Acute Kidney Failure: Current Challenges and New Perspectives.

Acute kidney failure, also called acute kidney injury (AKI), is defined by a sudden loss of kidney function that is conventionally determined on the basis of increased serum creatinine levels and reduced urinary output [...].

Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses.

Both high mobility group box-1 (HMGB1) and histones are major damage-associated molecular patterns (DAPMs) that mediate lethal systemic inflammation, activation of the complement and coagulation system, endothelial injury and multiple organ dysfunction syndrome in critical illnesses. Although accumulating evidence collectively shows that targeting HMGB1 or histones by their specific antibodies or inhibitors could significantly mitigate aberrant immune responses in multiple critically ill animal models, routine clinical use of such agents is still not recommended by any guideline. In contrast, extracorporeal blood purification, which has been widely used to replace dysfunctional organs and remove exogenous or endogenous toxins in intensive care units, may also exert an immunomodulatory effect by eliminating inflammatory mediators such as cytokines, endotoxin, HMGB1 and histones in patients with critical illnesses. In this review, we summarize the multiple immunopathological roles of HMGB1 and histones in mediating inflammation, immune thrombosis and organ dysfunction and discuss the rationale for the removal of these DAMPs using various hemofilters. The latest preclinical and clinical evidence for the use of extracorporeal blood purification to improve the clinical outcome of critically ill patients by targeting circulating HMGB1 and histones is also gathered.

Effect of extracorporeal hemoadsorption in critically ill patients with COVID-19: A narrative review.

COVID-19 has been affecting the world unprecedentedly and will remain widely prevalent due to its elusive pathophysiological mechanism and the continuous emergence of new variants. Critically ill patients with COVID-19 are commonly associated with cytokine storm, multiple organ dysfunction, and high mortality. To date, growing evidence has shown that extracorporeal hemoadsorption can exert its adjuvant effect to standard of care by regulating immune homeostasis, reducing viremia, and decreasing endotoxin activity in critically ill COVID-19 cases. However, the selection of various hemofilters, timing of initiation and termination of hemoadsorption therapy, anticoagulation management of extracorporeal circuits, identification of target subgroups, and ultimate survival benefit remain controversial. The purpose of this narrative review is to comprehensively summarize the rationale for the use of hemoadsorption in critically ill patients with COVID-19 and to gather the latest clinical evidence in this field.

How do temperature, humidity, and air saturation state affect the COVID-19 transmission risk?

Environmental parameters have a significant impact on the spread of respiratory viral diseases (temperature (T), relative humidity (RH), and air saturation state). T and RH are strongly correlated with viral inactivation in the air, whereas supersaturated air can promote droplet deposition in the respiratory tract. This study introduces a new concept, the dynamic virus deposition ratio (α), that reflects the dynamic changes in viral inactivation and droplet deposition under varying ambient environments. A non-steady-state-modified Wells-Riley model is established to predict the infection risk of shared air space and highlight the high-risk environmental conditions. Findings reveal that a rise in T would significantly reduce the transmission of COVID-19 in the cold season, while the effect is not significant in the hot season. The infection risk under low-T and high-RH conditions, such as the frozen seafood market, is substantially underestimated, which should be taken seriously. The study encourages selected containment measures against high-risk environmental conditions and cross-discipline management in the public health crisis based on meteorology, government, and medical research.

Effect of Continuous Renal Replacement Therapy with the oXiris Hemofilter on Critically Ill Patients: A Narrative Review.

Critically ill patients with sepsis and severe COVID-19 are commonly characterized by a dysregulated immune response and an acute kidney injury. Continuous renal replacement therapy (CRRT) is now proposed as a promising adjuvant therapy to treat these critically ill patients by removing cytokines, pathogen-associated molecular patterns, and damage-associated molecular patterns from the blood. Although multiple hemofilters, including high-cutoff membranes, the oXiris hemofilter, the CytoSorb hemoadsorption device, and the Toraymyxin hemoperfusion cartridge, have been used in current clinical practice, the use of the oXiris hemofilter in critically ill patients is of particular interest because it is the only kind of hemofilter that can provide renal replacement therapy, remove endotoxins, and adsorb cytokines simultaneously. During the past five years, a growing body of literature has shown that CRRT with the oXiris hemofilter can improve hemodynamics and organ function and can decrease cytokines and endotoxins in both septic and COVID-19 patients. Here, we performed a narrative review to describe the development history of the oXiris hemofilter and to discuss the therapeutic effect of oXiris-CRRT on critically ill patients by searching the PubMed, Web of Science, and clinicaltrials.gov databases for articles published from inception to 8 September 2022 (updated on 1 November) with an English language restriction. We also summarized the current knowledge on anticoagulation techniques and safety concerns when delivering oXiris-CRRT sessions.

