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Background: Cardiac surgery often represents the only treatment option in patients with infective endocarditis (IE). However, IE surgery may lead to a sudden release of inflammatory mediators, which is associated with postoperative organ dysfunction. We investigated the effect of hemoadsorption during IE surgery on postoperative organ dysfunction., Methods: This multicenter, randomized, nonblinded, controlled trial assigned patients undergoing cardiac surgery for IE to hemoadsorption (integration of CytoSorb to cardiopulmonary bypass) or control. The primary outcome (change in sequential organ failure assessment score [ΔSOFA]) was defined as the difference between the mean total postoperative SOFA score, calculated maximally to the 9th postoperative day, and the basal SOFA score. The analysis was by modified intention to treat. A predefined intergroup comparison was performed using a linear mixed model for ΔSOFA including surgeon and baseline SOFA score as fixed effect covariates and with the surgical center as random effect. The SOFA score assesses dysfunction in 6 organ systems, each scored from 0 to 4. Higher scores indicate worsening dysfunction. Secondary outcomes were 30-day mortality, duration of mechanical ventilation, and vasopressor and renal replacement therapy. Cytokines were measured in the first 50 patients., Results: Between January 17, 2018, and January 31, 2020, a total of 288 patients were randomly assigned to hemoadsorption (n=142) or control (n=146). Four patients in the hemoadsorption and 2 in the control group were excluded because they did not undergo surgery. The primary outcome, ΔSOFA, did not differ between the hemoadsorption and the control group (1.79±3.75 and 1.93±3.53, respectively; 95% CI, -1.30 to 0.83; P =0.6766). Mortality at 30 days (21% hemoadsorption versus 22% control; P =0.782), duration of mechanical ventilation, and vasopressor and renal replacement therapy did not differ between groups. Levels of interleukin-1β and interleukin-18 at the end of integration of hemoadsorption to cardiopulmonary bypass were significantly lower in the hemoadsorption than in the control group., Conclusions: This randomized trial failed to demonstrate a reduction in postoperative organ dysfunction through intraoperative hemoadsorption in patients undergoing cardiac surgery for IE. Although hemoadsorption reduced plasma cytokines at the end of cardiopulmonary bypass, there was no difference in any of the clinically relevant outcome measures., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03266302.

Introduction: Infective endocarditis (IE) is associated with high mortality and morbidity. Multiple organ failure is the main cause of death after surgery for IE. Cardiopulmonary bypass (CPB) can cause a systemic inflammatory response. In a pilot study (REMOVE-pilot (Revealing mechanisms and investigating efficacy of hemoad-sorption for prevention of vasodilatory shock in cardiac surgery patients with infective endocarditis - a multicentric randomized controlled group sequential trial)), we found that plasma profiles of cytokines during and after CPB were higher in patients with IE compared with patients with non-infectious valvular heart disease. Sequential Organ Failure Assessment (SOFA) scores on the first and second postoperative days and in-hospital mortality were also higher in IE patients. This protocol describes the design of the REMOVE trial on cytokine-adsorbing columns, for example, CytoSorb, for non-selective removal of cytokines. The aim of the REMOVE study is to demonstrate efficacy of CytoSorb on the prevention of multiorgan dysfunction in patients with IE undergoing cardiac surgery., Methods and Analysis: The REMOVE study is an interventional randomised controlled multicenter trial with a group sequential (Pocock) design for assessing efficacy of CytoSorb in patients undergoing cardiac surgery for IE. The change in mean total SOFA (∆ SOFA) score between preoperative and postoperative care will be used as primary endpoint. Data on 30-day mortality, changes in cytokines levels, duration of mechanical ventilation, length of intensive care unit and hospital stay, and postoperative stroke will be collected as secondary endpoints. An interim analysis will be conducted after including 25 participating patients per study arm (with a focus on feasibility of the recruitment as well as differences in cytokines and cell-free DNA levels)., Ethics and Dissemination: The protocol was approved by the institutional review board