Different Stages Of Sepsis Research Articles

Comparison of diagnostic criteria for sepsis-associated acute kidney injury in the pediatric intensive care unit: a retrospective cohort study.

pRIFLE (Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease), KDIGO (Kidney Disease Improving Global Outcomes) and pROCK (Pediatric Reference Change Value Optimized for AKI) are diagnostic criteria used for acute kidney injury (AKI) incidence evaluation. The aim of this study was to explore the diagnostic consistency, incidence and mortality rate, clinical signs, and influencing factors of renal injury related to sepsis in children diagnosed by three different AKI diagnostic criteria, and then evaluate which one was more valuable. A retrospective analysis was performed on the clinical data of children with severe sepsis. The patients were diagnosed and staged according to the 2007 pRIFLE standard, the 2012 KDIGO standard, and the 2018 pROCK standard. The clinical characteristics and prognosis of children with different stages of sepsis were compared between the three diagnostic standards. A total of 62 patients with sepsis were included. Blood stream infection is common (11 cases, 17.74%). According to pRIFLE, KDIGO, and pROCK standards, the incidence of sepsis-associated AKI (SA-AKI) was 74.2%, 67.7%, and 56.5%, respectively. The pRIFLE had the highest diagnostic rate of early detection of SA-AKI. There was no statistical difference in SA-AKI incidence or staging consistency between the pRIFLE and KDIGO groups (κ=0.0671; κ>0.60); the consistency of SA-AKI diagnoses across the three standards was good (all P values <0.05), and pROCK demonstrated a higher specificity. A high Pediatric Risk of Mortality (PRISM) score and high procalcitonin level were independent risk factors. Shock and renal replacement therapy were independent risk factors for SA-AKI death. Death from admission to 28 days after admission was used as an endpoint to draw a survival graph, which revealed that the AKI group had a significantly higher risk of death than did the non-AKI group. The consistency of diagnosing SA-AKI across the three classification criteria was similar, and mortality rate increased with increased SA-AKI staging. The pRIFLE criteria were more sensitive in the early detection of SA-AKI, while the pROCK had higher specificity. There was no significant difference between the pRIFLE and KDIGO in terms of incidence, diagnosis, or staging of SA-AKI.

Silenced-C5ar1 improved multiple organ injury in sepsis rats via inhibiting neutrophil extracellular trap.

Sepsis has a systemic inflammatory response syndrome caused by infection. While neutrophils play contradictory roles in different stages of sepsis. Neutrophils have been proven to play an antibacterial role by producing neutrophil extracellular traps (NETs). Although the NET is beneficial to bacteria resistance, abnormal NET increases tissue damage. The complement C5a receptor 1 (C5ar1) is a gene related to strong inflammatory reactions and is found to be associated with inflammatory factors. This study found that there were 45 down-regulated genes and 704 up-regulated genes in sepsis rats by transcriptome sequencing. And those genes were significantly related to inflammation and immunity by GO and KEGG enrichment analysis involving the chemokine signaling pathway, the Toll-like receptor (TLR) signaling pathway, and the Fc gamma R-mediated phagocytosis. Additionally, the C5ar1 gene was significantly upregulated with interesting potential in sepsis and used for further study. This study used cecum ligation and puncture (CLP) rats that were respectively injected intravenously with PBS or the lentivirus vector to explore the effect of C5ar1 on CLP rats. It demonstrated that silenced- C5ar1 inhibited the ALT, AST, BUN, and CREA levels, improved the lung and spleen injury, and reduced the TNF-α, IL-6, IL-1β, IL-10, cf-DNA, and cfDNA/MPO levels. Additionally, silenced C5ar1 inhibited the TLR2, TLR4, and peptidylarginine deiminase 4 expression levels, which suggested the improvement of silenced C5ar1 on sepsis via inhibiting NETs and the TLR signaling pathway. This study provides a basis and new direction for the study of treatment on sepsis.

Role of cell-free DNA levels in the diagnosis and prognosis of sepsis and bacteremia: A systematic review and meta-analysis.

