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Background: Numerous, mostly uncontrolled, observations suggest that artificial liver support with the Molecular Adsorbent Recirculating System (MARS) improves pathophysiologic sequelae and outcome of acute and acute-on-chronic liver failure. MARS is felt to be safe, but extracorporeal circuits may activate coagulation. Objective: To assess the frequency of and risk factors for activation of coagulation during MARS treatment. Patients/Methods: Retrospective analysis of coagulopathy/bleeding complications observed during 83 consecutive MARS sessions in 21 patients (11 men; median age 46 years; median three sessions per patient; median duration of session 8 h). Results: Nine clinically relevant episodes of coagulopathy/bleeding were observed in eight patients, forced to premature cessation of MARS in seven and ended lethal in four. Four complications occurred during the first, five during later (third to seventh) MARS sessions and two bleeders tolerated further sessions without complications. Coagulation parameters worsened significantly also during MARS sessions not associated with bleeding ( P≤0.004). In univariate analysis, patient's age, vasopressor therapy, pretreatment INR, fibrin D–dimer and fibrinogen concentrations, but not severity of underlying disease (MELD, Child-Pugh, SAPS II scores), were significantly associated with coagulopathy ( P<0.05). Only patient's age, fibrin D-dimer level and INR were retained in a multivariate model correctly classifying 98% of sessions without, but only 33% with complications. Conclusion: Coagulation is frequently activated during MARS therapy, potentially leading to bleeding complications and mortality. [ABSTRACT FROM AUTHOR]

Objectives: Critically ill coronavirus disease 2019 (COVID‐19) patients are characterised by a severely dysregulated cytokine profile and elevated neutrophil counts, impacting disease severity. However, it remains unclear how neutrophils contribute to pathophysiology during COVID‐19. Here, we assessed the impact of the dysregulated cytokine profile on the regulated cell death (RCD) programme of neutrophils. Methods: Regulated cell death phenotype of neutrophils isolated from critically ill COVID‐19 patients or healthy donors and stimulated with COVID‐19 or healthy plasma ex vivo was assessed by flow cytometry, time‐lapse microscopy and cytokine multiplex analysis. Immunohistochemistry of COVID‐19 patients and control biopsies were performed to assess the in situ neutrophil RCD phenotype. Plasma cytokine levels of COVID‐19 patients and healthy donors were measured by multiplex analysis. Clinical parameters were correlated to cytokine levels of COVID‐19 patients. Results: COVID‐19 plasma induced a necroptosis‐sensitive neutrophil phenotype, characterised by cell lysis, elevated release of damage‐associated molecular patterns (DAMPs), increased receptor‐interacting serine/threonine‐protein kinase (RIPK) 1 levels and mixed lineage kinase domain‐like pseudokinase (MLKL) involvement. The occurrence of neutrophil necroptosis MLKL axis was further confirmed in COVID‐19 thrombus and lung biopsies. Necroptosis was induced by the tumor necrosis factor receptor 1 (TNFRI)/TNF‐α axis. Moreover, reduction of soluble Fas ligand (sFasL) levels in COVID‐19 patients and hence decreased signalling to Fas directly increased RIPK1 levels, exacerbated TNF‐driven necroptosis and correlated with disease severity, which was abolished in patients treated with glucocorticoids. Conclusion: Our results suggest a novel role for sFasL signalling in the TNF‐α‐induced RCD programme in neutrophils during COVID‐19 and a potential therapeutic target to curb inflammation and thus influence disease severity and outcome. [ABSTRACT FROM AUTHOR]

Abstract: Grade 3 primary graft dysfunction (PGD3) represents the most important risk factor for patient mortality during the first year after lung transplantation (LTX). We investigated whether pretransplant pulmonary hypertension (PH) is a risk factor for the development of PGD3. This retrospective, single‐center cohort study included 96 candidates undergoing right heart catheterization (RHC) prior to being listed for LTX between March 2000 and October 2015. Based on their mean pulmonary artery pressure (mPAP) levels, the patients were classified into 3 groups: (1) <25 mm Hg, (2) 25‐34 mm Hg and (3) ≥35 mm Hg. Forty‐seven patients were classified in group 1, 31 in group 2, and 18 in group 3. Fifteen recipients (16%, 95%‐CI 8‐23) developed PGD3. In the univariate analysis, the diagnosis of interstitial lung disease (ILD) compared to COPD (OR: 7.06, P = .005), blood transfusion >1000 mL during surgery (OR: 5.25, P = .005), the need for intra‐operative cardio‐pulmonary bypass (CPB) or extra‐corporeal membrane oxygenation (ECMO) (OR: 4, P = .027), mPAP (OR 1.06, P = .007) and serum high density lipoprotein‐cholesterol (HDL‐C) (OR 0.09, P = .005) were associated with PGD3. In the multivariable logistic regression analysis, only HDL‐C (OR 0.10, P = .016) was associated with PGD3 based on our single‐center cohort data analysis. [ABSTRACT FROM AUTHOR]

Oberkofler CE, Stocker R, Raptis DA, Stover JF, Schuepbach RA, Müllhaupt B, Dutkowski P, Clavien P-A, Béchir M. Same quality - higher price? The paradox of allocation: the first national single center analysis after the implementation of the new Swiss transplantation law: the ICU view. Clin Transplant 2011: 25: 921-928. © 2010 John Wiley & Sons A/S. Abstract: This study was undertaken as the first national single-center analysis to assess the impact of the new Swiss transplantation law on patient selection, intensive care unit (ICU) complications, outcome, and, in particular, costs in liver transplant recipients treated in our surgical ICU. The first 35 consecutive liver transplant recipients following the new act were compared with the last 35 liver transplant recipients preceding July 1, 2007. Following execution of the new law, recipients were in poorer condition, reflected by significant higher Model for End-Stage Liver Disease (MELD) scores (12 vs. 22; p = 0.006). Furthermore, the MELD group obtained more renal replacement therapies (40.0% vs. 14.3%; p = 0.015). Cumulative one-yr patient survival was comparable in both groups (91.4% vs. 80.1%, p = 0.22). Finally, the additional costs per single case increased 27 000 Euros after the adoption of the new law. Our data serve as an example that political decisions influence patient's selection, and, in turn, complications, finally leading to higher costs of medical treatment. Liver graft allocation according to the MELD system may save lives at the price of increased intensive care efforts. [ABSTRACT FROM AUTHOR]