Intermediate-to-therapeutic versus prophylactic anticoagulation for coagulopathy in hospitalized COVID-19 patients: a systemic review and meta-analysis.

BACKGROUND: Anticoagulation in hospitalized COVID-19 patients has been associated with survival benefit; however, the optimal anticoagulant strategy has not yet been defined. The objective of this meta-analysis was to investigate the effect of intermediate-to-therapeutic versus prophylactic anticoagulation for thromboprophylaxis on the primary outcome of in-hospital mortality and other patient-centered secondary outcomes in COVID-19 patients. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched from inception to August 10th 2021. Cohort studies and randomized clinical trials that assessed the efficacy and safety of intermediate-to-therapeutic versus prophylactic anticoagulation in hospitalized COVID-19 patients were included. Baseline characteristics and relevant data of each study were extracted in a pre-designed standardized data-collection form. The primary outcome was all-cause in-hospital mortality and the secondary outcomes were incidence of thrombotic events and incidence of any bleeding and major bleeding. Pooled analysis with random effects models yielded relative risk with 95 % CIs. RESULTS: This meta-analysis included 42 studies with 28,055 in-hospital COVID-19 patients totally. Our pooled analysis demonstrated that intermediate-to-therapeutic anticoagulation was not associated with lower in-hospital mortality (RR=1.12, 95 %CI 0.99-1.25, p=0.06, I2=77 %) and lower incidence of thrombotic events (RR=1.30, 95 %CI 0.79-2.15, p=0.30, I2=88 %), but increased the risk of any bleeding events (RR=2.16, 95 %CI 1.79-2.60, p<0.01, I2=31 %) and major bleeding events significantly (RR=2.10, 95 %CI 1.77-2.51, p<0.01, I2=11 %) versus prophylactic anticoagulation. Moreover, intermediate-to-therapeutic anticoagulation decreased the incidence of thrombotic events (RR=0.71, 95 %CI 0.56-0.89, p=0.003, I2=0 %) among critically ill COVID-19 patients admitted to intensive care units (ICU), with increased bleeding risk (RR=1.66, 95 %CI 1.37-2.00, p<0.01, I2=0 %) and unchanged in-hospital mortality (RR=0.94, 95 %CI 0.79-1.10, p=0.42, I2=30 %) in such patients. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from very low to moderate. CONCLUSIONS: We recommend the use of prophylactic anticoagulation against intermediate-to-therapeutic anticoagulation among unselected hospitalized COVID-19 patients considering insignificant survival benefits but higher risk of bleeding in the escalated thromboprophylaxis strategy. For critically ill COVID-19 patients, the benefits of intermediate-to-therapeutic anticoagulation in reducing thrombotic events should be weighed cautiously because of its association with higher risk of bleeding. TRIAL REGISTRATION: The protocol was registered at PROSPERO on August 17th 2021 ( CRD42021273780 ).

Effect of Anticoagulant Administration on the Mortality of Hospitalized Patients With COVID-19: An Updated Systematic Review and Meta-Analysis.

Background: Anticoagulation is generally used in hospitalized patients with coronavirus disease 2019 (COVID-19) as thromboprophylaxis. However, results from different studies comparing the effect of anticoagulation on the mortality of COVID-19 patients with non-anticoagulation are inconclusive. Methods: Our systematic review included observational trials if they studied anticoagulant therapy in hospitalized patients with COVID-19 for mortality or bleeding events. Dichotomous variables from individual studies were pooled by risk ratio (RR) and their 95% confidence interval (95% CI) using the random-effects model. Grading of Recommendations Assessment, Development and Evaluation was used to assess the quality of evidence. Results: A total of 11 observational studies enrolling 20,748 hospitalized COVID-19 patients overall were included. A pooled meta-analysis of these studies showed that anticoagulation therapy, compared with non-anticoagulation therapy, was associated with lower mortality risk (RR 0.70, 95% CI 0.52-0.93, p = 0.01). The evidence of benefit was stronger among critically ill COVID-19 patients in the intensive care units (RR 0.59, 95% CI 0.43-0.83, p = 0.002). Additionally, severe bleeding events were not associated with the administration of anticoagulants (RR 0.93, 95% CI 0.71-1.23, p = 0.63). Conclusion: Among patients with COVID-19 admitted to hospital, the administration of anticoagulants was associated with a decreased mortality without increasing the incidence of bleeding events.