Survival Of Sepsis Patients Research Articles

Association between Beta-Hydroxybutyrate Levels and Survival in Sepsis Patients

Association between Beta-Hydroxybutyrate Levels and Survival in Sepsis Patients

PD-1 in Tregs predicts the survival in sepsis patients using sepsis-3 criteria: A prospective, two-stage study

BackgroundThe expression of Tregs co-signaling molecules serves as the marker of immune dysfunction. The present study aimed to verify their predictive role in the 28-day mortality of sepsis patients. MethodsA prospective, observational, two-stage cohort study was conducted. The patients who fulfilled the sepsis-3 criteria were enrolled, and peripheral blood samples were collected within 24 h post-enrollment. The expression of the four co-signaling molecules of Tregs, namely, PD-1, CD28, PD-L1 and CD86, was measured, and sequential organ failure assessment (SOFA) scores were recorded on day 1 of inclusion. Patients were followed up for 28 days or, otherwise, deceased. Multivariate regression analysis was used to assess the independent risk factors for 28-day mortality, and a prognostic prediction model was established, which was verified in the validation set. ResultsA total of 292 patients were recruited in the study, of which 120 patients were finally included in the analysis, that is 58 patients in stage I (test set) and 62 patients in stage II (validation set). In stage I, 14 (24.1%), patients died during 28 days, and the expression of PD-1 in Tregs (OR:1.037;95%CI:1.003–1.071) and SOFA scores(OR:1.262;95%CI:1.046–1.524) were independent risk factors for 28-day mortality. The ability of Tregs PD-1 in predicting 28-day mortality was validated in stage II (AUC = 0.792). ConclusionPD-1 overexpression in Tregs was associated with poor outcomes, and PD-1 in Tregs is considered to be a valuable tool for the prediction of prognosis in septic patients using sepsis-3.0 criteria.

Clinical significance of miR-19b-3p in patients with sepsis and its regulatory role in the LPS-induced inflammatory response

BackgroundMicroRNAs (miRNAs) play important roles in the development and progression of sepsis. This study investigated the clinical value of miR-19b-3p in sepsis patients, and explored its role in regulating inflammatory responses in HUVECs cells.Methods103 patients with sepsis and 98 healthy individuals were recruited. qRT-PCR was used for the measurement of miR-19b-3p level. Cell viability was evaluated using CCK-8. The protein levels of TNF-α and IL-6 were measured using ELISA. Receiver operating characteristic (ROC) curve and logistic regression analysis were constructed to evaluate the diagnostic and prognostic values of miR-19b-3p in sepsis patients.ResultsMiR-19b-3p level was significantly reduced in the serum from patients with sepsis compared with healthy controls (P < 0.001). Sepsis patients in the survival group had significantly high miR-19b-3p levels compared with the non-survival group (P < 0.001). MiR-19b-3p was of a good value in predicting sepsis risk, and was an independent prognostic factor for 28-day survival in sepsis patients (OR = 3.226, 95% CI 1.076–9.670, P = 0.037). MiR-19b-3p level was negatively associated with serum levels of IL-6 (r = − 0.852, P < 0.001) and TNF-α (r = − 0.761, P < 0.001). Overexpression of miR-19b-3p alleviated LPS-induced inflammatory response of HUVECs, which was reflected by the decrease of the levels of IL-6 and TNF-α induced by LPS treatment (P < 0.001).ConclusionMiR-19b-3p might be a potential biomarker for the early diagnosis and prognosis of sepsis patients. Overexpression of miR-19b-3p alleviated sepsis-induced inflammatory responses.

S1PR1-Associated Molecular Signature Predicts Survival in Patients with Sepsis.