Sepsis remains a major cause of mortality in intensive care units (ICUs). Prompt diagnosis and effective management are imperative for better outcomes. In this systematic review and meta-analysis, we explore the potential of circulating cell-free DNA (cfDNA), as a promising tool for early sepsis detection and prognosis assessment, aiming to address limitations associated with traditional diagnostic methods. Following PRISMA guidelines, we collected relevant literature from thirteen databases. Studies were included if they analyzed quantitative diagnostic or prognostic cfDNA levels in humans in case of sepsis. We collected data on basic study characteristics, baseline patient demographics (e.g. age and sex), and cfDNA levels across different stages of sepsis. Pooled SMD with 95%-CI was calculated, and Comprehensive Meta-Analysis (CMA) software facilitated meta-analysis. Receiver operating characteristic (ROC) curves were generated to assess cfDNA's combined sensitivity and specificity in diagnostics and prognostics. We included a final of 44 studies, of which, only 32 with 2950 participants were included in the meta-analysis. cfDNA levels were higher in septic patients compared to healthy controls (SMD = 3.303; 95%-CI [2.461-4.145], p<0.01). Furthermore, cfDNA levels were higher in non-survivors than survivors (SMD = 1.554; 95%-CI [0.905-2.202], p<0.01). Prognostic studies demonstrated a pooled sensitivity and specificity of 0.78, while diagnostic studies showed a sensitivity of 0.81 and a specificity of 0.87. These findings show that cfDNA levels are significantly higher in sepsis patients compared to control groups and non-survivors in comparison to survivors among both adult and pediatric populations.

Reconditioned monocytes are immunomodulatory and regulate inflammatory environment in sepsis

Sepsis is caused by dysregulated immune response to severe infection and hyper inflammation plays a central role in worsening the disease. The immunomodulatory properties of mesenchymal stem cells (MSCs) have been evaluated as a therapeutic candidate for sepsis. Reconditioned monocytes (RM), generated from healthy human peripheral blood mononuclear cells (PBMCs) exhibit both macrophage and MSCs-like properties. RM were administered at different stages of sepsis in a mouse model. It reduced serum levels of IL6, MCP-1, IL-10, improved hypothermia, increased survival, and recovery from 0 to 66% when combined with antibiotics in the mouse model. The reduced human leucocyte antigen DR molecules expression on RM enables their co-culture with PBMCs of sepsis patients which resulted in reduced ROS production, and up-regulated TGF-β while down-regulating IL6, IL8, and IL-10 in-vitro. RM are potentially immunomodulatory, enhance survival in sepsis mouse model and modulate inflammatory behaviour of sepsis patient’s PBMCs.

Pannexin1: insight into inflammatory conditions and its potential involvement in multiple organ dysfunction syndrome.

Sepsis represents a global health concern, and patients with severe sepsis are at risk of experiencing MODS (multiple organ dysfunction syndrome), which is associated with elevated mortality rates and a poorer prognosis. The development of sepsis involves hyperactive inflammation, immune disorder, and disrupted microcirculation. It is crucial to identify targets within these processes to develop therapeutic interventions. One such potential target is Panx1 (pannexin-1), a widely expressed transmembrane protein that facilitates the passage of molecules smaller than 1 KDa, such as ATP. Accumulating evidence has implicated the involvement of Panx1 in sepsis-associated MODS. It attracts immune cells via the purinergic signaling pathway, mediates immune responses via the Panx1-IL-33 axis, promotes immune cell apoptosis, regulates blood flow by modulating VSMCs' and vascular endothelial cells' tension, and disrupts microcirculation by elevating endothelial permeability and promoting microthrombosis. At the level of organs, Panx1 contributes to inflammatory injury in multiple organs. Panx1 primarily exacerbates injury and hinders recovery, making it a potential target for sepsis-induced MODS. While no drugs have been developed explicitly against Panx1, some compounds that inhibit Panx1 hemichannels have been used extensively in experiments. However, given that Panx1's role may vary during different phases of sepsis, more investigations are required before interventions against Panx1 can be applied in clinical. Overall, Panx1 may be a promising target for sepsis-induced MODS. Nevertheless, further research is needed to understand its complex role in different stages of sepsis fully and to develop suitable pharmaceutical interventions for clinical use.

