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Sample records for sepsis outcome acute

  1. Infection site is predictive of outcome in acute lung injury associated with severe sepsis and septic shock.

    PubMed

    Fujishima, Seitaro; Gando, Satoshi; Daizoh, Saitoh; Kushimoto, Shigeki; Ogura, Hiroshi; Mayumi, Toshihiko; Takuma, Kiyotsugu; Kotani, Joji; Yamashita, Norio; Tsuruta, Ryosuke; Takeyama, Naoshi; Shiraishi, Shin-Ichiro; Araki, Tsunetoshi; Suzuki, Koichiro; Ikeda, Hiroto; Miki, Yasuo; Suzuki, Yasushi; Yamaguchi, Yoshihiro; Aikawa, Naoki

    2016-07-01

    Sepsis is a leading cause of acute lung injury (ALI); however, the characteristics and outcome of sepsis-associated ALI are poorly understood. We aimed to elucidate factors that predict patient outcome in sepsis-associated ALI. Secondary analysis of a multicenter, prospective, observational study was performed. Among 624 patients with severe sepsis and septic shock, 251 (40.2%) fulfilled the definition of American-European Consensus Conference definition of ALI. All-cause 28-day and in-hospital mortalities were 30.7% and 38.6%, respectively. More than 40% of ALI patients had neurological, cardiovascular and haematological dysfunctions or disseminated intravascular coagulation, all of which were associated with higher mortality. We report a significant correlation between infection site and mortality in patients with ALI, but not in those without ALI. The proportion of ALI was significantly higher in pulmonary sepsis; further, a complication of ALI was associated with higher mortality in sepsis from pulmonary and other sources, but not in abdominal sepsis. Among the other sepsis sites, urinary tract, central nervous system, catheter-related and undetermined foci of infection had worse outcomes when associated with ALI. None of the individual severe sepsis bundles, including fluid resuscitation and early antibiotic administration, correlated with mortality. Compliance with a set of sepsis management bundles was associated with better outcomes. In severe sepsis and septic shock, the proportion and effect on outcome was not uniform among infection sites. The infection site was predictive of outcome in patients with ALI but not in those without ALI. © 2016 Asian Pacific Society of Respirology.

  2. Acute kidney injury in patients with sepsis and septic shock: risk factors and clinical outcomes.

    PubMed

    Suh, Sang Heon; Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

    2013-07-01

    The aim of this study was to investigate clinical characteristics and risk factors of acute kidney injury (AKI) in patients with sepsis and septic shock. Additionally, we explored whether the severity of AKI affects on the clinical outcomes. Data were collected retrospectively in a single center. Among 5680 patients who visited emergency department from January to December 2010, 992 patients with sepsis and septic shock were enrolled. Patients were divided into two groups, patients who developed AKI or not, to compare the baseline characteristics, and laboratory and physiologic data. Patients with AKI were subdivided according to its stages for survival analysis. AKI was developed in 57.7% of patients. Multivariable logistic regression analysis revealed that development of septic AKI was associated with older age, pre-existing chronic kidney disease, use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker, presence of shock, positive blood culture results, and low white blood cell and platelet counts. Hospital mortality was higher in AKI group. Crude Kaplan-Meier survival curves demonstrated reduced 30-day survival rate was significantly associated with the severity of acute kidney injury. The development of septic AKI was associated with poor clinical outcomes. Furthermore, the severity of AKI was associated with increased mortality.

  3. APACHE III Outcome Prediction in Patients Admitted to the Intensive Care Unit with Sepsis Associated Acute Lung Injury

    PubMed Central

    Chen, Lin

    2015-01-01

    Background and objective Acute Physiology and Chronic Health Evaluation (APACHE) III score has been widely used for prediction of clinical outcomes in mixed critically ill patients. However, it has not been validated in patients with sepsis-associated acute lung injury (ALI). The aim of the study was to explore the calibration and predictive value of APACHE III in patients with sepsis-associated ALI. Method The study was a secondary analysis of a prospective randomized controlled trial investigating the efficacy of rosuvastatin in sepsis-associated ALI (Statins for Acutely Injured Lungs from Sepsis, SAILS). The study population was sepsis-related ALI patients. The primary outcome of the current study was the same as in the original trial, 60-day in-hospital mortality, defined as death before hospital discharge, censored 60 days after enrollment. Discrimination of APACHE III was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC) with its 95% CI. Hosmer-Lemeshow goodness-of-fit statistic was used to assess the calibration of APACHE III. The Brier score was reported to represent the overall performance of APACHE III in predicting outcome. Main results A total of 745 patients were included in the study, including 540 survivors and 205 non-survivors. Non-survivors were significantly older than survivors (59.71±16.17 vs 52.00±15.92 years, p<0.001). The primary causes of ALI were also different between survivors and non-survivors (p = 0.017). Survivors were more likely to have the cause of sepsis than non-survivors (21.2% vs. 15.1%). APACHE III score was higher in non-survivors than in survivors (106.72±27.30 vs. 88.42±26.86; p<0.001). Discrimination of APACHE III to predict mortality in ALI patients was moderate with an AUC of 0.68 (95% confidence interval: 0.64–0.73). Conclusion this study for the first time validated the discrimination of APACHE III in sepsis associated ALI patients. The result shows that APACHE III

  4. Sepsis and Acute Kidney Injury.

    PubMed

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-12-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

  5. Pre-existing Renal Disease Promotes Sepsis-induced Acute Kidney Injury and Worsens Sepsis Outcome via Multiple Pathways

    PubMed Central

    Doi, Kent; Leelahavanichkul, Asada; Hu, Xuzhen; Sidransky, Karen L.; Qin, Yan; Eisner, Christoph; Schnermann, Jurgen; Yuen, Peter S. T.; Star, Robert A.

    2008-01-01

    Patients with chronic kidney disease (CKD) are at significantly higher risk of death from sepsis, although the mechanism by which CKD increases mortality has not been investigated. We established a mouse two-stage model of pre-existing renal disease with subsequent sepsis by combining folic acid (FA) injection and sub-lethal cecal ligation and puncture (CLP) surgery. Mice were injected with FA then made septic (FA-CLP) or were injected with vehicle then made septic (Veh-CLP). FA-CLP mice had significantly higher mortality than Veh-CLP mice. Sepsis increased serum creatinine in the FA-CLP but not in the Veh-CLP group. FA-CLP mice had more severe septic shock and significantly increased vascular permeability, plasma vascular endothelial growth factor (VEGF), bacteremia, serum IL-10 and splenocyte apoptosis compared to Veh-CLP. To evaluate the contribution of vascular and immunological dysfunction, we treated FA-CLP mice with soluble Flt-1 and chloroquine. Mice treated with combination therapy showed a significant improvement in kidney injury, hemodynamics, and survival. In conclusion, the sequential FA-CLP model mimics human sepsis that is frequently complicated with pre-existing conditions including CKD. This animal model would be useful to evaluate preventative and therapeutic strategies under conditions more typical of human sepsis. PMID:18633340

  6. Angiotensin-converting enzyme insertion/deletion polymorphism is not associated with susceptibility and outcome in sepsis and acute respiratory distress syndrome.

    PubMed

    Villar, Jesús; Flores, Carlos; Pérez-Méndez, Lina; Maca-Meyer, Nicole; Espinosa, Elena; Blanco, Jesús; Sangüesa, Ruben; Muriel, Arturo; Tejera, Paula; Muros, Mercedes; Slutsky, Arthur S

    2008-03-01

    The insertion/deletion (I/D) of a 289 base pair Alu repeat sequence polymorphism in the angiotensin-converting enzyme gene (ACE) has been shown to predict susceptibility and outcome in the acute respiratory distress syndrome (ARDS). We hypothesized that the I/D polymorphism also confers susceptibility to sepsis and is a predisposing factor for morbidity and mortality of patients with severe sepsis. Case-control study including 212 consecutive patients fulfilling criteria for severe sepsis admitted to a Spanish network of postsurgical and critical care units, and 364 population-based controls. Susceptibility to severe sepsis was evaluated as primary outcome; mortality in severe sepsis, susceptibility to sepsis-induced ARDS, and mortality in sepsis-induced ARDS were examined as secondary outcomes. An additive model of inheritance in which patients were classified into three genotype groups (II, ID, and DD) was used for association testing. Genotype and allele frequencies of I/D were distributed similarly in all septic, ARDS, and non-ARDS patients and in population-based controls. ACE I/D polymorphism was not associated with severe sepsis susceptibility or mortality. The ACE I/D polymorphism was associated neither with sepsis-induced ARDS susceptibility (p=0.895) or mortality (p=0.950). These results remained nonsignificant when adjusted for other covariates using multiple logistic regression analysis or Kaplan-Meier estimates of 28-day survival. Our data do not support an association of the ACE gene I/D polymorphism with susceptibility or mortality in severe sepsis or with sepsis-induced ARDS in Spanish patients.

  7. Post-Acute Care Use and Hospital Readmission after Sepsis.

    PubMed

    Jones, Tiffanie K; Fuchs, Barry D; Small, Dylan S; Halpern, Scott D; Hanish, Asaf; Umscheid, Craig A; Baillie, Charles A; Kerlin, Meeta Prasad; Gaieski, David F; Mikkelsen, Mark E

    2015-06-01

    The epidemiology of post-acute care use and hospital readmission after sepsis remains largely unknown. To examine the rate of post-acute care use and hospital readmission after sepsis and to examine risk factors and outcomes for hospital readmissions after sepsis. In an observational cohort study conducted in an academic health care system (2010-2012), we compared post-acute care use at discharge and hospital readmission after 3,620 sepsis hospitalizations with 108,958 nonsepsis hospitalizations. We used three validated, claims-based approaches to identify sepsis and severe sepsis. Post-acute care use at discharge was more likely after sepsis, driven by skilled care facility placement (35.4% after sepsis vs. 15.8%; P < 0.001), with the highest rate observed after severe sepsis. Readmission rates at 7, 30, and 90 days were higher postsepsis (P < 0.001). Compared with nonsepsis hospitalizations (15.6% readmitted within 30 d), the increased readmission risk was present regardless of sepsis severity (27.3% after sepsis and 26.0-26.2% after severe sepsis). After controlling for presepsis characteristics, the readmission risk was found to be 1.51 times greater (95% CI, 1.38-1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more likely to result in death or transition to hospice care (6.1% vs. 13.3% after sepsis; P < 0.001). Independent risk factors associated with 30-day readmissions after sepsis hospitalizations included age, malignancy diagnosis, hospitalizations in the year prior to the index hospitalization, nonelective index admission type, one or more procedures during the index hospitalization, and low hemoglobin and high red cell distribution width at discharge. Post-acute care use and hospital readmissions were common after sepsis. The increased readmission risk after sepsis was observed regardless of sepsis severity and was associated with adverse readmission outcomes.

