolated and combined [13, 16-18], or various other cardiac surgery operations with prolonged CPB times (>90 min) [14, 15, 19-21], including one study that enrolled patients who underwent combined aortic root and valve surgery [22]. Hemoadsorption was used exclusively intraoperatively in all studies, however in one study two adsorbers in parallel connection within the CPB circuit were used [19]. There was no significant reduction of circulating cytokine levels in two RCTs [13, 20], while one RCT [18] detected significant reductions in cytokine levels in the hemoadsorption group. Two studies [17, 19] had conflicting results about levels of plasma-free hemoglobin (pfHb) – Bernardi et al . [17] found no reduction of pfHb within the intervention arm, while Gleason et al . [19] did. The former additionally found significant differences in markers of hemolysis such as haptoglobin and lactate dehydrogenase. The Discussion section further elaborates on reported secondary outcomes and their clinical relevance. 3.3 Aortic surgery Three studies since 2019 investigated the effect of adjunctive intraoperative use of CytoSorb â in aortic surgery ( Table 3 ). The most extensive study [23] included various surgical interventions involving the thoracic aorta while patients were in hypothermic circulatory arrest, comprising elective and acute procedures. A small pilot study from India [24] mainly included elective aortic root replacements and a pilot RCT from Germany [25] enrolled patients who underwent open thoracoabdominal aortic aneurysm (TAAA) repair on CPB. This subgroup contains 186 patients treated with hemoadsorption who were compared to 193 control patients. Table 3 . Evidence overview – aortic surgery. No. Study Study design Device Interventions Controls Results of the intervention 1 2019 Saller, T., et al . [23] Retrospective Case-control (PSM) Procedure: Aortic surgery with hypothermic circulatory arrest CytoSorb® (intra-op on CPB) 168 168 Significantly: - lower requirement for intraoperative norepinephrine - less pRBC & FFP transfusions - higher requirement for PCC Notably: - improved acid-base balance - lower intraoperative mortality 2 2021 Mehta, Y., et al . [24] Retrospective Case-control Procedure: Ascending aorta replacement CytoSorb® (intra-op on CPB) 8 8 Significantly: - lower IL-6 (primary outcome) - requirement for norepinephrine - ICU and hospital stay Notably: - improved PaO 2 /FiO 2 ratio - duration of mechanical ventilation No significant differences in primary outcomes PCT, WBC count, and CRP. 3 2023 Doukas, P., et al . Prospective RCT Procedure: Thoracoabdominal aortic repair CytoSorb® (intra-op on CPB) 10 17 Significantly: - lower incidence of severe ARDS Notably: - shorter duration of mechanical ventilation Legend: PSM - propensity score matching, CPB – cardiopulmonary bypass, pRBC – packed red blood cells, FFP – fresh frozen plasma , PCC – prothrombin complex concentrate, IL - interleukin, ICU - intensive care unit, PCT – procalcitonin, WBC – white blood cells, CRP – C reactive protein, RCT – randomized controlled trial, ARDS – acute respiratory distress syndrome Overall, less need for vasopressor therapy and blood product transfusions was observed compared to controls, and there was a lower incidence of acute respiratory distress syndrome (ARDS) in the TAAA patients. Mechanical ventilation-related outcomes were notably better within the intervention groups. 3.4. Heart transplantation Nemeth et al . [26] conducted an observational pilot study in the setting of orthotopic heart transplantation (HTx). The results were published in 2018. The primary outcome was defined as hemodynamic stability and vasopressor demand during the first 48 hours postoperatively and the magnitude of postoperative inflammatory response described by the kinetics of procalcitonin (PCT) and C reactive protein (CRP). Patients undergoing orthotopic heart transplantation who received CytoSorb â intraoperatively were compared to propensity score-matched controls (16 vs. 16). In the postoperative period, a significant difference in the need for vasopressor was found between the groups. The control patients required more norepinephrine and terlipressin. The dynamics of PCT and CRP did not vary between the groups. In addition, the incidence of primary graft failure was significantly lower in the hemoadsorption group, and these patients required mechanical circulatory support and renal replacement therapy less frequently. Notably, lower lactate levels and reoperations for bleeding were observed in the hemoadsorption group, which was associated with a shorter duration of mechanical ventilation time and ICU stay. These benefits translate to lower 30-day mortality in intraoperative hemoadsorption patients treated significantly. Notably, no device-related adverse events were reported ( Evidence table , Additional file 2), suggesting that there was also no clinically relevant inadvertent immunosuppressant removal, consistent with the recently published animal study showing minimal removal of these agents by CytoSorb [27]. 3.5. LVAD One article, published in 2022, reported on hemoadsorption use intraoperatively during left ventricular assist device (LVAD) implantation [28]. A propensity score-matched comparison of 72 patients who received intraoperative hemoadsorption and 40 who did not, revealed a significantly higher incidence of respiratory failure within the intervention group, and higher rates of prolonged mechanical ventilation and tracheostomy. The primary outcome - overall survival after LVAD implantation, was comparable between the groups. Adverse events were reported equally in both groups ( Evidence table , Additional file 2). 3.6. Postoperative management Four of the 29 articles in this review, published between 2016 and 2021, reported using hemoadsorption in the postoperative period ( Table 4 ). All were retrospective single cohort studies evaluating the use of CytoSorb â in patients with evidence of ongoing hyperinflammation, or patients who required mechanical circulatory support for septic shock and multiorgan failure. The device was most frequently integrated via continuous renal replacement therapy (CRRT), followed by integration in veno-arterial extracorporeal membrane oxygenation (vaECMO) circuits or other platforms. In aggregate, 177 patients were included. Table 4 . Evidence overview – post-cardiac surgery complications. No. Study Study design Device Interventions Controls Results of the intervention 1 2016 Träger, K., et al . [29] Retrospective Case series Population: Post-op hyperinflammation (SIRS) CytoSorb® (post-op on CRRT) 16 / Pre- vs post-treatment: - IL-6 & IL-8 reductions - less vasopressor demand - improved MAP & CI - improved SOFA score - reduction of lactate levels - normalized base excess - shorter ICU length of stay 2 2019 Calabro, M. G., et al . [30] Retrospective Case series Population: Post-op MOF (cardiac-related) CytoSorb® (post-op on various platforms) 40 / Pre- vs post-treatment, significant: - reduction of bilirubin - reduction of lactate levels - reduction of CPK & LDH - lower VIS SOFA-predicted vs observed ICU mortality: 80% vs 55% 3 2020 Träger, K., et al . [31] Retrospective Case series Population: Post-op MOF (cardiac-related) CytoSorb® (on vaECMO) 23 / Pre- vs post-treatment, significant: - IL-6 reduction - norepinephrine reduction - reduction of lactate levels - normalized base excess 4 2021 Boss, K., et al . [32] Retrospective Case series Population: Post-op septic shock CytoSorb® (post-op on CRRT) 98 / Pre- vs post-treatment, significantly: - decreased VIS - reduced lactate levels - reduced SOFA & APACHE II scores SOFA/APACHE II-predicted vs observed mortality: 77/73% vs 59% Legend: SIRS – systemic inflammatory response syndrome, CRRT – continuous renal replacement therapy, IL - interleukin factor, MAP - mean arterial pressure, CI - cardiac index, SOFA – sequential organ failure assessment, ICU - intensive care unit, MOF - multiorgan failure, CPK -creatine phosphokinase, LDH - lactate dehydrogenase, VIS - vasoactive inotropic score, vaECMO - veno-arterial extracorporeal membrane oxygenation, APACHE - acute physiology and chronic health evaluation Results of the intervention are presented as pre- versus post-treatment. Hemoadsorption correlated with decreased vasoactive-inotropic score (VIS) [30, 32] and reductions in cytokines [29, 31]. Additionally, two studies compared the actual death rate with the expected mortality based on the standardized Sequential Organ Failure Assessment (SOFA) and/or Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction scores. In both cohorts, observed mortality was notably lower than SOFA-predicted – 55% vs . 80% [30] and SOFA/APACHE II-predicted 59% vs. 77/73% [32], respectively. 3.7. Safety The safety profile of CytoSorb â can be assessed by analyzing reported device-related adverse events ( Evidence table , Additional file 2). In 18 / 29 retrieved articles authors reported that unanticipated adverse events associated with hemoadsorption were not observed (62%). Six studies (21%) reported equal rates of clinical adverse events between the intervention and control groups but did not mention device-relatedness, and five publications (17%) did not report adverse events. In aggregate, no serious adverse device-related events were reported in the included articles. 4. Discussion This systematic review on hemoadsorption use in cardiac surgery has summarized the available published evidence on using CytoSorb â . The heterogeneity of the studies prevents the performance of a systematic meta-analysis of reported outcomes, hence the results are presented descriptively. Although other hemoadsorptive technologies may be used in cardiac surgery, our holistic literature search only identified published evidence for CytoSorb â . 4.1. Hyperinflammation after Cardiopulmonary Bypass The terms SIRS [33] and “cytokine storm” [34] were introduced in the early 1990s and are also frequently used to describe the underlying pathophysiological process to explain the problematic postoperative course underscored by vasoplegia that occurs in some patients after cardiac surgery [35]. Several triggers and pathophysiological mechanisms have been proposed [36] and there are ongoing efforts to identify novel solutions to address this serious complication. Treatment options mostly mirror those utilized in septic shock due to the comparable central role of the dysregulated immune response. Blood purification to remove elevated levels of cytokines and other inflammatory mediators has emerged as an attractive option to stop the vicious circle of auto-amplifying systemic hyperinflammation often leading to vasoplegic shock [37] and multiorgan failure. The CytoSorb â adsorber is the most researched device for attenuating hyperinflammation and for rebalancing the dysfunctional immune response [38, 39]. 4.2. CytoSorb â therapy CytoSorb â therapy is a blood purification technique based on the hemoadsorption of hydrophobic molecules of up to approximately 60 kDa of molecular weight ( Figure 2 ). It is easily integrated into extracorporeal circuits (CPB, (C)RRT, ECMO, etc.) and is CE mark approved for the removal of cytokines, bilirubin, myoglobin, ticagrelor, and rivaroxaban [40] ( Figure 3 ). As the adsorption process is concentration-dependent [41], clinically meaningful removal occurs only when the plasma concentration of the target molecule is substantially elevated. A recent, prospective RCT in healthy volunteers demonstrated definitively the ability of the device to remove cytokines, with no signs of long-term immune system suppression by the treatment [42]. In addition to reducing elevated levels of cytokines, there is evidence of concurrent removal of trigger molecules, such as PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns), which also reside in the above-described adsorption range [43] ( Figure 4 ). In this way, CytoSorb â therapy aims to help the patient’s body mitigate the cytokine hyper-release cytotoxic effect and attenuate the dysregulated inflammatory response, to prevent the progression of organ dysfunction. Figure 2. CytoSorb â polymer bead technology. Figure 3. Installation scheme of CytoSorb â device within cardiopulmonary bypass circuit. Figure 4. CytoSorb â adsorption range. 4.3. Interpretation of the available evidence Hemoadsorption represents a reasonably new technology and only a few relatively small RCTs exist. The intraoperative use of CytoSorb â by direct integration in the CPB circuit was first reported by Born et al . [44] in 2014 and showed significant reductions of interleukin (IL)-6 and procalcitonin (PCT). The first RCT in patients undergoing elective cardiac surgery was published 2 years later [13], but in contrast, it did not demonstrate the removal of measured cytokines. Given the trial’s results, and as described in the elective cardiac surgery part of this review, it seems that patients undergoing elective, low-risk cardiac surgery may not be the most relevant cohort for hemoadsorption to demonstrate any effect. While the RCTs included in this systematic review confirm that the intraoperative integration of CytoSorb â in CPB during cardiac surgery is both easy and safe, they mostly failed to show significant improvements in clinical endpoints, despite reducing circulating cytokine levels [8]. Considering the fact that hemoadsorption occurs in a concentration-dependent manner [41] and that effective removal requires highly increased circulating levels, it is understandable that hemoadsorption may not provide substantial clinical benefits in low-risk, elective cardiac surgery [13, 20], or even in lower-risk infective endocarditis (IE) patients [6], where cytokine concentrations are not substantially elevated. 4.3.1. Infective endocarditis Over one-third of all publications identified in this review report on outcomes with hemoadsorption in IE patients undergoing cardiac surgery ( Table 1 ). The results are not uniform, and their interpretation commands a thorough assessment. The REMOVE trial (Revealing Mechanisms and Investigating Efficacy of Hemoadsorption for Prevention of Vasodilatory Shock in Cardiac Surgery Patients with Infective Endocarditis - a Multicentric Randomized Controlled Group Sequential Trial) was the most extensive study within this group [8]. In a proof-of-concept pre-specified analysis in the first 50 enrolled patients, the REMOVE investigators showed a significant reduction of various cytokines. Based on these findings, they continued with full enrolment in the trial which ultimately did not show a statistically significant difference in the primary endpoint of postoperative organ function improvement assessed by the change in SOFA score between 138 patients who received intraoperative hemoadsorption and 144 patients without this treatment. All secondary outcomes and rates of adverse events were also comparable between the two groups. The patient population comprised of “all-comers” with IE requiring surgery with no further risk-stratification for inclusion except a European System for Cardiac Operative Risk Evaluation Score - EuroSCORE II > 3%. Approximately 1/3 of procedures were outpatients undergoing elective surgery, and, e.g., the median preoperative IL-6 levels were only 18.36 pg/mL in the treatment and 40.6 pg/mL (p=0.3) in the control group. Results from two other smaller RCTs in IE patients yielded different results. Asch et al . [6] found higher vasopressor and fluid therapy demand within the intervention group. In contrast, Holmen et al . [45] showed a reduction in the consumption of blood products and a substantial decrease in norepinephrine need and postoperative vasopressor therapy duration associated with CytoSorb â treatment. While patient selection in the first study was compromised with significant baseline differences between the groups ( Table 1 ), the second study included only acute, high-risk patients and demonstrated a clear trend towards faster hemodynamic stabilization correlating with hemoadsorption. Nevertheless, the minimal sample size of both trials requires caution with interpretations and conclusions. Kalisnik et al . [7] compared 99 high-risk IE patients with intraoperative hemoadsorption to 99 propensity-score-matched controls with a median EuroSCORE II of around 9% in both groups. Similarly, Haidari et al . [11] reported on a cohort of 70 patients with a EuroSCORE II > 8%, therefore including only high-risk patients. Both studies showed a significantly lower incidence of sepsis-related mortality using hemoadsorption. In addition, the former showed a lower incidence of sepsis, and the latter reduced cumulative vasopressor need in patients treated with CytoSorb â . In contrast, a study by Santer et al . [46], showed that intraoperative hemoadsorption was associated with increased vasopressor and blood product requirements in 41 IE patients compared with 200 matched controls. It is noteworthy, however, as the authors of this study acknowledged that despite the use of advanced statistical methods to address residual confounders, significant imbalances remained between the two groups specifically relating to the change in treatment protocols over time. The overall incidence of IE is increasing [47, 48] and around 50% of these patients will require valve surgery at some point [49]. Many patients will require emergency surgery under active infection and concomitant inflammation. In such cases, major surgical trauma and CPB may worsen the already primed and aggravated immune system, often leading to excessive release of cytokines and consequent systemic hyperinflammation [50]. Moreover, the proportion of IEs caused by Staph. aureus has increased in recent years [48], introducing even more complexity and risk within this field. This sub-population of IE patients was investigated explicitly in a recent dual-center study in which the use of hemoadsorption was associated with significantly lower VIS, incidence of renal failure requiring dialysis, and fewer deaths (sepsis-related, 30-day, and 90-day mortality) [12]. In addition, certain bacteria toxins may also be removed by CytoSorb â [43], specifically Staph. aureus exotoxins. This fact and the promising results from the above observational studies potentially promote CytoSorb â as an adjunctive and versatile tool in high-risk IE cases. The benefit of non-selective depletion of cytokines has not yet been proven in this population of patients. Notwithstanding, based on the results of studies presented here, it seems that hemoadsorption may improve outcomes in high-risk IE patients [5, 7, 9, 11, 12, 45]. This is supported by the high baseline risk scores (EuroSCORE-II > 8%) [51] in the studies that reported benefit with hemoadsorption. Therefore, appropriate patient selection at high risk for postoperative complications, relating to a heightened inflammatory response, is critical when considering the use of hemoadsorption. For example, Haidari et al . [10] showed favorable outcomes after carefully selecting patients to receive intraoperative hemoadsorption based on the presence of the following criteria prior to surgery: fever, severely elevated inflammatory parameters, and/or hemodynamic instability requiring high inotropic support. Moreover, Kühne et al . [5] suggested that IE patients who, despite receiving hemoadsorption treatment during CPB, develop intraoperative renal failure and require increasing vasopressor therapy, or have high-grade intraoperative findings (vegetations and aortic root abscess), might benefit from the continuation of hemoadsorptive therapy in the ICU. Accordingly, REMOVE’s “neutral” results may potentially be reflective of the “all-comer” nature of the population [8], which is also supported by the low median IL-6 levels prior to surgery. In contrast, the average IL-6 levels seen by Jansen et al . [42] were above 500 pg/mL and demonstrated significant cytokine clearance with CytoSorb â . 