Sepsis is a condition of severe organ failure caused by the maladaptive response of the host to an infection. It is a severe complication affecting critica

Background: Thrombosis and coagulopathy are highly prevalent in critically ill patients with COVID-19 and increase the risk of death. Immunothrombosis has recently been demonstrated to contribute to the thrombotic events in COVID-19 patients with coagulopathy. As the primary components of immunothrombosis, neutrophil extracellular traps (NETs) could be induced by complement cascade components and other proinflammatory mediators. We aimed to explore the clinical roles of NETs and the regulation of complement on the NET formation in COVID-19. Methods: We recruited 135 COVID-19 patients and measured plasma levels of C5, C3, cell-free DNA and myeloperoxidase (MPO)-DNA. Besides, the formation of NETs was detected by immunofluorescent staining and the cytotoxicity to vascular endothelial HUVEC cells was evaluated by CCK-8 assay. Results: We found that the plasma levels of complements C3 and MPO-DNA were positively related to coagulation indicator fibrin(-ogen) degradation products (C3: r = 0.300, p = 0.005; MPO-DNA: r = 0.316, p = 0.002) in COVID-19 patients. Besides, C3 was positively related to direct bilirubin (r = 0.303, p = 0.004) and total bilirubin (r = 0.304, p = 0.005), MPO-DNA was positively related to lactate dehydrogenase (r = 0.306, p = 0.003) and creatine kinase (r = 0.308, p = 0.004). By using anti-C3a and anti-C5a antibodies, we revealed that the complement component anaphylatoxins in the plasma of COVID-19 patients strongly induced NET formation. The pathological effect of the anaphylatoxin-NET axis on the damage of vascular endothelial cells could be relieved by recombinant carboxypeptidase B (CPB), a stable homolog of enzyme CPB2 which can degrade anaphylatoxins to inactive products. Conclusions: Over-activation in anaphylatoxin-NET axis plays a pathological role in COVID-19. Early intervention in anaphylatoxins might help prevent thrombosis and disease progression in COVID-19 patients.

Carbapenem-resistant Klebsiella pneumoniae (CRKp) is a major pathogen causing nosocomial infections with a high mortality and poor prognosis. Gastrointestinal carriage has been acknowledged as the primary reservoir of CRKp infections. To explore the incidence and risk factors associated with CRKp infection following colonization. The PubMed, Web of Science, and Cochrane Library databases were searched for relevant articles published between December 1998 and June 2023. Pooled estimates with a 95% confidence interval (CI) were calculated for the incidence rate, whereas pooled odds ratios (ORs) were calculated for the risk factors for which the OR was reported in three or more studies. Fourteen studies were included in the review with 5483 patients for the assessment of incidence, whereas seven of these studies with 2170 patients were included for the analysis of risk factors. In the meta-analysis, the incidence of CRKp infections after colonization was 23.2% (17.9-28.5). Additionally, three independent risk factors for subsequent CRKp infections were identified as admission to the intensive care unit (ICU) (2.59; 95% CI: 1.64-4.11), invasive procedures (2.53; 95% CI: 1.59-4.03), and multi-site colonization (6.24; 95% CI: 2.38-16.33). This review reveals the incidence of CRKp infections in rectal carriers in different countries, emphasizing the role of rectal colonization with CRKp as an important source of nosocomial infections. Significantly, the risk factors indicated in this review can assist clinicians in identifying CRKp carriers with an elevated risk of subsequent infections, thereby enabling further measures to be taken to prevent nosocomial infections.

The yellow fever virus (YFV) recently reemerged in the large outbreaks in Africa and Brazil, and the first imported patients into Asia have recalled the concerns of YFV evolution. Here we show phylogenomics of YFV with serial clinical samples of the 2016 YFV infections. Phylogenetics exhibited that the 2016 strains were close to Angola 1971 strains and only three amino acid changes presented new to other lineages. Deep sequencing of viral genomes discovered 101 intrahost single nucleotide variations (iSNVs) and 234 single nucleotide polymorphisms (SNPs). Analysis of iSNV distribution and mutated allele frequency revealed that the coding regions were under purifying selection. Comparison of the evolutionary rates estimated by iSNV and SNP showed that the intrahost rate was ~2.25 times higher than the epidemic rate, and both rates were higher than the long-term YFV substitution rate, as expected. In addition, the result also hinted that short viremia duration of YFV might further hinder the evolution of YFV. The first importation of infections into China in 2016 and the following outbreaks in Africa and Brazil of yellow fever virus (YFV) have raised again the concerns of the potential viral spread into new territories. In this study, we aimed to know the evolution dynamics of YFV by using intrahost phylogenomics and to assess the risk of virus epidemics. Through deep sequencing of consecutive samples from 12 patients, we identified hundreds of genomic variations (iSNVs and SNPs), and noticed the nearly linear accumulation of variations within individuals. The estimated evolutionary rate within host is much higher than the epidemic evolutionary rate. In comparison with Dengue virus (DENV) and Zika virus (ZIKV), which share similar host vectors (Aedes spp.), life cycles, mutation rates and replication strategies to YFV, the lower epidemic evolutionary rate of YFV might have been hindered by the shorter viremia duration, which decreased the accumulated variations to get into the transmission cycle.

Background: Citrate refers to an anticoagulant agent commonly used in extracorporeal organ support. Its application is limited in patients with liver failure (LF) due to the increased risk of citrate accumulation induced by liver metabolic dysfunction. This systematic review aims to assess the efficacy and safety of regional citrate anticoagulation in extracorporeal circulation for patients with liver failure.Methods: PubMed, Web of Science, Embase, and Cochrane Library were searched. Studies regarding extracorporeal organ support therapy for LF were included to assess the efficacy and safety of regional citrate anticoagulation. Methodological quality of included studies were assessed using the Methodological Index for Non-randomized Studies (MINORS). Meta-analysis was performed using R software (version 4.2.0).Results: There were 19 eligible studies included, involving 1026 participants. Random-effect model showed an in-hospital mortality of 42.2% [95%CI (27.2, 57.9)] in LF patients receiving extracorporeal organ support. The during-treatment incidence of filter coagulation, citrate accumulation, and bleeding were 4.4% [95%CI (1.6-8.3)], 6.7% [95%CI (1.5-14.4)], and 5.0% [95%CI (1.9-9.3)], respectively. The total bilirubin(TBIL), alanine transaminase (ALT), aspartate transaminase(AST), serum creatinine(SCr), blood urea nitrogen(BUN), and lactate(LA) decreased, compared with those before the treatment, and the total calcium/ionized calcium ratio, platelet(PLT), activated partial thromboplastin time(APTT), serum potential of hydrogen(pH), buffer base(BB), and base excess(BE) increased.Conclusion: Regional citrate anticoagulation might be effective and safe in LF extracorporeal organ support. Closely monitoring and timely adjusting during the process could reduce the risk for complications. More prospective clinical trials of considerable quality are needed to further support our findings.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022337767.