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BACKGROUND: Sepsis is a syndrome characterized by host immune dysfunction, with the extent of immunoparalysis differing among patients. Lipopolysaccharide (LPS) is used commonly to assess the immune function of critically ill patients with sepsis. However, the reliability of this ex vivo diagnostic test in predicting clinical outcomes remains uncertain. RESEARCH QUESTION: Does LPS-induced tumor necrosis factor (TNF) production from the blood of patients with sepsis predict mortality? Secondary outcomes included ICU and hospital stay durations, nosocomial infection rate, and organ recovery rate. STUDY DESIGN AND METHODS: Human sepsis studies from various databases through April 2023 were evaluated. Inclusion criteria encompassed LPS-stimulated blood assays, English language, and reported clinical outcomes. Bias risk was evaluated using the Newcastle-Ottawa scale (NOS). Relationships between TNF production and mortality were analyzed at sepsis onset and during established sepsis, alongside secondary outcomes. RESULTS: Of 11,580 studies, 17 studies (14 adult and three pediatric) were selected for analysis. Although 15 studies were evaluated as moderate to high quality using the NOS, it is important to note that some of these studies also had identifiable biases, such as unclear methods of participant recruitment. Nine studies detailed survival outcomes associated with LPS-induced TNF production at sepsis onset, whereas five studies explored TNF production's relationship with mortality during established sepsis. Trends suggested that lower LPS-induced TNF production correlated with higher mortality. However, heterogeneity in methodologies, especially the LPS assay protocol, hindered definitive conclusions. Publication bias was highlighted using funnel plot analysis. Concerning secondary outcomes, diminished TNF production might signify worsening organ dysfunction, although the link between cytokine production and nosocomial infection varied among studies. INTERPRETATION: For functional immune profiling in sepsis, streamlined research methodologies are essential. This entails organizing cohorts based on microbial sources of sepsis, establishing standardized definitions of immunoparalysis, using consistent types and dosages of immune stimulants, adhering to uniform blood incubation conditions, and adopting consistent clinical outcomes.
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OBJECTIVE: Perioperative venous thromboembolism (VTE) is generally considered preventable. Whereas the non-vascular surgery literature is rich in providing data about the impact of VTE prophylaxis on VTE outcomes, vascular surgery data are relatively sparse on this topic. This study sought to evaluate the evidence for VTE prophylaxis specifically for the population of vascular surgery patients. METHODS: A systematic search was conducted in MEDLINE, Cochrane, and Embase databases in December 2018. Included were studies reporting primary and secondary outcomes for common vascular surgery procedures (open aortic operation, endovascular aneurysm repair [EVAR], peripheral artery bypass, amputation, venous reflux operation). A meta-analysis was performed comparing the patients who did not receive VTE prophylaxis and had VTE complications with patients who developed VTE despite receiving prophylaxis. RESULTS: From 3757 uniquely identified articles, 42 publications met the criteria for inclusion in this review (1 for the category of all vascular operations, 5 for open aortic reconstructions, 2 for EVAR, 1 for open aortic surgery or EVAR, 3 for abdominal or bypass surgery, 2 for peripheral bypass surgery, 2 for amputations, 1 for vascular trauma, and 25 for surgical treatment of superficial venous disease). Five studies met the criteria for inclusion in the meta-analysis. The results demonstrated slightly lower relative risk for development of VTE among patients receiving VTE prophylaxis (relative risk, 0.70; 95% confidence interval, 0.26-1.87). After open aortic reconstruction, the risk of VTE is 13% to 18% and is not reduced by VTE prophylaxis. For EVAR patients, the risk of VTE without prophylaxis is 6%. For patients undergoing peripheral bypass surgery and not receiving therapeutic or prophylactic anticoagulation, the risk of VTE is <2%. For patients undergoing amputations, VTE prophylaxis reduces the risk of VTE. For patients undergoing surgical treatment of superficial venous disease, there is an abundance of literature exploring the utility of VTE prophylaxis, but the evidence is conflicting; some studies demonstrated a benefit, whereas others showed no reduction of VTE with prophylaxis. CONCLUSIONS: Overall, there is a paucity of literature that addresses the effectiveness of VTE prophylaxis specifically in the population of vascular surgery patients. Our meta-analysis of the literature does not demonstrate a statistically significant benefit of VTE prophylaxis among the vascular surgery patients evaluated; however, it does suggest a low incidence of VTE among patients who receive VTE prophylaxis. Clinicians should identify the patients at high risk for development of postoperative VTE as the risk-benefit ratio may favor VTE prophylaxis in a selected group of patients. Clinicians should use their judgment and established VTE risk prediction models to assess VTE risk for patients. Vascular surgeons should consider reporting VTE incidence as a secondary outcome in publications.