4.3.2. Aortic surgery Complex and combined open aortic surgery and high-risk operations to treat aortic dissections or thoracoabdominal aortic aneurism (TAAA), may also result in systemic hyperinflammation. Hypothermic circulatory arrest (HCA), commonly employed during aortic surgery extending into the arch, may be a further trigger for an exaggerated inflammatory response, often leading to vasoplegia, compromised microcirculation, increased lactate levels, and subsequent organ failure [52]. Saller et al . [23] observed significantly lower norepinephrine concentrations and better acid-base status (reflected by less frequent low pH, lower lactate concentrations, and decreased need for buffer solution) compared to standard therapy in 168 patients who underwent various open thoracic aortic surgical procedures under HCA with intraoperative CytoSorb â treatment compared to 168 propensity score-matched controls. Interestingly, hemoadsorption correlated with a significantly decreased need for transfusion of packed red blood cells and fresh frozen plasma but an increased requirement of prothrombin complex concentrate. The authors observed that the overall benefit of the therapy was explicitly prominent in the subgroup of emergency patients with acute aortic dissections. A significant reduction in norepinephrine and IL-6 in patients who mainly underwent Bentall procedures adjunctly treated with CytoSorb â on CPB was also shown in a small pilot observational study, together with better mean arterial pressure, and PaO 2 /FiO 2 ratio, shorter mechanical ventilation duration, and ICU and hospital stay [24]. A pilot RCT investigated the feasibility and effect of intraoperative hemoadsorption during open TAAA repair and showed a significantly lower incidence of ARDS [25]. However, both these pilot study results should be interpreted with caution due to their small sample size. The available evidence in the population of complex aortic surgery seems promising but remains very preliminary and requires confirmation in prospective trials. Decreased vasopressor requirements observed in high-risk aortic surgery patients who received CytoSorb â therapy are similar to findings within other populations discussed in this review and may represent a meaningful clinical endpoint for future trials. 4.3.3. Post-cardiac surgery complications Data from sizeable cardiac surgery registries show a downward trend in mortality and morbidities after cardiac surgery over the last 20 years. However, despite decades of innovation in cardiopulmonary support, on-pump cardiac surgery still carries the risk for a postoperative systemic inflammatory response and vasoplegia which in turn leads to worse outcomes [53]. In this fairly heterogeneous patient population, hemoadsorption is frequently used in daily practice to attenuate the post-operative hyperinflammatory response. To the best of our knowledge, no prospective trials have been conducted in this population so far, and the four studies in this review provide promising but highly speculative results, involving patients with predominantly SIRS, multiorgan failure (MOF), cardiogenic and septic shock. Almost all patients required renal or circulatory support, thus CytoSorb â was used adjacent to CRRT or vaECMO. It seems that hemoadsorption was associated with hemodynamic stabilization and lower actual versus expected mortality. The versatile nature of hemoadsorption may benefit postoperative patients in complex and severely impaired conditions, as CytoSorb â not only removes cytokines, but also bilirubin, bile acids, myoglobin, some toxins, and various PAMPs and DAMPs [43, 54-56]. As with any other blood purification technology, hemoadsorption carries a risk of inadvertent drug removal. Critical care patients are specifically prone to this due to the usually high numbers of administered medications over long treatment periods. Assessment of the clinical relevance of potential drug removal requires consideration of the patient’s condition, the impact of concomitantly applied extracorporeal therapies, duration of device exposure, and timing of drug administration. Clinical decision-making regarding adjustments in drug dosing should always be made in the broader clinical context supported by therapeutic drug monitoring when available [57]. 4.3.4. Heart transplant surgery and Ex vivo organ perfusion One study suggested favorable outcomes in HTx patients associated with intraoperative hemoadsorption [26], and an animal experiment in ex vivo lung perfusion (EVLP) showed that CytoSorb â treatment significantly decreased cytokine levels and levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury and primary graft dysfunction (PGD) incidence was significantly reduced among treated animals [58]. Authors suggest this treatment will increase the availability of the donor’s lungs and provide better graft tolerability in the recipient. The first-in-human (micro)study published by the same group [59] suggests that cytokine adsorption adjacent to extracorporeal lung support during lung transplantation supports graft acceptance. Promising results in an EVLP animal model were previously reported by Iskender et al . [60] and in animal studies involving hearts and kidneys donated after circulatory death (DCD) [61, 62]. Considering the ongoing unmet need for organs for transplantation, ex vivo organ perfusion with adjunctive hemoadsorptive treatment may play an essential role in combatting organ shortage and early graft rejection. The use of hemoadsorption in organ transplants has been controversial due to the already discussed potential for unwanted drug removal, specifically immunosuppressants. However, a detailed investigation in a large animal model reassuringly reported a minimal level of removal with frequently used immunosuppressant regimens [27]. A very recent RCT [63] confirmed CytoSorb â did not affect levels of mycophenolic acid, used to prevent organ transplant rejection, and found that concentrations were comparable to the control group at all pre-defined time points. There was also no increase in the frequency of early cardiac allograft rejection in the intervention group. In their proof-of-concept trial, Nemeth et al. compared the effect of intra-operative CytoSorb ® use to standard care in 55 orthotopic heart transplantation patients (30 CytoSorb ® and 25 standard care). Results showed that the CytoSorb® group had significantly lower vasoactive-inotropic scores (p=0.046), a 6.4-fold decrease in the odds of developing vasoplegic syndrome (p=0.028), lower PCT levels, shorter duration of mechanical ventilation hours (p=0.025), and ICU (p=0.022). Patients in the CytoSorb ® group also had lower rates of acute kidney injury (p=0.004), renal replacement therapy (p=0.037) and more stable hepatic bilirubin excretion. Furthermore, 30-day mortality and 1-year survival did not differ between groups. There were no reported device-related adverse events during the study period. 4.3.5. LVAD LVAD implantation in patients with advanced heart failure carries a substantial risk of a dysregulated inflammatory response mediated by exaggerated cytokine production. Since hemoadsorption has recently yielded promising results in high-risk patients undergoing cardiac surgery by immunomodulation and consequent attenuation of over-shooting inflammation [64], the rationale for its utilization during CPB-assisted LVAD implantation surgery was investigated. However, results from the only study on this topic found in the current literature search demonstrated a significantly increased incidence of respiratory failure in the CytoSorb ® group compared to propensity score-matched controls. Consequently, the need for prolonged mechanical ventilation and tracheostomy was also increased with hemoadsorption. Furthermore, in-hospital mortality was notably lower in the control group [28]. The ongoing RCT CytoSorb ® Modulation of Surgical Inflammation During LVAD Insertion (CYCLONE-LVAD) will evaluate the role of hemoadsorption in this field (ClinicalTrials.gov Identifier: NCT04596813). 4.3.6. ECMO/ECLS Extracorporeal life support (ECLS) for patients with severely compromised circulation via vaECMO is known to provoke a complex inflammatory reaction. This innate immune response, if severe, may lead to disrupted microcirculation, and end-organ dysfunction. Despite dramatic technological improvements with newer ECMO platforms, systemic hyperinflammation remains a relevant clinical concern [65]. Apart from the widely known pathophysiological mechanism of artificial surface contact-mediated coagulation, platelet, and complement system activation, and consequent endothelial injury, another potent trigger for cytokine hyperproduction is the release of endotoxins in response to translocation of bacteria from ischemic gut mucosa into the bloodstream [66]. If such an already explosive immune response is dysregulated, and instead of self-limiting, the cytokine storm becomes auto-amplifying, it may lead to a vicious circle and eventually death. Cytokine adsorption has recently been introduced as an adjunctive tool to limit the hyperinflammatory response to ECMO. Clinical evidence so far is limited and controversial. It has been recommended that parameters for appropriate patient selection should include signs of shock, high vasopressor requirements, elevated lactate levels, and/or elevated IL-6, lactate, bilirubin, or myoglobin plasma levels. Potential examples where hemoadsorption may be considered include profound shock on ECMO, post-cardiotomy ECMO in patients with infection, and ECMO in the context of organ donation [67]. A recent study from Soltesz et al . [68] evaluated the impact of vaECMO-integrated hemoadsorption on the reversal of multiorgan and microcirculatory dysfunction and early mortality of refractory cardiogenic shock patients. Among 29 vs. 29 propensity score-matched patients, CytoSorb â treatment resulted in significantly lower VIS, lactate levels, and ECMO-associated bleeding complications. Hemoadsorption was used continuously for 72 hours with vaECMO therapy in those with persistent hemodynamic instability. Well-designed, prospective trials will be necessary to answer complex questions regarding the right timing for adjunctive hemoadsorption therapy, optimal duration, and proper patient selection. 4.4. Safety and other systematic findings This review assessed the safety of CytoSorb â therapy based on the incidence of reported unanticipated device-related adverse events (UADE). Among studies that reported adverse events, there were no UADE noted. It appears, therefore, that CytoSorb â has a favorable safety profile when used in cardiac surgery patients ( Evidence table , Additional file 2). A recent meta-analysis from the United Kingdom investigated operative mortality, ventilation duration, ICU and hospital stays, and postoperative day 1 inflammatory markers in studies involving CPB and hemoadsorption. Of 15 selected studies, 12 used CytoSorb â , 2 investigated Alteco ® LPS adsorber (Alteco Medical AB, Lund, Sweden), and 1 Toraymyxin ® (Toray Industries, Tokyo, Japan). When comparing cytokine adsorption cases and controls across all studies, authors found no significant difference in operative mortality, ventilation duration, hospital stay, and ICU length of stay. However, a significant reduction in 30-day mortality ( Figure 5 ) and ICU stay ( Figure 6 ) was shown to be associated with hemoadsorption therapy during non-elective cardiac surgery, especially emergency surgery, and in patients with a higher inflammatory burden such as with infective endocarditis [69]. Figure 5. Naruka et al . [69] Forest plot: meta-analysis for the difference in operative mortality between CPB-assisted cardiac surgery with and without hemoadsorption. Figure 6. Naruka et al . [69] Forest plot: meta-analysis for the difference in an intensive care unit (ICU) stay between CPB-assisted cardiac surgery with and without hemoadsorption. The authors’ conclusions that hemoadsorption devices are likely to be more beneficial in patients with higher inflammatory responses, such as infective endocarditis and emergency operations, align with the findings of the current systematic review. Furthermore, Liu et al . [2] in their narrative review concluded that although data on the use of hemoadsorption in cardiac surgery is scarce and even controversial, there is no denying that adsorptive extracorporeal blood purification technology, especially CytoSorb â , opens a new door for the ongoing e fforts in battling CPB-associated SIRS. A meta-analysis from Heymann et al . [70], however, showed that in fact, the use of CytoSorb ® might increase mortality in critically ill patients with inflammatory conditions, although the authors did acknowledge the low certainty of the evidence, primarily due to the lack of power to independently assess mortality across the vasty heterogeneous populations included. Interestingly, in a subgroup analysis of complex cardiac surgery, increased mortality associated with CytoSorb â was not found, which is in agreement with the findings of Naruka et al . [69] and Liu et al ., [2] as well as with the current systematic review. In general, leading experts in intensive care medicine are increasingly calling for new realistic clinical endpoints instead of mortality for the assessment of potential clinical benefits of novel therapies in critical patients. [71-73]. Similarly, hemoadsorption is an adjunct therapy in critically ill or high-risk surgical patients. As such, it represents a small piece in a very complex puzzle of medical treatments, therapeutic protocols, surgical procedures and techniques, and advanced diagnostics currently used in the cardiac surgery setting and beyond. Although solid clinical evidence demonstrating survival benefits from using hemoadsorption in cardiac surgery is currently lacking, this systematic literature review, despite its limitations regarding the heterogeneity of study designs and endpoint measures, suggests that meaningful outcomes such as faster hemodynamic stabilization may be achieved with hemoadsorption in high-risk cardiac surgery patients. 5. Conclusions Hemoadsorption in cardiac surgery is an emerging field with CytoSorb â being the only available device with published evidence discovered in this systematic review. The reviewed evidence shows that its use intraoperatively with CPB or postoperatively with CRRT or vaECMO is feasible and safe with no unanticipated device-related adverse events reported in any of the retrieved publications. However, in relation to the evidence supporting the efficacy of the device, the available evidence is mixed, but in aggregate suggests limited value with use in routine elective surgery and low-risk patients. On the other hand, the role of hemoadsorption with on-pump cardiac surgery seems attractive in high-risk infective endocarditis cases and possibly aortic surgery, and among patients who develop a dysregulated inflammatory response, vasoplegia or septic shock postoperatively. The most frequently reported clinical benefit associated with hemoadsorption treatment is reduced vasopressor demand resulting in better hemodynamic stability. 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Blood Purification Studies in the ICU: What Endpoints Should We Use? Blood Purif. 2022;51(12):990-6. doi: 10.1159/000523761. 73. Cavaillon JM, Singer M, Skirecki T. Sepsis therapies: learning from 30 years of failure of translational research to propose new leads. EMBO Mol Med. 2020;12(4):e10128. doi: 10.15252/emmm.201810128. 74. Taleska Stupica G, Sostaric M, Bozhinovska M, Rupert L, Bosnic Z, Jerin A, et al. Extracorporeal Hemadsorption versus Glucocorticoids during Cardiopulmonary Bypass: A Prospective, Randomized, Controlled Trial. Cardiovasc Ther. 2020;2020:7834173. doi: 10.1155/2020/7834173. Declarations Additional Materials: Additional file 1 – PRISMA 2020 Checklist, Additional file 2 – Evidence table Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and materials: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Competing interests: MMS, DW, and ED are employees of CytoSorbents corp. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions: the conception and design - MMS, MT, DW; acquisition of data - MMS, MT, DW, ED, PS, CB; analysis and interpretation of data - all authors; drafting the article - MMS, MT, DW, ED, OD, StG; revising it critically for important intellectual content - all authors; final approval of the version to be submitted - all authors. Acknowledgments: Authors thank Mrs. Harriet Adamson for the administrative support and native speaker proofreading. Tables Table 1 . Evidence overview – infective endocarditis associated valve surgery. No. Study Study design Device Interventions Controls Results of the intervention 1 2017 Träger, K., et al . [9] Retrospective Case-control* CytoSorb â (intra-op on CPB) 39 28 Notably: - shorter ICU length of stay Pre- vs post-treatment: - reduction in vasopressor demand - reduction of cytokine IL-6 & IL-8 levels Rapid normalization of: - lactate levels and base excess - MAP 2 2019 Kühne, L. U., et al . [5] Retrospective Case-control* CytoSorb â (intra-op on CPB + post-op on CRRT) 10 10 Despite a more pronounced disease severity in patients who received the therapy both intra- and postoperatively, compared to those with only intra-op hemoadsorption, equal post-op: - vasopressors - CRP - lactate - ventilator time 3 2020 Haidari, Z., et al . [10] Retrospective Case-control CytoSorb (intra-op on CPB) 30 28 Significantly: - lower incidence of sepsis (primary outcome) - lower sepsis-related mortality (primary outcome) - reduced vasopressor requirements - higher SVR Notably lower overall 30-day mortality 4 2021 Asch, S., et al . [6] Prospective RCT CytoSorb (intra-op on CPB + post-op on CRRT) 10 10 Significantly: - higher vasopressor need - higher volume of fluids - longer ICU length of stay No significant difference in cytokine levels – primary outcome (IL-6, TNF-α). CRP and PCT baseline levels were significantly higher in the intervention group, equalizing after surgery. 5 2021 Santer, D., et al . [46] Retrospective Case-control (IPTW) CytoSorb â (intra-op on CPB) 41 200 Significantly: - higher norepinephrine and milrinone demand - more RBC and PLT transfusions - higher incidence of reoperations for bleeding - prolonged hospitalization No significant difference in in-hospital mortality – primary outcome. 6 2022 Diab, M., et al . [8] Prospective RCT CytoSorb â (intra-op on CPB) 138 144 Significantly: - lower levels of cytokines IL-1β, IL-18 (in the first 25 vs 25 patients) No significant difference in SOFA score change (primary outcome), as well as in clinical outcomes. 7 2022 Haidari, Z., et al . [11] Retrospective Case-control (PSM) CytoSorb â (intra-op on CPB) 35 35 Significantly: - lower sepsis-related mortality (primary outcome) - reduced vasopressor demand - higher SVRI - faster SOFA score normalization - lower respiratory failure rate No significant difference in the postoperative sepsis incidence and in-hospital mortality – primary outcomes. 8 2022 Holmen, A., et al . [45] Prospective RCT CytoSorb â (intra-op on CPB) 10 9 Significantly: - fewer transfusions (RBC, PLT, FFP) Notably: - lower and shorter norepinephrine demand (primary outcome) - lower creatinine levels - lower chest-tube drainage volume - shorter ventilator time 9 2022 Kalisnik, J. M., et al . [7] Retrospective Case-control (PSM) CytoSorb â (intra-op on CPB) 99 99 Significantly: - lower incidence of sepsis (primary outcome) - lower sepsis-related mortality (primary outcome) - lower CRP levels - fewer transfusions (RBC & FFP) - lower WBC counts - higher hemoglobin level Notably lower in-hospital mortality. 