Sepsis is a potentially life-threatening complication of an underlying infection that quickly triggers tissue damage in multiple organ systems. To date, there are no established useful prognostic biomarkers for sepsis survival prediction. Sphingosine-1-phosphate (S1P) and its receptor S1P receptor 1 (S1PR1) are potential therapeutic targets and biomarkers for sepsis, as both are active regulators of sepsis-relevant signaling events. However, the identification of an S1PR1-related gene signature for prediction of survival in sepsis patients has yet to be identified. This study aims to find S1PR1-associated biomarkers which could predict the survival of patients with sepsis using gene expression profiles of peripheral blood to be used as potential prognostic and diagnostic tools. Gene expression analysis from sepsis patients enrolled in published datasets from Gene Expression Omnibus was utilized to identify both S1PR1-related genes (co-expression genes or functional-related genes) and sepsis survival-related genes. We identified 62-gene and 16-gene S1PR1-related molecular signatures (SMS) associated with survival of patients with sepsis in discovery cohort. Both SMS genes are significantly enriched in multiple key immunity-related pathways that are known to play critical roles in sepsis development. Meanwhile, the SMS performs well in a validation cohort containing sepsis patients. We further confirmed our SMSs, as newly developed gene signatures, perform significantly better than random gene signatures with the same gene size, in sepsis survival prognosis. Our results have confirmed the significant involvement of S1PR1-dependent genes in the development of sepsis and provided new gene signatures for predicting survival of sepsis patients.

Evaluation of 16S rRNA broad range PCR assay for microbial detection in serum specimens in sepsis patients

BackgroundEarly and accurate laboratory diagnosis and appropriate management of infection improves the survival rate in sepsis. In this study we evaluated broad range 16S rRNA and 16 S–23 S intergenic spacer region (ISR) PCR assays followed by nucleotide sequencing directly from patients’ serum and automated blood culture for laboratory diagnosis in admitted sepsis patients. MethodsA broad range 16S rRNA PCR and 16 S–23 S ISR PCR assay followed by nucleotide sequencing was used directly from patients’ serum in hospital admitted patients in 62 sepsis and 16 suspected blood stream infection (sBSI) patients. Automated blood culture was also used in the same patients. Nucleotide sequences were analyzed against NCBI Genbank database and organisms were identified using CLSI MM18A guidelines. ResultsBacterial culture were positive in 10/62 (16.12%) sepsis and 3/16 (18.75%) suspected BSI patients along with 3 detected fungi (2 in sepsis and 1 in suspected BSI group). PCR assay was positive in 36/62 (58.06%) sepsis and 6/16 (37.5%) suspected BSI patients respectively. All but 2 bacteria (both from culture negative patients) detected by PCR assay could be identified from nucleotide sequencing. Survival in sepsis patients was 77%. PCR assay could detect bacteria in 9/14 (64.28%) of sepsis patients with death. ConclusionBroad range PCR assay was far superior for early diagnosis of infection. The bacteria which could not be detected by culture and were not commonly reported from this centre, were detected by the broad range PCR assays. Detection of these rare bacteria/fungi had significant clinical correlation with patient’s underlying clinical conditions, immune status and prognosis. The tests could provide definitive diagnosis of infection in >58% of sepsis patients, which helped in patient management and better survival.

Provider-to-provider telemedicine improves adherence to sepsis bundle care in community emergency departments

Introduction Sepsis is a life-threatening emergency. Together, early recognition and intervention decreases mortality. Protocol-based resuscitation in the emergency department (ED) has improved survival in sepsis patients, but guideline-adherent care is less common in low-volume EDs. This study examined the association between provider-to-provider telemedicine and adherence with sepsis bundle components in rural community hospitals. Methods This is a prospective cohort study of adults presenting with sepsis or septic shock in community EDs participating in rural telemedicine networks. The primary outcome was adherence to four sepsis bundle requirements: lactate measurement within 3 hours, blood culture before antibiotics, broad-spectrum antibiotics, and adequate fluid resuscitation. Multivariable generalized estimating equations estimated the association between telemedicine and adherence. Results In this cohort (n = 655), 5.6% of subjects received ED telemedicine consults. The telemedicine group was more likely to be male and have a higher severity of illness. After adjusting for severity and chief complaint, total sepsis bundle adherence was higher in the telemedicine group compared with the non-telemedicine group (aOR 17.27 [95%CI 6.64–44.90], p < 0.001). Telemedicine consultation was associated with higher adherence with three of the individual bundle components: lactate, antibiotics, and fluid resuscitation. Discussion Telemedicine patients were more likely to receive initial blood lactate measurement, timely broad-spectrum antibiotics, and adequate fluid resuscitation. In rural, community EDs, telemedicine may improve sepsis care and potentially reduce disparities in sepsis outcomes at low-volume facilities. Future work should identify specific components of telemedicine-augmented care that improve performance with sepsis quality indicators.

A 10-Year Longitudinal Analysis of Protocol-Based Sepsis Management in a Philippine Tertiary ICU.