and ethics committee of the University of Jena as well as by the corresponding ethics committee of each participating study centre. The results will be published in a renowned international medical journal, irrespective of the outcomes of the study., Trial Registration Number: The ClinicalTrials.gov registry (NCT03266302)., Competing Interests: Competing interests: FMB reports grants and personal fees from CytoSorbents Europe,outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: More than 50% of patients with infective endocarditis (IE) develop an indication for surgery. Despite its benefit, surgery is associated with a high incidence of multiple organ dysfunction syndrome (MODS) and mortality, which may be linked to increased release of inflammatory mediators during cardiopulmonary bypass (CPB). We therefore assessed plasma cytokine profiles in patients undergoing valve surgery with or without IE., Methods: We performed a prospective case-control pilot study comparing patients undergoing cardiac valve surgery with or without IE. Plasma profiles of inflammatory mediators were measured at 7 defined time points and reported as median (interquartile). The degree of MODS was measured using sequential organ failure assessment (SOFA) score., Results: Between May and December 2016 we included 40 patients (20 in each group). Both groups showed similar distribution of age and gender. Patients with IE had higher preoperative SOFA (6.9± 2.6 vs 3.8 ± 1.1, p<0.001) and operative risk scores (EuroSCORE II 18.6±17.4 vs. 1.8±1.3, p<0.001). In-hospital mortality was higher in IE patients (35% vs. 5%; p<0.001). Multiple organ failure was the cause of death in all non-survivors. At the end of CPB, median levels of following inflammatory mediators were higher in IE compared to control group: IL-6 (119.73 (226.49) vs. 24.48 (40.09) pg/ml, p = 0.001); IL-18 (104.82 (105.99) vs. 57.30 (49.53) pg/ml, p<0.001); Mid-regional pro-adrenomedullin (MR-proADM) (2.06 (1.58) vs. 1.11 (0.53) nmol/L, p = 0.003); MR- pro-atrial natriuretic peptide (MR-proANP) (479.49 (224.74) vs. 266.55 (308.26) pmol/l, p = 0.028). IL-1β and TNF- α were only detectable in IE patients and first after starting CPB. Plasma levels of IL-6, IL-18, MRproADM, and MRproANP during CPB were significantly lower in survivors than in those who died., Conclusion: The presence of infective endocarditis during cardiac valve surgery is associated with increased inflammatory response as evident by higher plasma cytokine levels and other inflammatory mediators. Actively reducing inflammatory response appears to be a plausible therapeutic concept., Trial Registration: ClinicalTrials.gov, ID: NCT02727413., Competing Interests: All other authors declare no competing interests

Background: Infective endocarditis (IE) is still associated with high morbidity and mortality. The impact of pre-operative stroke on mortality and long-term survival is controversial. In addition, data on the severity of neurological disability due to pre-operative stroke are scarce. We analysed the impact of pre-operative stroke and the severity of its related neurological disability on short- and long-term outcome., Methods: We retrospectively reviewed our data from patients operated for left-sided IE between 01/2007 and 04/2013. We performed univariate (Chi-Square and independent samples t test) and multivariate analyses., Results: Among 308 consecutive patients who underwent cardiac surgery for left-sided IE, pre-operative stroke was present in 87 (28.2 %) patients. Patients with pre-operative stroke had a higher pre-operative risk profile than patient without it: higher Charlson comorbidity index (8.1 ± 2.6 vs. 6.6 ± 3.3) and higher incidence of Staphylococcus aureus infection (43 vs. 17 %) and septic shock (37 vs. 19 %). In-hospital mortality was equal but 5-year survival was significantly worse with pre-operative stroke (33.1 % vs. 45 %, p = 0.006). 5-year survival was worst in patients with severe neurological disability compared to mild disability (19.0 vs. 0.58 %, p = 0.002). However, neither pre-operative stroke nor the degree of neurological disability appeared as an independent risk factor for short or long-term mortality by multivariate analysis., Conclusions: Pre-operative stroke and the severity of neurological disability do not independently affect short- and long-term mortality in patients with infective endocarditis. It appears that patients with pre-operative stroke present with a generally higher risk profile. This information may substantially affect decision-making.