10 2023 Haidari, Z., et al . [12] Retrospective Case-control CytoSorb â (intra-op on CPB) 75 55 Significantly: - decreased VIS (primary outcome) - lower incidence of sepsis-related mortality - lower 30-day & 90-day mortality - lower incidence of renal failure requiring hemodialysis Notably: - lower incidence of revisions for bleeding Legend: CPB - cardiopulmonary bypass, IL - interleukin, MAP - mean arterial pressure, ICU - intensive care unit, CRRT – continuous renal replacement therapy, CRP - C reactive protein, SVR – systemic vascular resistance, RCT – randomized controlled trial, TNF – tumor necrosis factor, PCT – procalcitonin, IPTW - inverse probability treatment weighting, RBC - red blood cells, PLT – platelets, SOFA – sequential organ failure assessment, PSM - propensity score matching, SVRI – systemic vascular resistance index, FFP - fresh frozen plasma, WBC - white blood cells, VIS – vasoactive-inotropic score * Statistical analysis for significant differences was not performed Table 2 . Evidence overview – elective complex cardiac surgery (various procedures with prolonged CPB). No. Study Study design Device Interventions Controls Results of the intervention 1 2016 Bernardi, M. H., et al . [13] Prospective RCT CytoSorb â (intra-op on CPB) 19 18 No significant difference in primary outcome - cytokine levels (IL-1ß, IL-6, IL-18, TNF- ⍺ ), except for IL-10. 2 2019 Bernardi, M. H., et al . [17] Prospective RCT (post hoc subgroup analysis of No. 1) CytoSorb â (intra-op on CPB) 17 18 Significantly: - higher haptoglobin (primary outcome) - lower LDH No significant difference between the groups in levels of plasma-free hemoglobin (primary outcome) and total bilirubin. 3 2019 Garau, I., et al [18] Prospective RCT CytoSorb â (intra-op on CPB) 20 20 Significantly: - lower cytokine levels (IL-8, TNF- ⍺ ) - primary outcome - higher CI No significant difference in levels of IL-6 (primary outcome). 4 2019 Gleason, T. G., et al . [19] Prospective RCT 2 CytoSorb â (intra-op on CPB) 23 23 Significant reduction in: - plasma-free hemoglobin (primary outcome) - activated complement C3a & C5a. 5 2019 Poli, E. C., et al . [20] Prospective RCT CytoSorb (intra-op on CPB) 15 15 No significant difference in primary outcome - cytokine levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1), as well as in clinical outcomes. Significantly lower activity of coagulation factors II and XII. 6 2019 Wagner, R., et al . [22] Prospective RCT CytoSorb â (intra-op on CPB) 15 13 Significantly higher level of miRNA-133 – primary outcome. No significant differences in levels of miRNA-1, miRNA-126, and miRNA-223 (primary outcomes), as well as in clinical outcomes. 7 2019 Taleska-Stupica, G., et al . [74] Prospective RCT CytoSorb â (intra-op on CPB) 20 20 & 20* Significantly: - higher CD64 and CD163 antigen expression on immune cells - increased activated complement C5a (primary outcomes). No significant difference in primary outcome - cytokine levels (TNF- α , IL-1 β , IL-6, IL-8, and IL-10). 8 2020 Wisgrill, L., et al . [16] Prospective RCT (post hoc subgroup analysis of No. 1) CytoSorb â (intra-op on CPB) 9 9 No significant differences in circulating microvesicles, apoptotic body counts and kinetics. 9 2021 Hohn, A., et al . [14] Prospective Case series (part of the ongoing RECCAS** study) CytoSorb â (intra-op on CPB) 15 / Significant, pre- vs post-adsorber: - reduction of heparan sulphate - increase of hyaluronan 10 2022 Manohar, M., et al . [15] Retrospective Case-control CytoSorb® (intra-op on CPB) 23 29 Significantly lower: - increase of VIS from pre- to postoperative value (primary outcome) Notably lower: - in-hospital mortality Legend: CPB - cardiopulmonary bypass, RCT - randomized controlled trial, IL - interleukin, TNF - tumor necrosis factor, LDH - lactate dehydrogenase, CI – cardiac index, IFN - interferon, MCP - monocyte chemoattractant protein, miRNA - micro ribonucleic acid, VIS – vasoactive-inotropic score * Three groups, 20 given intraoperative methylprednisolone, 20 intraoperative CytoSorb®, 20 controls; results shown for comparison between hemoadsorption and controls ** German Clinical Trials Register number DRKS00007928 (Date of registration August 3 rd , 2015). Additional Declarations The authors declare potential competing interests as follows: MMS, DW, and ED are employees of CytoSorbents corp. 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Introduction\",\"content\":\"\\u003cp\\u003eMajor surgery-related trauma and cardiopulmonary bypass (CPB) itself, are associated with hyperinflammation, formerly described in the literature as SIRS \\u0026ndash; Systemic Inflammatory Response Syndrome. Despite recent advancements in surgical and anesthetic techniques, open cardiac surgery \\u003cem\\u003eper se\\u003c/em\\u003e still carries a significant risk for morbidity and mortality\\u0026nbsp;[1]. Even with recent developments towards minimally invasive techniques, cardiac surgery using CPB is still the current \\u0026ldquo;gold standard\\u0026rdquo;. Moreover, the complexity of cardiac surgery will further increase due to the aging population, frailty, and many comorbidities. Despite recent advantages in myocardial protection for several hours, systemic pathological inflammation derived from extracorporeal circulation might still occur\\u0026nbsp;[2].\\u003c/p\\u003e\\n\\u003cp\\u003eVarious measures have been introduced to prevent or treat dysregulated inflammatory response in cardiac surgery and reduce its serious harm. However, a single approach cannot block multiple (severe) inflammation pathways. Extracorporeal blood purification techniques have been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or for postoperative complications\\u0026nbsp;[2].\\u003c/p\\u003e\\n\\u003cp\\u003eThis review aims to critically assess the role of hemoadsorption in cardiac surgery, by summarizing the results of published studies conducted in this clinical setting in the last decade.\\u003c/p\\u003e\"},{\"header\":\"2. Methods\",\"content\":\"\\u003cp\\u003eThe scope of the current literature search was to identify all relevant studies to summarize the current level of evidence concerning the use of hemoadsorption in the field of cardiac surgery. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search and retrieve all available data.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eLiterature search strategy\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA comprehensive literature search was conducted of the online database of the United States National Library of Medicine (PubMed) and Cochrane Library. In the literature screening and selection process, we followed the principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement\\u0026nbsp;[3], to preserve an objective approach (Additional file 1:\\u0026nbsp;PRISMA 2020 Checklist). A search of both databases was made on June 1\\u003csup\\u003est\\u003c/sup\\u003e, 2023, using the following key search words: \\u0026ldquo;cardiac surgery\\u0026rdquo; OR \\u0026ldquo;cardiothoracic surgery\\u0026rdquo; AND \\u0026ldquo;hemoadsorption\\u0026rdquo; OR \\u0026ldquo;hemoadsorbtion\\u0026rdquo; OR \\u0026ldquo;hemadsorption\\u0026rdquo; OR \\u0026ldquo;hemadsorbtion\\u0026rdquo; OR \\u0026ldquo;haemoadsorption\\u0026rdquo; OR \\u0026ldquo;haemoadsorbtion\\u0026rdquo; OR \\u0026ldquo;haemadsorption\\u0026rdquo; OR \\u0026ldquo;haemadsorbtion\\u0026rdquo;. Abstracts were considered for inclusion if they were written in English and published within the last ten years.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eEligibility criteria\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePublications were eligible for assessment if reporting on original data from comparative studies in which hemoadsorptive device was investigated during or after cardiac surgery.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eData extraction and critical appraisal\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe most important details about all the studies are presented in a tabular view (Additional file 2:\\u0026nbsp;\\u003cstrong\\u003eEvidence table\\u003c/strong\\u003e). Outcomes related to the intervention were deemed eligible to be included if statistically significant differences were found. For defined primary outcomes, statistically non-significant findings were also included. Considering secondary outcomes, if the difference was not statistically significant but still striking, or the observed trend was evident, such results were added and described as \\u0026ldquo;notable\\u0026rdquo;. Three researchers (P.S., M.T., C.B.) independently assessed these results and the final agreement on the inclusion of notable differences in the analysis was reached by consensus. Primary outcomes were highlighted if defined as such in the respective study. In studies without statistical analysis, findings highlighted in respective articles were copied.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"3. Results\",\"content\":\"\\u003cp\\u003eThe search resulted in 186 hits in total. After duplicates were removed (n=71), the remaining abstracts were screened and an additional seven were excluded (details given within the flowchart, \\u003cstrong\\u003eFigure 1\\u003c/strong\\u003e). Furthermore, 108 reports were assessed out of which 79 were deemed ineligible\\u0026mdash;29 included the wrong patient population (26 studies not associated with cardiac surgery and 3 publications reporting on hemoadsorption utilized for the removal of antithrombotic drugs \\u0026ndash; a topic already comprehensively covered elsewhere\\u0026nbsp;[4]), 33 articles contained no original data, and 17 were case reports or conference papers.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFigure 1.\\u003c/strong\\u003e Systematic literature search flowchart.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eQuantity of evidence\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe literature search resulted in a total of 29 publications that investigated hemoadsorption in cardiac surgery. The technology described in all of them was exclusively the CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e device (CytoSorbents Inc., Princeton, NJ, USA). The summary of retrieved articles in chronological order, and intervention-reported outcomes, are given in the \\u003cstrong\\u003eEvidence table\\u003c/strong\\u003e (Additional file\\u0026nbsp;2). This review included a total of 1.057 patients who were treated with hemoadsorption and 988 control patients (subjects from \\u003cem\\u003epost hoc\\u003c/em\\u003e analyses excluded). Considering the fact that several studies were conducted in the same centers and during overlapping periods, a portion of the above patients may be duplicates, however, it was impossible to identify them and exclude them from the present analysis. Appropriate notes are, therefore, included in respective sections.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eAssessment of endpoints\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe variability in study design, patient population, and reported endpoints was vast. Therefore, we decided to report the results of this search in systematic subgroups according to the underlying clinical indication or main surgical procedure. A separate subgroup for patients treated with hemoadsorption in the postoperative cardio-surgical period was also created. The most significant proportion of publications reported on intraoperative hemoadsorption utilization (25/29, 86.2%), including surgery for infective endocarditis (10/29, 34.5%), complex elective cardiothoracic surgery with prolonged CPB time (10/29, 34.5%), aortic surgery (3/29, 10.3%), left ventricular assist device implantation (1/29, 3.4%), and heart transplantation (1/29, 3.4%). The remaining four publications (4/29, 13.8%) reported on the postoperative use of hemoadsorption therapy adjacent to other extracorporeal blood purification techniques such as continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO). The most critical details from the grouped publications are given in the respective sections below. Finally, we assessed the safety of this technique by analyzing device-related adverse events outlined within the obtained literature.\\u003c/p\\u003e\\n\\u003cp\\u003e3.1. Infective endocarditis\\u003c/p\\u003e\\n\\u003cp\\u003eBetween 2017 and 2023, 10 published studies investigated the use of hemoadsorption in infective endocarditis surgery (\\u003cstrong\\u003eTable 1\\u003c/strong\\u003e). Three were randomized controlled trials (RCTs), one case series, and six were comparative retrospective case-controlled studies with three employing dedicated statistical methods for case/control matching. The total cohort of this subgroup comprised\\u0026nbsp;497\\u0026nbsp;patients treated with hemoadsorption and 608 controls (a portion of subjects are likely duplicates, however, the identification and exclusion could not be performed).\\u003c/p\\u003e\\n\\u003cp\\u003eIndicator for Table 1 (as per instructions, table placed at the end of the document text file)\\u003c/p\\u003e\\n\\u003cp\\u003eIn all studies, CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e was used intraoperatively by integration into the CPB-circuit, but in the K\\u0026uuml;hne \\u003cem\\u003eet al\\u003c/em\\u003e. case series\\u0026nbsp;[5]\\u0026nbsp;and the small RCT from Asch \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[6], hemoadsorption therapy was additionally continued postoperatively during the intensive care unit (ICU) period.\\u003c/p\\u003e\\n\\u003cp\\u003eThe most frequently reported outcome was vasopressor requirements and in all but two studies\\u0026nbsp;[7, 8], a significant reduction (where statistical analysis was performed) in vasopressor drug demand was observed with intraoperative hemoadsorption. Cytokine reductions with CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e were confirmed in two studies\\u0026nbsp;[8, 9], while significantly lower postoperative sepsis-related mortality with hemoadsorption was observed in four studies\\u0026nbsp;[7, 10-12]. Out of these four, one recent study showed a significantly reduced 30- and 90-day mortality in selected patients suffering from \\u003cem\\u003eStaphylococcus aureus\\u003c/em\\u003e-derived infective endocarditis\\u0026nbsp;[12].\\u003c/p\\u003e\\n\\u003cp\\u003eOther reported outcomes varied according to each study and are discussed in more detail in the Discussion part of this review.\\u003c/p\\u003e\\n\\u003cp\\u003e3.2. Elective complex cardiac surgery\\u003c/p\\u003e\\n\\u003cp\\u003eThe search yielded 10 articles reporting on studies that enrolled patients undergoing elective, but complex, cardiac surgical procedures (\\u003cstrong\\u003eTable 2\\u003c/strong\\u003e). Eight of the 10 studies were RCTs, six original and two \\u003cem\\u003epost hoc\\u003c/em\\u003e subgroup analyses from the oldest RCT in this group from Bernardi \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[13], while the remaining two studies were a prospective case series\\u0026nbsp;[14], and a retrospective comparative study\\u0026nbsp;[15]. The total cohort of this subgroup comprised 109 patients treated with hemoadsorption and 131 controls (subjects from \\u003cem\\u003epost hoc\\u003c/em\\u003e analyses excluded) in the period 2016-2022.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eIndicator for Table 2 (as per instructions, table placed at the end of the document text file)\\u003c/p\\u003e\\n\\u003cp\\u003eProcedures included open valve surgery, coronary artery bypass grafting (CABG) - isolated and combined\\u0026nbsp;[13, 16-18], or various other cardiac surgery operations with prolonged CPB times (\\u0026gt;90 min)\\u0026nbsp;[14, 15, 19-21], including one study that enrolled patients who underwent combined aortic root and valve surgery\\u0026nbsp;[22]. Hemoadsorption was used exclusively intraoperatively in all studies, however in one study two adsorbers in parallel connection within the CPB circuit were used\\u0026nbsp;[19].\\u003c/p\\u003e\\n\\u003cp\\u003eThere was no significant reduction of circulating cytokine levels in two RCTs\\u0026nbsp;[13, 20], while one RCT\\u0026nbsp;[18]\\u0026nbsp;detected significant reductions in cytokine levels in the hemoadsorption group. Two studies\\u0026nbsp;[17, 19]\\u0026nbsp;had conflicting results about levels of plasma-free hemoglobin (pfHb) \\u0026ndash; Bernardi \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[17]\\u0026nbsp;found no reduction of pfHb within the intervention arm, while Gleason \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[19]\\u0026nbsp;did. The former additionally found significant differences in markers of hemolysis such as haptoglobin and lactate dehydrogenase.\\u003c/p\\u003e\\n\\u003cp\\u003eThe Discussion section further elaborates on reported secondary outcomes and their clinical relevance.\\u003c/p\\u003e\\n\\u003cp\\u003e3.3 Aortic surgery\\u003c/p\\u003e\\n\\u003cp\\u003eThree studies since 2019 investigated the effect of adjunctive intraoperative use of CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e in aortic surgery (\\u003cstrong\\u003eTable 3\\u003c/strong\\u003e). The most extensive study [23] included various surgical interventions involving the thoracic aorta while patients were in hypothermic circulatory arrest, comprising elective and acute procedures. A small pilot study from India [24] mainly included elective aortic root replacements and a pilot RCT from Germany [25] enrolled patients who underwent open thoracoabdominal aortic aneurysm (TAAA) repair on CPB. This subgroup contains 186 patients treated with hemoadsorption who were compared to 193 control patients.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cbr\\u003e\\u003c/p\\u003e\\n\\u003cp style='margin:0in;text-align:left;line-height:150%;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:12.0pt;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eTable 3\\u003c/span\\u003e\\u003c/strong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e. Evidence overview \\u0026ndash; aortic surgery.\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003ctable style=\\\"width: 100%;border-collapse:collapse;border:none;\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width:6.28%;border:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo.\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:9.42%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eStudy\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:15.72%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eStudy\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003edesign\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:14.12%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eDevice\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:15.72%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eInterventions\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:11.0%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eControls\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:27.76%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eResults of the intervention\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 6.28%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 106.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e1\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 9.42%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 106.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2019\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSaller, T., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[23]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.72%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 106.