  8. Outcome of patients with acute kidney injury in severe sepsis and septic shock treated with early goal-directed therapy in an intensive care unit.

    PubMed

    Ahmed, Wasim; Memon, Javed I; Rehmani, Rifat; Al Juhaiman, Abdulmajeed

    2014-05-01

    Acute kidney injury (AKI) in the intensive care unit (ICU) is commonly caused by severe sepsis and septic shock. There is limited data regarding the incidence and outcomes of patients developing AKI treated with early goal-directed therapy (EGDT). Our aim was to observe the incidence and outcomes of patients with AKI in severe sepsis and septic shock, treated with EGDT as compared with historic controls. Study subjects included all adults admitted to the ICU with a diagnosis of severe sepsis and septic shock prior to (historic controls) and after introduction of EGDT (intervention group). Two groups were compared for incidence of AKI, length of ICU and hospital stay, incidence and requirement for renal replacement therapy, serum creatinine at discharge, maximum RIFLE (Risk, injury, failure, loss, end stage) in each group and 28-day mortality. Two groups were well matched for age, sex, (April 16, 2014) and acute physiological and chronic health evaluation (APACHE) II scores. We found no significant difference in the incidence of AKI (51% vs. 46%). There was no statistical difference in any of the above outcomes, including 28-day mortality in historic controls versus patients treated with EGDT. Septic AKI is a complex syndrome. The incidence and outcomes have not improved despite advances in sepsis management and EGDT. Very early detection of septic AKI and targeted therapies may improve outcomes.

  9. The Coagulopathy of Acute Sepsis

    PubMed Central

    Simmons, Jeff; Pittet, Jean-Francois

    2015-01-01

    Purpose of Review Sepsis, defined by the presence of infection and host inflammation, is a lethal clinical syndrome with an increasing mortality rate worldwide. In severe disease, the coagulation system becomes diffusely activated, with consumption of multiple clotting factors resulting in Disseminated Intravascular Coagulation (DIC). When present, DIC portends a higher mortality rate. Understanding the mechanisms that tie inflammation and diffuse thrombosis will allow therapeutic interventions to be developed. The Coagulopathy of Acute Sepsis is a dynamic process that is time and disease burden specific. Whole blood testing of coagulation may provide more clinically useful information than classical tests. Natural anticoagulants that regulate thrombosis are down regulated in sepsis. Patients may benefit from modulation of the coagulation system when systemic inflammation and hypercoagulopathy exist. Proper timing of anticoagulant therapy may ultimately lead to decreased incidence of multisystem organ dysfunction (MODS). Recent Findings The pathogenesis of coagulopathy in sepsis is driven by an up-regulation of procoagulant mechanisms and simultaneous down-regulation of natural anticoagulants. Inflammation caused by the invading organism is a natural host defense than cannot be eliminated during treatment. Successful strategies to prevent MODS center on stratifying patients at high risk for DIC and restoring the balance of inflammation and coagulation. Summary The prevention of DIC in septic patients is a key therapeutic target in preventing death from multisystem organ failure. Stratifying patients for therapy using thromboelastometry, specific markers for DIC, and composite scoring systems is an area of growing research. PMID:25590467

  10. Sepsis and Acute Kidney Injury

    PubMed Central

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-01-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically “Risk-Injury-Failure-Loss-Endstage” (RIFLE), “Acute Kidney Injury Netwok” (AKIN) and “The Kidney Disease/ Improving Global Outcomes” (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also “cell cycle arrest” molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated. PMID:27366441

  11. One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome: prospective follow-up of SAILS randomised trial.

    PubMed

    Dinglas, Victor D; Hopkins, Ramona O; Wozniak, Amy W; Hough, Catherine L; Morris, Peter E; Jackson, James C; Mendez-Tellez, Pedro A; Bienvenu, O Joseph; Ely, E Wesley; Colantuoni, Elizabeth; Needham, Dale M

    2016-05-01

    Prior randomised trials have evaluated statins in patients with sepsis and acute respiratory distress syndrome (ARDS), but there has been no comprehensive evaluation of long-term effects, despite potential neuromuscular and mental health adverse effects of these drugs. To evaluate the effect of rosuvastatin versus placebo on survival, physical function and performance, and mental health outcomes in patients with sepsis-associated ARDS. Prospective follow-up evaluation of the ARDS Clinical Trials Network Statins for Acutely Injured Lungs from Sepsis trial of rosuvastatin versus placebo in 568 mechanically ventilated patients with sepsis-associated ARDS, with blinded 6-month outcome assessment performed in the 272 eligible survivors for age-adjusted and sex-adjusted 36-Item Short Form Health Survey (SF-36) physical function and mental health domains, and in 84 eligible survivors for the 6 min walk test, along with secondary outcomes evaluations of survival, and additional patient-reported and performance-based measures at 6-month and 12-month follow-up. Over 1-year follow-up, there was no significant difference in cumulative survival in the rosuvastatin versus placebo groups (58% vs 61%; p=0.377), with survivors demonstrating substantial impairments in physical function and mental health. Rosuvastatin versus placebo had no effect (mean treatment effect (95% CI)) on SF-36 physical function (0 (-7 to 8), p=0.939) or mental health (-6 (-12 to 1) p=0.085) domains, 6 min walk distance (per cent predicted: 2 (-9 to 14), p=0.679) or the vast majority of secondary outcomes. Over 1-year follow-up, patients with sepsis-associated ARDS had high cumulative mortality, with survivors commonly experiencing impairments in physical functioning and performance, and mental health. Randomisation to rosuvastatin had no effect on these outcomes. NCT00979121 and NCT00719446. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

  12. Risk Factors and Outcomes in Patients With Hypernatremia and Sepsis.

    PubMed

    Ni, Hai-Bin; Hu, Xing-Xing; Huang, Xiao-Fei; Liu, Ke-Qin; Yu, Chen-Bin; Wang, Xiao-Meng; Ke, Lu

    2016-06-01

    Hypernatremia is an uncommon but important electrolyte abnormality in intensive care unit patients. Sepsis is one of the most common causes of intensive care unit admission, but few studies about the role of hypernatremia in sepsis has been published yet. In this study, we aimed to explore the risk factors for developing hypernatremia in patients with sepsis, and the prognosis of patients with sepsis with or without hypernatremia was also assessed. In this retrospective cohort study of 51 septic intensive care unit patients at a single center, we examined the risk factors for the development of hypernatremia and the association of hypernatremia with clinical outcomes using univariate and multivariable analyses. Clinical outcomes such as mortality and hospital duration of patients with or without hypernatremia were also compared. Acute Physiology and Chronic Health Evaluation II score (odds ratio = 1.15; 95% CI: 1.022-1.294) was found to be the only independent risk factor for hypernatremia in patients with sepsis. Moreover, patients developing hypernatremia during hospitalization showed significantly higher morbidity and mortality. Acute Physiology and Chronic Health Evaluation II score may be an independent risk factor for hypernatremia in patients with sepsis. Moreover, hypernatremia is strongly associated with worse outcome in sepsis. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  13. Scoring systems for the characterization of sepsis and associated outcomes

    PubMed Central

    McLymont, Natalie

    2016-01-01

    Sepsis is responsible for the utilisation of a significant proportion of healthcare resources and has high mortality rates. Early diagnosis and prompt interventions are associated with better outcomes but is impeded by a lack of diagnostic tools and the heterogeneous and enigmatic nature of sepsis. The recently updated definitions of sepsis have moved away from the centrality of inflammation and the systemic inflammatory response syndrome (SIRS) criteria which have been shown to be non-specific. Sepsis is now defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection”. The Quick (q) Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score is proposed as a surrogate for organ dysfunction and may act as a risk predictor for patients with known or suspected infection, as well as being a prompt for clinicians to consider the diagnosis of sepsis. Early warning scores (EWS) are track and trigger physiological monitoring systems that have become integrated within many healthcare systems for the detection of acutely deteriorating patients. The recent study by Churpek and colleagues sought to compare qSOFA to more established alerting criteria in a population of patients with presumed infection, and compared the ability to predict death or unplanned intensive care unit (ICU) admission. This perspective paper discusses recent advances in the diagnostic criteria for sepsis and how qSOFA may fit into the pre-existing models of acute care and sepsis quality improvement. PMID:28149888

  14. Scoring systems for the characterization of sepsis and associated outcomes.

    PubMed

    McLymont, Natalie; Glover, Guy W

    2016-12-01

    Sepsis is responsible for the utilisation of a significant proportion of healthcare resources and has high mortality rates. Early diagnosis and prompt interventions are associated with better outcomes but is impeded by a lack of diagnostic tools and the heterogeneous and enigmatic nature of sepsis. The recently updated definitions of sepsis have moved away from the centrality of inflammation and the systemic inflammatory response syndrome (SIRS) criteria which have been shown to be non-specific. Sepsis is now defined as a "life-threatening organ dysfunction caused by a dysregulated host response to infection". The Quick (q) Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score is proposed as a surrogate for organ dysfunction and may act as a risk predictor for patients with known or suspected infection, as well as being a prompt for clinicians to consider the diagnosis of sepsis. Early warning scores (EWS) are track and trigger physiological monitoring systems that have become integrated within many healthcare systems for the detection of acutely deteriorating patients. The recent study by Churpek and colleagues sought to compare qSOFA to more established alerting criteria in a population of patients with presumed infection, and compared the ability to predict death or unplanned intensive care unit (ICU) admission. This perspective paper discusses recent advances in the diagnostic criteria for sepsis and how qSOFA may fit into the pre-existing models of acute care and sepsis quality improvement.