A new convolutional neural network-construct for sepsis enhances pattern identification of microcirculatory dysfunction

BackgroundTriggers of organ dysfunction have been associated with the worsening of microcirculatory dysfunction in sepsis, and because microcirculatory changes occur before macro-hemodynamic abnormalities, they can potentially detect disease progression early on. The difficulty in distinguishing altered microcirculatory characteristics corresponding to varying stages of sepsis severity has been a limiting factor for the use of microcirculatory imaging as a diagnostic and prognostic tool in sepsis. The aim of this study was to develop a convolutional neural network (CNN) based on progressive sublingual microcirculatory dysfunction images in sepsis, and test its diagnostic accuracy for these progressive stages. MethodsSepsis was induced in Wistar rats (2 mL of E. coli 108 CFU/mL inoculation into the jugular vein), and 2 mL saline injection in sham animals was the control. Sublingual microvessels of all animals with surrounding tissue images were captured by Sidestream dark field imaging (SDF) at T0 (basal) and T2, T4, and T6 h after sepsis induction. From a total of 137 videos, 37.930 frames were extracted; a part (29.341) was used for the training of Resnet-50 (CNN-construct), and the remaining (8.589) was used for validation of accuracy. ResultsThe CNN-construct successfully classified the various stages of sepsis with a high accuracy (97.07%). The average AUC value of the ROC curve was 0.9833, and the sensitivity and specificity ranged from 94.57% to 99.91%, respectively, at all time points. ConclusionsBy blind testing with new sublingual microscopy images captured at different periods of the acute phase of sepsis, the CNN-construct was able to accurately diagnose the four stages of sepsis severity. Thus, this new method presents the diagnostic potential for different stages of microcirculatory dysfunction and enables the prediction of clinical evolution and therapeutic efficacy. Automated simultaneous assessment of multiple characteristics, both microvessels and adjacent tissues, may account for this diagnostic skill. As such a task cannot be analyzed with human visual criteria only, CNN is a novel method to identify the different stages of sepsis by assessing the distinct features of each stage.

Macrophages-regulating nanomedicines for sepsis therapy

Sepsis is the leading cause of death in intensive care unit (ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive care, while there still lacks of specific molecular therapy. As a type of immune dysfunction disease, macrophages have been recognized as the key immune cells precipitating in the whole process of sepsis, which is activated into M1-like to trigger various inflammatory responses at early stage whereas polarized into M2-like to cause immunosuppression in later stage. Therefore, great attention has been paid on the design of nanomedicines to regulate the functions of macrophages for etiological treatment of sepsis, by virtue of the unique advantages of nano-drug delivery systems, such as enhanced drug bioavailability, targetability, reduced side-effects. This critical review aims to summarize the recent progress of macrophages-regulating nanoparticles for sepsis therapy. First, the essential roles of macrophages in the development and progression of sepsis have been introduced, including the positive roles of macrophages to combat infections and dysfunction of macrophages to cause body damages. We then focus our main attention to discuss the nanomedicines with different therapeutic mechanisms corresponding to each stage of sepsis, such as infection blockage, inflammation inhibition, immune functions recovery, as well as multifunctional nanomedicines. Finally, a few limitations of current nanomedicines are highlighted, and future perspective are speculated for potential clinical translation, which might pave the way for the development of macrophages-centered nanomedicines for more effective sepsis therapy. Given the critical roles of macrophages in the development and progression of sepsis, this review summarized the macrophages-targeting nanomedicines with various therapeutic mechanisms to combat different stages of sepsis.

Multiorgan dysfunction syndrome in sepsis: Is macrophage activation syndrome secondary to infection?

To assess macrophage activation syndrome (MAS) in septic shock leading to multiorgan dysfunction syndrome (MODS). A prospective observational study was conducted at a tertiary care hospital to evaluate the MAS criteria in different stages of sepsis. Children aged 6 months to 12 years in different stages of septic shock were recruited. The Paediatric Rheumatology International Trials Organisation Collaborative Initiative (PRINTO) criteria of MAS were applied initially at the stage of septic shock and subsequently at the stage of MODS (MODS cohort) or following recovery from septic shock without going through MODS (non-MODS cohort). A total of 127 subjects were studied, with 53 comprising the MODS cohort and the rest 74 the non-MODS cohort. At the initial assessment, a comparable proportion of subjects in the MODS and non-MODS groups satisfied the MAS criteria (20.75% and 25.68%, respectively; p=0.529). However, by the time of progression to MODS, 81.13% of the subjects satisfied the MAS criteria in the MODS group, whereas only 16.18% subjects in the non-MODS group continued to satisfy the MAS criteria (p<0.001). Thus, there was a definite increase in the proportion of subjects showing MAS by the time they progressed to multiorgan dysfunction (p<0.001). In contrast, the proportion declined significantly (25.68% to 16.18%; p=0.008) in the subjects who had recovered. The findings bear out the hypothesis that MODS in sepsis is a reflection of MAS secondary to sepsis. However, studies in larger cohorts are needed to validate these findings and explore the therapeutic implications.

