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Indeed, systemic concentrations of pro-inflammatory cytokines in patients with severe COVID-19 are not as high as has been reported in patients with other causes of acute respiratory distress syndrome. On April 10, 2020, the U.S. Food and Drug Administration granted Emergency Use Authorization for CytoSorb use in critically ill COVID-19 patients with confirmed or imminent respiratory failure. Keywords: COVID-19; cytokine adsorber; organ failure; vasoplegic shock EN COVID-19 cytokine adsorber organ failure vasoplegic shock 1026 1029 4 05/27/22 20220601 NES 220601 "However beautiful the strategy, you should occasionally look at the results." is a famous saying by Sir Winston Churchill. In a prospective, randomized, open-label study, Supady et al ([11]) investigated 34 COVID-19 patients with ECMO therapy and showed that the median IL-6 drop over 72 hours occurred regardless of the use of CytoSorb ([11]). [Extracted from the article]

We advocate that after more than 170,000 human CytoSorb treatments performed in the last decade, it is the highest time for compelling evidence from RCTs showing improvement of clinically relevant endpoints before using the CytoSorb in ever expanding indications. We appreciate the letter by Kogelmann ([1]) raising concerns that our editorial comment concentrated only on a few negative studies from various application. Kogelmann ([1]) argued that some studies investigated the CytoSorb in patient populations who had low cytokine levels and that the device only works in patients who have high cytokine levels. [Extracted from the article]

Background: In a multicenter, randomized trial, the authors enrolled patients at high-risk for acute kidney injury as identified by a Cleveland Clinic Foundation score of 6 or more. The authors enrolled 240 patients at four hospitals and randomized them to remote ischemic preconditioning or control. The authors found that remote ischemic preconditioning reduced acute kidney injury in high-risk patients undergoing cardiac surgery. The authors now report on the effects of remote ischemic preconditioning on 90-day outcomes.Methods: In this follow-up study of the RenalRIP trial, the authors examined the effect of remote ischemic preconditioning on the composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction at 90 days. Secondary outcomes were persistent renal dysfunction and dialysis dependence in patients with acute kidney injury.Results: Remote ischemic preconditioning significantly reduced the occurrence of major adverse kidney events at 90 days (17 of 120 [14.2%]) versus control (30 of 120 [25.0%]; absolute risk reduction, 10.8%; 95% CI, 0.9 to 20.8%; P = 0.034). In those patients who developed acute kidney injury after cardiac surgery, 2 of 38 subjects in the remote ischemic preconditioning group (5.3%) and 13 of 56 subjects in the control group (23.2%) failed to recover renal function at 90 days (absolute risk reduction, 17.9%; 95% CI, 4.8 to 31.1%; P = 0.020). Acute kidney injury biomarkers were also increased in patients reaching the major adverse kidney event endpoint compared to patients who did not.Conclusions: Remote ischemic preconditioning significantly reduced the 3-month incidence of a composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction in high-risk patients undergoing cardiac surgery. Furthermore, remote ischemic preconditioning enhanced renal recovery in patients with acute kidney injury. [ABSTRACT FROM AUTHOR]

A Novel Approach for the Targeted Inhibition of Platelet Activation - Separating the Good From the Bad* But more importantly, ADP by itself is a rather weak platelet agonist, but it might act synergistically with other platelet agonists (e.g., thrombin or TxA SB 2 sb ) to booster the response of platelets. They used the nucleoside triphosphate hydrolase (NTPase) CD39 to convert the platelet agonist ADP into inactive adenosine monophosphate by hydrolysis, thus limit platelet activation. Thus, the hydrolytic activity of CD39 enriched in the proximity of activated platelets, as only these platelets possess the platelet integrin glycoprotein IIb/IIIa in its activated state. [Extracted from the article]