  15. Fluid strategies and outcomes in patients with acute respiratory distress syndrome, systemic inflammatory response syndrome and sepsis: a protocol for a systematic review and meta-analysis.

    PubMed

    Silversides, Jonathan A; Ferguson, Andrew J; McAuley, Daniel F; Blackwood, Bronagh; Marshall, John C; Fan, Eddy

    2015-11-12

    Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding the relationship between fluid administration or balance and clinically important patient outcomes in critical illness. We will search Medline, EMBASE, the Cochrane Central Register of Controlled Trials from 1980 to the present and key conference proceedings from 2009 to the present. We will include studies of critically ill adults and children with acute respiratory distress syndrome (ARDS), sepsis and systemic inflammatory response syndrome (SIRS). We will include randomised controlled trials comparing two or more fluid regimens of different volumes of fluid and observational studies reporting the relationship between volume of fluid administered or fluid balance and outcomes including mortality, lengths of intensive care unit and hospital stay and organ dysfunction. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. We will conduct a narrative and/or meta-analysis as appropriate. While fluid management has been extensively studied and discussed in the critical care literature, no systematic review has attempted to summarise the evidence for post-resuscitation fluid strategies in critical illness. Results of the proposed systematic review will inform practice and the design of future clinical trials. PROSPERO CRD42013005608. ( http://www.crd.york.ac.uk/PROSPERO/ ).

  16. Functional outcomes of general medical patients with severe sepsis.

    PubMed

    Odden, Andrew J; Rohde, Jeffrey M; Bonham, Catherine; Kuhn, Latoya; Malani, Preeti N; Chen, Lena M; Flanders, Scott A; Iwashyna, Theodore J

    2013-12-12

    Severe sepsis is a common cause for admission to the general medical ward. Previous work has demonstrated substantial new long-term disability in patients with severe sepsis, but the short-term functional outcomes of patients admitted to the general medical floor -- where the majority of severe sepsis is treated -- are largely unknown. A retrospective cohort study was performed of patients initially admitted to non-ICU medical wards at a tertiary care academic medical center. Severe sepsis was confirmed by three physician reviewers, using the International Consensus Conference definition of sepsis. Baseline functional status, disposition location, and receipt of post-acute skilled care were recorded using a structured abstraction instrument. 3,146 discharges had severe sepsis by coding algorithm; from a random sample of 111 patients, 64 had the diagnosis of severe sepsis confirmed by reviewers. The mean age of the 64 patients was 63.5 years +/- 18.0. Prior to admission, 80% of patients lived at home and 50.8% of patients were functionally independent. Inpatient mortality was 12.5% and 37.5% of patients were discharged to a nursing facility. Of all patients in the cohort, 50.0% were discharged home, and 66.7% of patients who were functionally independent at baseline were discharged to home. New physical debility is a common feature of severe sepsis in patients initially cared for on the general medical floor. Debility occurs even in those with good baseline physical function. Interventions to improve the poor functional outcomes of this population are urgently needed.

  17. Sepsis

    PubMed Central

    Karnatovskaia, Lioudmila V.; Festic, Emir

    2012-01-01

    Sepsis represents a major challenge in medicine. It begins as a systemic response to infection that can affect virtually any organ system, including the central and peripheral nervous systems. Akin to management of stroke, early recognition and treatment of sepsis are just as crucial to a successful outcome. Sepsis can precipitate myasthenic crisis and lead to encephalopathy and critical illness neuropathy. Stroke and traumatic brain injury can predispose a patient to develop sepsis, whereas Guillain-Barré syndrome is similarly not uncommon following infection. This review article will first describe the essential principles of sepsis recognition, pathophysiology, and management and will then briefly cover the neurologic aspects associated with sepsis. Vigilant awareness of the clinical features of sepsis and timeliness of intervention can help clinicians prevent progression of this disease to a multisystem organ failure, which can be difficult to reverse even after the original source of infection is under control. PMID:23983879

  18. Culture-Negative Severe Sepsis: Nationwide Trends and Outcomes.

    PubMed

    Gupta, Shipra; Sakhuja, Ankit; Kumar, Gagan; McGrath, Eric; Nanchal, Rahul S; Kashani, Kianoush B

    2016-12-01

    Although 28% to 49% of severe sepsis hospitalizations have been described as being "culture negative," there are very limited data on the epidemiology and outcomes of those with culture-negative severe sepsis (CNSS). The objectives of this study were to investigate the proportion and trends of CNSS and its association with mortality. Using the Nationwide Inpatient Sample (NIS) database from 2000 to 2010, we identified adults hospitalized with severe sepsis. Those without any specific organism codes were identified as "with CNSS." We examined the proportion of CNSS hospitalizations and rates of mortality associated with it. We also assessed the independent effect of CNSS on mortality. Of 6,843,279 admissions of patients with severe sepsis, 3,226,406 (47.1%) had culture-negative results. The age-adjusted proportion of CNSS increased from 33.9% in 2000 to 43.5% in 2010 (P < .001). Those with CNSS had more comorbidities, acute organ dysfunction (respiratory, cardiac, hepatic, and renal dysfunction), and in-hospital mortality (34.6% vs 22.7%; P < .001), although acute kidney injury requiring dialysis was less frequent (5.3% vs 6.1%; P < .001). CNSS was an independent predictor of mortality in those with severe sepsis (OR, 1.75; 95% CI, 1.72-1.77). CNSS among hospitalized patients is common, and its proportion is on the rise. CNSS is associated with greater acute organ dysfunction and mortality. Having CNSS is an independent predictor of death. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Sepsis progression and outcome: a dynamical model

    PubMed Central

    Zuev, Sergey M; Kingsmore, Stephen F; Gessler, Damian DG

    2006-01-01

    Background Sepsis (bloodstream infection) is the leading cause of death in non-surgical intensive care units. It is diagnosed in 750,000 US patients per annum, and has high mortality. Current understanding of sepsis is predominately observational and correlational, with only a partial and incomplete understanding of the physiological dynamics underlying the syndrome. There exists a need for dynamical models of sepsis progression, based upon basic physiologic principles, which could eventually guide hourly treatment decisions. Results We present an initial mathematical model of sepsis, based on metabolic rate theory that links basic vascular and immunological dynamics. The model includes the rate of vascular circulation, a surrogate for the metabolic rate that is mechanistically associated with disease progression. We use the mass-specific rate of blood circulation (SRBC), a correlate of the body mass index, to build a differential equation model of circulation, infection, organ damage, and recovery. This introduces a vascular component into an infectious disease model that describes the interaction between a pathogen and the adaptive immune system. Conclusion The model predicts that deviations from normal SRBC correlate with disease progression and adverse outcome. We compare the predictions with population mortality data from cardiovascular disease and cancer and show that deviations from normal SRBC correlate with higher mortality rates. PMID:16480490

  20. Outcomes of whole-body computed tomography in spinal cord-injured patients with sepsis.

    PubMed

    Ahmed, W A; de Heredia, L L; Hughes, R J; Belci, M; Meagher, T M

    2014-07-01

    Retrospective case series. To evaluate the efficacy of body computed tomography (CT) in spinal cord injury (SCI) patients with sepsis. Specialist acute care and rehabilitation SCI centre in United Kingdom. Patients with SCI and suspected or known sepsis, who had CT of the chest, abdomen and pelvis, over a 4-year period, were identified. Only patients who fulfilled the definition of sepsis or severe sepsis were included. Their medical notes and CT scans were reviewed and clinical outcomes and radiological findings recorded. Twenty-two patients with sepsis were identified including seven categorised as having severe sepsis. A specific radiological diagnosis was found in three patients (14%) and non-specific findings were found in 15 patients (68%). Although in the majority of cases, the findings were non-specific, a small number of patients had significant pathology identified by CT, which influenced their management significantly.

  1. Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

    PubMed

    Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

    2016-12-01

    The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

  2. The immune system's role in sepsis progression, resolution, and long-term outcome.

    PubMed

    Delano, Matthew J; Ward, Peter A

    2016-11-01

    Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after "recovery" from acute events. As so many sepsis survivors succumb later to persistent, recurrent, nosocomial, and secondary infections, many investigators have turned their attention to the long-term sepsis-induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis-associated immune cell defects correlate with long-term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long-term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long-term sepsis mortality.

  3. Impact of Sepsis Classification and Multidrug-Resistance Status on Outcome Among Patients Treated With Appropriate Therapy.

    PubMed

    Burnham, Jason P; Lane, Michael A; Kollef, Marin H

    2015-08-01

    To assess the impact of sepsis classification and multidrug-resistance status on outcome in patients receiving appropriate initial antibiotic therapy. A retrospective cohort study. Barnes-Jewish Hospital, a 1,250-bed teaching hospital. Individuals with Enterobacteriaceae sepsis, severe sepsis, and septic shock who received appropriate initial antimicrobial therapy between June 2009 and December 2013. Clinical outcomes were compared according to multidrug-resistance status, sepsis classification, demographics, severity of illness, comorbidities, and antimicrobial treatment. We identified 510 patients with Enterobacteriaceae bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients (13.1%) were nonsurvivors. Mortality increased significantly with increasing severity of sepsis (3.5%, 9.9%, and 28.6%, for sepsis, severe sepsis, and septic shock, respectively; p < 0.05). Time to antimicrobial therapy was not significantly associated with outcome. Acute Physiology and Chronic Health Evaluation II was more predictive of mortality than age-adjusted Charlson comorbidity index. Multidrug-resistance status did not result in excess mortality. Length of ICU and hospital stay increased with more severe sepsis. In multivariate logistic regression analysis, African-American race, sepsis severity, Acute Physiology and Chronic Health Evaluation II score, solid-organ cancer, cirrhosis, and transfer from an outside hospital were all predictors of mortality. Our results support sepsis severity, but not multidrug-resistance status as being an important predictor of death when all patients receive appropriate initial antibiotic therapy. Future sepsis trials should attempt to provide appropriate antimicrobial therapy and take sepsis severity into careful account when determining outcomes.

