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Aim: Extracorporeal cardiopulmonary resuscitation (ECPR) by veno-arterial extracorporeal membrane oxygenation (VA-ECMO) during refractory cardiac arrest presents significant medical and psychological challenges for healthcare providers. Beyond managing cardiac arrest and preparing for potential coronary angiography, the ECMO circuit must be assembled and primed under strictly sterile conditions, contributing to additional psychological stress and potential delays in ECMO cannulation. This pragmatic study thought to evaluate whether pre-assembled and pre-primed ECMO circuits (pre-primed group) maintain sterility over a 21-day period, expedite ECMO initiation in ECPR patients and alleviate the psychological burden on the ECPR team, compared to newly assembled and primed ECMO circuits (on-demand group)., Methods: In a prospective manner, ECMO circuits were either pre-assembled and pre-primed under sterile conditions, maintained for 21 days with culture samples taken every seventh day, or newly assembled and primed during the acute emergency situation. The transition from on-demand assembly and priming of ECMO circuits to pre-primed ECMO circuits occurred on January 1st, 2021. The interval between patients' arrival in the cardiac catheterization laboratory and the initiation of ECMO was recorded and retrospectively compared between the two treatment groups. The ECPR team, comprising experienced cardiologists and nurses, was prospectively surveyed using the modified Perceived Stress Questionnaire (PSQ-20)., Results: All aseptically pre-assembled and pre-primed ECMO circuits demonstrated sterile cultures for aerobic and anaerobic microorganisms as well as fungal agents over the 21-day period: 0/120 positive cultures (0 %, 95 % CI for binomial probability 0-0.03). The time to ECMO initiation was significantly reduced in the pre-primed group compared to the on-demand group: 13 [IQR 9-17] versus 31 [IQR 27-44] minutes, P < 0.001. Responses from ECPR physicians and nurses on the PSQ-20 were similar across all items. With the use of pre-primed ECMO circuits, all ECPR professionals reported a greater sense of settled inner feeling, considerably less psychological tension, fewer worries and insecurities, as well as more effective ICU shifts with improved personal goal achievement. However, treating ECPR patients with pre-primed ECMO circuits did not lead to increased job satisfaction or higher physical energy levels., Conclusion: Aseptically pre-assembled and pre-primed ECMO circuits maintain sterility for multiple weeks, significantly reducing ECMO initiation times and alleviating psychological strain on the ECPR team. Consequently, implementing these circuits in ECPR centers could enhance both patient outcomes and healthcare provider well-being., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aim: Understanding the public health burden of cardiac arrest (CA) is important to inform healthcare policies, particularly during healthcare crises such as the COVID-19 pandemic. This study aimed to analyse outcomes of in-hospital mortality and healthcare resource utilisation in adult patients with CA in the United States over the last decade prior to the COVID-19 pandemic., Methods: The United States (US) National Inpatient Sample was utilised to identify hospitalised adult patients with CA between 2010 and 2019. Logistic and Poisson regression models were used to analyse outcomes by adjusting for 47 confounders., Results: 248,754 adult patients with CA (without "Do Not Resuscitate"-orders) were included in this study, out of which 57.5% were male. In-hospital mortality was high with 51.2% but improved significantly from 58.3% in 2010 to 46.4% in 2019 (P < 0.001). Particularly, elderly patients, non-white patients and patients requiring complex therapy had a higher mortality rate. Although the average hospital LOS decreased by 11%, hospital expenses have increased by 13% between 2010 and 2019 (each P < 0.001), presumably due to more frequent use of mechanical circulatory support (MCS, e.g. ECMO from 2.6% to 8.7% or Impella® micro-axial flow pump from 1.8% to 14.2%). Strong disparities existed among patient age groups and ethnicities across the US. Of note, the number of young adults with CA and opioid-induced CA has almost doubled within the study period., Conclusion: Over the last ten years prior to the COVID-19 pandemic, CA-related survival has incrementally improved with shorter hospitalisations and increased medical expenses, while strong disparities existed among different age groups and ethnicities. National standards for CA surveillance should be considered to identify trends and differences in CA treatment to allow for standardised medical care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Guidelines advocate the use of extracorporeal cardio-pulmonary resuscitation with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in selected patients with cardiac arrest. Effects