Objectives: Infective endocarditis (IE) is associated with high mortality (20-40%) and neurological complications (20-50%). Postoperative intracranial haemorrhage (ICH) is a feared complication especially in patients with preoperative cerebral infarcts. The aim of this study was to determine the radiological characteristics of cerebral lesions that could predict the occurrence of postoperative ICH in IE patients., Methods: We retrospectively reviewed all charts, brain imaging and follow-up data from patients operated for left-sided endocarditis between January 2007 and April 2013., Results: A total of 308 patients (age 62.0 ± 13.9) underwent surgery for IE. Preoperative cerebrovascular complications were present in 122 patients (39.6%), representing stroke in 87, silent cerebral infarctions in 31 patients and transient ischaemic attacks in 4 patients. Among 118 patients with cerebral lesions, the aetiological classification of the lesions was ischaemic in 63.6%, ischaemic with haemorrhagic transformation (HT) in 17.8%, ischaemic with concomitant microbleeds in 16.1% and intracerebral bleeding in 2.5%. Postoperative ICH occurred in 17 patients and its incidence was slightly higher in patients with preoperative cerebral infarcts compared with those without preoperative cerebral infarcts [7.6 vs 4.2%, respectively, odds ratio (OR) 1.88, 95% confidence interval (CI) 0.70-5.02, P = 0.21]. However, the difference was not statistically significant. Similarly, the incidence of postoperative ICH was higher in cases of HT of ischaemic infarcts than in cases of ischaemic infarcts not complicated with HT (19.0 vs 5.3%). However, the difference was not statistically significant (P = 0.24). The radiological pattern of preoperative cerebral lesions was single in 35.6% and multiple in 60.0% of cases. Multiple cerebral lesions were associated with a non-significantly lower incidence of postoperative ICH than single lesions (5.6 vs 11.9%, respectively, OR: 0.44, CI: 0.11-1.73, P = 0.29)., Conclusions: The results suggest that the incidence of postoperative ICH in IE patients was slightly higher in the presence of preoperative cerebral infarcts. In addition, preoperative cerebral ischaemic infarcts complicated with HT tended to have a higher incidence of postoperative ICH than those not complicated with HT. However, the difference was not statistically significant. Multiple preoperative cerebral infarcts were not associated with higher incidence of postoperative ICH compared with single cerebral infarcts., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Infective endocarditis (IE) requires multidisciplinary management. We established an endocarditis team within our hospital in 2011 and a state-wide endocarditis network with referring hospitals in 2015. We aimed to investigate their impact on perioperative outcomes. Methods: We retrospectively analyzed data from patients operated on for IE in our center between 01/2007 and 03/2018. To investigate the impact of the endocarditis network on referral latency and pre-operative complications we divided patients into two eras: before (n = 409) and after (n = 221) 01/2015. To investigate the impact of the endocarditis team on post-operative outcomes we conducted multivariate binary logistic regression analyses for the whole population. Kaplan–Meier estimates of 5-year survival were reported. Results: In the second era, after establishing the endocarditis network, the median time from symptoms to referral was halved (7 days (interquartile range: 2–19) vs. 15 days (interquartile range: 6–35)), and pre-operative endocarditis-related complications were reduced, i.e., stroke (14% vs. 27%, p < 0.001), heart failure (45% vs. 69%, p < 0.001), cardiac abscesses (24% vs. 34%, p = 0.018), and acute requirement of hemodialysis (8% vs. 14%, p = 0.026). In both eras, a lack of recommendations from the endocarditis team was an independent predictor for in-hospital mortality (adjusted odds ratio: 2.12, 95% CI: 1.27–3.53, p = 0.004) and post-operative stroke (adjusted odds ratio: 2.23, 95% CI: 1.12–4.39, p = 0.02), and was associated with worse 5-year survival (59% vs. 40%, log-rank < 0.001). Conclusion: The establishment of an endocarditis network led to the earlier referral of patients with fewer pre-operative endocarditis-related complications. Adhering to endocarditis team recommendations was an independent predictor for lower post-operative stroke and in-hospital mortality, and was associated with better 5-year survival. [ABSTRACT FROM AUTHOR]