Role of deacetylase sirtuins in sepsis: beneficial or harmful?

Sepsis, life-threatening organ dysfunction caused by a dysregulated host response to infection, is a major public health concern. To date, the mechanism of sepsis is not completely understood, which is still a huge task ahead of numerous clinical and laboratory researchers. Recently, increasing evidences show that deacetylase sirtuins play an important role in sepsis and the function of sirtuins are varied in different stages of sepsis. More importantly, the mechanism of sirutins is not fully understood. The sirtuins family is composed by sirtuin 1-7 members. Among them, sirtuin 1 is widely reported. In addition to sirtuin 1, other members of sirtuins are also involved in the regulation of inflammation or metabolism signaling following sepsis. Of note, the sirtuins may interact with each other and form a precious control mechanism. Herein, we tried to summarize the recent paper from PubMed, to explain the possible mechanism of distinct role of sirtuin 1/2, to generalize the downstream effects of sirtuin 3 action, and to describe the interactions among sirtuins members on sepsis, which might be helpful for our future research and potential clinical applications.

The level and clinical significance of Rab11 in children with sepsis

Objective To investigate the expression of Rab11 in children with sepsis at different stages and severe sepsis and its relationship with the occurrence and development of sepsis in children. Methods A prospective control study was performed.All cases were enrolled from Bao′an Maternal and Children Health Care Hospital, and they were divided into sepsis group(40 cases) who were diagnosed as sepsis, severe sepsis group(20 cases) with diagnosis of severe sepsis, and healthy control group(40 healthy children). Venous blood samples were collected at admission, and the expression level of blood leukocyte Rab11 was determined by Western blot.In the sepsis group, the expression levels of Rab11 were evaluated at the initial, the extreme and the recovery stages of sepsis, and were compared with those in severe sepsis group and healthy control group, respectively.Spearman correlation analysis was used to evaluate the relationship between the expressions of Rab11 and the levels of some parameters in blood, including white blood cell, neutrophils, lymphocytes, monocytes, eosinophilic granulocyte, C-reactive protein and procalcitonin in blood, at the extreme stage.Meanwhile, the levels of Rab11 at extreme stage of sepsis, caused by different diseases, such as severe pneumonia, bronchiectasis complicated pulmonary infection, biliary tract infection, urinary tract infection, necrotizing enterocolitis and severe enteric viruses infection, were compared with each other. Results At the initial and the extreme stages of sepsis, as well as in severe sepsis group, the levels of Rab11 were significantly lower than that in the healthy control group(0.54 times, 0.23 times and 0.07 times, P 0.05). There was no relationship between the level of Rab11 and the number of white blood cell, neutrophils, lymphocytes, monocytes, eosinophilic granulocyte, while the level of Rab11 was negatively correlated with C-reactive protein(r=-0.58, P=0.014) and procalcitonin(r=-0.63, P=0.003) at the extreme stage of sepsis.There was no significant difference in the expression level of Rab11, at the extreme stage of sepsis, among those patients with severe pneumonia, bronchiectasis and pulmonary infection, biliary tract infection, urinary tract infection, necrotizing enterocolitis and severe enterovirus infection(P>0.05). Conclusion The level of Rab11 is differently expressed at different stages of sepsis, and could be used as a predictor of the severity of sepsis in children. Key words: Sepsis; Rab11; Expression

Sialic Acids in the Immune Response during Sepsis.

Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a group of cell surface transmembrane receptors expressed on immune cells, and regulate immune balance in inflammatory diseases. Sepsis is a life-threatened inflammatory syndrome induced by infection, and the pathogenesis of sepsis includes immune dysregulation, inflammation, and coagulation disorder. Here, we reviewed the various roles acted by Siglecs family in the pathogenesis of sepsis. Siglec-1, Siglec-5, and Siglec-14 play bidirectional roles through modulation of inflammation and immunity. Siglec-2 regulates the immune balance during infection by modulating B cell and T cell response. Siglec-9 helps endocytosis of toll-like receptor 4, regulates macrophages polarization, and inhibits the function of neutrophils during infection. Siglec-10 inhibits danger-associated molecular patterns induced inflammation, helps the initiation of antigen response by T cells, and decreases B-1a cell population to weaken inflammation. Regulating the Siglecs function in the different stages of sepsis holds great potential in the therapy of sepsis.

Platelet reactivity in sepsis syndrome: results from the PRESS study.

Platelet activation mediates systemic inflammatory response during infection. However, data on platelet reactivity (PR) varies among different settings. We assessed PR along different stages of sepsis and tried to predict for determinants of its variance. In parallel, we evaluated it as an early bedside diagnostic biomarker. This was an observational prospective cohort study. Incoming patients were assorted to distinct groups of uncomplicated infection, sepsis, and severe sepsis/septic shock. A control group of healthy volunteers was used as comparison. PR was assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU) alongside with levels of major inflammatory markers and whole blood parameters. A total of 101 patients and 27 healthy volunteers were enrolled. PR significantly and reversibly increases during sepsis compared to uncomplicated infection and healthy controls (244±66.7 vs 187.33±60.98, p<0.001 and 192.17±47.51, p<0.001, respectively). In severe sepsis, PR did not significantly differ compared to other groups. Sepsis stage uniquely accounts for 15.5% of PR in a linear regression prediction model accounting for 30% of the variance of PR (F=8.836, p<0.001). PRU >253 had specificity of 91.2% and sensitivity of 40.8% in discriminating septic from non-septic patients. The addition of PRU to SOFA and qSOFA scores significantly increased their c-statistic (AUC SOFA+PRU, 0.867 vs SOFA, 0.824, p<0.003 and AUC qSOFA+PRU, 0.842 vs qSOFA, 0.739, p<0.001), making them comparable (AUC SOFA+PRU vs qSOFA+PRU, p=0.4). PR significantly and reversibly increases early in sepsis, but seems to exhaust while disease progresses. Bedside assessment of PR can provide robust discriminative accuracy in the early diagnosis of septic patients.

Variation of subsets of myeloid derived suppressor cells and their ratio in septic mice

To investigate the dynamic variation of subsets of myeloid derived suppressor cells (MDSC) and their ratio in septic mice, and to discuss their role in the development of sepsis. Male C57BL/6 mice were randomly divided into sepsis model group and sham group according to random number table. Polymicrobial sepsis was induced by using cecal ligation and puncture (CLP), while mice in sham group only underwent laparotomy and laparorrhaphy without CLP. Thirty mice in each group were used to observe living condition, and the 20-day survival rate was compared between the two groups. In addition, subsets of MDSC in peripheral blood, spleen and bone marrow were analyzed with flow cytometry for other 60 mice (12 mice at each time point, as 0, 3, 7, 12 and 20 days). Spleens were harvested at 7 days for weighing, and single cell suspension of spleen tissue was prepared for splenocyte counting. Histopathologic changes in spleen tissue and liver tissue were observed under light microscope after hematoxylin and eosin (HE) stain. (1) No mice died in sham group within 20 days after the operation. On the other hand, 10 mice in model group died within 20 days, and the difference in survival rate between the two groups was statistically significant (100.0% vs. 66.7%, χ(2) = 11.861, P = 0.001). (2) The spleens in model group showed obvious enlargement and significantly outweighed as compared with those in sham group (mg: 413.33±41.63 vs. 111.67±17.56, t = 11.564, P = 0.000), and the total count of splenocytes was significantly higher than that in sham group (×10(9)/L: 21.20±2.43 vs. 1.87±0.06, t = 13.578, P = 0.005). (3) Pathological sections with HE staining showed that the liver tissue and spleen tissue remained normal in sham group. In model group, the hepatic tissue showed acute inflammatory reaction, including tissue disruption, capillary congestion, infiltration of neutrophils, marked edema of hepatocytes and focal hepatocellular necrosis. Abnormalities were also found in the spleen tissue: the red pulp and white pulp were disordered, splenic sinus was congested with numerous red cells, the splenic capsule thickened, immature myeloid cells with circular nuclei proliferated in the subcapsular region and perivascular region, splenic cord and splenic sinus were infiltrated with a large number of hematopoietic cells. (4) No significant changes in the monocytic MDSC (M-MDSC) and granulocytic MDSC (G-MDSC), and their ratio were found in peripheral blood, spleen and bone marrow at every time point in sham group. On the other hand, in model group, the ratio of M-MDSC and G-MDSC was continuously increased in peripheral blood, spleen and bone marrow, and M-MDSC only slightly decreased at 20 days. On the other hand, the ratio of M-MDSC/G-MDSC rose at first followed by a decrease. The ratio of M-MDSC/G-MDSC in peripheral blood was higher than 1 from 3 days after the operation, reaching the peak at 12 days (compared with 0 day: 4.16±0.53 vs. 0.79±0.11, P < 0.05), while the ratio of M-MDSC/G-MDSC in spleen and bone marrow after CLP were lower than 1 at all time points, reaching the peak on 7 days after the operation (compared with 0 day: 0.70±0.06 vs. 0.25±0.02 in spleen, 0.39±0.06 vs. 0.11±0.01 in bone marrow, both P < 0.05), and then gradually decreased afterwards. Subgroups of MDSCs were continuously aggregated in the peripheral blood, spleen and bone marrow, and their ratio rose first and decreased afterwards along with the development of sepsis, and the changes may reflect the change of immune status at different stages of sepsis.