of concomitant left-ventricular (LV) unloading with Impella® (ECMELLA) remain unclear. This is the first study to investigate whether treatment with ECMELLA was associated with improved outcomes in patients with refractory cardiac arrest caused by acute myocardial infarction (AMI)., Methods: This study was approved by the local ethical committee. Patients treated with ECMELLA at three centers between 2016 and 2021 were propensity score (PS)-matched to patients receiving VA-ECMO based on age, electrocardiogram rhythm, cardiac arrest location and Survival After Veno-Arterial ECMO (SAVE) score. Cox proportional-hazard and Poisson regression models were used to analyse 30-day mortality rate (primary outcome), hospital and intensive care unit (ICU) length of stay (LOS) (secondary outcomes). Sensitivity analyses on patient demographics and cardiac arrest parameters were performed., Results: 95 adult patients were included in this study, out of whom 34 pairs of patients were PS-matched. ECMELLA treatment was associated with decreased 30-day mortality risk (Hazard Ratio [HR] 0.53 [95% Confidence Interval (CI) 0.31-0.91], P = 0.021), prolonged hospital (Incidence Rate Ratio (IRR) 1.71 [95% CI 1.50-1.95], P < 0.001) and ICU LOS (IRR 1.81 [95% CI 1.57-2.08], P < 0.001). LV ejection fraction significantly improved until ICU discharge in the ECMELLA group. Especially patients with prolonged low-flow time and high initial lactate benefited from additional LV unloading., Conclusions: LV unloading with Impella® concomitant to VA-ECMO therapy in patients with therapy-refractory cardiac arrest due to AMI was associated with improved patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: The present in vitro study was undertaken to learn about the effects of leukocytes on tenocytes in respect to complement regulation simulating an inflammatory scenario of the traumatized tissue., Methods: Human hamstring tendon-derived tenocyte monolayers were co-cultured indirectly with human leukocytes (either Peripheral Blood Mononuclear Cells [PBMCs] or neutrophils) using a transwell system with/without (+ / wo ) 10 ng/ml tumor necrosis factor α (TNFα) for 4 and 24 h. Tenocyte and leukocyte cell survival was assessed by live-dead assay. Tenocyte gene expression of TNFα, the anaphylatoxin receptor C5aR and the cytoprotective complement regulatory proteins (CRP) CD46, CD55 and CD59 was monitored using qPCR. TNFα was detected in the culture supernatants using ELISA., Results: C5aR gene expression was significantly induced by TNFα after 4 h, but impaired in the presence of leukocytes + TNFα after 24 h. At 4 h, PBMCs activated by TNFα induced the CRP CD46 gene expression. However, CD55 was significantly suppressed after 24 h by neutrophils + / wo TNFα. Leukocytes activated by TNFα decreased also significantly the gene expression of the more downstream acting CRP CD59 after 4 h. TNFα gene expression and ELISA analysis revealed an amplified TNFα expression/release in tenocyte co-cultures with PBMC + / wo TNFα, probably contributing to complement regulation., Conclusion: TNFα might represent a crucial soluble mediator exerting diverse time-dependent effects on tenocyte complement regulation.

The aim of this study was to compare endothelial permeability, which is considered a hallmark of coronary artery disease, between patients with different HbA 1c levels using an albumin-binding magnetic resonance (MR) probe. This cross-sectional study included 26 patients with clinical indication for X-ray angiography who were classified into three groups according to HbA 1c level (<5.7% [<39 mmol/mol], 5.7-6.4% [39-47 mmol/mol], and ≥6.5% [48 mmol/mol]). Subjects underwent gadofosveset-enhanced coronary magnetic resonance and X-ray angiography including optical coherence within 24 h. Contrast-to-noise ratios (CNRs) were assessed to measure the probe uptake in the coronary wall by coronary segment, excluding those with culprit lesions in X-ray angiography. In the group of patients with HbA 1c levels between 5.7 and 6.4%, 0.30 increased normalized CNR values were measured, compared with patients with HbA 1c levels <5.7% (0.30 [95% CI 0.04, 0.57]). In patients with HbA 1c levels ≥6.5%, we found 0.57 higher normalized CNR values compared with patients with normal HbA 1c levels (0.57 [95% CI 0.28, 0.85]) and 0.26 higher CNR values for patients with HbA 1c level ≥6.5% compared with patients with HbA 1c levels between 5.7 and 6.4% (0.26 [95% CI -0.04, 0.57]). Additionally, late atherosclerotic lesions were more common in patients with high HbA 1c levels (HbA 1c ≥6.5%, n = 14 [74%]; HbA 1c 5.7-6.4%, n = 6 [60%]; and HbA 1c <5.7%, n = 10 [53%]). In conclusion, coronary MRI in combination with an albumin-binding MR probe suggests that both patients with intermediate and patients with high HbA 1c levels are associated with a higher extent of endothelial damage of the coronary arteries compared with patients with HbA 1c levels <5.7%., (© 2018 by the American Diabetes Association.)