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control\\u003cbr\\u003e\\u0026nbsp;(PSM)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProcedure: Aortic surgery with hypothermic circulatory arrest\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.12%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 106.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u0026reg;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.72%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 106.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e168\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 106.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e168\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27.76%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 106.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower requirement for intraoperative norepinephrine\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- less pRBC \\u0026amp; FFP transfusions\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- higher requirement for PCC\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNotably:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- improved acid-base balance\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower intraoperative mortality\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 6.28%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 34.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 9.42%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 34.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2021\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eMehta, Y., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[24]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.72%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 34.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProcedure: Ascending aorta replacement\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.12%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 34.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u0026reg;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.72%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 34.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e8\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 34.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e8\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27.76%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 34.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower IL-6 (primary outcome)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- requirement for norepinephrine\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- ICU and hospital stay\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNotably:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- improved PaO\\u003csub\\u003e2\\u003c/sub\\u003e/FiO\\u003csub\\u003e2\\u003c/sub\\u003e ratio\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- duration of mechanical ventilation\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant differences in primary outcomes PCT, WBC count, and CRP.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 6.28%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 45.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e3\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 9.42%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2023\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eDoukas, P., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.72%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProcedure: Thoracoabdominal aortic repair\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.12%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u0026reg;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.72%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e10\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e17\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27.76%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower incidence of severe ARDS\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNotably:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- shorter duration of mechanical ventilation\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"7\\\" style=\\\"width: 100%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 38.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:6.0pt;'\\u003e\\u003cu\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003eLegend:\\u003c/span\\u003e\\u003c/u\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;PSM - propensity score matching, CPB \\u0026ndash; cardiopulmonary bypass, pRBC \\u0026ndash; packed red blood cells, FFP \\u0026ndash; fresh frozen plasma\\u003c/span\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;color:windowtext;'\\u003e, PCC \\u0026ndash; prothrombin complex concentrate, IL - interleukin, ICU - intensive care unit, PCT \\u0026ndash; procalcitonin, WBC \\u0026ndash; white blood cells, CRP \\u0026ndash; C reactive protein, RCT \\u0026ndash; randomized controlled trial, ARDS \\u0026ndash; acute respiratory distress syndrome\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp style='margin:0in;text-align:justify;line-height:150%;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:12.0pt;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eOverall, less need for vasopressor therapy and blood product transfusions was observed compared to controls, and there was a lower incidence of acute respiratory distress syndrome (ARDS) in the TAAA patients. Mechanical ventilation-related outcomes were notably better within the intervention groups.\\u003c/p\\u003e\\n\\u003cp\\u003e3.4. Heart transplantation\\u003c/p\\u003e\\n\\u003cp\\u003eNemeth \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[26]\\u0026nbsp;conducted an observational pilot study in the setting of orthotopic heart transplantation (HTx). The results were published in 2018. The primary outcome was defined as hemodynamic stability and vasopressor demand during the first 48 hours postoperatively and the magnitude of postoperative inflammatory response described by the kinetics of procalcitonin (PCT) and C reactive protein (CRP). Patients undergoing orthotopic heart transplantation who received CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e intraoperatively were compared to propensity score-matched controls (16 \\u003cem\\u003evs.\\u003c/em\\u003e 16). In the postoperative period, a significant difference in the need for vasopressor was found between the groups. The control patients required more norepinephrine and terlipressin. The dynamics of PCT and CRP did not vary between the groups. In addition, the incidence of primary graft failure was significantly lower in the hemoadsorption group, and these patients required mechanical circulatory support and renal replacement therapy less frequently. Notably, lower lactate levels and reoperations for bleeding were observed in the hemoadsorption group, which was associated with a shorter duration of mechanical ventilation time and ICU stay. These benefits translate to lower 30-day mortality in intraoperative hemoadsorption patients treated significantly. Notably, no device-related adverse events were reported (\\u003cstrong\\u003eEvidence table\\u003c/strong\\u003e, Additional file 2), suggesting that there was also no clinically relevant inadvertent immunosuppressant removal, consistent with the recently published animal study showing minimal removal of these agents by CytoSorb\\u0026nbsp;[27].\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e3.5. LVAD\\u003c/p\\u003e\\n\\u003cp\\u003eOne article, published in 2022, reported on hemoadsorption use intraoperatively during left ventricular assist device (LVAD) implantation\\u0026nbsp;[28]. A propensity score-matched comparison of 72 patients who received intraoperative hemoadsorption and 40 who did not, revealed a significantly higher incidence of respiratory failure within the intervention group, and higher rates of prolonged mechanical ventilation and tracheostomy. The primary outcome - overall survival after LVAD implantation, was comparable between the groups. Adverse events were reported equally in both groups (\\u003cstrong\\u003eEvidence table\\u003c/strong\\u003e, Additional file 2).\\u003c/p\\u003e\\n\\u003cp\\u003e3.6. Postoperative management\\u003c/p\\u003e\\n\\u003cp\\u003eFour of the 29 articles in this review, published between 2016 and 2021, reported using hemoadsorption in the postoperative period (\\u003cstrong\\u003eTable 4\\u003c/strong\\u003e). All were retrospective single cohort studies evaluating the use of CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e in patients with evidence of ongoing hyperinflammation, or patients who required mechanical circulatory support for septic shock and multiorgan failure. The device was most frequently integrated via continuous renal replacement therapy (CRRT), followed by integration in veno-arterial extracorporeal membrane oxygenation (vaECMO) circuits or other platforms. In aggregate, 177 patients were included.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cbr\\u003e\\u003c/p\\u003e\\n\\u003cp style='margin:0in;text-align:left;line-height:150%;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:12.0pt;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eTable 4\\u003c/span\\u003e\\u003c/strong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e. Evidence overview \\u0026ndash; post-cardiac surgery complications.\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003ctable style=\\\"width:100.0%;border-collapse:collapse;border:none;\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width:5.66%;border:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo.\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:9.98%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eStudy\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:19.38%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eStudy\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003edesign\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:12.58%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eDevice\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:15.08%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eInterventions\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:10.64%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eControls\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:26.68%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eResults of the intervention\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e1\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 9.98%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2016\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eTr\\u0026auml;ger, K., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[29]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 19.38%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase series\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePopulation: Post-op hyperinflammation (SIRS)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u0026reg;\\u003cbr\\u003e\\u0026nbsp;(post-op on CRRT)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e16\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e/\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 26.68%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePre- \\u003cem\\u003evs\\u003c/em\\u003e post-treatment:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- IL-6 \\u0026amp; IL-8 reductions\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- less vasopressor demand\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- improved MAP \\u0026amp; CI\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- improved SOFA score\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduction of lactate levels\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- normalized base excess\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- shorter ICU length of stay\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 78.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 9.98%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 78.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2019\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCalabro, M. G., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[30]\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 19.38%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 78.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase series\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePopulation: Post-op MOF\\u003cbr\\u003e\\u0026nbsp;(cardiac-related)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 78.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u0026reg;\\u003cbr\\u003e\\u0026nbsp;(post-op on various platforms)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 78.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e40\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 78.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e/\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 26.68%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 78.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePre- \\u003cem\\u003evs\\u003c/em\\u003e post-treatment, significant:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduction of bilirubin\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduction of lactate levels\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduction of CPK \\u0026amp; LDH\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower VIS\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSOFA-predicted \\u003cem\\u003evs\\u003c/em\\u003e observed ICU mortality: 80% \\u003cem\\u003evs\\u003c/em\\u003e 55%\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 66.75pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e3\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 9.98%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 66.75pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2020\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eTr\\u0026auml;ger, K., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[31]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 19.38%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 66.75pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase series\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePopulation: Post-op MOF\\u003cbr\\u003e\\u0026nbsp;(cardiac-related)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 66.75pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u0026reg;\\u003cbr\\u003e\\u0026nbsp;(on vaECMO)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 66.75pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e23\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 66.75pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e/\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 26.68%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 66.75pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePre- \\u003cem\\u003evs\\u003c/em\\u003e post-treatment, significant:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- IL-6 reduction\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- norepinephrine reduction\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduction of lactate levels\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- normalized base excess\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 42.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e4\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 9.98%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2021\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eBoss, K., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[32]\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 19.38%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase series\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePopulation: Post-op septic shock\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u0026reg;\\u003cbr\\u003e\\u0026nbsp;(post-op on CRRT)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e98\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e/\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 26.68%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePre- \\u003cem\\u003evs\\u003c/em\\u003e post-treatment, significantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- decreased VIS\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduced lactate levels\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduced SOFA \\u0026amp; APACHE II scores\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSOFA/APACHE II-predicted \\u003cem\\u003evs\\u003c/em\\u003e observed mortality: 77/73% \\u003cem\\u003evs\\u003c/em\\u003e 59%\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"7\\\" style=\\\"width: 100%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 44.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:6.0pt;'\\u003e\\u003cu\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003eLegend:\\u003c/span\\u003e\\u003c/u\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;SIRS \\u0026ndash; systemic inflammatory response syndrome, CRRT \\u0026ndash; continuous renal replacement therapy, IL - interleukin factor, MAP - mean arterial pressure, CI - cardiac index, SOFA \\u0026ndash; sequential organ failure assessment, ICU - intensive care unit, MOF - multiorgan failure, CPK -creatine phosphokinase, LDH - lactate dehydrogenase, VIS - vasoactive inotropic score, vaECMO - veno-arterial extracorporeal membrane oxygenation, APACHE - acute physiology and chronic health evaluation\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp style='margin:0in;text-align:justify;line-height:150%;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:12.0pt;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eResults of the intervention are presented as pre- \\u003cem\\u003eversus\\u003c/em\\u003e post-treatment. Hemoadsorption correlated with decreased vasoactive-inotropic score (VIS)\\u0026nbsp;[30, 32]\\u0026nbsp;and reductions in cytokines\\u0026nbsp;[29, 31].\\u003c/p\\u003e\\n\\u003cp\\u003eAdditionally, two studies compared the actual death rate with the expected mortality based on the standardized Sequential Organ Failure Assessment (SOFA) and/or Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction scores. In both cohorts, observed mortality was notably lower than SOFA-predicted \\u0026ndash; 55% \\u003cem\\u003evs\\u003c/em\\u003e. 80%\\u0026nbsp;[30]\\u0026nbsp;and SOFA/APACHE II-predicted 59% \\u003cem\\u003evs.\\u003c/em\\u003e 77/73%\\u0026nbsp;[32], respectively.\\u003c/p\\u003e\\n\\u003cp\\u003e3.7. Safety\\u003c/p\\u003e\\n\\u003cp\\u003eThe safety profile of CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e can be assessed by analyzing reported device-related adverse events (\\u003cstrong\\u003eEvidence table\\u003c/strong\\u003e, Additional file 2). In 18 / 29 retrieved articles authors reported that unanticipated adverse events associated with hemoadsorption were not observed (62%). Six studies (21%) reported equal rates of clinical adverse events between the intervention and control groups but did not mention device-relatedness, and five publications (17%) did not report adverse events. In aggregate, no serious adverse device-related events were reported in the included articles.