  4. Rosuvastatin for sepsis-associated acute respiratory distress syndrome.

    PubMed

    Truwit, Jonathon D; Bernard, Gordon R; Steingrub, Jay; Matthay, Michael A; Liu, Kathleen D; Albertson, Timothy E; Brower, Roy G; Shanholtz, Carl; Rock, Peter; Douglas, Ivor S; deBoisblanc, Bennett P; Hough, Catherine L; Hite, R Duncan; Thompson, B Taylor

    2014-06-05

    In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14. The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung

  5. TRPV1 and SP: key elements for sepsis outcome?

    PubMed Central

    Bodkin, Jennifer Victoria; Fernandes, Elizabeth Soares

    2013-01-01

    Sensory neurons play important roles in many disorders, including inflammatory diseases, such as sepsis. Sepsis is a potentially lethal systemic inflammatory reaction to a local bacterial infection, affecting thousands of patients annually. Although associated with a high mortality rate, sepsis outcome depends on the severity of systemic inflammation, which can be directly influenced by several factors, including the immune response of the patient. Currently, there is a lack of effective drugs to treat sepsis, and thus there is a need to develop new drugs to improve sepsis outcome. Several mediators involved in the formation of sepsis have now been identified, but the mechanisms underlying the pathology remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) receptor and the neuropeptide substance P (SP) have recently been demonstrated as important targets for sepsis and are located on sensory neurones and non-neuronal cells. Herein, we highlight and review the importance of sensory neurones for the modulation of sepsis, with specific focus on recent findings relating to TRPV1 and SP, with their distinct abilities to alter the transition from local to systemic inflammation and also modify the overall sepsis outcome. We also emphasize the protective role of TRPV1 in this context. LINKED ARTICLES This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7 PMID:23145480

  6. Chronic kidney disease-induced HMGB1 elevation worsens sepsis and sepsis-induced acute kidney injury

    PubMed Central

    Leelahavanichkul, Asada; Huang, Yuning; Hu, Xuzhen; Zhou, Hua; Tsuji, Takayuki; Chen, Richard; Kopp, Jeffrey B.; Schnermann, Jürgen; Yuen, Peter S.T.; Star, Robert A.

    2012-01-01

    We previously showed that kidney dysfunction/interstitial fibrosis by folate predisposes mice to sepsis mortality (normal/sepsis: 15%; folate/sepsis: 90%); agents that increased survival in normal septic mice were ineffective in the two-stage model. We used a recently characterized 5/6 nephrectomy (Nx) mouse model of progressive chronic kidney disease (CKD) to study how CKD impacts sepsis and acute kidney injury (AKI) induced by cecal ligation-puncture (CLP). CKD intensified sepsis severity (by kidney and liver injury, cytokines, and spleen apoptosis). Accumulation of HMGB1, VEGF, TNF-α, IL-6, or IL-10 was increased in CKD or sepsis alone and to a greater extent in CKD-sepsis, and only part of this effect could be explained by decreased renal clearance. Surprisingly, we found splenic apoptosis in CKD, even in the absence of sepsis. Although sFLT-1 effectively treated sepsis, it was ineffective against CKD-sepsis. Conversely, a single dose of HMGB1-neutralizing antiserum, administered 6h after sepsis alone was ineffective; however, CKD/sepsis was attenuated by anti-HMGB1. Splenectomy transiently decreased circulating HMGB1 levels, which reversed the effectiveness of anti-HMGB1 treatment on CKD/sepsis. We conclude that progressive CKD increases sepsis severity, in part, by reducing renal clearance of cytokines; CKD-induced splenic apoptosis and HMGB1 could be important common mediators for both CKD and sepsis. PMID:21832986

  7. Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

    PubMed Central

    Weiss, Scott L.; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C.; Salloo, Asma; Singhi, Sunit C.; Erickson, Simon; Roy, Jason A.; Bush, Jenny L.; Nadkarni, Vinay M.; Thomas, Neal J.

    2015-01-01

    Rationale: Limited data exist about the international burden of severe sepsis in critically ill children. Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. Methods: A point prevalence study was conducted on 5 days throughout 2013–2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Measurements and Main Results: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6–8.9%). The patients’ median age was 3.0 (interquartile range [IQR], 0.7–11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0–25), and vasoactive-free days were 23 (IQR, 12–28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5–10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,437 patients per group. Conclusions: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted. PMID:25734408

  8. Low triiodothyronine syndrome: a prognostic marker for outcome in sepsis?

    PubMed

    Meyer, Stefanie; Schuetz, Philipp; Wieland, Melanie; Nusbaumer, Charly; Mueller, Beat; Christ-Crain, Mirjam

    2011-04-01

    There is ongoing controversy as to whether hormonal changes of the euthyroid sick syndrome are predictors of poor outcome in sepsis and critical illness. In this prospective study, the prognostic accuracy of thyroid hormone levels in 103 critically ill adult patients on admission and during follow up in a medical intensive care unit (ICU) was assessed and was compared to clinical risk scores, namely, the acute physiology and chronic health evaluation and the simplified acute physiology score. Median T3 levels on admission to the ICU were lower in the 53 septic cases [0.9 nmol/l (IQR 0.6-1.1)] as compared with the 50 patients with a systemic inflammatory response syndrome [1.2 nmol/l (IQR 0.8-1.4), P < 0.001]. The lowest T3 levels were found in patients with severe sepsis [0.8 nmol/l (IQR 0.55-0.95)] and septic shock [0.8 nmol/l (IQR 0.6-1.0)]. There was no difference in T3 and free thyroxin (fT4) levels on admission in non-survivors compared with survivors overall and in subgroups of patients with SIRS and sepsis. During the follow up, fT4 levels decreased significantly in non-survivors, while they increased in survivors [fT4 difference -1.3 (IQR -2.5 to 0.2) vs. 0.8 (IQR -0.85 to 4.1), P = 0.003]. In addition, on the day of death, non-survivors had lower T3 and fT4 levels as compared with survivors (P = 0.04 and P = 0.02). T3 and fT4 levels on admission were not prognostic in this cohort of critically ill patients. A decrease in fT4 levels in the course of disease, however, may point to adverse outcome.

  9. Pulmonary vs Nonpulmonary Sepsis and Mortality in Acute Lung Injury

    PubMed Central

    Sevransky, Jonathan E.; Martin, Greg S.; Mendez-Tellez, Pedro; Shanholtz, Carl; Brower, Roy; Pronovost, Peter J.; Needham, Dale M.

    2010-01-01

    Background Acute lung injury (ALI) is a frequent complication of sepsis. It is unclear if a pulmonary vs nonpulmonary source of sepsis affects mortality in patients with sepsis-induced ALI. Methods Two hundred eighty-eight consecutive patients with sepsis-induced ALI from 14 ICUs at four hospitals in Baltimore,MDwere prospectively classified as having a pulmonary vs nonpulmonary source of sepsis. Multiple logistic regression was conducted to evaluate the independent association of a pulmonary vs nonpulmonary source of sepsis with inpatient mortality. Results In an unadjusted analysis, in-hospital mortality was lower for pulmonary vs nonpulmonary source of sepsis (42% vs 66%, p < 0.0001). Patients with pulmonary sepsis had lower acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, shorter ICU stays prior to the development of ALI, and higher lung injury scores. In the adjusted analysis, several factors were predictive of mortality: age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01 to 1.06), Charlson comorbidity index (OR, 1.15; 95% CI, 1.02 to 1.30), ICU length of stay prior to ALI diagnosis (OR, 1.19; 95% CI, 1.01 to 1.39), APACHE II score (OR, 1.07; 95% CI, 1.03 to 1.12), lung injury score (OR, 1.64; 95% CI, 1.11 to 2.43), SOFA score (OR, 1.15; 95% CI, 1.06 to 1.26), and cumulative fluid balance in the first 7 days after ALI diagnosis (OR, 1.06; 95% CI, 1.03 to 1.10). A pulmonary vs nonpulmonary source of sepsis was not independently associated with mortality (OR, 0.72; 95% CI, 0.38 to 1.35). Conclusions Although lower mortality was observed for ALI patients with a pulmonary vs nonpulmonary source of sepsis, this finding is likely due to a lower severity of illness in those with pulmonary sepsis. Pulmonary vs nonpulmonary source of sepsis was not independently predictive of mortality for patients with ALI. PMID:18641112

  10. Epidemiology of sepsis in Catalonia: analysis of incidence and outcomes in a European setting.

    PubMed

    Yébenes, Juan Carlos; Ruiz-Rodriguez, Juan Carlos; Ferrer, Ricard; Clèries, Montserrat; Bosch, Anna; Lorencio, Carol; Rodriguez, Alejandro; Nuvials, Xavier; Martin-Loeches, Ignacio; Artigas, Antoni

    2017-12-01

    Up-to-date identification of local trends in sepsis incidence and outcomes is of considerable public health importance. The aim of our study was to estimate annual incidence rates and in-hospital mortality trends for hospitalized patients with sepsis in a European setting, while avoiding selection bias in relation to different complexity hospitals. A large retrospective analysis of a 5-year period (2008-2012) was conducted of hospital discharge records obtained from the Catalan Health System (CatSalut) Minimum Basic Data Set for Acute-Care Hospitals (a mandatory population-based register of admissions to all public and private acute-care hospitals in Catalonia). Patients hospitalized with sepsis were detected on the basis of ICD-9-CM codes used to identify acute organ dysfunction and infectious processes. Of 4,761,726 discharges from all acute-care hospitals in Catalonia, 82,300 cases (1.72%) had sepsis diagnoses. Annual incidence was 212.7 per 100,000 inhabitants/year, rising from 167.2 in 2008 to 261.8 in 2012. Length of hospital stay fell from 18.4 to 15.3 days (p < .00001), representing a relative reduction of 17%. Hospital mortality fell from 23.7 to 19.7% (p < .0001), representing a relative reduction of 16.9%. These differences were confirmed in the multivariate analysis (adjusted for age group, sex, comorbidities, ICU admission, emergency admission, organ dysfunction, number of organ failures, sepsis source and bacteraemia). Sepsis incidence has risen in recent years, whereas mortality has fallen. Our findings confirm reports for other parts of the world, in the context of scarce administrative data on sepsis in Europe.