Formal modelling of toll like receptor 4 and JAK/STAT signalling pathways: insight into the roles of SOCS-1, interferon-β and proinflammatory cytokines in sepsis.

Sepsis is one of the major causes of human morbidity and results in a considerable number of deaths each year. Lipopolysaccharide-induced sepsis has been associated with TLR4 signalling pathway which in collaboration with the JAK/STAT signalling regulate endotoxemia and inflammation. However, during sepsis our immune system cannot maintain a balance of cytokine levels and results in multiple organ damage and eventual death. Different opinions have been made in previous studies about the expression patterns and the role of proinflammatory cytokines in sepsis that attracted our attention towards qualitative properties of TLR4 and JAK/STAT signalling pathways using computer-aided studies. René Thomas’ formalism was used to model septic and non-septic dynamics of TLR4 and JAK/STAT signalling. Comparisons among dynamics were made by intervening or removing the specific interactions among entities. Among our predictions, recurrent induction of proinflammatory cytokines with subsequent downregulation was found as the basic characteristic of septic model. This characteristic was found in agreement with previous experimental studies, which implicate that inflammation is followed by immunomodulation in septic patients. Moreover, intervention in downregulation of proinflammatory cytokines by SOCS-1 was found desirable to boost the immune responses. On the other hand, interventions either in TLR4 or transcriptional elements such as NFκB and STAT were found effective in the downregulation of immune responses. Whereas, IFN-β and SOCS-1 mediated downregulation at different levels of signalling were found to be associated with variations in the levels of proinflammatory cytokines. However, these predictions need to be further validated using wet laboratory experimental studies to further explore the roles of inhibitors such as SOCS-1 and IFN-β, which may alter the levels of proinflammatory cytokines at different stages of sepsis.

Kinetics of circulating immunoglobulin M in sepsis: relationship with final outcome

IntroductionThe aim of this study was to investigate the kinetics of immunoglobulin M (IgM) during the different stages of sepsis.MethodsIn this prospective multicenter study, blood sampling for IgM measurement was done within the first 24 hours from diagnosis in 332 critically ill patients; in 83 patients this was repeated upon progression to more severe stages. Among these 83 patients, 30 patients with severe sepsis progressed into shock and IgM was monitored daily for seven consecutive days. Peripheral blood mononuclear cells (PBMCs) were isolated from 55 patients and stimulated for IgM production.ResultsSerum IgM was decreased in septic shock compared to patients with systemic inflammatory response syndrome (SIRS) and patients with severe sepsis. Paired comparisons at distinct time points of the sepsis course showed that IgM was decreased only when patients deteriorated from severe sepsis to septic shock. Serial measurements in these patients, beginning from the early start of vasopressors, showed that the distribution of IgM over time was significantly greater for survivors than for non-survivors. Production of IgM by PBMCs was significantly lower at all stages of sepsis compared with healthy controls.ConclusionsSpecific changes of circulating IgM occur when patients with severe sepsis progress into septic shock. The distribution of IgM is lower among non-survivors.