\\u003c/p\\u003e\"},{\"header\":\"4. Discussion\",\"content\":\"\\u003cp\\u003eThis systematic review on hemoadsorption use in cardiac surgery has summarized the available published evidence on using CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e. The heterogeneity of the studies prevents the performance of a systematic meta-analysis of reported outcomes, hence the results are presented descriptively. Although other hemoadsorptive technologies may be used in cardiac surgery, our holistic literature search only identified published evidence for CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e4.1. Hyperinflammation after Cardiopulmonary Bypass\\u003c/p\\u003e\\n\\u003cp\\u003eThe terms SIRS\\u0026nbsp;[33]\\u0026nbsp;and \\u0026ldquo;cytokine storm\\u0026rdquo;\\u0026nbsp;[34]\\u0026nbsp;were introduced in the early 1990s and are also frequently used to describe the underlying pathophysiological process to explain the problematic postoperative course underscored by vasoplegia that occurs in some patients after cardiac surgery\\u0026nbsp;[35]. Several triggers and pathophysiological mechanisms have been proposed\\u0026nbsp;[36]\\u0026nbsp;and there are ongoing efforts to identify novel solutions to address this serious complication. Treatment options mostly mirror those utilized in septic shock due to the comparable central role of the dysregulated immune response. Blood purification to remove elevated levels of cytokines and other inflammatory mediators has emerged as an attractive option to stop the vicious circle of auto-amplifying systemic hyperinflammation often leading to vasoplegic shock\\u0026nbsp;[37]\\u0026nbsp;and multiorgan failure. The CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e adsorber is the most researched device for attenuating hyperinflammation and for rebalancing the dysfunctional immune response\\u0026nbsp;[38, 39]. \\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e4.2.\\u0026nbsp;CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e therapy\\u003c/p\\u003e\\n\\u003cp\\u003eCytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e therapy is a blood purification technique based on the hemoadsorption of hydrophobic molecules of up to approximately 60 kDa of molecular weight (\\u003cstrong\\u003eFigure 2\\u003c/strong\\u003e). It is easily integrated into extracorporeal circuits (CPB, (C)RRT, ECMO, etc.) and is CE mark approved for the removal of cytokines, bilirubin, myoglobin, ticagrelor, and rivaroxaban\\u0026nbsp;[40]\\u0026nbsp;(\\u003cstrong\\u003eFigure 3\\u003c/strong\\u003e). As the adsorption process is concentration-dependent\\u0026nbsp;[41], clinically meaningful removal occurs only when the plasma concentration of the target molecule is substantially elevated. A recent, prospective RCT in healthy volunteers demonstrated definitively the ability of the device to remove cytokines, with no signs of long-term immune system suppression by the treatment\\u0026nbsp;[42]. In addition to reducing elevated levels of cytokines, there is evidence of concurrent removal of trigger molecules, such as PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns), which also reside in the above-described adsorption range\\u0026nbsp;[43]\\u0026nbsp;(\\u003cstrong\\u003eFigure 4\\u003c/strong\\u003e). In this way,\\u0026nbsp;CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e therapy aims to help the patient\\u0026rsquo;s body mitigate the cytokine hyper-release cytotoxic effect and attenuate the dysregulated inflammatory response, to prevent the progression of organ dysfunction.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFigure 2.\\u003c/strong\\u003e CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e\\u003csup\\u003e\\u0026nbsp;\\u003c/sup\\u003epolymer bead technology.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFigure 3.\\u003c/strong\\u003e Installation scheme of CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e device within cardiopulmonary bypass circuit.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFigure 4.\\u003c/strong\\u003e CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e\\u003csup\\u003e\\u0026nbsp;\\u003c/sup\\u003eadsorption range.\\u003c/p\\u003e\\n\\u003cp\\u003e4.3. Interpretation of the available evidence\\u003c/p\\u003e\\n\\u003cp\\u003eHemoadsorption represents a reasonably new technology and only a few relatively small RCTs exist. The intraoperative use of CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e by direct integration in the CPB circuit was first reported by Born \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[44]\\u0026nbsp;in 2014 and showed significant reductions of interleukin (IL)-6 and procalcitonin (PCT). The first RCT in patients undergoing elective cardiac surgery was published 2 years later\\u0026nbsp;[13], but in contrast, it did not demonstrate the removal of measured cytokines. Given the trial\\u0026rsquo;s results, and as described in the elective cardiac surgery part of this review, it seems that patients undergoing elective, low-risk cardiac surgery may not be the most relevant cohort for hemoadsorption to demonstrate any effect. While the RCTs included in this systematic review confirm that the intraoperative integration of CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e in CPB during cardiac surgery is both easy and safe, they mostly failed to show significant improvements in clinical endpoints, despite reducing circulating cytokine levels\\u0026nbsp;[8]. Considering the fact that hemoadsorption occurs in a concentration-dependent manner\\u0026nbsp;[41]\\u0026nbsp;and that effective removal requires highly increased circulating levels, it is understandable that hemoadsorption may not provide substantial clinical benefits in low-risk, elective cardiac surgery\\u0026nbsp;[13, 20], or even in lower-risk infective endocarditis (IE) patients\\u0026nbsp;[6], where cytokine concentrations are not substantially elevated.\\u003c/p\\u003e\\n\\u003cp\\u003e4.3.1. Infective endocarditis\\u003c/p\\u003e\\n\\u003cp\\u003eOver one-third of all publications identified in this review report on outcomes with hemoadsorption in IE patients undergoing cardiac surgery (\\u003cstrong\\u003eTable 1\\u003c/strong\\u003e). The results are not uniform, and their interpretation commands a thorough assessment. The REMOVE trial (Revealing Mechanisms and Investigating Efficacy of Hemoadsorption for Prevention of Vasodilatory Shock in Cardiac Surgery Patients with Infective Endocarditis - a Multicentric Randomized Controlled Group Sequential Trial) was the most extensive study within this group\\u0026nbsp;[8]. In a proof-of-concept pre-specified analysis in the first 50 enrolled patients, the REMOVE investigators showed a significant reduction of various cytokines. Based on these findings, they continued with full enrolment in the trial which ultimately did not show a statistically significant difference in the primary endpoint of postoperative organ function improvement assessed by the change in SOFA score between 138 patients who received intraoperative hemoadsorption and 144 patients without this treatment. All secondary outcomes and rates of adverse events were also comparable between the two groups. The patient population comprised of \\u0026ldquo;all-comers\\u0026rdquo; with IE requiring surgery with no further risk-stratification for inclusion except a European System for Cardiac Operative Risk Evaluation Score - EuroSCORE II \\u0026gt; 3%. Approximately 1/3 of procedures were outpatients undergoing elective surgery, and, e.g., the median preoperative IL-6 levels were only 18.36 pg/mL in the treatment and 40.6 pg/mL (p=0.3) in the control group.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eResults from two other smaller RCTs in IE patients yielded different results. Asch \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[6]\\u0026nbsp;found higher vasopressor and fluid therapy demand within the intervention group. In contrast, Holmen \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[45]\\u0026nbsp;showed a reduction in the consumption of blood products and a substantial decrease in norepinephrine need and postoperative vasopressor therapy duration associated with CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e treatment. While patient selection in the first study was compromised with significant baseline differences between the groups (\\u003cstrong\\u003eTable 1\\u003c/strong\\u003e), the second study included only acute, high-risk patients and demonstrated a clear trend towards faster hemodynamic stabilization correlating with hemoadsorption. Nevertheless, the minimal sample size of both trials requires caution with interpretations and conclusions.\\u003c/p\\u003e\\n\\u003cp\\u003eKalisnik \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[7]\\u0026nbsp;compared 99 high-risk IE patients with intraoperative hemoadsorption to 99 propensity-score-matched controls with a median EuroSCORE II of around 9% in both groups. Similarly, Haidari \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[11]\\u0026nbsp;reported on a cohort of 70 patients with a EuroSCORE II \\u0026gt; 8%, therefore including only high-risk patients. Both studies showed a significantly lower incidence of sepsis-related mortality using hemoadsorption. In addition, the former showed a lower incidence of sepsis, and the latter reduced cumulative vasopressor need in patients treated with CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e. In contrast, a study by Santer \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[46], showed that intraoperative hemoadsorption was associated with increased vasopressor and blood product requirements in 41 IE patients compared with 200 matched controls. It is noteworthy, however, as the authors of this study acknowledged that despite the use of advanced statistical methods to address residual confounders, significant imbalances remained between the two groups specifically relating to the change in treatment protocols over time.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eThe overall incidence of IE is increasing\\u0026nbsp;[47, 48]\\u0026nbsp;and around 50% of these patients will require valve surgery at some point\\u0026nbsp;[49]. Many patients will require emergency surgery under active infection and concomitant inflammation. In such cases, major surgical trauma and CPB may worsen the already primed and aggravated immune system, often leading to excessive release of cytokines and consequent systemic hyperinflammation\\u0026nbsp;[50]. Moreover, the proportion of IEs caused by \\u003cem\\u003eStaph. aureus\\u003c/em\\u003e has increased in recent years\\u0026nbsp;[48], introducing even more complexity and risk within this field. This sub-population of IE patients was investigated explicitly in a recent dual-center study in which the use of hemoadsorption was associated with significantly lower VIS, incidence of renal failure requiring dialysis, and fewer deaths (sepsis-related, 30-day, and 90-day mortality)\\u0026nbsp;[12]. In addition, certain bacteria toxins may also be removed by CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e [43], specifically \\u003cem\\u003eStaph. aureus\\u003c/em\\u003e exotoxins. This fact and the promising results from the above observational studies potentially promote CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e as an adjunctive and versatile tool in high-risk IE cases.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eThe benefit of non-selective depletion of cytokines has not yet been proven in this population of patients. Notwithstanding, based on the results of studies presented here, it seems that hemoadsorption may improve outcomes in high-risk IE patients\\u0026nbsp;[5, 7, 9, 11, 12, 45]. This is supported by the high baseline risk scores (EuroSCORE-II \\u0026gt; 8%)\\u0026nbsp;[51]\\u0026nbsp;in the studies that reported benefit with hemoadsorption. Therefore, appropriate patient selection at high risk for postoperative complications, relating to a heightened inflammatory response, is critical when considering the use of hemoadsorption. For example, Haidari \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[10]\\u0026nbsp;showed favorable outcomes after carefully selecting patients to receive intraoperative hemoadsorption based on the presence of the following criteria prior to surgery: fever, severely elevated inflammatory parameters, and/or hemodynamic instability requiring high inotropic support. Moreover, K\\u0026uuml;hne \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[5]\\u0026nbsp;suggested that IE patients who, despite receiving hemoadsorption treatment during CPB, develop intraoperative renal failure and require increasing vasopressor therapy, or have high-grade intraoperative findings (vegetations and aortic root abscess), might benefit from the continuation of hemoadsorptive therapy in the ICU. Accordingly, REMOVE\\u0026rsquo;s \\u0026ldquo;neutral\\u0026rdquo; results may potentially be reflective of the \\u0026ldquo;all-comer\\u0026rdquo; nature of the population\\u0026nbsp;[8], which is also supported by the low median IL-6 levels prior to surgery. In contrast, the average IL-6 levels seen by Jansen \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[42]\\u0026nbsp;were above 500 pg/mL and demonstrated significant cytokine clearance with CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003e4.3.2. Aortic surgery\\u003c/p\\u003e\\n\\u003cp\\u003eComplex and combined open aortic surgery and high-risk operations to treat aortic dissections or thoracoabdominal aortic aneurism (TAAA), may also result in systemic hyperinflammation. Hypothermic circulatory arrest (HCA), commonly employed during aortic surgery extending into the arch, may be a further trigger for an exaggerated inflammatory response, often leading to vasoplegia, compromised microcirculation, increased lactate levels, and subsequent organ failure\\u0026nbsp;[52].\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eSaller \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[23]\\u0026nbsp;observed significantly lower norepinephrine concentrations and better acid-base status (reflected by less frequent low pH, lower lactate concentrations, and decreased need for buffer solution) compared to standard therapy in 168 patients who underwent various open thoracic aortic surgical procedures under HCA with intraoperative\\u0026nbsp;CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e treatment compared to 168 propensity score-matched controls. Interestingly, hemoadsorption correlated with a significantly decreased need for transfusion of packed red blood cells and fresh frozen plasma but an increased requirement of prothrombin complex concentrate. The authors observed that the overall benefit of the therapy was explicitly prominent in the subgroup of emergency patients with acute aortic dissections. A significant reduction in norepinephrine and IL-6 in patients who mainly underwent Bentall procedures adjunctly treated with\\u0026nbsp;CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e on CPB was also shown in a small pilot observational study, together with better mean arterial pressure, and PaO\\u003csub\\u003e2\\u003c/sub\\u003e/FiO\\u003csub\\u003e2\\u003c/sub\\u003e ratio, shorter mechanical ventilation duration, and ICU and hospital stay\\u0026nbsp;[24]. A pilot RCT investigated the feasibility and effect of intraoperative hemoadsorption during open TAAA repair and showed a significantly lower incidence of ARDS\\u0026nbsp;[25]. However, both these pilot study results should be interpreted with caution due to their small sample size.\\u003c/p\\u003e\\n\\u003cp\\u003eThe available evidence in the population of complex aortic surgery seems promising but remains very preliminary and requires confirmation in prospective trials. Decreased vasopressor requirements observed in high-risk aortic surgery patients who received\\u0026nbsp;CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e therapy are similar to findings within other populations discussed in this review and may represent a meaningful clinical endpoint for future trials.\\u003c/p\\u003e\\n\\u003cp\\u003e4.3.3. Post-cardiac surgery complications\\u003c/p\\u003e\\n\\u003cp\\u003eData from sizeable cardiac surgery registries show a downward trend in mortality and morbidities after cardiac surgery over the last 20 years. However, despite decades of innovation in cardiopulmonary support, on-pump cardiac surgery still carries the risk for a postoperative systemic inflammatory response and vasoplegia which in turn leads to worse outcomes\\u0026nbsp;[53]. In this fairly heterogeneous patient population, hemoadsorption is frequently used in daily practice to attenuate the post-operative hyperinflammatory response.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eTo the best of our knowledge, no prospective trials have been conducted in this population so far, and the four studies in this review provide promising but highly speculative results, involving patients with predominantly SIRS, multiorgan failure (MOF), cardiogenic and septic shock. Almost all patients required renal or circulatory support, thus CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e was used adjacent to CRRT or vaECMO. It seems that hemoadsorption was associated with hemodynamic stabilization and lower actual \\u003cem\\u003eversus\\u003c/em\\u003e expected mortality.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eThe versatile nature of hemoadsorption may benefit postoperative patients in complex and severely impaired conditions, as CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e not only removes cytokines, but also bilirubin, bile acids, myoglobin, some toxins, and various PAMPs and DAMPs\\u0026nbsp;[43, 54-56]. As with any other blood purification technology, hemoadsorption carries a risk of inadvertent drug removal. Critical care patients are specifically prone to this due to the usually high numbers of administered medications over long treatment periods. Assessment of the clinical relevance of potential drug removal requires consideration of the patient\\u0026rsquo;s condition, the impact of concomitantly applied extracorporeal therapies, duration of device exposure, and timing of drug administration. Clinical decision-making regarding adjustments in drug dosing should always be made in the broader clinical context supported by therapeutic drug monitoring when available\\u0026nbsp;[57].\\u003c/p\\u003e\\n\\u003cp\\u003e4.3.4. Heart transplant surgery and \\u003cem\\u003eEx vivo\\u003c/em\\u003e organ perfusion\\u003c/p\\u003e\\n\\u003cp\\u003eOne study suggested favorable outcomes in HTx patients associated with intraoperative hemoadsorption\\u0026nbsp;[26], and an animal experiment in \\u003cem\\u003eex vivo\\u003c/em\\u003e lung perfusion (EVLP) showed that CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e treatment significantly decreased cytokine levels and levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury and primary graft dysfunction (PGD) incidence was significantly reduced among treated animals\\u0026nbsp;[58]. Authors suggest this treatment will increase the availability of the donor\\u0026rsquo;s lungs and provide better graft tolerability in the recipient. The first-in-human (micro)study published by the same group\\u0026nbsp;[59]\\u0026nbsp;suggests that cytokine adsorption adjacent to extracorporeal lung support during lung transplantation supports graft acceptance. Promising results in an EVLP animal model were previously reported by Iskender \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[60]\\u0026nbsp;and in animal studies involving hearts and kidneys donated after circulatory death (DCD)\\u0026nbsp;[61, 62]. Considering the ongoing unmet need for organs for transplantation, \\u003cem\\u003eex vivo\\u003c/em\\u003e organ perfusion with adjunctive hemoadsorptive treatment may play an essential role in combatting organ shortage and early graft rejection.