To compare the outcomes of sepsis management using protocol-based therapy versus non-protocolized care, assessed over 10 years. Retrospective cohort study, analyzed longitudinally with risk-adjusted control charts, referenced against hospital- and unit-level programs or interventions. Private, tertiary teaching hospital ICU in the Philippines. Nine-hundred fifty adult patients (19 yr old or older) diagnosed with severe sepsis or septic shock, using 2001 consensus definitions, admitted to the ICU from September 2007 to August 2017. Three iterations of a standard clinical pathway (including early antibiotics, prescribed fluid resuscitation, and hemodynamic management) versus concurrent non-protocolized care. Seven-hundred sixty patients were in the protocol-based care group versus 190 in the non-protocolized care group. Protocol-based management was associated with lower hospital mortality (28.4% vs 44.7%; p = 0.00) and ICU mortality (24.2% vs 31.6%; p = 0.038). There were no differences in ICU or hospital length-of-stay, mechanical ventilator days, or vasoactive days. Risk-Adjusted Cumulative Sum and Risk-Adjusted Exponentially Weighted Moving Average control charts showed that a survival advantage was achieved after 1 year and was sustained over the duration of the study. Protocol-based management was associated with sustained improvements in the survival of sepsis patients over 10 years in this hospital setting, after a run-in period of 1 year. Hospital- and unit-level interventions may have measurable impacts on the efficacy of sepsis clinical pathways.

Peripheral blood leukocyte telomere length is associated with survival of sepsis patients.

Shorter peripheral blood leukocyte (PBL) telomere length (TL) has been associated with poor outcomes in various chronic lung diseases. Whether PBL-TL is associated with survival from critical illness was tested in this study.We analysed data from a prospective observational cohort study of 937 critically ill patients at Vanderbilt University Medical Center (VUMC). PBL-TL was measured using quantitative PCR of DNA isolated from PBLs. Findings were validated in an independent cohort of 394 critically ill patients with sepsis admitted to the University of California San Francisco (UCSF).In the VUMC cohort, shorter PBL-TL was associated with worse 90-day survival (adjusted hazard ratio (aHR) 1.3, 95% CI 1.1-1.6 per 1 kb TL decrease; p=0.004); in subgroup analyses, shorter PBL-TL was associated with worse 90-day survival for patients with sepsis (aHR 1.5, 95% CI 1.2-2.0 per 1 kb TL decrease; p=0.001), but not trauma. Although not associated with development of acute respiratory distress syndrome (ARDS), among ARDS subjects, shorter PBL-TL was associated with more severe ARDS (OR 1.7, 95% CI 1.2-2.5 per 1 kb TL decrease; p=0.006). The associations of PBL-TL with survival (adjusted HR 1.6, 95% CI 1.2-2.1 per 1 kb TL decrease; p=0.003) and risk for developing severe ARDS (OR 2.5, 95% CI 1.1-6.3 per 1 kb TL decrease; p=0.044) were validated in the UCSF cohort.Short PBL-TL is strongly associated with worse survival and more severe ARDS in critically ill patients, especially patients with sepsis. These findings suggest that telomere dysfunction may contribute to outcomes from critical illness.

Increased body mass index linked to greater short- and long-term survival in sepsis patients: A retrospective analysis of a large clinical database

ObjectivesWe investigated the impact of obesity (proxied as body mass index (BMI)), on short- and long-term mortality in sepsis patients. MethodsWe conducted a retrospective analysis with adult sepsis ICU patients in a US medical institution from 2001 to 2012 in the MIMIC-III database. The WHO BMI categories were used. Multivariate logistic regression assessed the relationships between BMI and 30-day and 1-year mortality. ResultsIn total, 5563 patients were enrolled. Obese patients tended to be younger (P<0.001), to be female (P<0.001), to acquire worse SOFA scores (P<0.001), and to receive more aggressive treatment compared with their normal weight counterparts. Obese patients had notably longer mechanical ventilation periods and ICU and hospital lengths of stay (LOSs). In the final model, overweight and obese patients had lower 30-day (OR 0.77, 95% CI 0.66–0.91; OR 0.65, 95% CI 0.56–0.77, respectively) and 1-year (OR 0.83, 95% CI 0.71–0.96; OR 0.70, 95% CI 0.60–0.81, respectively) mortality risks than normal weight patients. In contrast, underweight patients had worse 30-day and 1-year outcomes compared with normal weight patients (P=0.01, P<0.001, respectively). In morbidly obese, severe sepsis and septic shock patients, obesity remained protective. ConclusionsObesity was correlated with short- and long-term survival advantages in sepsis patients.