  11. Improving Outcomes in Patients With Sepsis.

    PubMed

    Armen, Scott B; Freer, Carol V; Showalter, John W; Crook, Tonya; Whitener, Cynthia J; West, Cheri; Terndrup, Thomas E; Grifasi, Marissa; DeFlitch, Christopher J; Hollenbeak, Christopher S

    2016-01-01

    Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. © The Author(s) 2014.

  12. Neonatal sepsis: progress towards improved outcomes.

    PubMed

    Shane, Andi L; Stoll, Barbara J

    2014-01-01

    Neonates are predisposed to infections during the perinatal period due to multiple exposures and a relatively compromised immune system. The burden of disease attributed to neonatal infections varies by geographic region and maternal and neonatal risk factors. Worldwide, it is estimated that more than 1.4 million neonatal deaths annually are the consequence of invasive infections. Risk factors for early-onset neonatal sepsis (EOS) include prematurity, immunologic immaturity, maternal Group B streptococcal colonization, prolonged rupture of membranes, and maternal intra-amniotic infection. Intrapartum antimicrobial prophylaxis administered to GBS-colonized women has reduced the burden of disease associated with early onset GBS invasive infections. Active surveillance has identified Gram-negative pathogens as an emerging etiology of early-onset invasive infections. Late-onset neonatal sepsis (LOS) attributable to Gram-positive organisms, including coagulase negative Staphylococci and Staphylococcus aureus, is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of late-onset sepsis, especially among infants who receive broad spectrum antimicrobial agents. Prophylactic fluconazole administration to very low birthweight (VLBW) neonates during the first 6 weeks of life reduces invasive candidiasis in neonatal intensive care units with high rates of fungal infection. Prevention of healthcare associated infections through antimicrobial stewardship, limited steroid use, early enteral feeding, limited use of invasive devices and standardization of catheter care practices, and meticulous hand hygiene are important and cost-effective strategies for reducing the burden of late-onset neonatal sepsis. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  13. [Extracorporeal treatment of acute kidney injury during sepsis].

    PubMed

    Nalesso, Federico; Brendolan, Alessandro; Zanella, Monica; Ronco, Claudio

    2012-01-01

    The clinical syndromes known as sepsis and septic shock are a frequent cause of morbidity and mortality in intensive care units. Acute kidney injury (AKI) according to the modern RIFLE criteria complicates sepsis and increases the mortality; it often requires the implementation of methods for extracorporeal blood purification and patient support. During sepsis AKI is an independent risk factor for mortality and increases the complexity and cost of patient care. Among the treatments for AKI, hemofiltration and its pulse high-volume variant are able to support all organs and boost an immune system compromised by systemic inflammation. Thanks to modern technology, they can also apply adsorption in order to remove complex molecules such as LPS from the bloodstream during sepsis due to gram-negative bacteria, preventing endothelial damage that can result in multiorgan dysfunction and failure. These treatments can be combined to obtain other treatments to remove more specifically inflammatory molecules such as during convection combined with plasma adsorption in CPFA. Moreover, the use of high-cutoff membranes allows the implementation of methods able to remove high-molecular-weight mediators of inflammation by diffusion. Given the wide range of available treatments, there is ongoing discussion about the timing, dose and efficacy of each, and more studies are necessary to clarify their role in the management of AKI during sepsis.

  14. Acute kidney injury in severe sepsis: pathophysiology, diagnosis, and treatment recommendations.

    PubMed

    Keir, Iain; Kellum, John A

    2015-01-01

    To review the unique pathophysiology of sepsis-induced acute kidney injury (AKI) and highlight the relevant aspects of the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury that may apply to veterinary patients. Electronic search of MEDLINE database. Sepsis-induced AKI is diagnosed in up to 47% of human ICU patients and is seen as a major public health concern associated with increased mortality and increased progression to chronic kidney disease (CKD). Consensus criteria for the definition and classification of AKI has allowed for accurate description of the epidemiology of patients with AKI. AKI develops from a complex relationship between the initial insult and activation of inflammation and coagulation. In contrast to the traditional view, clinical and experimental data dispute the role of renal ischemia-reperfusion in the development of sepsis-induced AKI. Renal tubular dysfunction with activation of the tubuloglomerular feedback mechanism appears to be a crucial contributor to sepsis-induced AKI. Furosemide and n-acetylcysteine (NAC) do not appear to be helpful in the treatment of AKI. Hydroxyethyl starches (HES), dopamine, and supraphysiological concentrations of chloride are harmful in patients with AKI. Community and hospital-acquired AKI is a significant factor affecting survival in critical ill patients. Sepsis-induced AKI occurs in 12% of dogs with abdominal sepsis and is an important contributor to mortality. Early detection of AKI in hospitalized patients currently offers the best opportunity to improve patient outcome. The use of urinary biomarkers to diagnose early AKI should be evaluated in critical care patients. Veterinary clinical trials comparing treatment choices with the development of AKI are needed to make evidence-based recommendations for the prevention and treatment of AKI. © Veterinary Emergency and Critical Care Society 2015.

  15. Scrub typhus with sepsis and acute respiratory distress syndrome.

    PubMed

    Kurup, Asok; Issac, Aneesh; Loh, Jin Phang; Lee, Too Bou; Chua, Robert; Bist, Pradeep; Chao, Chien-Chung; Lewis, Michael; Gubler, Duane J; Ching, Wei Mei; Ooi, Eng Eong; Sukumaran, Bindu

    2013-08-01

    Scrub typhus is a major infectious threat in the Asia-Pacific region. We report an unusual case of scrub typhus in a patient in Singapore who presented with sepsis and acute respiratory distress syndrome but lacked the pathognomonic eschar. The patient recovered after appropriate diagnosis and doxycycline treatment. Rickettsial diseases should be included in the differential diagnosis of febrile illnesses in regions where the diseases are endemic, and absence of eschar should not be the criterion used to rule out scrub typhus.

  16. Human Sepsis Eicosanoid and Proresolving Lipid Mediator Temporal Profiles: Correlations With Survival and Clinical Outcomes.

    PubMed

    Dalli, Jesmond; Colas, Romain A; Quintana, Carolina; Barragan-Bradford, Diana; Hurwitz, Shelley; Levy, Bruce D; Choi, Augustine M; Serhan, Charles N; Baron, Rebecca M

    2017-01-01

    To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of acute-inflammation, and correlate measurements with clinical outcomes. Herein, deidentified plasma was collected from sepsis patients (n = 22 subjects) within 48 hours of admission to the ICU and on days 3 and 7 thereafter and subjected to lipid mediator profiling. Brigham and Women's Hospital Medical Intensive Care Unit. Patients in the medical ICU with sepsis. In all patients, we identified more than 30 bioactive mediators and pathway markers in peripheral blood using established criteria for arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolomes. These included inflammation initiating mediators leukotriene B4 and prostaglandin E2 and pro-resolving mediators resolvin D1, resolvin D2, and protectin D1. In sepsis nonsurvivors, we found significantly higher inflammation-initiating mediators including prostaglandin F2α and leukotriene B4 and pro-resolving mediators, including resolvin E1, resolvin D5, and 17R-protectin D1 than was observed in surviving sepsis subjects. This signature was present at ICU admission and persisted for 7 days. Further analysis revealed increased respiratory failure in nonsurvivors. Higher inflammation-initiating mediators (including prostaglandin F2α) and select proresolving pathways were associated with the development of acute respiratory distress syndrome, whereas other traditional clinical indices were not predictive of acute respiratory distress syndrome development. These results provide peripheral blood lipid mediator profiles in sepsis that correlate with survival and acute respiratory distress syndrome development, thus suggesting plausible novel biomarkers and biologic targets for critical illness.

  17. Update on sepsis-associated acute kidney injury: emerging targeted therapies

    PubMed Central

    Doyle, James F; Forni, Lui G

    2016-01-01

    Sepsis-associated acute kidney injury (SA-AKI) is an independent predictor of increased mortality and morbidity. It is essential that further advances in the treatment of sepsis should prioritize targeted therapies in SA-AKI in order to improve these bleak outcomes. As yet, a unique therapy that effectively reduces the impact of acute kidney injury has not been demonstrated. However, the emergence of novel targeted therapies, perhaps in combination, has the possibility of significantly reducing the long-term sequelae of an episode of SA-AKI. In this review, we will focus on the shared etiology of these conditions and how this is managed with targeted therapy and finally the emerging novel therapies that may play an additional role to current treatment strategies. PMID:27853353

  18. Cannabinoid receptor 2 protects against acute experimental sepsis in mice.

    PubMed

    Gui, Huan; Sun, Yang; Luo, Zhu-Min; Su, Ding-Feng; Dai, Sheng-Ming; Liu, Xia

    2013-01-01

    The systemic inflammatory response syndrome can be self-limited or can progress to severe sepsis and septic shock. Despite significant advances in the understanding of the molecular and cellular mechanisms of septic shock, it is still one of the most frequent and serious problems confronting clinicians in the treatments. And the effects of cannabinoid receptor 2 (CB2R) on the sepsis still remain undefined. The present study was aimed to explore the role and mechanism of CB2R in acute sepsis model of mice. Here, we found that mice were more vulnerable for lipopolysaccharide- (LPS-) induced death and inflammation after CB2R deletion (CB2R(-/-)). CB2R agonist, GW405833, could significantly extend the survival rate and decrease serum proinflammatory cytokines in LPS-treated mice. GW405833 dose-dependently inhibits proinflammatory cytokines release in splenocytes and peritoneal macrophages as well as splenocytes proliferation, and these effects were partly abolished in CB2R(-/-) splenocytes but completely abolished in CB2R(-/-) peritoneal macrophages. Further studies showed that GW405833 inhibits LPS-induced phosphorylation of ERK1/2 and STAT3 and blocks I κ B α degradation and NF- κB p65 nuclear translocation in macrophages. All data together showed that CB2R provides a protection and is a potential therapeutic target for the sepsis.