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eThe use of hemoadsorption in organ transplants has been controversial due to the already discussed potential for unwanted drug removal, specifically immunosuppressants. However, a detailed investigation in a large animal model reassuringly reported a minimal level of removal with frequently used immunosuppressant regimens\\u0026nbsp;[27]. A very recent RCT\\u0026nbsp;[63]\\u0026nbsp;confirmed CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e\\u003csup\\u003e\\u0026nbsp;\\u003c/sup\\u003edid not affect levels of mycophenolic acid, used to prevent organ transplant rejection, and found that concentrations were comparable to the control group at all pre-defined time points. There was also no increase in the frequency of early cardiac allograft rejection in the intervention group. In their proof-of-concept trial, Nemeth \\u003cem\\u003eet al.\\u003c/em\\u003e compared the effect of intra-operative CytoSorb\\u003csup\\u003e\\u0026reg;\\u003c/sup\\u003e use to standard care in 55 orthotopic heart transplantation patients (30 CytoSorb\\u003csup\\u003e\\u0026reg;\\u003c/sup\\u003e and 25 standard care). Results showed that the CytoSorb\\u0026reg; group had significantly lower vasoactive-inotropic scores (p=0.046), a 6.4-fold decrease in the odds of developing vasoplegic syndrome (p=0.028), lower PCT levels, shorter duration of mechanical ventilation hours (p=0.025), and ICU (p=0.022). Patients in the CytoSorb\\u003csup\\u003e\\u0026reg;\\u003c/sup\\u003e group also had lower rates of acute kidney injury (p=0.004), renal replacement therapy (p=0.037) and more stable hepatic bilirubin excretion. Furthermore, 30-day mortality and 1-year survival did not differ between groups. There were no reported device-related adverse events during the study period.\\u003c/p\\u003e\\n\\u003cp\\u003e4.3.5. LVAD\\u003c/p\\u003e\\n\\u003cp\\u003eLVAD implantation in patients with advanced heart failure carries a substantial risk of a dysregulated inflammatory response mediated by exaggerated cytokine production. Since hemoadsorption has recently yielded promising results in high-risk patients undergoing cardiac surgery by immunomodulation and consequent attenuation of over-shooting inflammation\\u0026nbsp;[64], the rationale for its utilization during CPB-assisted LVAD implantation surgery was investigated. However, results from the only study on this topic found in the current literature search demonstrated a significantly increased incidence of respiratory failure in the CytoSorb\\u003csup\\u003e\\u0026reg;\\u003c/sup\\u003e group compared to propensity score-matched controls. Consequently, the need for prolonged mechanical ventilation and tracheostomy was also increased with hemoadsorption. Furthermore, in-hospital mortality was notably lower in the control group\\u0026nbsp;[28].\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eThe ongoing RCT CytoSorb\\u003csup\\u003e\\u0026reg;\\u003c/sup\\u003e Modulation of Surgical Inflammation During LVAD Insertion (CYCLONE-LVAD) will evaluate the role of hemoadsorption in this field (ClinicalTrials.gov Identifier: NCT04596813).\\u003c/p\\u003e\\n\\u003cp\\u003e4.3.6. ECMO/ECLS\\u003c/p\\u003e\\n\\u003cp\\u003eExtracorporeal life support (ECLS) for patients with severely compromised circulation via vaECMO is known to provoke a complex inflammatory reaction. This innate immune response, if severe, may lead to disrupted microcirculation, and end-organ dysfunction. Despite dramatic technological improvements with newer ECMO platforms, systemic hyperinflammation remains a relevant clinical concern\\u0026nbsp;[65]. Apart from the widely known pathophysiological mechanism of artificial surface contact-mediated coagulation, platelet, and complement system activation, and consequent endothelial injury, another potent trigger for cytokine hyperproduction is the release of endotoxins in response to translocation of bacteria from ischemic gut mucosa into the bloodstream\\u0026nbsp;[66]. If such an already explosive immune response is dysregulated, and instead of self-limiting, the cytokine storm becomes auto-amplifying, it may lead to a vicious circle and eventually death.\\u003c/p\\u003e\\n\\u003cp\\u003eCytokine adsorption has recently been introduced as an adjunctive tool to limit the hyperinflammatory response to ECMO. Clinical evidence so far is limited and controversial. It has been recommended that parameters for appropriate patient selection should include signs of shock, high vasopressor requirements, elevated lactate levels, and/or elevated IL-6, lactate, bilirubin, or myoglobin plasma levels. Potential examples where hemoadsorption may be considered include profound shock on ECMO, post-cardiotomy ECMO in patients with infection, and ECMO in the context of organ donation\\u0026nbsp;[67].\\u003c/p\\u003e\\n\\u003cp\\u003eA recent study from Soltesz \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[68]\\u0026nbsp;evaluated the impact of vaECMO-integrated hemoadsorption on the reversal of multiorgan and microcirculatory dysfunction and early mortality of refractory cardiogenic shock patients. Among 29 \\u003cem\\u003evs.\\u003c/em\\u003e 29 propensity score-matched patients,\\u0026nbsp;CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e treatment resulted in significantly lower VIS, lactate levels, and ECMO-associated bleeding complications. Hemoadsorption was used continuously for 72 hours with vaECMO therapy in those with persistent hemodynamic instability. Well-designed, prospective trials will be necessary to answer complex questions regarding the right timing for adjunctive hemoadsorption therapy, optimal duration, and proper patient selection.\\u003c/p\\u003e\\n\\u003cp\\u003e4.4. Safety and other systematic findings\\u003c/p\\u003e\\n\\u003cp\\u003eThis review assessed the safety of CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e therapy based on the incidence of reported unanticipated device-related adverse events (UADE). Among studies that reported adverse events, there were no UADE noted. It appears, therefore, that CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e has a favorable safety profile when used in cardiac surgery patients (\\u003cstrong\\u003eEvidence table\\u003c/strong\\u003e, Additional file 2).\\u003c/p\\u003e\\n\\u003cp\\u003eA recent meta-analysis from the United Kingdom investigated operative mortality, ventilation duration, ICU and hospital stays, and postoperative day 1 inflammatory markers in studies involving CPB and hemoadsorption. Of 15 selected studies, 12 used CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e, 2 investigated Alteco\\u003csup\\u003e\\u0026reg;\\u003c/sup\\u003e LPS adsorber (Alteco Medical AB, Lund, Sweden), and 1 Toraymyxin\\u003csup\\u003e\\u0026reg;\\u003c/sup\\u003e (Toray Industries, Tokyo, Japan). When comparing cytokine adsorption cases and controls across all studies, authors found no significant difference in operative mortality, ventilation duration, hospital stay, and ICU length of stay. However, a significant reduction in 30-day\\u0026nbsp;mortality (\\u003cstrong\\u003eFigure 5\\u003c/strong\\u003e) and ICU stay (\\u003cstrong\\u003eFigure 6\\u003c/strong\\u003e) was shown\\u0026nbsp;to be associated with hemoadsorption therapy during non-elective cardiac surgery, especially emergency surgery, and in patients with a higher inflammatory burden such as with infective\\u0026nbsp;endocarditis\\u0026nbsp;[69].\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFigure 5.\\u003c/strong\\u003e Naruka \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[69]\\u0026nbsp;Forest plot: meta-analysis for the difference in operative mortality between CPB-assisted cardiac surgery with and without hemoadsorption.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFigure 6.\\u003c/strong\\u003e Naruka \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[69]\\u0026nbsp;Forest plot: meta-analysis for the difference in an intensive care unit (ICU) stay between CPB-assisted cardiac surgery with and without hemoadsorption.\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors\\u0026rsquo; conclusions that hemoadsorption devices are likely to be more beneficial in patients with higher inflammatory responses, such as infective endocarditis and emergency operations, align with the findings of the current systematic review. Furthermore, Liu \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[2]\\u0026nbsp;in their narrative review concluded that although data on the use of hemoadsorption in cardiac surgery is scarce and even controversial, there is no denying that adsorptive extracorporeal blood purification technology, especially CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e, opens a new door for the ongoing \\u003cs\\u003ee\\u003c/s\\u003efforts in battling CPB-associated SIRS. A meta-analysis from Heymann \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[70], however, showed that in fact, the use of CytoSorb\\u003csup\\u003e\\u0026reg;\\u003c/sup\\u003e might increase mortality in critically ill patients with inflammatory conditions, although the authors did acknowledge the low certainty of the evidence, primarily due to the lack of power to independently assess mortality across the vasty heterogeneous populations included. Interestingly, in a subgroup analysis of complex cardiac surgery, increased mortality associated with\\u0026nbsp;CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e was not found, which is in agreement with the findings of Naruka \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;[69]\\u0026nbsp;and Liu \\u003cem\\u003eet al\\u003c/em\\u003e.,\\u0026nbsp;[2]\\u0026nbsp;as well as with the current systematic review. In general, leading experts in intensive care medicine are increasingly calling for new realistic clinical endpoints instead of mortality for the assessment of potential clinical benefits of novel therapies in critical patients.\\u0026nbsp;[71-73].\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eSimilarly, hemoadsorption is an adjunct therapy in critically ill or high-risk surgical patients. As such, it represents a small piece in a very complex puzzle of medical treatments, therapeutic protocols, surgical procedures and techniques, and advanced diagnostics currently used in the cardiac surgery setting and beyond. Although solid clinical evidence demonstrating survival benefits from using hemoadsorption in cardiac surgery is currently lacking, this systematic literature review, despite its limitations regarding the heterogeneity of study designs and endpoint measures, suggests that meaningful outcomes such as faster hemodynamic stabilization may be achieved with hemoadsorption in high-risk cardiac surgery patients.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"5. Conclusions\",\"content\":\"\\u003cp\\u003eHemoadsorption in cardiac surgery is an emerging field with CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e being the only available device with published evidence discovered in this systematic review. The reviewed evidence shows that its use intraoperatively with CPB or postoperatively with CRRT or vaECMO is feasible and safe with no unanticipated device-related adverse events reported in any of the retrieved publications. However, in relation to the evidence supporting the efficacy of the device, the available evidence is mixed, but in aggregate suggests limited value with use in routine elective surgery and low-risk patients. On the other hand, the role of hemoadsorption with on-pump cardiac surgery seems attractive in high-risk infective endocarditis cases and possibly aortic surgery, and among patients who develop a dysregulated inflammatory response, vasoplegia or septic shock postoperatively. The most frequently reported clinical benefit associated with hemoadsorption treatment is reduced vasopressor demand resulting in better hemodynamic stability. CytoSorb\\u003csup\\u003e\\u0026acirc;\\u003c/sup\\u003e also represents a promising new approach within the field of heart transplantation and \\u003cem\\u003eex vivo\\u003c/em\\u003e organ perfusion, where in addition to improved outcomes it may also contribute to greater organ availability. Further prospective studies are needed to enhance the body of evidence for the potential benefits associated with the use of hemoadsorption in cardiac surgery-related settings. \\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003cp\\u003e1. Chakravarthy M. Modifying risks to improve outcome in cardiac surgery: An anesthesiologist\\u0026apos;s perspective. Ann Card Anaesth. 2017;20(2):226-33. doi: 10.4103/aca.ACA_20_17.\\u003c/p\\u003e\\n\\u003cp\\u003e2. Liu MH, Yu H, Zhou RH. Application of Adsorptive Blood Purification Techniques during Cardiopulmonary Bypass in Cardiac Surgery. Oxid Med Cell Longev. 2022;2022:6584631. doi: 10.1155/2022/6584631.\\u003c/p\\u003e\\n\\u003cp\\u003e3. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71.\\u003c/p\\u003e\\n\\u003cp\\u003e4. Matejic-Spasic M, Hassan K, Thielmann M, Geidel S, Storey RF, Schmoeckel M, et al. Management of perioperative bleeding risk in patients on antithrombotic medications undergoing cardiac surgery-a systematic review. J Thorac Dis. 2022;14(8):3030-44. doi: 10.21037/jtd-22-428.\\u003c/p\\u003e\\n\\u003cp\\u003e5. Kuhne LU, Binczyk R, Riess FC. Comparison of intraoperative versus intraoperative plus postoperative hemoadsorption therapy in cardiac surgery patients with endocarditis. Int J Artif Organs. 2019;42(4):194-200. doi: 10.1177/0391398819831301.\\u003c/p\\u003e\\n\\u003cp\\u003e6. Asch S, Kaufmann TP, Walter M, Leistner M, Danner BC, Perl T, et al. The effect of perioperative hemadsorption in patients operated for acute infective endocarditis-A randomized controlled study. Artif Organs. 2021;45(11):1328-37. doi: 10.1111/aor.14019.\\u003c/p\\u003e\\n\\u003cp\\u003e7. Kalisnik JM, Leiler S, Mamdooh H, Zibert J, Bertsch T, Vogt FA, et al. Single-Centre Retrospective Evaluation of Intraoperative Hemoadsorption in Left-Sided Acute Infective Endocarditis. J Clin Med. 2022;11(14):3954. doi: 10.3390/jcm11143954.\\u003c/p\\u003e\\n\\u003cp\\u003e8. Diab M, Lehmann T, Bothe W, Akhyari P, Platzer S, Wendt D, et al. Cytokine Hemoadsorption During Cardiac Surgery Versus Standard Surgical Care for Infective Endocarditis (REMOVE): Results From a Multicenter Randomized Controlled Trial. Circulation. 2022;145(13):959-68. doi: 10.1161/CIRCULATIONAHA.121.056940.\\u003c/p\\u003e\\n\\u003cp\\u003e9. Traeger K, Skrabal C, Fischer G, Datzmann T, Schroeder J, Fritzler D, et al. Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass - a case series. Int J Artif Organs. 2017;40(5):240-9. doi: 10.5301/ijao.5000583.\\u003c/p\\u003e\\n\\u003cp\\u003e10. Haidari Z, Wendt D, Thielmann M, Mackowiak M, Neuhauser M, Jakob H, et al. Intraoperative Hemoadsorption in Patients With Native Mitral Valve Infective Endocarditis. Ann Thorac Surg. 2020;110(3):890-6. doi: 10.1016/j.athoracsur.2019.12.067.\\u003c/p\\u003e\\n\\u003cp\\u003e11. Haidari Z, Demircioglu E, Boss K, Tyczynski B, Thielmann M, Schmack B, et al. Intraoperative hemoadsorption in high-risk patients with infective endocarditis. PLoS One. 2022;17(7):e0266820. doi: 10.1371/journal.pone.0266820.\\u003c/p\\u003e\\n\\u003cp\\u003e12. Haidari Z, Leiler S, Mamdooh H, Fittkau M, Boss K, Tyczynski B, et al. Effect of intraoperative haemoadsorption therapy on cardiac surgery for active infective endocarditis with confirmed Staphylococcus aureus bacteraemia. Interdiscip Cardiovasc Thorac Surg. 2023;36(1):ivad.010. doi: 10.1093/icvts/ivad010.\\u003c/p\\u003e\\n\\u003cp\\u003e13. Bernardi MH, Rinoesl H, Dragosits K, Ristl R, Hoffelner F, Opfermann P, et al. Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent. Crit Care. 2016;20(1):96. doi: 10.1186/s13054-016-1270-0.\\u003c/p\\u003e\\n\\u003cp\\u003e14. Hohn A, Baumann A, Pietroschinsky E, Franklin J, Illerhaus A, Buchwald D, et al. Hemoadsorption: effective in reducing circulating fragments of the endothelial glycocalyx during cardiopulmonary bypass in patients undergoing on-pump cardiac surgery? Minerva Anestesiol. 2021;87(1):35-42. doi: 10.23736/S0375-9393.20.14525-5.\\u003c/p\\u003e\\n\\u003cp\\u003e15. Manohar M, Jawali V, Neginahal S, Gt S, Muniraj G, Chakravarthy M. Hemoadsorption in Complex Cardiac Surgery-A Single Center Experience. J Clin Med. 2022;11(23):7005. doi: 10.3390/jcm11237005.\\u003c/p\\u003e\\n\\u003cp\\u003e16. Wisgrill L, Lamm C, Hell L, Thaler J, Berger A, Weiss R, et al. Influence of hemoadsorption during cardiopulmonary bypass on blood vesicle count and function. J Transl Med. 2020;18(1):202. doi: 10.1186/s12967-020-02369-x.\\u003c/p\\u003e\\n\\u003cp\\u003e17. Bernardi MH, Rinoesl H, Ristl R, Weber U, Wiedemann D, Hiesmayr MJ. Hemoadsorption does not Have Influence on Hemolysis During Cardiopulmonary Bypass. ASAIO J. 2019;65(7):738-43. doi: 10.1097/MAT.0000000000000897.\\u003c/p\\u003e\\n\\u003cp\\u003e18. Garau I, Marz A, Sehner S, Reuter DA, Reichenspurner H, Zollner C, et al. Hemadsorption during cardiopulmonary bypass reduces interleukin 8 and tumor necrosis factor alpha serum levels in cardiac surgery: a randomized controlled trial. Minerva Anestesiol. 2019;85(7):715-23. doi: 10.23736/S0375-9393.18.12898-7.\\u003c/p\\u003e\\n\\u003cp\\u003e19. Gleason TG, Argenziano M, Bavaria JE, Kane LC, Coselli JS, Engelman RM, et al. Hemoadsorption to Reduce Plasma-Free Hemoglobin During Cardiac Surgery: Results of REFRESH I Pilot Study. Semin Thorac Cardiovasc Surg. 2019;31(4):783-93. doi: 10.1053/j.semtcvs.2019.05.006.\\u003c/p\\u003e\\n\\u003cp\\u003e20. Poli EC, Alberio L, Bauer-Doerries A, Marcucci C, Roumy A, Kirsch M, et al. Cytokine clearance with CytoSorb(R) during cardiac surgery: a pilot randomized controlled trial. Crit Care. 2019;23(1):108. doi: 10.1186/s13054-019-2399-4.\\u003c/p\\u003e\\n\\u003cp\\u003e21. Taleska Stupica G, Music S, Podbregar M, Sostaric M. Cytokine hemadsorption for the treatment of severe postoperative systemic inflammatory response syndrome in cardiovascular intensive care unit. \\u0026nbsp;ESICM Lives 2022. Paris, France: ICMx; 2022.\\u003c/p\\u003e\\n\\u003cp\\u003e22. Wagner R, Soucek P, Ondrasek J, Fila P, Sterba J, Spacilova H, et al. Plasma Levels of Myocardial MicroRNA-133a Increase by Intraoperative Cytokine Hemoadsorption in the Complex Cardiovascular Operation. J Clin Med Res. 2019;11(12):789-97. doi: 10.14740/jocmr3989.\\u003c/p\\u003e\\n\\u003cp\\u003e23. Saller T, Hagl C, Woitsch S, Li Y, Niedermayer S, Born F, et al. Haemadsorption improves intraoperative haemodynamics and metabolic changes during aortic surgery with hypothermic circulatory arrest. Eur J Cardiothorac Surg. 2019;56(4):731-7. doi: 10.1093/ejcts/ezz074.\\u003c/p\\u003e\\n\\u003cp\\u003e24. Mehta Y, Singh A, Singh A, Gupta A, Bhan A. Modulating the Inflammatory Response With Hemadsorption (CytoSorb) in Patients Undergoing Major Aortic Surgery. J Cardiothorac Vasc Anesth. 2021;35(2):673-5. doi: 10.1053/j.jvca.2020.06.028.\\u003c/p\\u003e\\n\\u003cp\\u003e25. Doukas P, Hellfritsch G, Wendt D, Magliani M, Barbati ME, Jalaie H, et al. Intraoperative Hemoadsorption (Cytosorb) during Open Thoracoabdominal Aortic Repair: A Pilot Randomized Controlled Trial. J Clin Med. 2023;12(2):546. doi: 10.3390/jcm12020546.\\u003c/p\\u003e\\n\\u003cp\\u003e26. Nemeth E, Kovacs E, Racz K, Soltesz A, Szigeti S, Kiss N, et al. Impact of intraoperative cytokine adsorption on outcome of patients undergoing orthotopic heart transplantation-an observational study. Clin Transplant. 2018;32(4):e13211. doi: 10.1111/ctr.13211.\\u003c/p\\u003e\\n\\u003cp\\u003e27. Leber B, Liebchen U, Rohrhofer L, Weber J, Klaus T, Scheier J, et al. Pharmacokinetics of immunosuppressive agents during hemoperfusion in a sheep model. Front Med (Lausanne). 2023;10:1258661. doi: 10.3389/fmed.2023.1258661.