Downregulation of JKAP is correlated with elevated disease risk, advanced disease severity, higher inflammation, and poor survival in sepsis.

ObjectiveThis study aimed to explore the association of JKAP with sepsis risk and investigate its correlation with disease severity, inflammatory cytokines, and survival in sepsis patients.MethodsA hundred and one sepsis patients along with 100 healthy controls were enrolled, and their blood serum samples were collected for JKAP and inflammatory cytokines measurement by enzyme‐linked immunoassay. The difference in serum JKAP between sepsis patients and healthy controls was determined. Among sepsis patients, the correlation of JKAP with disease severity, laboratory indexes, inflammatory cytokines, 28‐day mortality, and accumulating survival was analyzed.ResultsJNK pathway–associated phosphatase level was decreased in sepsis patients compared with healthy controls and presented with good value in predicting decreased sepsis risk (AUC = 0.896 [95% CI: 0.851‐0.941]). And its low expression was associated with advanced disease severity (APACHE II score and SOFA score) and systemic inflammation (CRP, PCT, TNF‐α, IL‐1β, IL‐6, and IL‐17) in sepsis patients. Additionally, JKAP level was decreased in deaths compared with survivors and had good value in distinguishing deaths from survivors (AUC = 0.742 [95% CI: 0.636‐0.849]). Further, Kaplan‐Meier curve analysis disclosed that JKAP high expression predicted more prolonged accumulating survival in sepsis patients.ConclusionJNK pathway–associated phosphatase is of good value in predicting lower sepsis risk, and its downregulation correlates with advanced disease severity, higher level of systemic inflammation, and poor survival in sepsis patients.

Circulating long noncoding RNA ZNFX1 antisense RNA negatively correlates with disease risk, severity, inflammatory markers, and predicts poor prognosis in sepsis patients.

This study aimed to investigate the correlation of long noncoding RNA (lncRNA) ZNFX1 antisense RNA (ZFAS1) with disease risk, severity, inflammation markers, and prognosis in sepsis patients.A total of 202 sepsis patients were consecutively enrolled, and 200 healthy volunteers were also recruited as healthy controls (HCs). Plasma samples of all patients and HCs were collected. LncRNA ZFAS1 expression was determined by quantitative polymerase chain reaction assay and inflammatory cytokines levels were detected by enzyme-linked immunosorbent assay.The median value of lncRNA ZFAS1 expression in sepsis patients was (0.639 [0.325–1.071]), which was lower compared to HCs (1.957 [0.876–3.245], P < .001], and receiver operating characteristics (ROC) curve revealed that lncRNA ZFAS1 expression had a good diagnostic value for sepsis with area under curve (AUC) of 0.814 (95% confidence interval [CI]: 0.771–0.857). Spearman test disclosed that lncRNA ZFAS1 expression was negatively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score (r = −0.505, P < .001), and it was negatively associated with levels of C-creative protein (r = −0.241, P = .001), tumor necrosis factor-α (r = −0.253, P < .001), and interleukin (IL)-6 (r = −0.177, P = .012) while positively associated with IL-10 level (r = 0.173, P = .014). Also, lncRNA ZFAS1 expression was lower in survivor group compared to nonsurvivor group (P < .001), and it presented with a good predictive value on distinguishing nonsurvivors from survivors in sepsis patients with AUC of 0.628 (95% CI: 0.538–0.717).Circulating lncRNA ZFAS1 expression negatively correlates with disease risk, severity, and inflammatory markers levels, and might predict worse survival in sepsis patients.

Circulating lncRNA ITSN1-2 is upregulated, and its high expression correlates with increased disease severity, elevated inflammation, and poor survival in sepsis patients.