Objective: Acute renal failure remains a major challenge in critical care medicine. Both neutrophils and chemokines have been proposed as key components in the development of acute renal failure. Although the Duffy antigen receptor for chemokines (DARC) is present in several tissues and a highly specific ligand for various chemokines, its exact role in vivo remains unclear.Design: Prospective, controlled experimental study.Setting: University-based research laboratory.Subjects: C57BL/6 wild-type and DARC gene-deficient mice (DARC-/-).Interventions: To unravel the functional relevance of DARC in vivo, we compared wild-type and DARC-/- using neutrophil-dependent models of acute renal failure, induced by either local (renal ischemia-reperfusion) or systemic (endotoxemia, lipopolysaccharide) injury.Measurements and Main Results: Plasma creatinine and blood urea nitrogen concentrations served as indicators of renal function or dysfunction. Enzyme-linked immunosorbent assays were used to measure tissue and plasma chemokine concentrations. We also performed immunostaining to localize chemokine expression and flow cytometry to evaluate neutrophil recruitment into the kidney. Following renal injury, wild-type mice developed moderate renal ischemia-reperfusion(lipopolysaccharide, 300% increase in plasma creatinine concentrations) to severe acute renal failure (renal ischemia-reperfusion, 40% mortality) as well as extensive renal neutrophil recruitment. DARC-/- mice exhibited no renal dysfunction (renal ischemia-reperfusion) or only very mild renal dysfunction (lipopolysaccharide, 20% increase in serum creatinine concentrations). DARC-/- mice showed no postischemic neutrophil infiltration. Although DARC-/- and wild-type mice exhibited similar global renal neutrophil-recruitment during endotoxemia, DARC-/- mice showed significantly impaired neutrophil extravasation. Total renal concentrations of the chemokine macrophage inflammatory protein 2, which has been shown to bind to DARC and to be crucial in postischemic acute renal failure, were either identical (lipopolysaccharide) or only moderately different (renal ischemia-reperfusion) between wild-type and DARC-/- mice. Immunostaining revealed an absence of macrophage inflammatory protein-2 in renal endothelial cells of DARC-/- mice.Conclusions: We suggest that DARC predominantly exerts its effects by controlling spatial chemokine distribution, which in turn regulates neutrophil recruitment and subsequent acute renal failure. [ABSTRACT FROM AUTHOR]

Objective: Acute kidney injury is a common complication in critically ill patients and is associated with increased morbidity and mortality. Sepsis, major surgery, and nephrotoxic drugs are the most common causes of acute kidney injury. There is currently no effective strategy available to prevent or treat acute kidney injury. Therefore, novel treatment regimens are required to decrease acute kidney injury prevalence and to improve clinical outcomes. Remote ischemic preconditioning, triggered by brief episodes of ischemia and reperfusion applied in distant tissues or organs before the injury of the target organ, attempts to invoke adaptive responses that protect against acute kidney injury. We sought to evaluate the clinical evidence for remote ischemic preconditioning as a potential strategy to protect the kidney and to review the underlying mechanisms in light of recent studies.Data Sources: We searched PubMed for studies reporting the effect of remote ischemic preconditioning on kidney function in surgical patients (search terms: "remote ischemic preconditioning," "kidney function," and "surgery"). We also reviewed bibliographies of relevant articles to identify additional citations.Study Selection: Published studies, consisting of randomized controlled trials, are reviewed.Data Extraction: The authors used consensus to summarize the evidence behind the use of remote ischemic preconditioning.Data Synthesis: In addition, the authors suggest patient populations and clinical scenarios in which remote ischemic preconditioning might be best applied.Conclusions: Several experimental and clinical studies have shown tissue-protective effects of remote ischemic preconditioning in various target organs, including the kidneys. Remote ischemic preconditioning may offer a novel, noninvasive, and inexpensive treatment strategy for decreasing acute kidney injury prevalence in high-risk patients. Although many new studies have further advanced our knowledge in this area, the appropriate intensity of remote ischemic preconditioning, its mechanisms of action, and the role of biomarkers for patient selection and monitoring are still unknown. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Remote ischemic preconditioning and protection of the kidney - a novel therapeutic option" in the March 2016 issue is presented.