392 Prevalence of the Systemic Inflammatory Response Syndrome, Sepsis, Severe Sepsis and Septic Shock in a Neonatal Intensive Care Unit

AimTo examine the prevalence of the definitions of the systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock during the first three days of life.MethodsRetrospective cohort study including...

Fibrinogen, Coagulation Times and Some Inflammation Markers In Patients with Different Stages of Sepsis

Abstract 5257Fibrinogen, Coagulation Times and Some Inflammation Markers In Patients with Different Stages of Sepsis. Mariscal II MD, Lim-BagaGJ MD. Hospital Gómez Farias ISSSTE. Zapopan, México.Inflammation and coagulation pathways, among others, are activated during sepsis (Sp). We tested a priori hypothesis that coagulation changes are related to clinical stages of Sp. DESIGN.Prospective non interventional study on patients with Sp, from November 2009–2010 SETTING.Medicine hospitalization areas in a single third level hospital in western México PATIENTS.One hundred and eighty eight patients with Sp who were admitted to Medicine wards received standard critical care treatment. INTERVENTION.Patients were stratified into Sp, severe Sp and septic shock. Mortality was assessed at discharge and clotting test and inflammation markers were measured at admission and at discharge MEASUREMENTS AND MAIN RESULTS.Sp incidence was 9.6%. There were 114 patients with Sp, 57 severe Sp and 17 with septic shock; the mortality for the group was 23%; 6%, 34%, and 94% in Sp, severe Sp, and septic shock respectively. Initial fibrinogen (Fg) showed a trend to be higher as clinical stages of Sp advanced (346, 361,393 mg PNS), and final Fg decreased in Sp** and severe Sp* and shock (PNS). PT** and PTT** at discharge, were prolonged. Initial and final bands* were higher as the stages of Sp increased and decreased at discharge, except in those with septic shock. Comparing results by survivorship it was observed that initially and at discharge, non survivors had greater abnormalities of PT**, PTT**, and bands** than survivors. Fg**was lower in those who diedCLINICAL STAGES OF SEPSISSURVIVORSHIPSepsisSevere SpShockINITIALFINALInitial/FinalInit/FinalInit/FinalSurvive/DeadSurvive/DeadFg (mg/dL)346/310**361/300*393/238414/318254/289**PT (sec)14/20**15/17*15/2114.8/20.2**16.6/31**PTT (sec)31/32**31/35**32/3932.7/31.2**34.5/37.4**Platelets (uL)233/240210/198211/126220/216183/118WBC(103/uL)10.1/6.210.6/6.111.9/9.513.6/9.912.8/11.7Stabs6.2/2.9**6.1/5.5*9.4/12.76.2/7.9**6.3/10.1****P<.000*P<.02 CONCLUSIONS.The trend of the Initial Fg levels to increase as severity of Sp, its decrease at discharge, the prolongation of PT and PTT and the descend of platelets, suggest that the activation of the coagulation cascade increases as Sp progresses and, that this could be related to the severity of the inflammatory response and the vascular damage. The coagulopathy is suggestive of DIC andthat this participates in the prognosis. It would be important to set the clinical role of coagulation in the stages of Sp. A mayor numbers of patients must be studied and markers of DIC investigated. Disclosures:No relevant conflicts of interest to declare.

