Impact of Vasodilator Administration on Survival in Patients with Sepsis: A Systematic Review and Meta-Analysis
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Rationale: Sepsis and septic shock are associated with microcirculatory dysfunction, which is believed to contribute to sepsis-induced organ failure. Vasodilators have been proposed to improve tissue perfusion in sepsis, but the overall survival impact of this strategy is unclear. Objectives: To evaluate the impact of systemic vasodilator administration in patients with sepsis and septic shock on mortality. Methods: We conducted a meta-analysis using a random effects model. Published and unpublished randomized trials in adult patients with sepsis and septic shock were included when comparing the use of systemic vasodilators against no vasodilators. The primary outcome was 28-30-day mortality, and secondary outcomes were organ function and resource use measures. Results: We included eight randomized trials (1,076 patients). In patients randomized to vasodilator arms compared with those randomized to treatment without vasodilators, the 28-30-day mortality risk ratio was 0.74 (95% confidence interval, 0.54-1.01). In a chronological cumulative meta-analysis, the association between vasodilators and survival improved over time. In a prespecified subgroup analysis in 104 patients in two randomized trials, prostacyclin analogues were associated with a decreased rate of 28-30-day mortality among patients with sepsis and septic shock (risk ratio, 0.46; 95% confidence interval, 0.25-0.85). Conclusions: In patients with sepsis and septic shock, administration of vasodilators is not associated with decreased 28-30-day mortality, but the confidence interval suggests potential benefit, and the meta-analysis might lack power. Prostacyclin appears the most promising. The results of this meta-analysis should encourage randomized trials evaluating the impact of vasodilators on mortality in sepsis.The post‐translational modification of proteins by O ‐GlcNAcylation ( O ‐GlcNAc) is highly dynamic and modulates cell‐signaling processes. Acute increases in O ‐GlcNAc levels reduce migration of inflammatory cells and the release of pro‐inflammatory mediators, important events in sepsis caused by bacterial infection or multiple non‐infectious causes. This study tested the hypothesis that acute increases of O ‐GlcNAc levels reduce mortality and inflammatory processes in experimental models of sepsis. C57/BL6 mice were used in experimental sepsis protocols cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)‐induced severe and mild sepsis. Glucosamine treatment (300mg/Kg, i.v. 30 min. before the sepsis induction) acutely increased vascular and spleen O ‐GlcNAc levels and increased survival of mice with LPS‐induced sepsis (50%) and CLP sepsis (40%). In mice with LPS‐induced sepsis, glucosamine also reduced neutrophil migration to the peritoneal cavity (severe LPS sepsis, p <0.05; mild LPS sepsis, p <0.01), myeloperoxidase (MPO) activity of lung neutrophils (severe LPS sepsis, p <0.01; mild LPS sepsis, p <0.001) and aortic IL‐1beta mRNA expression (mild LPS sepsis, p <0.01). In the CLP model, glucosamine reduced MPO activity of lung neutrophils (p<0.05). These results show that glucosamine‐induced acute increases of O ‐GlcNAc levels increase survival in the CLP and LPS experimental models of sepsis. This study suggests that the O ‐GlcNAc pathway represents a potential target in sepsis‐related systemic inflammatory responses. Grant Funding Source : CNPq, CAPES and FAPESP
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Comparison of search strategies in systematic reviews of adverse effects to other systematic reviews
Abstract Background Research indicates that the methods used to identify data for systematic reviews of adverse effects may need to differ from other systematic reviews. Objectives To compare search methods in systematic reviews of adverse effects with other reviews. Methods The search methodologies in 849 systematic reviews of adverse effects were compared with other reviews. Results Poor reporting of search strategies is apparent in both systematic reviews of adverse effects and other types of systematic reviews. Systematic reviews of adverse effects are less likely to restrict their searches to MEDLINE or include only randomised controlled trials ( RCT s). The use of other databases is largely dependent on the topic area and the year the review was conducted, with more databases searched in more recent reviews. Adverse effects search terms are used by 72% of reviews and despite recommendations only two reviews report using floating subheadings. Conclusions The poor reporting of search strategies in systematic reviews is universal, as is the dominance of searching MEDLINE . However, reviews of adverse effects are more likely to include a range of study designs (not just RCT s) and search beyond MEDLINE .
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Abstract Background: Sepsis was recently redefined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. With this redefinition (Sepsis-3), clinical and microbiological characteristics of patients with sepsis may differ from the patients fulfilling the previous described definition (Sepsis-2). Purpose: To describe differences in clinical and microbiological characteristics of sepsis episodes between Sepsis-3 and Sepsis-2. The secondary aim was to compare blood culture outcomes between episodes fulfilling Sepsis-3 and Sepsis-2 criteria, respectively. Methods: A prospective study design was used to include patients presenting with clinically suspected sepsis in the emergency department. Six blood culture bottles were collected from each patient. Blood cultures were described as having clinically relevant growth, contaminant growth, or no growth. Clinical and laboratory data were collected from medical records and the laboratory information system. Results: The analysis included 549 episodes. There were 387/549 (70.5%) Sepsis-3 and 443/549 (80.7%) Sepsis-2 episodes. In total, 369/549 (67.2%) episodes fulfilled both Sepsis-3 and Sepsis-2 criteria. Blood cultures were positive for clinically relevant growth in 140/387 (36.1%) and 155/443 (35.0%) episodes in Sepsis-3 and Sepsis-2, respectively. Other clinical and microbiological characteristics did not differ between Sepsis-3 and Sepsis-2. Conclusions: A high proportion of patients included through a sepsis alert system fulfilled both Sepsis-3 and Sepsis-2 criteria. The performance of blood cultures in detection of microorganisms was poor and were similar in Sepsis-3 and Sepsis-2 patients.
