Potential Use of Albumin Administration in Severe Sepsis
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Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan, R.O.C. *Correspondence to: Dr Tsann-Long Hwang, Department of Surgery, Chang Gung Memorial Hospital, 199, Tunghwa North Road, Taipei 105, Taiwan, R.O.C. E-mail: [email protected] Received: April 13, 2009; • Accepted: April 24, 2009.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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To the Editor: Evidence of earlier detection of sepsis would greatly support adoption of the sepsis-3 definition (1). We therefore read with great interest the recent study by Scheer et al. (2), comparatively evaluating sepsis onset based on sepsis-3 criteria in patients identified with the previous SIRS-based approach (sepsis-1). We believe the choice of study population does not permit a fair comparison of sepsis criteria and the study leaves important methodological questions unanswered, motivating us to caution against the rather strong conclusion that sepsis-3 criteria facilitate an earlier and more predictive sepsis diagnosis than sepsis-1. Notably, the study included only patients with severe sepsis and septic shock imposing two restrictions on the study population: it leaves out patients with simple sepsis according to sepsis-1 and patients detected with sepsis-3 not detected by sepsis-1. The first leads to a narrowed patient spectrum that shrinks the denominator of sepsis-1 cases that had to be successfully identified by sepsis-3 to show performance superior to sepsis-1. With the impact of simple sepsis cases unknown, patient selection may have favored sepsis-3, making the comparison unbalanced. Patients who developed severe sepsis or septic shock from simple sepsis would only be detected by this selection procedure once they developed organ dysfunction, although their septic status according to sepsis-1 may have been known before this point in time. In our opinion, evidence must first be provided that simple sepsis in the intensive care unit (ICU) should rather be classified as uncomplicated infection as per sepsis-3 and can, therefore, be deliberately excluded when comparing sepsis criteria. The second restriction disadvantages sepsis-3 as patients detected by sepsis-3 but not sepsis-1 would all formally have been detected earlier by sepsis-3. It also precludes determination of diagnostic specificity. The net effect of both restrictions on the comparison of sepsis criteria for early sepsis detection is unclear. The prospective identification of severe sepsis and septic shock and the retrospective assignment of sepsis-3 represent disparate approaches, and add uncertainty to the validity of the results. This could have been addressed by reporting how suspicion of infection was retrospectively identified, how the absence of SIRS was determined in those detected earlier with sepsis-3, if mechanical ventilation and pharmacological circulatory support masking SIRS (3, 4) were taken into account, and how many of the patients with non-ICU acquired sepsis detected earlier with sepsis-3 were SIRS negative. Unfortunately, we failed to reproduce the reported P value of 0.011 (Fig. 3A in (2)) used as evidence of superior early detection capability of sepsis-3 in ICU-acquired sepsis that, according to the Methods section, appears to come from a one-sided binomial test. Instead, when we compared 93% with 100% with a two-sided chi-squared test with Yates correction, we obtained a P value of 0.0118, which however underscores that a significant proportion went undetected by sepsis-3. Timely recognition was achieved in 86%, which means that in 14% it was delayed on day 0. Instead, the result of 93% on day +1 is emphasized in the study; the reason for granting what appears to be a grace period of 1 day to sepsis-3 remains unclear with the methodology presented. Finally, we wonder what proportion of undetected patients is considered acceptable as a tradeoff for potentially earlier recognition of patients with organ dysfunction. Evidence for global superiority of either set of sepsis criteria, in our view, requires studies with unselected patients and transparent methodology. Sincerely yours,
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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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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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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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New Definitions of Sepsis and the Quest for Specific Biomarkers.Are the miRNAs the Answer?
Organ dysfunction
SOFA score
Pathophysiology
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Objectives: Recently, the definition of sepsis has changed from a physiologic derangement (Sepsis-1 and -2) to organ dysfunction (Sepsis-3) based. We sought to determine the concordance between the different sepsis phenotypes and how that affected mortality. Design: Retrospective, multicenter study. Setting: Three academic medical centers. Patients: 29,459 patients who had suspected infection, defined as obtaining blood cultures and receiving antibiotics: 18,183 (62%) had either Sepsis-2 or Sepsis-3. Measurements and Main Results: Kappa was used to show agreement between phenotypes. Conditional logistic regression was used to create models of associations between factors and phenotypes and between factors and mortality. About 12,981 patients had Sepsis-2; 12,043 had Sepsis-3; and 6,841 patients had both Sepsis-2 and Sepsis-3. Fifty-three percent of Sepsis-2 patients also had Sepsis-3, whereas 57% of Sepsis-3 patients also had Sepsis-2. Agreement between the two phenotypes was poor: kappa = 0.213 ± 0.006. Mortality was 6% in patients with only Sepsis-2, 10% with only Sepsis-3, and 18% in patients who had both phenotypes. Combining the variables in Sepsis-2 and Sepsis-3 improved the discrimination (C-statistic = 0.742 ± 0.005, p < 0.001) of mortality. Conclusions: We found that Sepsis-2 and Sepsis-3-based sepsis diagnoses represent separate phenotypes with poor agreement. Patients who have both phenotypes are at increased risk of mortality compared with having either phenotype alone. Inclusion of both systemic inflammatory response syndrome and Sequential Organ Failure Assessment criteria in the same model improves the discrimination of mortality.
Concordance
Organ dysfunction
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