Objectives: This study sought to investigate the potential of the noninvasive albumin-binding probe gadofosveset-enhanced cardiac magnetic resonance (GE-CMR) for detection of coronary plaques that can cause acute coronary syndromes (ACS)., Background: ACS are frequently caused by rupture or erosion of coronary plaques that initially do not cause hemodynamically significant stenosis and are therefore not detected by invasive x-ray coronary angiography (XCA)., Methods: A total of 25 patients with ACS or symptoms of stable coronary artery disease underwent GE-CMR, clinically indicated XCA, and optical coherence tomography (OCT) within 24 h. GE-CMR was performed approximately 24 h following a 1-time application of gadofosveset-trisodium. Contrast-to-noise ratio (CNR) was quantified within coronary segments in comparison with blood signal., Results: A total of 207 coronary segments were analyzed on GE-CMR. Segments containing a culprit lesion in ACS patients (n = 11) showed significant higher signal enhancement (CNR) following gadofosveset-trisodium application than segments without culprit lesions (n = 196; 6.1 [3.9 to 16.5] vs. 2.1 [0.5 to 3.5]; p < 0.001). GE-CMR was able to correctly identify culprit coronary lesions in 9 of 11 segments (sensitivity 82%) and correctly excluded culprit coronary lesions in 162 of 195 segments (specificity 83%). Additionally, segmented areas of thin-cap fibroatheroma (n = 22) as seen on OCT demonstrated significantly higher CNR than segments without coronary plaque or segments containing early atherosclerotic lesions (n = 185; 9.2 [3.3 to 13.7] vs. 2.1 [0.5 to 3.4]; p = 0.001)., Conclusions: In this study, we demonstrated for the first time the noninvasive detection of culprit coronary lesions and thin-cap fibroatheroma of the coronary arteries in vivo by using GE-CMR. This method may represent a novel approach for noninvasive cardiovascular risk prediction., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Inferior tendon healing can lead to scarring and tendinopathy. The role of complement in tendon healing is still unclear. The aim of this study was to understand tenocytes response to mechanical injury and whether complement is regulated by injury. Tenocytes were injured using an optimized automated scratch assay model. Using a self-assembled plotter system, 50 parallel lines of injury were created in a 6 cm diameter tenocyte cell layer. Tenocytes mitotic activity and survival post injury was assessed using FDA/ethidiumbromide assay. Furthermore, this injury model was combined with stimulation of the tenocytes with the complement split fragment C3a. Gene expression of C3aR, C5aR (CD88), CD46, CD55, tumor necrosis factor (TNF)α, interleukin (IL)-1β, matrix metalloproteinase (MMP)-1 was analyzed. Immunolabeling for C5aR and CD55 was performed. An enhanced mitotic activity and some dead cells were detected in the vicinity of the scratches. Gene expression of the C3aR was suppressed after 4 h but induced after 24 h post injury. C5aR was down-regulated at 24 h, CD46 and CD55 were induced at 24 h in response to injury and CD55 was also elevated at 4 h. MMP-1 was upregulated by injury but both proinflammatory cytokines remained mainly unaffected. Combination of injury with C3a stimulation led to an enhanced C3aR, CD55 and TNFα gene expression. According to the gene expression data, the protein expression of C5aR was reduced and that of CD55 induced. In summary, a specific response of complement regulation was found in mechanically injured tenocytes which may be involved in healing responses., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Interplay between complement factors, regulatory proteins, anaphylatoxins and cytokines could be involved in tendon healing and scar formation. The expression and regulation of complement factors by cytokines or anaphylatoxins are completely unclear in tendon. Hence, the gene expression of the anaphylatoxin receptors C3aR, C5aR and cytoprotective complement regulatory proteins (CRPs) was analysed in human tendon, cultured primary tenocytes and to directly compare the general expression level, additionally in human leukocytes. Time-dependent regulation of complement by cytokines and the anaphylatoxin C3a was assessed in cultured tenocytes. Gene expression of the anaphylatoxin receptors C3aR, C5aR and the CRPs CD46, CD55 and CD59 was detected in tendon, cultured tenocytes and leukocytes, whereas CD35 could only be found in tendon and leukocytes. Compared with cultured tenocytes, complement expression was higher in tendon and compared with leukocytes C3aR, C5aR, CD35 and CD55, but not CD46 and CD59 gene expression levels were lower in tendon. C3aR mRNA was up-regulated by both TNFα and C3a in cultured tenocytes in a time-dependent manner whereby C5aR gene expression was only induced by C3a. IL-6 or C3a impaired the CRP gene expression. C3a stimulation lead to an up-regulation of TNFα and IL-1β mRNA in tenocytes. Degenerated tendons revealed an increased C5aR and a reduced CD55 expression. The expression profile of the investigated complement components in tendon and cultured tenocytes clearly differed from that of leukocytes. Tenocytes respond to the complement split fragment C3a with CRP suppression and enhanced pro-inflammatory cytokine gene expression suggesting their sensitivity to complement activation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)