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In this article, we describe the strengths and weaknesses of several methods of locating systematic reviews, including electronic databases such as MEDLINE, Best Evidence (the electronic version of ACP Journal Club and Evidence-Based Medicine), and the Cochrane Library (a regularly updated source of reviews and controlled trials produced by the Cochrane Collaboration). We also present steps that can be used to critically appraise review articles; as an example, we use a systematic review that evaluates the gastrointestinal toxicity of various nonsteroidal anti-inflammatory drugs in the context of a clinical scenario.
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Immunosuppression
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Sepsis is one of the main causes of death in severely infected patients, and the complexity of its pathogenesis increases the difficulty of clinical treatment. Ferroptosis is a new cell death mode discovered in recent years, which is closely related to the severity of sepsis. Research has found that iron accumulation can not only serve as an effective indicator for evaluating the severity of sepsis in patients, but also predict the prognosis of sepsis patients. In recent years, studies have pointed out that severe Ferroptosis exists in the body after sepsis, and inhibiting Ferroptosis is expected to become a new target for sepsis treatement. This article summarizes the evidence of Ferroptosis in sepsis organ injury, and provides new ideas for further research and treatment of sepsis.
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The book entitled Sepsis will provide a great and up-to-date information in this field to students and researchers involved in sepsis research with its chapters targeting host-pathogen interaction at a metabolic level during sepsis pathogenesis, how age affects sepsis pathogenesis and its outcome in old-age population as compared to young population, sepsis-associated acute organ injury mainly targeting acute kidney injury in sepsis, and kallistatin as host-derived immunomodulatory mechanism during sepsis, along with developments in techniques required for early diagnosis of sepsis and sepsis-associated encephalitis, a devastating medical condition observed during severe sepsis. The book is written by experts in their fields associated with sepsis, a critical condition needing great medical attention.
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Background The original equine sepsis score provided a method of identifying foals with sepsis. New variables associated with sepsis have been evaluated, but the sepsis score has not been updated. Objectives To evaluate the sensitivity and specificity of 2 updated sepsis scores and the systemic inflammatory response syndrome (SIRS) criteria in regard to detecting sepsis in foals. Animals Two‐hundred and seventy‐three ill foals and 25 healthy control foals. Methods Historical, physical examination, and clinicopathologic findings were used to calculate the original sepsis score and 2 updated sepsis scores. SIRS criteria were also evaluated. Sepsis scores and positive SIRS scores were statistically compared to foals with sepsis. Results One‐hundred and twenty‐six foals were septic and 147 sick‐nonseptic. The original and updated sepsis scores were significantly higher in septic foals as compared to sick‐nonseptic and healthy foals. The sensitivity and specificity of the updated sepsis scores to predict sepsis were not significantly better than those of the original sepsis score. One‐hundred and twenty‐seven of 273 (46.5%) foals met the original SIRS criteria and 88/273 (32%) foals met the equine neonatal SIRS criteria. The original SIRS criteria had similar sensitivity and specificity for predicting sepsis as did the 3 sepsis scores in our study. Conclusions and Clinical Importance The updated sepsis scores did not provide improved ability in predicting sepsis. Fulfilling the original SIRS criteria provided similar sensitivity and specificity in predicting sepsis as the modified sepsis score and might serve as a diagnostic aid in identifying foals at risk for sepsis.
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Abstract Background Results of new studies should be interpreted in the context of what is already known to compare results and build the state of the science. This systematic review and meta-analysis aimed to identify and synthesise results from meta-research studies examining if original studies within health use systematic reviews to place their results in the context of earlier, similar studies. Methods We searched MEDLINE (OVID), EMBASE (OVID), and the Cochrane Methodology Register for meta-research studies reporting the use of systematic reviews to place results of original clinical studies in the context of existing studies. The primary outcome was the percentage of original studies included in the meta-research studies using systematic reviews or meta-analyses placing new results in the context of existing studies. Two reviewers independently performed screening and data extraction. Data were synthesised using narrative synthesis and a random-effects meta-analysis was performed to estimate the mean proportion of original studies placing their results in the context of earlier studies. The protocol was registered in Open Science Framework. Results We included 15 meta-research studies, representing 1724 original studies. The mean percentage of original studies within these meta-research studies placing their results in the context of existing studies was 30.7% (95% CI [23.8%, 37.6%], I 2 =87.4%). Only one of the meta-research studies integrated results in a meta-analysis, while four integrated their results within a systematic review; the remaining cited or referred to a systematic review. The results of this systematic review are characterised by a high degree of heterogeneity and should be interpreted cautiously. Conclusion Our systematic review demonstrates a low rate of and great variability in using systematic reviews to place new results in the context of existing studies. On average, one third of the original studies contextualised their results. Improvement is still needed in researchers’ use of prior research systematically and transparently—also known as the use of an evidence-based research approach, to contribute to the accumulation of new evidence on which future studies should be based. Systematic review registration Open Science registration number https://osf.io/8gkzu/
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Since the definition of sepsis has been first proposed in 1991, the main content of the definition has been developed by infection + systemic inflammatory response syndrome as infection + organ dysfunction, and organ dysfunction is indicated by an increase in sequential organ failure assessment(SOFA) score.These are components of Sepsis-3 which was published in 2016.In Sepsis-3, the SOFA score in the identification and diagnosis of sepsis plays an important role, but Sepsis-3 was mainly used in adults, how to adjust it to children, some questions and details were proposed in this article.
Key words:
Sepsis; Diagnosis; Children,
SOFA score
Organ dysfunction
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