\\u003c/p\\u003e\\n\\u003cp\\u003e28. Zhigalov K, Van den Eynde J, Zubarevich A, Chrosch T, Goerdt L, Arjomandi Rad A, et al. Initial experience with CytoSorb therapy in patients receiving left ventricular assist devices. 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Eur Heart J. 2019;40(39):3222-32. doi: 10.1093/eurheartj/ehz620.\\u003c/p\\u003e\\n\\u003cp\\u003e50. Diab M, Tasar R, Sponholz C, Lehmann T, Pletz MW, Bauer M, et al. Changes in inflammatory and vasoactive mediator profiles during valvular surgery with or without infective endocarditis: A case control pilot study. PLoS One. 2020;15(2):e0228286. doi: 10.1371/journal.pone.0228286.\\u003c/p\\u003e\\n\\u003cp\\u003e51. Arangalage D, Cimadevilla C, Alkhoder S, Chiampan A, Himbert D, Brochet E, et al. Agreement between the new EuroSCORE II, the Logistic EuroSCORE and the Society of Thoracic Surgeons score: implications for transcatheter aortic valve implantation. Arch Cardiovasc Dis. 2014;107(6-7):353-60. doi: 10.1016/j.acvd.2014.05.002.\\u003c/p\\u003e\\n\\u003cp\\u003e52. Stoppelkamp S, Veseli K, Stang K, Schlensak C, Wendel HP, Walker T. Identification of Predictive Early Biomarkers for Sterile-SIRS after Cardiovascular Surgery. PLoS One. 2015;10(8):e0135527. doi: 10.1371/journal.pone.0135527.\\u003c/p\\u003e\\n\\u003cp\\u003e53. Squiccimarro E, Stasi A, Lorusso R, Paparella D. Narrative review of the systemic inflammatory reaction to cardiac surgery and cardiopulmonary bypass. Artif Organs. 2022;46(4):568-77. doi: 10.1111/aor.14171.\\u003c/p\\u003e\\n\\u003cp\\u003e54. Nierhaus A, Morales J, Wendt D, Scheier J, Gutzler D, Jarczak D, et al. Comparison of the CytoSorb((R)) 300 mL and Jafron HA380 hemoadsorption devices: an in vitro study. Minim Invasive Ther Allied Technol. 2022;31(7):1058-65. doi: 10.1080/13645706.2022.2104617.\\u003c/p\\u003e\\n\\u003cp\\u003e55. Dominik A, Stange J. Similarities, Differences, and Potential Synergies in the Mechanism of Action of Albumin Dialysis Using the MARS Albumin Dialysis Device and the CytoSorb Hemoperfusion Device in the Treatment of Liver Failure. Blood Purif. 2021;50(1):119-28. doi: 10.1159/000508810.\\u003c/p\\u003e\\n\\u003cp\\u003e56. Denzinger M, Staendker L, Ehlers K, Schneider JM, Schulz T, Hein T, et al. Bioassay for Endothelial Damage Mediators Retrieved by Hemoadsorption. Sci Rep. 2019;9(1):14522. doi: 10.1038/s41598-019-50517-1.\\u003c/p\\u003e\\n\\u003cp\\u003e57. Scheier J, Nelson PJ, Schneider A, Colombier S, Kindgen-Milles D, Deliargyris EN, et al. Mechanistic Considerations and Pharmacokinetic Implications on Concomitant Drug Administration During CytoSorb Therapy. Crit Care Explor. 2022;4(5):e0688. doi: 10.1097/CCE.0000000000000688.\\u003c/p\\u003e\\n\\u003cp\\u003e58. Ghaidan H, Stenlo M, Niroomand A, Mittendorfer M, Hirdman G, Gvazava N, et al. Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation. Nat Commun. 2022;13(1):4173. doi: 10.1038/s41467-022-31811-5.\\u003c/p\\u003e\\n\\u003cp\\u003e59. Lindstedt S, Niroomand A, Mittendorfer M, Hirdman G, Hyllen S, Pierre L, et al. Nothing but NETs: Cytokine adsorption correlates with lower circulating nucleosomes and is associated with decreased primary graft dysfunction. J Heart Lung Transplant. 2023;42(10):1358-62. doi: 10.1016/j.healun.2023.06.011.\\u003c/p\\u003e\\n\\u003cp\\u003e60. Iskender I, Arni S, Maeyashiki T, Citak N, Sauer M, Monn\\u0026eacute; Rodriguez J, et al. Perfusate-adsorption during ex vivo lung perfusion improves early post-transplant lung function. Journal of Thoracic and Cardiovascular Surgery. 2021;161(2):e109 - e21. doi: DOI: 10.1016/j.jtcvs.2019.12.128.\\u003c/p\\u003e\\n\\u003cp\\u003e61. Saemann L, Hoorn F, Georgevici AI, Pohl S, Korkmaz-Icoz S, Veres G, et al. Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction. Antioxidants (Basel). 2022;11(11):2280. doi: 10.3390/antiox11112280.\\u003c/p\\u003e\\n\\u003cp\\u003e62. Olausson M, Antony D, Travnikova G, Johansson M, Nayakawde NB, Banerjee D, et al. Novel Ex-Vivo Thrombolytic Reconditioning of Kidneys Retrieved 4 to 5 Hours After Circulatory Death. Transplantation. 2022;106(8):1577-88. doi: 10.1097/TP.0000000000004037.\\u003c/p\\u003e\\n\\u003cp\\u003e63. Nemeth E, Soltesz A, Kovacs E, Szakal-Toth Z, Tamaska E, Katona H, et al. Use of intraoperative haemoadsorption in patients undergoing heart transplantation: a proof-of-concept randomized trial. ESC Heart Fail. 2023:epub. doi: 10.1002/ehf2.14632.\\u003c/p\\u003e\\n\\u003cp\\u003e64. Ozturk M, Popov AF. Hemoadsorption in LVAD Surgery: Suitable in Theory? J Cardiovasc Dev Dis. 2023;10(7). doi: 10.3390/jcdd10070286.\\u003c/p\\u003e\\n\\u003cp\\u003e65. Millar JE, Fanning JP, McDonald CI, McAuley DF, Fraser JF. The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology. Crit Care. 2016;20(1):387. doi: 10.1186/s13054-016-1570-4.\\u003c/p\\u003e\\n\\u003cp\\u003e66. Al-Fares A, Pettenuzzo T, Del Sorbo L. Extracorporeal life support and systemic inflammation. Intensive Care Med Exp. 2019;7(Suppl 1):46. doi: 10.1186/s40635-019-0249-y.\\u003c/p\\u003e\\n\\u003cp\\u003e67. Napp LC, Lebreton G, De Somer F, Supady A, Pappalardo F. Opportunities, controversies, and challenges of extracorporeal hemoadsorption with CytoSorb during ECMO. Artif Organs. 2021;45(10):1240-9. doi: 10.1111/aor.14025.\\u003c/p\\u003e\\n\\u003cp\\u003e68. Soltesz A, Molnar ZA, Szakal-Toth Z, Tamaska E, Katona H, Fabry S, et al. Influence of Venoarterial Extracorporeal Membrane Oxygenation Integrated Hemoadsorption on the Early Reversal of Multiorgan and Microcirculatory Dysfunction and Outcome of Refractory Cardiogenic Shock. J Clin Med. 2022;11(21):6517. doi: 10.3390/jcm11216517.\\u003c/p\\u003e\\n\\u003cp\\u003e69. Naruka V, Salmasi MY, Arjomandi Rad A, Marczin N, Lazopoulos G, Moscarelli M, et al. Use of Cytokine Filters During Cardiopulmonary Bypass: Systematic Review and Meta-Analysis. Heart Lung Circ. 2022;31(11):1493-503. doi: 10.1016/j.hlc.2022.07.015.\\u003c/p\\u003e\\n\\u003cp\\u003e70. Heymann M, Schorer R, Putzu A. Mortality and adverse events of hemoadsorption with CytoSorb(R) in critically ill patients: A systematic review and meta-analysis of randomized controlled trials. Acta Anaesthesiol Scand. 2022;66(9):1037-50. doi: 10.1111/aas.14115.\\u003c/p\\u003e\\n\\u003cp\\u003e71. Vincent JL, Sakr Y. Clinical trial design for unmet clinical needs: a spotlight on sepsis. Expert Rev Clin Pharmacol. 2019;12(9):893-900. doi: 10.1080/17512433.2019.1643235.\\u003c/p\\u003e\\n\\u003cp\\u003e72. Forni LG. Blood Purification Studies in the ICU: What Endpoints Should We Use? Blood Purif. 2022;51(12):990-6. doi: 10.1159/000523761.\\u003c/p\\u003e\\n\\u003cp\\u003e73. Cavaillon JM, Singer M, Skirecki T. Sepsis therapies: learning from 30 years of failure of translational research to propose new leads. EMBO Mol Med. 2020;12(4):e10128. doi: 10.15252/emmm.201810128.\\u003c/p\\u003e\\n\\u003cp\\u003e74. Taleska Stupica G, Sostaric M, Bozhinovska M, Rupert L, Bosnic Z, Jerin A, et al. Extracorporeal Hemadsorption versus Glucocorticoids during Cardiopulmonary Bypass: A Prospective, Randomized, Controlled Trial. Cardiovasc Ther. 2020;2020:7834173. doi: 10.1155/2020/7834173.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cu\\u003eAdditional Materials:\\u003c/u\\u003e Additional file\\u0026nbsp;1 \\u0026ndash; PRISMA 2020 Checklist,\\u0026nbsp;Additional file\\u0026nbsp;2 \\u0026ndash; Evidence table\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cu\\u003e\\u0026nbsp;\\u003c/u\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cu\\u003eEthics approval and consent to participate:\\u003c/u\\u003e Not applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cu\\u003eConsent for publication:\\u003c/u\\u003e Not applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cu\\u003eAvailability of data and materials:\\u003c/u\\u003e Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cu\\u003eCompeting interests:\\u003c/u\\u003e MMS, DW, and ED are employees of CytoSorbents corp.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cu\\u003eFunding:\\u003c/u\\u003e This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cu\\u003eAuthors\\u0026apos; contributions:\\u003c/u\\u003e the conception and design - MMS, MT, DW; acquisition of data - MMS, MT, DW, ED, PS, CB; analysis and interpretation of data - all authors; drafting the article - MMS, MT, DW, ED, OD, StG; revising it critically for important intellectual content - all authors; final approval of the version to be submitted - all authors.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cu\\u003eAcknowledgments:\\u003c/u\\u003e Authors thank Mrs. Harriet Adamson for the administrative support and native speaker proofreading.\\u003c/p\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height:150%;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:12.0pt;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eTable 1\\u003c/span\\u003e\\u003c/strong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e. 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5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eStudy\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:13.0%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eStudy\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino 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Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eInterventions\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:10.28%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eControls\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:32.58%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eResults of the intervention\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 42.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e1\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2017\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eTr\\u0026auml;ger, K., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[9]\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control*\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e39\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e28\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNotably:\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- shorter ICU length of stay\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePre- \\u003cem\\u003evs\\u003c/em\\u003e post-treatment:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduction in vasopressor demand\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduction of cytokine IL-6 \\u0026amp; IL-8 levels\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRapid normalization of:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lactate levels and base excess\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- MAP\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 113.3pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 113.3pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2019\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eK\\u0026uuml;hne, L. U., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[5]\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 113.3pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control*\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 113.3pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB + post-op on CRRT)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 113.3pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e10\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 113.3pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e10\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 113.3pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eDespite a more pronounced disease severity in patients who received the therapy both intra- and postoperatively, compared to those with only intra-op hemoadsorption, equal post-op:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- vasopressors\\u003cbr\\u003e\\u0026nbsp;- CRP\\u003cbr\\u003e\\u0026nbsp;- lactate\\u003cbr\\u003e\\u0026nbsp;- ventilator time\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 70.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e3\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2020\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eHaidari, Z., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[10]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e30\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e28\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower incidence of sepsis (primary outcome)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower sepsis-related mortality (primary outcome)\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduced vasopressor requirements\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- higher SVR\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNotably lower overall 30-day mortality\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 49.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e4\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2021\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eAsch, S., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[6]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB + post-op on CRRT)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e10\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e10\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- higher vasopressor need\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- higher volume of fluids\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- longer ICU length of stay\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant difference in cytokine levels \\u0026ndash; primary outcome (IL-6, TNF-\\u0026alpha;).\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCRP and PCT baseline levels were significantly higher in the intervention group, equalizing after surgery.\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 62.45pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e5\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 62.45pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2021\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSanter, D., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[46]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 62.45pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control \\u003cbr\\u003e\\u0026nbsp;(IPTW)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 62.45pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 62.45pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e41\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 62.45pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e200\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 62.45pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- higher norepinephrine and milrinone demand\\u003cbr\\u003e\\u0026nbsp;- more RBC and PLT transfusions\\u003cbr\\u003e\\u0026nbsp;- higher incidence of reoperations for bleeding\\u003cbr\\u003e\\u0026nbsp;- prolonged hospitalization\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant difference in in-hospital mortality \\u0026ndash; primary outcome.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 49.85pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e6\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.85pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2022\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eDiab, M., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[8]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.85pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.85pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.85pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e138\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.85pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e144\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.85pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower levels of cytokines IL-1\\u0026beta;, IL-18 (in the first 25 \\u003cem\\u003evs\\u003c/em\\u003e 25 patients)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant difference in SOFA score change (primary outcome), as well as in clinical outcomes.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e7\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2022\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eHaidari, Z., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[11]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control\\u003cbr\\u003e\\u0026nbsp;(PSM)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e35\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e35\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower sepsis-related mortality (primary outcome)\\u003cbr\\u003e\\u0026nbsp;- reduced vasopressor demand\\u003cbr\\u003e\\u0026nbsp;- higher SVRI\\u003cbr\\u003e\\u0026nbsp;- faster SOFA score normalization\\u003cbr\\u003e\\u0026nbsp;- lower respiratory failure rate\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant difference in the postoperative sepsis incidence and in-hospital mortality \\u0026ndash; primary outcomes.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e8\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2022\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eHolmen, A., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[45]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e10\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e9\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- fewer transfusions (RBC, PLT, FFP)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNotably:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower and shorter norepinephrine demand (primary outcome)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower creatinine levels\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower chest-tube drainage volume\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- shorter ventilator time\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 49.65pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e9\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.65pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2022\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eKalisnik, J. M., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[7]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.65pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control\\u003cbr\\u003e\\u0026nbsp;(PSM)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.65pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.65pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e99\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.65pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e99\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 49.65pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower incidence of sepsis (primary outcome)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower sepsis-related mortality (primary outcome)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower CRP levels\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- fewer transfusions (RBC \\u0026amp; FFP)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower WBC counts\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- higher hemoglobin level\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNotably lower in-hospital mortality.\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.46%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 63.