  19. Sepsis

    MedlinePlus

    ... Sepsis syndrome; Systemic inflammatory response syndrome; SIRS; Septic shock ... In sepsis, blood pressure drops, resulting in shock . Major organs ... system may stop working properly because of poor blood flow. ...

  20. Outcomes and Resource Use of Sepsis-associated Stays by Presence on Admission, Severity, and Hospital Type.

    PubMed

    Jones, Stephen L; Ashton, Carol M; Kiehne, Lisa B; Nicolas, Juan C; Rose, Alexis L; Shirkey, Beverly A; Masud, Faisal; Wray, Nelda P

    2016-03-01

    To establish a baseline for the incidence of sepsis by severity and presence on admission in acute care hospital settings before implementation of a broad sepsis screening and response initiative. A retrospective cohort study using hospital discharge abstracts of 5672 patients, aged 18 years and above, with sepsis-associated stays between February 2012 and January 2013 at an academic medical center and 5 community hospitals in Texas. Sepsis was present on admission in almost 85% of cases and acquired in-hospital in the remainder. The overall inpatient death rate was 17.2%, but was higher in hospital-acquired sepsis (38.6%, medical; 29.2%, surgical) and Stages 2 (17.6%) and 3 (36.4%) compared with Stage 1 (5.9%). Patients treated at the academic medical center had a higher death rate (22.5% vs. 15.1%, P<0.001) and were more costly ($68,050±184,541 vs. $19,498±31,506, P<0.001) versus community hospitals. Greater emphasis is needed on public awareness of sepsis and the detection of sepsis in the prehospitalization and early hospitalization period. Hospital characteristics and case mix should be accounted for in cross-hospital comparisons of sepsis outcomes and costs.

  1. Emerging Therapeutic Targets of Sepsis-Associated Acute Kidney Injury

    PubMed Central

    Swaminathan, Sundararaman; Rosner, Mitchell H.; Okusa, Mark D.

    2015-01-01

    Sepsis-associated acute kidney injury (SA-AKI) is linked to high morbidity and mortality. Thus far singular approaches to target specific pathways known to contribute to the pathogenesis of SA-AKI have failed. Because of the complexity of the pathogenesis of SA-AKI, a reassessment necessitates integrative approaches to therapeutics of SA-AKI that include general supportive therapies such as the use of vasopressors, fluids, antimicrobial and target specific and time dependent therapeutics. There has been recent progress in our understanding of the pathogenesis and treatment of SA-AKI including temporal nature of pro- and anti-inflammatory processes. In this review, we will discuss the clinical and experimental basis of emerging therapeutic approaches that focus on targeting early proinflammatory and late anti-inflammatory processes as well as therapeutics that may enhance cellular survival and recovery. Lastly we include ongoing clinical trials in sepsis. PMID:25795498

  2. [Blood concentrations of lactate, C-reactive protein, and creatinine as early indicators of severity and outcome of sepsis].

    PubMed

    Mikić, Dragan; Arsić-Komljenović, Gordana; Nozić, Darko; Cućuz, Milica; Dimitrijević, Radmila; Vukadinov, Jovan

    2010-01-01

    Since the outcome in septic patients can significantly be improved if the appropriate therapy is introduced timely early, the early diagnosis of sepsis and its complications is essential. The aim of this study was to compare mean values of the initial blood concentrations of lactate, C-reactive protein and creatinine and the severity of illness and the outcome of sepsis. A total of 30 septic patients were included in the study. The diagnosis of sepsis and its complications was made according to consensus criteria. The severity of illness was scored by an acute physiology, age and chronic health evaluation septic score. The patients were subdivided into different groups, those with sepsis, severe sepsis or septic shock, those with or without multiple organ dysfunction syndrome, and survivors and nonsurvivors. The differences in mean values of lactate levels among all studied groups were significantly high, whereas the level of C-reactive protein were significantly higher only in the non-survivors compared to the survivors (p < 0.05). The concentrations of creatinine were significantly higher in the patients with septic shock compared to the patients with sepsis, and in the patients with multiple organ dysfunction syndrome and the non-survivors compared to the corresponding groups (p < 0.05). The septic score clearly discriminated patients with different severity of sepsis, development of multiple organ dysfunction syndrome and survival and positively correlated with the concentrations of lactate, C-reactive protein and creatinine (the best correlation ranks were with lactate levels, p < 0.001). Our results suggest that lactate level is a better parameter of illness severity and outcome of sepsis than levels of C-reactive protein and creatinine. When compared to the above parameters, the septic score determined on the day of admission to hospital is a much better criterion to classify patients into groups with different severity of sepsis, with and without multiple

  3. The epidemiology of acute respiratory distress syndrome in patients presenting to the emergency department with severe sepsis.

    PubMed

    Mikkelsen, Mark E; Shah, Chirag V; Meyer, Nuala J; Gaieski, David F; Lyon, Sarah; Miltiades, Andrea N; Goyal, Munish; Fuchs, Barry D; Bellamy, Scarlett L; Christie, Jason D

    2013-11-01

    Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis, and sepsis-associated ARDS is associated with significant morbidity and mortality. To date, no study has directly examined the epidemiology of ARDS in severe sepsis from the earliest presentation to the health care system, the emergency department (ED). This was a single-center retrospective, observational cohort study of 778 adults with severe sepsis presenting to the ED. The primary outcome was the development of ARDS requiring mechanical ventilation during the first 5 hospital days. Acute respiratory distress syndrome was defined using the Berlin definition. We used multivariable logistic regression to identify risk factors associated independently with ARDS development. The incidence of ARDS was 6.2% (48/778 patients) in the entire cohort. Acute respiratory distress syndrome development varied across the continuum of care: 0.9% of patients fulfilled criteria for ARDS in the ED, 1.4% admitted to the ward developed ARDS, and 8.9% admitted to the intensive care unit developed ARDS. Acute respiratory distress syndrome developed a median of 1 day after admission and was associated with a 4-fold higher risk of in-hospital mortality (14% vs. 60%, P < 0.001). Independent risk factors associated with increased risk of ARDS development included intermediate (2-3.9 mmol/L) (P = 0.04) and high (≥4) serum lactate levels (P = 0.008), Lung Injury Prediction score (P < 0.001), and microbiologically proven infection (P = 0.01). In patients presenting to the ED with severe sepsis, the rate of sepsis-associated ARDS development varied across the continuum of care. Acute respiratory distress syndrome developed rapidly and was associated with significant mortality. Elevated serum lactate levels in the ED and a recently validated clinical prediction score were independently associated with the development of ARDS in severe sepsis.

  4. Toll-like Receptor 1 Polymorphisms Affect Innate Immune Responses and Outcomes in Sepsis

    PubMed Central

    Wurfel, Mark M.; Gordon, Anthony C.; Holden, Tarah D.; Radella, Frank; Strout, Jeanna; Kajikawa, Osamu; Ruzinski, John T.; Rona, Gail; Black, R. Anthony; Stratton, Seth; Jarvik, Gail P.; Hajjar, Adeline M.; Nickerson, Deborah A.; Rieder, Mark; Sevransky, Jonathan; Maloney, James P.; Moss, Marc; Martin, Greg; Shanholtz, Carl; Garcia, Joe G. N.; Gao, Li; Brower, Roy; Barnes, Kathleen C.; Walley, Keith R.; Russell, James A.; Martin, Thomas R.

    2008-01-01

    Rationale: Polymorphisms affecting Toll-like receptor (TLR)–mediated responses could predispose to excessive inflammation during an infection and contribute to an increased risk for poor outcomes in patients with sepsis. Objectives: To identify hypermorphic polymorphisms causing elevated TLR-mediated innate immune cytokine and chemokine responses and to test whether these polymorphisms are associated with increased susceptibility to death, organ dysfunction, and infections in patients with sepsis. Methods: We screened single-nucleotide polymorphisms (SNPs) in 43 TLR-related genes to identify variants affecting TLR-mediated inflammatory responses in blood from healthy volunteers ex vivo. The SNP associated most strongly with hypermorphic responses was tested for associations with death, organ dysfunction, and type of infection in two studies: a nested case–control study in a cohort of intensive care unit patients with sepsis, and a case–control study using patients with sepsis, patients with sepsis-related acute lung injury, and healthy control subjects. Measurements and Main Results: The SNP demonstrating the most hypermorphic effect was the G allele of TLR1−7202A/G (rs5743551), which associated with elevated TLR1-mediated cytokine production (P < 2 × 10−20). TLR1−7202G marked a coding SNP that causes higher TLR1-induced NF-κB activation and higher cell surface TLR1 expression. In the cohort of patients with sepsis TLR1−7202G predicted worse organ dysfunction and death (odds ratio, 1.82; 95% confidence interval, 1.07–3.09). In the case-control study TLR1−7202G was associated with sepsis-related acute lung injury (odds ratio, 3.40; 95% confidence interval, 1.59–7.27). TLR1−7202G also associated with a higher prevalence of gram-positive cultures in both clinical studies. Conclusions: Hypermorphic genetic variation in TLR1 is associated with increased susceptibility to organ dysfunction, death, and gram-positive infection in sepsis. PMID

  5. Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome

    PubMed Central

    Fialkow, Léa; Fochesatto Filho, Luciano; Bozzetti, Mary C; Milani, Adriana R; Rodrigues Filho, Edison M; Ladniuk, Roberta M; Pierozan, Paula; de Moura, Rafaela M; Prolla, João C; Vachon, Eric; Downey, Gregory P

    2006-01-01

    Introduction Apoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS. Methods A prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys. Results In medical patients, the mean percentage of neutrophil apoptosis (± standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% ± 3.3%; n = 9) when compared with uncomplicated sepsis (57% ± 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% ± 3.0%; n = 11; p < 0.001) and healthy controls (69% ± 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% ± 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% ± 3.6%; n = 11; p < 0.001). Conclusion In medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of