Cecal Ligation Puncture Procedure

Human sepsis is characterized by a set of systemic reactions in response to intensive and massive infection that failed to be locally contained by the host. Currently, sepsis ranks among the top ten causes of mortality in the USA intensive care units. During sepsis there are two established haemodynamic phases that may overlap. The initial phase (hyperdynamic) is defined as a massive production of proinflammatory cytokines and reactive oxygen species by macrophages and neutrophils that affects vascular permeability (leading to hypotension), cardiac function and induces metabolic changes culminating in tissue necrosis and organ failure. Consequently, the most common cause of mortality is acute kidney injury. The second phase (hypodynamic) is an anti-inflammatory process involving altered monocyte antigen presentation, decreased lymphocyte proliferation and function and increased apoptosis. This state known as immunosuppression or immune depression sharply increases the risk of nocosomial infections and ultimately, death. The mechanisms of these pathophysiological processes are not well characterized. Because both phases of sepsis may cause irreversible and irreparable damage, it is essential to determine the immunological and physiological status of the patient. This is the main reason why many therapeutic drugs have failed. The same drug given at different stages of sepsis may be therapeutic or otherwise harmful or have no effect. To understand sepsis at various levels it is crucial to have a suitable and comprehensive animal model that reproduces the clinical course of the disease. It is important to characterize the pathophysiological mechanisms occurring during sepsis and control the model conditions for testing potential therapeutic agents. To study the etiology of human sepsis researchers have developed different animal models. The most widely used clinical model is cecal ligation and puncture (CLP). The CLP model consists of the perforation of the cecum allowing the release of fecal material into the peritoneal cavity to generate an exacerbated immune response induced by polymicrobial infection. This model fulfills the human condition that is clinically relevant. As in humans, mice that undergo CLP with fluid resuscitation show the first (early) hyperdynamic phase that in time progresses to the second (late) hypodynamic phase. In addition, the cytokine profile is similar to that seen in human sepsis where there is increased lymphocyte apoptosis (reviewed in). Due to the multiple and overlapping mechanisms involved in sepsis, researchers need a suitable sepsis model of controlled severity in order to obtain consistent and reproducible results.

Cecal Ligation Puncture Procedure

Human sepsis is characterized by a set of systemic reactions in response to intensive and massive infection that failed to be locally contained by the host. Currently, sepsis ranks among the top ten causes of mortality in the USA intensive care units 1. During sepsis there are two established haemodynamic phases that may overlap. The initial phase (hyperdynamic) is defined as a massive production of proinflammatory cytokines and reactive oxygen species by macrophages and neutrophils that affects vascular permeability (leading to hypotension), cardiac function and induces metabolic changes culminating in tissue necrosis and organ failure. Consequently, the most common cause of mortality is acute kidney injury. The second phase (hypodynamic) is an anti-inflammatory process involving altered monocyte antigen presentation, decreased lymphocyte proliferation and function and increased apoptosis. This state known as immunosuppression or immune depression sharply increases the risk of nocosomial infections and ultimately, death. The mechanisms of these pathophysiological processes are not well characterized. Because both phases of sepsis may cause irreversible and irreparable damage, it is essential to determine the immunological and physiological status of the patient. This is the main reason why many therapeutic drugs have failed. The same drug given at different stages of sepsis may be therapeutic or otherwise harmful or have no effect 2,3. To understand sepsis at various levels it is crucial to have a suitable and comprehensive animal model that reproduces the clinical course of the disease. It is important to characterize the pathophysiological mechanisms occurring during sepsis and control the model conditions for testing potential therapeutic agents. To study the etiology of human sepsis researchers have developed different animal models. The most widely used clinical model is cecal ligation and puncture (CLP). The CLP model consists of the perforation of the cecum allowing the release of fecal material into the peritoneal cavity to generate an exacerbated immune response induced by polymicrobial infection. This model fulfills the human condition that is clinically relevant. As in humans, mice that undergo CLP with fluid resuscitation show the first (early) hyperdynamic phase that in time progresses to the second (late) hypodynamic phase. In addition, the cytokine profile is similar to that seen in human sepsis where there is increased lymphocyte apoptosis (reviewed in 4,5). Due to the multiple and overlapping mechanisms involved in sepsis, researchers need a suitable sepsis model of controlled severity in order to obtain consistent and reproducible results.

Treatment of Fournier's Gangrene with Combination of Vacuum-Assisted Closure Therapy, Hyperbaric Oxygen Therapy, and Protective Colostomy

Fournier's gangrene is a rare process which affects soft tissue in the genital and perirectal area. It can also progress to all different stages of sepsis, and abdominal compartment syndrome can be one of its complications. Two patients in septic shock due to Fournier gangrene were admitted to the Intensive Care Unit of Emergency Department. In both cases, infection started from the scrotum and the necrosis quickly involved genitals, perineal, and inguinal regions. Patients were treated with surgical debridement, protective colostomy, hyperbaric oxygen therapy, and broad-spectrum antibacterial chemotherapy. Vacuum-assisted closure (VAC) therapy was applied to the wound with the aim to clean, decontaminate, and avoid abdominal compartmental syndrome development. Both patients survived and were discharged from Intensive Care Unit after hyperbaric oxygen therapy cycles and abdominal closure.