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e10\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 11.16%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2023\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eHaidari, Z., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[12]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 13%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.96%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.56%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e75\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.28%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e55\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 32.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.6pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- decreased VIS (primary outcome)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower incidence of sepsis-related mortality\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower 30-day \\u0026amp; 90-day mortality\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower incidence of renal failure requiring hemodialysis\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNotably:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower incidence of revisions for bleeding\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"7\\\" style=\\\"width: 100%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 47.05pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align: left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:6.0pt;'\\u003e\\u003cu\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003eLegend:\\u003c/span\\u003e\\u003c/u\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;CPB - cardiopulmonary bypass, IL - interleukin, MAP - mean arterial pressure, ICU - intensive care unit, CRRT \\u0026ndash; continuous renal replacement therapy, CRP - C reactive protein, SVR \\u0026ndash; systemic vascular resistance, RCT \\u0026ndash; randomized controlled trial, TNF \\u0026ndash; tumor necrosis factor, PCT \\u0026ndash; procalcitonin, IPTW - inverse probability treatment weighting, RBC - red blood cells, PLT \\u0026ndash; platelets, SOFA \\u0026ndash; sequential organ failure assessment, PSM - propensity score matching, SVRI \\u0026ndash; systemic vascular resistance index, FFP - fresh frozen plasma, WBC - white blood cells, VIS \\u0026ndash; vasoactive-inotropic score\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align: left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:6.0pt;'\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003e* Statistical analysis for significant differences was not performed\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n\\u003c/div\\u003e\\n\\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height:150%;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:12.0pt;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height:150%;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:12.0pt;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eTable 2\\u003c/span\\u003e\\u003c/strong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e. Evidence overview \\u0026ndash; elective complex cardiac surgery (various procedures with prolonged CPB).\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cdiv align=\\\"left\\\" dir=\\\"ltr\\\" style='margin:0in;text-align:justify;line-height:13.0pt;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\n \\u003ctable style=\\\"width:100.0%;border-collapse:collapse;border:none;\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width:5.66%;border:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo.\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:10.94%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eStudy\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:14.58%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eStudy\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003edesign\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:12.58%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eDevice\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:15.08%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eInterventions\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:10.64%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eControls\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:30.52%;border:solid windowtext 1.0pt;border-left: none;padding:0in 5.4pt 0in 5.4pt;height:17.0pt;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cstrong\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eResults of the intervention\\u003c/span\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 45.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e1\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2016\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eBernardi, M. H., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[13]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e19\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e18\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 45.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant difference in primary outcome - cytokine levels (IL-1\\u0026szlig;, IL-6, IL-18, TNF-\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Cambria Math\\\",serif;'\\u003e⍺\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e), except for IL-10.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 70.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2019\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eBernardi, M. H., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[17]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003cbr\\u003e\\u0026nbsp;(post hoc subgroup analysis of No. 1)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e17\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e18\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- higher haptoglobin (primary outcome)\\u003cbr\\u003e\\u0026nbsp;- lower LDH\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant difference between the groups in levels of plasma-free hemoglobin (primary outcome) and total bilirubin.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 56.8pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e3\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 56.8pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2019\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eGarau, I., \\u003cem\\u003eet al\\u003c/em\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[18]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 56.8pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 56.8pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 56.8pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e20\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 56.8pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e20\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 56.8pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- lower cytokine levels (IL-8, TNF-\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Cambria Math\\\",serif;'\\u003e⍺\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e) - primary outcome\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- higher CI\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant difference in levels of IL-6 (primary outcome).\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e4\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2019\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eGleason, T. G., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[19]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2 CytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e23\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e23\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 42.55pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificant reduction in:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- plasma-free hemoglobin (primary outcome)\\u003cbr\\u003e\\u0026nbsp;- activated complement C3a \\u0026amp; C5a.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 96.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e5\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 96.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2019\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003ePoli, E. C., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[20]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 96.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 96.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 96.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e15\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 96.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e15\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 96.1pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant difference in primary outcome - cytokine levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-\\u0026alpha;, IFN-\\u0026gamma;, MCP-1), as well as in clinical outcomes.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly lower activity of coagulation factors II and XII.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 70.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e6\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2019\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eWagner, R., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[22]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e15\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e13\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 70.2pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly higher level of miRNA-133 \\u0026ndash; primary outcome.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant differences in levels of miRNA-1, miRNA-126, and miRNA-223 (primary outcomes), as well as in clinical outcomes.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 27.9pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:justify;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e7\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 27.9pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2019\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eTaleska-Stupica, G., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[74]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 27.9pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 27.9pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 27.9pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e20\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 27.9pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e20\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026amp;\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e20*\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 27.9pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- higher CD64 and CD163 antigen expression on immune cells\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- increased activated complement C5a (primary outcomes).\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant difference in primary outcome - cytokine levels (TNF-\\u003cem\\u003e\\u0026alpha;\\u003c/em\\u003e, IL-1\\u003cem\\u003e\\u0026beta;\\u003c/em\\u003e, IL-6, IL-8, and IL-10).\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 63.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e8\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2020\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eWisgrill, L., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[16]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRCT\\u003cbr\\u003e\\u0026nbsp;(post hoc subgroup analysis of No. 1)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e9\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e9\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 63.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNo significant differences in circulating microvesicles, apoptotic body counts and kinetics.\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 71.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e9\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2021\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eHohn, A., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[14]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eProspective\\u003cbr\\u003e\\u0026nbsp;Case series\\u003cbr\\u003e\\u0026nbsp;(part of the ongoing RECCAS** study)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u003c/span\\u003e\\u003csup\\u003e\\u003cspan style=\\\"font-family:Symbol;\\\"\\u003e\\u0026acirc;\\u003c/span\\u003e\\u003c/sup\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e15\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e/\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 71.7pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificant, pre- \\u003cem\\u003evs\\u003c/em\\u003e post-adsorber:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- reduction of heparan sulphate\\u003cbr\\u003e\\u0026nbsp;- increase of hyaluronan\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 5.66%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 69.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e10\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.94%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 69.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e2022\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eManohar, M., \\u003cem\\u003eet al\\u003c/em\\u003e.\\u0026nbsp;\\u003c/span\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e[15]\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 14.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 69.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eRetrospective\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCase-control\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 12.58%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 69.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eCytoSorb\\u0026reg;\\u003cbr\\u003e\\u0026nbsp;(intra-op on CPB)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 15.08%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 69.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e23\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 10.64%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 69.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:center;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e29\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 30.52%;border-width: medium 1pt 1pt medium;border-style: none solid solid none;border-color: currentcolor windowtext windowtext currentcolor;padding: 0in 5.4pt;height: 69.95pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eSignificantly lower:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- increase of VIS from pre- to postoperative value (primary outcome)\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003eNotably lower:\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height: normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;'\\u003e- in-hospital mortality\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"7\\\" style=\\\"width: 0%;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor windowtext windowtext;border-image: none;padding: 0in 5.4pt;height: 37.8pt;vertical-align: top;\\\"\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align: left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:6.0pt;'\\u003e\\u003cu\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003eLegend:\\u003c/span\\u003e\\u003c/u\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003e\\u0026nbsp;CPB - cardiopulmonary bypass, RCT - randomized controlled trial, IL - interleukin, TNF - tumor necrosis factor, LDH - lactate dehydrogenase, CI \\u0026ndash; cardiac index, IFN - interferon, MCP - monocyte chemoattractant protein, miRNA - micro ribonucleic acid, VIS \\u0026ndash; vasoactive-inotropic score\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align: left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:6.0pt;'\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003e* Three groups, 20 given intraoperative methylprednisolone, 20 intraoperative CytoSorb\\u0026reg;, 20 controls; results shown for comparison between hemoadsorption and controls\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align: left;line-height:normal;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:6.0pt;'\\u003e\\u003cspan style='font-size:11px;font-family:\\\"Times New Roman\\\",serif;'\\u003e** German Clinical Trials Register number DRKS00007928 (Date of registration August 3\\u003csup\\u003erd\\u003c/sup\\u003e, 2015).\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n\\u003c/div\\u003e\\n\\u003cp dir=\\\"LTR\\\" style='margin:0in;text-align:left;line-height:150%;font-size:13px;font-family:\\\"Palatino Linotype\\\",serif;color:black;margin-bottom:12.0pt;'\\u003e\\u003cspan style='font-family:\\\"Times New Roman\\\",serif;color:windowtext;'\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"cardiac surgery, hemoadsorption, hyperinflammation, blood purification, CytoSorb, infective endocarditis, aortic surgery, heart transplantation, ECMO\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-3805383/v3\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-3805383/v3\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eDespite advancements, cardiopulmonary bypass-assisted cardiac surgery still carries a significant risk for morbidity and mortality, often related to postoperative hyperinflammation. Hemoadsorption of cytokines and various exogenous and endogenous inflammation triggers has been increasingly used in cardiac surgery to mitigate the risk of inflammation-mediated complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to assess the role of perioperative hemoadsorption in cardiac surgery critically.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA comprehensive literature search with predefined criteria was conducted. The screening and selection process followed rigorous scientific principles (PRISMA statement). The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search and retrieve all available data.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe search resulted in 29 publications that were grouped and descriptively analyzed due to the remarkable variability in study designs, however, they all reported exclusively on CytoSorb\\u003csup\\u003eâ\\u003c/sup\\u003e therapy. CytoSorb\\u003csup\\u003eâ\\u003c/sup\\u003e use was proven feasible and safe with no unanticipated device-related adverse events reported in the retrieved articles. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery of patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Current evidence suggests limited value from CytoSorb\\u003csup\\u003e®\\u003c/sup\\u003e use in routine elective surgery and low-risk patients. Further evaluation in more extensive prospective trials is required concerning proper patient selection and postoperative timing and administration.\\u003c/p\\u003e\",\"manuscriptTitle\":\"The role of hemoadsorption in cardiac surgery – a systematic review\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":3,\"date\":\"2024-02-06 19:52:17\",\"doi\":\"10.21203/rs.3.rs-3805383/v3\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}},{\"code\":2,\"date\":\"2024-02-05 20:57:16\",\"doi\":\"10.21203/rs.3.rs-3805383/v2\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}},{\"code\":1,\"date\":\"2024-01-05 12:01:45\",\"doi\":\"10.21203/rs.3.rs-3805383/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"237d66b3-f007-49f9-af0c-f13ea5e17c09\",\"owner\":[],\"postedDate\":\"February 6th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-01-12T06:44:27+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-02-06 19:52:17\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v3\",\"identity\":\"rs-3805383\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-3805383\",\"identity\":\"rs-3805383\",\"version\":[\"v3\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}