  6. The Prehospital Sepsis Project: out-of-hospital physiologic predictors of sepsis outcomes.

    PubMed

    Baez, Amado Alejandro; Hanudel, Priscilla; Wilcox, Susan Renee

    2013-12-01

    Severe sepsis and septic shock are common, expensive and often fatal medical problems. The care of the critically sick and injured often begins in the prehospital setting; there is limited data available related to predictors and interventions specific to sepsis in the prehospital arena. The objective of this study was to assess the predictive effect of physiologic elements commonly reported in the out-of-hospital setting in the outcomes of patients transported with sepsis. This was a cross-sectional descriptive study. Data from the years 2004-2006 were collected. Adult cases (≥18 years of age) transported by Emergency Medical Services to a major academic center with the diagnosis of sepsis as defined by ICD-9-CM diagnostic codes were included. Descriptive statistics and standard deviations were used to present group characteristics. Chi-square was used for statistical significance and odds ratio (OR) to assess strength of association. Statistical significance was set at the .05 level. Physiologic variables studied included mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR) and shock index (SI). Sixty-three (63) patients were included. Outcome variables included a mean hospital length of stay (HLOS) of 13.75 days (SD = 9.97), mean ventilator days of 4.93 (SD = 7.87), in-hospital mortality of 22 out of 63 (34.9%), and mean intensive care unit length-of-stay (ICU-LOS) of 7.02 days (SD = 7.98). Although SI and RR were found to predict intensive care unit (ICU) admissions, [OR 5.96 (CI, 1.49-25.78; P = .003) and OR 4.81 (CI, 1.16-21.01; P = .0116), respectively] none of the studied variables were found to predict mortality (MAP <65 mmHg: P = .39; HR >90: P = .60; RR >20 P = .11; SI >0.7 P = .35). This study demonstrated that the out-of-hospital shock index and respiratory rate have high predictability for ICU admission. Further studies should include the development of an out-of-hospital sepsis score.

  7. Interaction Effects of Acute Kidney Injury, Acute Respiratory Failure, and Sepsis on 30-Day Postoperative Mortality in Patients Undergoing High-Risk Intraabdominal General Surgical Procedures.

    PubMed

    Kim, Minjae; Brady, Joanne E; Li, Guohua

    2015-12-01

    Acute kidney injury (AKI), acute respiratory failure, and sepsis are distinct but related pathophysiologic processes. We hypothesized that these 3 processes may interact to synergistically increase the risk of short-term perioperative mortality in patients undergoing high-risk intraabdominal general surgery procedures. We performed a retrospective, observational cohort study of data (2005-2011) from the American College of Surgeons-National Surgical Quality Improvement Program, a high-quality surgical outcomes data set. High-risk procedures were those with a risk of AKI, acute respiratory failure, or sepsis greater than the average risk in all intraabdominal general surgery procedures. The effects of AKI, acute respiratory failure, and sepsis on 30-day mortality were assessed using a Cox proportional hazards model. Additive interactions were assessed with the relative excess risk due to interaction. Of 217,994 patients, AKI, acute respiratory failure, and sepsis developed in 1.3%, 3.7%, and 6.8%, respectively. The 30-day mortality risk with sepsis, acute respiratory failure, and AKI were 11.4%, 24.1%, and 25.1%, respectively, compared with 0.85% without these complications. The adjusted hazard ratios and 95% confidence intervals for a single complication (versus no complication) on mortality were 7.24 (6.46-8.11), 10.8 (8.56-13.6), and 14.2 (12.8-15.7) for sepsis, AKI, and acute respiratory failure, respectively. For 2 complications, the adjusted hazard ratios were 30.8 (28.0-33.9), 42.6 (34.3-52.9), and 65.2 (53.9-78.8) for acute respiratory failure/sepsis, AKI/sepsis, and acute respiratory failure/AKI, respectively. Finally, the adjusted hazard ratio for all 3 complications was 105 (92.8-118). Positive additive interactions, indicating synergism, were found for each combination of 2 complications. The relative excess risk due to interaction for all 3 complications was not statistically significant. In high-risk general surgery patients, the development of AKI

  8. Sepsis-induced acute kidney injury in patients with cirrhosis.

    PubMed

    Angeli, Paolo; Tonon, Marta; Pilutti, Chiara; Morando, Filippo; Piano, Salvatore

    2016-01-01

    Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment.

  9. Long-term Outcomes Following Development of New-Onset Atrial Fibrillation During Sepsis

    PubMed Central

    Walkey, Allan J.; Hammill, Bradley G.; Curtis, Lesley H.; Benjamin, Emelia J.

    2014-01-01

    BACKGROUND: New-onset atrial fibrillation (AF) is associated with adverse outcomes during a sepsis hospitalization; however, long-term outcomes following hospitalization with sepsis-associated new-onset AF are unclear. METHODS: We used a Medicare 5% sample to identify patients who survived hospitalization with sepsis between 1999 and 2010. AF status was defined as no AF, prior AF, or new-onset AF based on AF claims during and prior to a sepsis hospitalization. We used competing risk models to determine 5-year risks of AF occurrence, heart failure, ischemic stroke, and mortality after the sepsis hospitalization, according to AF status during the sepsis admission. RESULTS: We identified 138,722 sepsis survivors, of whom 95,536 (69%) had no AF during sepsis, 33,646 (24%) had prior AF, and 9,540 (7%) had new-onset AF during sepsis. AF occurrence following sepsis hospitalization was more common among patients with new-onset AF during sepsis (54.9%) than in patients with no AF during sepsis (15.5%). Compared with patients with no AF during sepsis, those with new-onset AF during sepsis had greater 5-year risks of hospitalization for heart failure (11.2% vs 8.2%; multivariable-adjusted hazard ratio [HR], 1.25; 95% CI, 1.16-1.34), ischemic stroke (5.3% vs 4.7%; HR, 1.22; 95% CI, 1.10-1.36), and death (74.8% vs 72.1%; HR, 1.04; 95% CI,1.01-1.07). CONCLUSIONS: Most sepsis survivors with new-onset AF during sepsis have AF occur after discharge from the sepsis hospitalization and have increased long-term risks of heart failure, ischemic stroke, and death. Our findings may have implications for posthospitalization surveillance of patients with new-onset AF during a sepsis hospitalization. PMID:24723004

  10. Acute abdomen. Outcomes.

    PubMed

    Madonna, M B; Boswell, W C; Arensman, R M

    1997-05-01

    The outcome for children with common surgical conditions that cause an acute abdomen is discussed. These conditions include appendicitis, intussusception, malrotation, inflammatory bowel disease, intestinal obstructions, and nonorganic pain. Emphasis is placed on surgical intervention and disease processes that significantly affect outcome. The outcome of many of the diseases discussed is strongly influenced by the timing of diagnosis and treatment. These children should have prompt care and intervention to prevent morbidity and mortality. In addition, many children who present with common pediatric surgical emergencies have other medical conditions and are best treated in an environment that has a multidisciplinary team to handle their care and decrease the long-term complications.

  11. Sex-Related Differences in the Risk of Hospital-Acquired Sepsis and Pneumonia Post Acute Ischemic Stroke.

    PubMed

    Colbert, James F; Traystman, Richard J; Poisson, Sharon N; Herson, Paco S; Ginde, Adit A

    2016-10-01

    Infectious complications after ischemic stroke are frequent and lead to neurological deterioration, poor functional outcomes, and higher mortality. Local and systemic inflammatory responses to brain ischemia differ between males and females, but little is known about differences in poststroke susceptibility to infection by sex. The purpose of this study was to compare sex-related differences in the risk of hospital-acquired sepsis and pneumonia after acute ischemic stroke (AIS). This is a retrospective, secondary analysis of the 2010-2011 California State Inpatient Database. Previously validated International Classification of Disease, Ninth Revision (ICD-9) codes were used to identify adult hospitalizations for AIS. The primary outcome was hospital-acquired sepsis or pneumonia, also identified using ICD-9 codes. Associations between sex and hospital-acquired sepsis or pneumonia were adjusted for baseline characteristics and comorbidities using multivariable logistic regression. There were 91,643 hospitalizations for AIS included in this analysis, of which 1027 had hospital-acquired sepsis and 1225 had hospital-acquired pneumonia. The in-hospital mortality without infection was 4.6%; the presence of hospital-acquired infections was associated with higher mortality for sepsis (32.7%) and pneumonia (21.9%). Female (versus male) sex was associated with lower adjusted odds of hospital-acquired sepsis (odds ratio [OR] .74, 95% confidence interval [CI] .65-.84) and pneumonia (OR .69, 95% CI .62-.78). This difference was similar across age strata. Among hospitalizations with either hospital-acquired sepsis or pneumonia, sex did not influence mortality. Female sex was associated with a lower risk of hospital-acquired sepsis and pneumonia after AIS. Further investigation is needed to determine the mechanisms underlying this clinical observation. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  12. Sepsis

    MedlinePlus

    ... breathing Abnormal heart pumping function Abdominal pain Septic shock To be diagnosed with septic shock, you must have the signs and symptoms of ... mild sepsis, but the mortality rate for septic shock is nearly 50 percent. Also, an episode of ...

  13. Acute kidney injury in patients with severe sepsis or septic shock: a comparison between the 'Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease' (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) classifications.

    PubMed

    Pereira, Marta; Rodrigues, Natacha; Godinho, Iolanda; Gameiro, Joana; Neves, Marta; Gouveia, João; Costa E Silva, Zélia; Lopes, José António

    2017-06-01

    Using the Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) systems, the incidence of acute kidney injury (AKI) and their ability to predict in-hospital mortality in severe sepsis or septic shock was compared. We performed a retrospective analysis of 457 critically ill patients with severe sepsis or septic shock hospitalized between January 2008 and December 2014. Multivariate logistic regression was employed to evaluate the association between the RIFLE, AKIN and KDIGO systems with in-hospital mortality. Model fit was assessed by the goodness-of-fit test and discrimination by the area under the receiver operating characteristic (AUROC) curve. Statistical significance was defined as P < 0.05. RIFLE (84.2%) and KDIGO (87.5%) identified more patients with AKI than AKIN (72.8%) (P < 0.001). AKI defined by AKIN and KDIGO was associated with in-hospital mortality {AKIN: adjusted odds ratio [OR] 2.3[95% confidence interval (CI) 1.3-4], P = 0.006; KDIGO: adjusted OR 2.7[95% CI 1.2-6.2], P = 0.021} while AKI defined by RIFLE was not [adjusted OR 2.0 (95% CI 1-4), P = 0.063]. The AUROC curve for in-hospital mortality was similar between the three classifications (RIFLE 0.652, P < 0.001; AKIN 0.686, P < 0.001; KDIGO 0.658, P < 0.001). RIFLE and KDIGO diagnosed more patients with AKI than AKIN, but the prediction ability for in-hospital mortality was similar between the three systems.