BackgroundThis study aimed to assess the correlation of long noncoding (lnc) RNA intersectin (ITSN) 1‐2 expression with disease risk, severity, inflammation, and survival in sepsis patients.MethodsThree hundred and nine intensive care unit (ICU)‐treated sepsis patients and 300 healthy controls were consecutively recruited in this study. Blood samples were collected from all sepsis patients within 24 hours after admitted to ICU and from healthy controls at the time of health screening, and the expression of lncRNA ITSN1‐2 in plasma was detected by quantitative polymerase chain reaction. Disease severity was assessed by physicians using acute physiology and chronic health evaluation (APACHE) II score on day 1 after ICU admission. Additionally, the plasma inflammatory cytokines (including tumor necrosis factor α (TNF‐α), interleukin 1β (IL‐1β), IL‐6, IL‐8, IL‐10, and IL‐17) were measured by enzyme‐linked immunosorbent assay (ELISA) kits.ResultslncRNA ITSN1‐2 was highly expressed in sepsis patients compared to healthy controls and could differentiate sepsis patients from healthy controls with area under the curve (AUC) 0.777 (95% CI: 0.740‐0.813). lncRNA ITSN1‐2 expression was positively correlated with APACHE II score, C‐reactive protein (CRP), TNF‐α, IL‐6, and IL‐8 levels, but negatively correlated with IL‐10 level. In addition, lncRNA ITSN1‐2 was highly expressed in non‐survivors compared to survivors and could distinguish survivors from non‐survivors in sepsis patients with AUC 0.654 (95% CI: 0.581‐0.726).ConclusionCirculating lncRNA ITSN1‐2 is upregulated, and its high expression associates with increased disease severity and inflammation as well as poor prognosis in sepsis patients.

Reactive Oxygen Species–Associated Molecular Signature Predicts Survival in Patients with Sepsis

Sepsis-related multiple organ dysfunction syndrome is a leading cause of death in intensive care units. There is overwhelming evidence that oxidative stress plays a significant role in the pathogenesis of sepsis-associated multiple organ failure; however, reactive oxygen species (ROS)-associated biomarkers and/or diagnostics that define mortality or predict survival in sepsis are lacking. Lung or peripheral blood gene expression analysis has gained increasing recognition as a potential prognostic and/or diagnostic tool. The objective of this study was to identify ROS-associated biomarkers predictive of survival in patients with sepsis. In-silico analyses of expression profiles allowed the identification of a 21-gene ROS-associated molecular signature that predicts survival in sepsis patients. Importantly, this signature performed well in a validation cohort consisting of sepsis patients aggregated from distinct patient populations recruited from different sites. Our signature outperforms randomly generated signatures of the same signature gene size. Our findings further validate the critical role of ROSs in the pathogenesis of sepsis and provide a novel gene signature that predicts survival in sepsis patients. These results also highlight the utility of peripheral blood molecular signatures as biomarkers for predicting mortality risk in patients with sepsis, which could facilitate the development of personalized therapies.

Paraoxonase 1 Activity and Survival in Sepsis Patients.

Sepsis is a state of augmented oxidative stress and diminished antioxidant capacity. High density lipoprotein (HDL) particles were shown to possess antioxidant and anti-inflammatory properties, as well as Paraoxonase 1 (PON1), which is an enzyme that is also protective against HDL oxidation. Previous studies suggested a possible role of decreased PON1 activity or HDL levels in sepsis patients. The present study was designed to test a hypothesis that higher PON1 activity and HDL-cholesterol levels could predict a better survival in sepsis patients. Observational study. Venous blood samples were collected from sepsis patients for HDL-cholesterol levels, PON1 activity and cytokine assays (TNF-α and IL-6) and Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores were calculated in order to weight patients' disease severity on the day of sepsis diagnosis. Patients were followed-up until the 28(th) day for any cause intra-hospital mortality. Data were statistically analyzed for effects of study parameters on patients' survival. In total, 85 patients with sepsis were included in the study. The mean age was 65.2±17.9 years and 48 were male; at the end of the 28-day follow-up period, 46 survived. TNF-α (86.9±10.5 vs 118.6±16.4) and IL-6 levels (906.7±82.7 vs 1323.1±54.3) were significantly higher in non-survivors, while PON1 activity (140.7±42.3 vs 66.7±46.6) and HDL-cholesterol levels (43.6±8.1 vs 34.5±8.9) were significantly higher in survivors (p<0.001 for all). TNF-α (r=-0.763) and IL-6 levels (r=-0.947) showed strong negative correlations, PON1 activity (r=0.644) and HDL-cholesterol levels (r=0.477) showed positive correlations with patient survival (p<0.001 for all). Survival estimates significantly favored TNF-α (Log Rank 59.5, p<0.001) and IL-6 levels (Log Rank 53.2, p<0.001) according to PON1 activity (Log Rank 5.4, p<0.03) and HDL-cholesterol levels (Log Rank 8.3, p<0.005). Regression analyses for relative contributions of parameters to survival showed that higher IL-6 levels (t: -16.489, p<0.001) were the most significant negative factor for survival, and TNF-α levels (t: -4.417, p<0.001), whereas PON1 activity had a positive effect (t:3.210, p<0.003). The present study showed that although low PON1 activity and HDL-cholesterol levels were related to mortality, higher levels were not found to be as predictive as cytokine levels for survival.

Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis.

Complement 5a (C5a) has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors (C5aRs; C5aR and C5L2) as biomarkers for the management of sepsis is uncertain. This study investigated the dynamic expression of C5aR and C5L2 on neutrophils and their effects on neutrophil function. We found that sepsis patients displayed low expression levels of C5aR and C5L2 on neutrophils compared to healthy and systemic inflammatory response syndrome (SIRS) subjects, and this expression pattern was correlated with disease severity. Additionally, the expression levels of C5aR and C5L2 were associated with the survival of sepsis patients. In vitro, the addition of C5a significantly reduced C5aR and C5L2 expression levels and IL-8 production in neutrophils from sepsis patients. Those findings suggest that the reduced expression of C5aRs was associated with the functional impairment of neutrophils and a poor prognosis for sepsis patients. Overall, these findings may help establish C5aRs expression levels as early markers to predict the severity of sepsis.

High circulating CD39+ regulatory T cells predict poor survival for sepsis patients

Sepsis encompasses two phases, the 'hyper'-reactive phase and the 'hypo'-reactive phase. The initial inflammatory stage is quickly counterbalanced by an anti-inflammatory response, which compromises the immune system, leading to immune suppression. Regulatory T cells (Tregs) have been implicated in the pathogenesis of sepsis by inducing immunosuppression; however, the role of CD39(+) Tregs in the process of sepsis is uncertain. This study investigated the dynamic levels of CD39(+) Tregs and their phenotypic change in sepsis. Fourteen patients with systemic inflammatory response syndrome (SIRS), 42 patients with sepsis, and 14 healthy controls were enrolled. Sequential blood samples were used to analyze the numbers of CD39(+) Tregs and their phenotypic changes. Survival at 28 days was used to evaluate the capacity of CD39(+) Treg levels to predict mortality in sepsis patients. Sepsis patients displayed a high percentage (3.13%, 1.46%, and 0.35%, respectively) and mean fluorescence intensity (MFI) (59.65, 29.7, and 24.3, respectively) of CD39(+) Tregs compared with SIRS patients and healthy subjects. High-level expression of CD39(+) Tregs was correlated with the severity of sepsis, which was reflected by the sepsis-related organ failure assessment score (r=0.322 and r=0.31, respectively). In addition, the expression of CD39(+) Tregs was associated with survival of sepsis patients (p<0.01). By receiver-operating characteristic (ROC) curve analysis, the percentage and MFI of CD39(+) Tregs showed similar sensitivities and specificities to predict mortality (74.2% and 85.1%, and 73.9% and 84.1%, respectively). Using Kaplan-Meier curves to assess the impact of CD39(+) Tregs percentage and MFI on overall survival, we found that a high CD39(+) Tregs percentage (p<0.001; >4.1%) and MFI (p<0.001; >49.2) were significantly associated with mortality. Phenotypically, CD39(+) Tregs from sepsis patients showed high expression of CD38 and PD-1 (p<0.01 and p<0.01 respectively). Increased expression of CD39(+) Tregs was associated with a poor prognosis for sepsis patients, which suggests that CD39(+) Treg levels could be used as a biomarker to predict the outcome of sepsis patients.

