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The hallmark of acute respiratory distress syndrome (ARDS) pathobiology is unchecked inflammation-driven diffuse alveolar damage and alveolar-capillary barrier dysfunction. Currently, therapeutic interventions for ARDS remain largely limited to pulmonary-supportive strategies, and there is an unmet demand for pharmacologic therapies targeting the underlying pathology of ARDS in patients suffering from the illness. The complement cascade (ComC) plays an integral role in the regulation of both innate and adaptive immune responses. ComC activation can prime an overzealous cytokine storm and tissue/organ damage. The ARDS and acute lung injury (ALI) have an established relationship with early maladaptive ComC activation. In this review, we have collected evidence from the current studies linking ALI/ARDS with ComC dysregulation, focusing on elucidating the new emerging roles of the extracellular (canonical) and intracellular (non-canonical or complosome), ComC (complementome) in ALI/ARDS pathobiology, and highlighting complementome as a vital nexus of the pathobiological connectome for ALI/ARDS via its crosstalking with other systems of the immunome, DAMPome, PAMPome, coagulome, metabolome, and microbiome. We have also discussed the diagnostic/therapeutic potential and future direction of ALI/ARDS care with the ultimate goal of better defining mechanistic subtypes (endotypes and theratypes) through new methodologies in order to facilitate a more precise and effective complement-targeted therapy for treating these comorbidities. This information leads to support for a therapeutic anti-inflammatory strategy by targeting the ComC, where the arsenal of clinical-stage complement-specific drugs is available, especially for patients with ALI/ARDS due to COVID-19. [ABSTRACT FROM AUTHOR]

Background and Purpose: Traumatic haemorrhage (TH) is the leading cause of potentially preventable deaths that occur during the prehospital phase of care. No effective pharmacological therapeutics are available for critical TH patients yet. Here, we identify terminal complement activation (TCA) as a therapeutic target in combat casualties and evaluate the efficacy of a TCA inhibitor (nomacopan) on organ damage and survival in vivo. Experimental Approach: Complement activation products and cytokines were analysed in plasma from 54 combat casualties. The correlations between activated complement pathway(s) and the clinical outcomes in trauma patients were assessed. Nomacopan was administered to rats subjected to lethal TH (blast injury and haemorrhagic shock). Effects of nomacopan on TH were determined using survival rate, organ damage, physiological parameters, and laboratory profiles. Key Results: Early TCA was associated with systemic inflammatory responses and clinical outcomes in this trauma cohort. Lethal TH in the untreated rats induced early TCA that correlated with the severity of tissue damage and mortality. The addition of nomacopan to a damage‐control resuscitation (DCR) protocol significantly inhibited TCA, decreased local and systemic inflammatory responses, improved haemodynamics and metabolism, attenuated tissue and organ damage, and increased survival. Conclusion and Implications: Previous findings of our and other groups revealed that early TCA represents a rational therapeutic target for trauma patients. Nomacopan as a pro‐survival and organ‐protective drug, could emerge as a promising adjunct to DCR that may significantly reduce the morbidity and mortality in severe TH patients while awaiting transport to critical care facilities. [ABSTRACT FROM AUTHOR]

Introduction: Fluid overload in extracorporeal membrane oxygenation (ECMO) patients has been associated with increased mortality. Patients receiving ECMO and continuous renal replacement therapy (CRRT) who achieve a negative fluid balance have improved survival. Limited data exist on the use of CRRT solely for fluid management in ECMO patients. Methods: We performed a single-center retrospective review of 19 adult ECMO patients without significant renal dysfunction who received CRRT for fluid management. These patients were compared to a cohort of propensity-matched controls. Results: After 72 h, the treatment group had a fluid balance of −3840 mL versus + 425 mL (p ≤ 0.05). This lower fluid balance correlated with survival to discharge (odds ratio 2.54, 95% confidence interval 1.10–5.87). Improvement in the ratio of arterial oxygen content to fraction of inspired oxygen was also significantly higher in the CRRT group (102.4 vs. 0.7, p ≤ 0.05). We did not observe any significant difference in renal outcomes. Conclusions: The use of CRRT for fluid management is effective and, when resulting in negative fluid balance, improves survival in adult ECMO patients without significant renal dysfunction. [ABSTRACT FROM AUTHOR]

Purpose Bicaval dual-lumen catheters allow for single-site cannulation venovenous extracorporeal gas exchange and facilitate early mobilization of patients. Using these catheters blood is drained from the superior and inferior venae cavae, pumped through a respiratory membrane, and returned into the right atrium. The insertion of these catheters is challenging as their correct positioning is fundamental to reduce recirculation and avoid severe complications. We describe here a new technique for the positioning of bicaval dual-lumen catheters. Materials and methods The right internal jugular vein was percutaneously cannulated in nine sheep. The distance between skin and tricuspid valve was measured from the point of pressure change in the waveform of a Swan-Ganz catheter being retracted from the right ventricle into the right atrium. The atrium-tricuspid valve-ventricle axis was determined by observing the fluctuations of the tip of the Swan-Ganz entering the ventricle during fluoroscopy. A bicaval dual-lumen catheter was placed on the basis of these evaluations and connected to an extracorporeal respiratory support system. Results The position of the catheter was verified at necropsy approximately 18 h after insertion. In all cases the catheter was correctly placed, with the central port situated in front of the tricuspid valve. Conclusions The described technique may help to position bicaval dual-lumen catheters for venovenous extracorporeal gas exchange without the use of transesophageal echocardiography or contrast media during fluoroscopy., Author(s): Thomas Langer [sup.1] [sup.2] [sup.4] , Vittoria Vecchi [sup.1] [sup.3] [sup.4] , Slava M. Belenkiy [sup.1] , Leopoldo C. Cancio [sup.1] , Luciano Gattinoni [sup.2] , Andriy I. Batchinsky [...]