Serial Changes in Plasma Annexin A1 and Cortisol Levels in Sepsis Patients

Annexin A1 (AnxA1), originally identified as a glucocorticoid-regulated protein, is an impor- tant endogenous anti-inflammatory mediator during the resolution phase of inflammation, and its cir- culating level has been rarely studied in sepsis patients. Glucocorticoid has been extensively used in treating patients with sepsis. However, it is unclear whether endogenous cortisol or exogenous glucocor- ticoid contributes to the regulation of AnxA1 levels in peripheral blood of sepsis patients. The aim of this study was to investigate: [1] serial changes over time in the plasma levels of AnxA1 and cortisol in sepsis patients; and [2] prognostic value of AnxA1 level in the survival of sepsis patients. Fifty-eight adult sepsis patients admitted to an intensive care unit (ICU) were enrolled. The plasma levels of cortisol and AnxA1 were determined by specific enzyme-link immunosorbent assay. Results show that the median daily levels of cortisol at the 1st, 3rd, 5th and 7th day after admission to ICU were signifi- cantly elevated over the cortisol level of the control subjects. However, the AnxA1 level was elevated in only thirty-three patients (56%) over the observation period. There was no significant correlation between cortisol levels and AnxA1 levels. Further analysis indicated that steroid treatment resulted in significant elevation of the cortisol level over time, but did not affect the AnxA1 level. AnxA1 levels were also not statistically different between surviving and non-surviving patients. In conclusions, the circu- lating level of AnxA1 is elevated in a subgroup of sepsis patients, and the AnxA1 level does not correlate with the cortisol level in the peripheral blood of sepsis patients.

Passive immunotherapy of sepsis with intravenous immune globulin: not all IVIg preparations are created equal

Normal intravenous immunoglobulin (IVIg) preparations are potentially promising drugs for the adjunctive treatment of sepsis as the pool of IgG antibodies neutralizes a wide array of pathogens plus their virulence factors and in addition possesses broad anti-inflammatory and immunomodulating activities. However, several high quality clinical studies have failed to show an effect of IVIg therapy on survival of sepsis patients. The reason behind this lack of success could be that the wrong immunoglobulin preparations have been used so far. We review evidence from experimental sepsis studies proving that licensed IVIg with additionally enhanced antigen-binding polyspecificity have significant beneficial effects in all sepsis models used.

Difference in Protein Markers According to the Survival of Sepsis Patients using Protein Chips

Background; Several clinical scoring systems are currently being used to predict the outcome of sepsis, but they all have certain limitations. Therefore, we sought to identify the proteomic biomarkers, with wsing proteomic tools, that differed according to the outcome of sepsis patients. Methods; Upon admission to the ICU, blood samples were obtained from the 16 patients with sepsis who were enrolled in this study. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI –TOF MS) was used to identify the markers that could predict the outcome of sepsis. Results; We found six peaks, by using cation and anion chips, that statistically differed between those patients who died and those who survived. Conclusion; The biomarkers we found by using proteomic tools may help predi ct the prognosis and also plan the treatment of sepsis. (Tuberc Respir Dis 2006; 61: 41-45)

High interleukin 12 and low interleukin 10 production after in vitro stimulation detected in sepsis survivors

To evaluate viability of isolated peripheral blood mononuclear cells (PBMC) and production of cytokines in vitro after stimulation as prognostic factors for survival in sepsis patients. Prospective study of the biological response of PBMC in the onset of severe sepsis. Research laboratory of molecular biology and immunology and university hospital ICU, Faculty of Medicine, Trakia University. Twenty-three patients meeting the criteria for severe sepsis, and 14 control subjects. Isolated PBMC were stimulated in vitro with: C3-binding glycoprotein (C3bgp; 30 microg), lipopolysaccharide (30 microg), phytohemagglutinin (20 microg), pokeweed mitogen (30 microg), and dexamethasone (500 microg). We measured the levels of interleukins (IL) 6, 10, and 12 in culture supernatants. Stimulation with C3bgp and phytohemagglutinin led to significantly lower PBMC secretion of IL-6 in nonsurvivors than in survivors and healthy donors. Stimulation with C3bgp, lipopolysaccharide, and pokeweed mitogen considerably reduced IL-12 production in nonsurvivors. Stimulation with lipopolysaccharide and pokeweed mitogen caused immune cells in nonsurvivors to produce higher levels of IL-10 than in survivors. Survival of PBMC reduced viability for nonsurvivors' PBMC, both spontaneously and as induced by lipopolysaccharide or pokeweed mitogen. The viability of PBMC at the onset of sepsis and enhanced production of IL-12 and diminished production of IL-10 after stimulation with all stimuli used may be a favorable prognostic factor in sepsis.