  14. Acute kidney injury in patients with severe sepsis or septic shock: a comparison between the ‘Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease’ (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) classifications

    PubMed Central

    Pereira, Marta; Rodrigues, Natacha; Godinho, Iolanda; Gameiro, Joana; Neves, Marta; Gouveia, João; Costa e Silva, Zélia; Lopes, José António

    2017-01-01

    Purpose Using the Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) systems, the incidence of acute kidney injury (AKI) and their ability to predict in-hospital mortality in severe sepsis or septic shock was compared. Materials and methods We performed a retrospective analysis of 457 critically ill patients with severe sepsis or septic shock hospitalized between January 2008 and December 2014. Multivariate logistic regression was employed to evaluate the association between the RIFLE, AKIN and KDIGO systems with in-hospital mortality. Model fit was assessed by the goodness-of-fit test and discrimination by the area under the receiver operating characteristic (AUROC) curve. Statistical significance was defined as P < 0.05. Results RIFLE (84.2%) and KDIGO (87.5%) identified more patients with AKI than AKIN (72.8%) (P < 0.001). AKI defined by AKIN and KDIGO was associated with in-hospital mortality {AKIN: adjusted odds ratio [OR] 2.3[95% confidence interval (CI) 1.3–4], P = 0.006; KDIGO: adjusted OR 2.7[95% CI 1.2–6.2], P = 0.021} while AKI defined by RIFLE was not [adjusted OR 2.0 (95% CI 1–4), P = 0.063]. The AUROC curve for in-hospital mortality was similar between the three classifications (RIFLE 0.652, P < 0.001; AKIN 0.686, P < 0.001; KDIGO 0.658, P < 0.001). Conclusions RIFLE and KDIGO diagnosed more patients with AKI than AKIN, but the prediction ability for in-hospital mortality was similar between the three systems. PMID:28616211

  15. Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis

    PubMed Central

    Mayr, Florian B.; Yende, Sachin; Linde-Zwirble, Walter T.; Peck-Palmer, Octavia M.; Barnato, Amber E.; Weissfeld, Lisa A.; Angus, Derek C.

    2013-01-01

    Context Severe sepsis, defined as infection complicated by acute organ dysfunction, occurs more frequently and leads to more deaths in black than in white individuals. The optimal approach to minimize these disparities is unclear. Objective To determine the extent to which higher severe sepsis rates in black than in white patients are due to higher infection rates or to a higher risk of acute organ dysfunction. Design, Setting, and Participants Analysis of infection-related hospitalizations from the 2005 hospital discharge data of 7 US states and infection-related emergency department visits from the 2003-2007 National Hospital Ambulatory Care Survey. Main Outcome Measure Age- and sex-standardized severe sepsis and infection hospitalization rates and the risk of acute organ dysfunction. Results Of 8 661 227 non–childbirth-related discharges, 2 261 857 were associated with an infection, and of these, 381 787 (16.8%) had severe sepsis. Black patients had a 67% higher age- and sex-standardized severe sepsis rate than did white patients (9.4; 95% confidence interval [CI], 9.3-9.5 vs 5.6; 95% CI, 5.6-5.6 per 1000 population; P<.001) and 80% higher standardized mortality (1.8, 95% CI, 1.8-1.9 vs 1.0, 95% CI, 1.0-1.1 per 1000 population; P<.001). The higher severe sepsis rate was explained by both a higher infection rate in black patients (47.3; 95% CI, 47.1-47.4 vs 34.0; 95% CI, 33.9-34.0 per 1000 population; incidence rate ratio, 1.39; P<.001) and a higher risk of developing acute organ dysfunction (age- and sex-adjusted odds ratio [OR],1.29; 95% CI, 1.27-1.30; P<.001). Differences in infection presented broadly across different sites and etiology of infection and for community- and hospital-acquired infections and occurred despite a lower likelihood of being admitted for infection from the emergency department (adjusted OR, 0.70; 95% CI, 0.64-0.76; P<.001). The higher risk of organ dysfunction persisted but was attenuated after adjusting for age, sex, comorbid

  16. Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study.

    PubMed

    Weiss, Scott L; Keele, Luke; Balamuth, Fran; Vendetti, Neika; Ross, Rachael; Fitzgerald, Julie C; Gerber, Jeffrey S

    2017-03-01

    To test the hypothesis that resuscitation with balanced fluids (lactated Ringer [LR]) is associated with improved outcomes compared with normal saline (NS) in pediatric sepsis. We performed matched analyses using data from 12 529 patients <18 years of age with severe sepsis/septic shock at 382 US hospitals between 2000 and 2013 to compare outcomes with vs without LR as part of initial resuscitation. Patients receiving LR were matched 1:1 to patients receiving only NS (NS group), including separate matches for any (LR-any group) or exclusive (LR-only group) LR use. Outcomes included 30-day hospital mortality, acute kidney injury, new dialysis, and length of stay. The LR-any group was older, received larger crystalloid volumes, and was less likely to have malignancies than the NS group. After matching, mortality was not different between LR-any (7.2%) and NS (7.9%) groups (risk ratio 0.99, 95% CI 0.98, 1.01; P = .20). There were no differences in secondary outcomes except longer hospital length of stay in LR-any group (absolute difference 2.4, 95% CI 1.4, 5.0 days; P < .001). Although LR was preferentially used as adjunctive fluid with large-volume resuscitation or first-line fluid in patients with lower illness severity, outcomes were not different after matching stratified by volume and proportionate LR utilization, including for patients in the LR-only group. Balanced fluid resuscitation with LR was not associated with improved outcomes compared with NS in pediatric sepsis. Although the current practice of NS resuscitation is justified, selective LR use necessitates a prospective trial to definitively determine comparative effectiveness among crystalloids. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. [Pathophysiology of sepsis--will the basic research contribute to the improvement of outcome in clinical sepsis?].

    PubMed

    Karima, Risuke

    2008-03-01

    In this decade, the molecular mechanism of sepsis has been strikingly clarified. Especially, the identification of toll-like receptors as the pivotal molecules for the recognition of the stimulation of the inflammatory products of microorganisms has contributed to the elucidation of intracellular signaling pathways which result in severe systemic inflammatory response in sepsis. The production and release of a variety of pro-inflammatory mediators have been found to be associated with severe systemic inflammation and multiple organ dysfunction syndrome (MODS). In the pathophysiology of the development of MODS in sepsis, the disturbance of peripheral microcirculation, the insult of tissues and cells by leukocytes and activated complements and the augmentation of the disorder of fibrinolytic and coagulation systems, which often results in the outbreak of disseminated intravascular coagulopathy (DIC), will be critically involved. Despite of the advance in the basic research regarding molecular pathophysiology of sepsis, sepsis is still accompanied by high mortality in clinical settings. Almost all clinical trials targeting sepsis-associated mediators have failed, except the substitution therapy of activated protein C. However, further trials based on the basic findings, including the therapies targeting the multiple mediators, will contribute to the improvement of outcome of clinical sepsis. ple organ dysfunction syndrome (MODS), pro-inflammatory mediator, disseminated intravascular coagulopathy (DIC).

  18. The impact of cardiac dysfunction on acute respiratory distress syndrome and mortality in mechanically ventilated patients with severe sepsis and septic shock: an observational study.

    PubMed

    Fuller, Brian M; Mohr, Nicholas M; Graetz, Thomas J; Lynch, Isaac P; Dettmer, Matthew; Cullison, Kevin; Coney, Talia; Gogineni, Swetha; Gregory, Robert

    2015-02-01

    Acute respiratory distress syndrome (ARDS) is associated with significant mortality and morbidity in survivors. Treatment is only supportive, therefore elucidating modifiable factors that could prevent ARDS could have a profound impact on outcome. The impact that sepsis-associated cardiac dysfunction has on ARDS is not known. In this retrospective observational cohort study of mechanically ventilated patients with severe sepsis and septic shock, 122 patients were assessed for the impact of sepsis-associated cardiac dysfunction on incidence of ARDS (primary outcome) and mortality. Sepsis-associated cardiac dysfunction occurred in 44 patients (36.1%). There was no association of sepsis-associated cardiac dysfunction with ARDS incidence (p= 0.59) or mortality, and no association with outcomes in patients that did progress to ARDS after admission. Multivariable logistic regression demonstrated that higher BMI was associated with progression to ARDS (adjusted OR 11.84, 95% CI 1.24 to 113.0, p= 0.02). Cardiac dysfunction in mechanically ventilated patients with sepsis did not impact ARDS incidence, clinical outcome in ARDS patients, or mortality. This contrasts against previous investigations demonstrating an influence of nonpulmonary organ dysfunction on outcome in ARDS. Given the frequency of ARDS as a sequela of sepsis, the impact of cardiac dysfunction on outcome should be further studied. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. [Acute phase reaction and immunocompetence in sepsis and SIRS].

    PubMed

    Burdon, Dan; Zabel, Peter

    2002-01-01

    The incidence of sepsis and SIRS, respectively is still rising. Mortality is 40 to 70% and, thus, remains very high in spite of major advances in intensive care medicine. Numerous experimental data have helped to explain isolated aspects of the pathophysiology of these disease states but the complex patho-mechanism remains to be elucidated. The discovery of the toll-like receptors and of the endotoxin-binding proteins LBP and BPI have substantially contributed to the understanding of the bacterial toxin-host interactions and may stimulate the development of new therapeutic strategies in the future. Pro- and anti-inflammatory cytokines play a central role in disease evolution, however the concept of organ-derived and organ-specific damage is gaining importance. Both inflammation and counter-regulation can occur at the same time in the circulation thus, making the evaluation of the patients' immunological status difficult. Additionally, several gene polymorphisms have been detected for example within the toll-like receptor genes and TNF genes. These polymorphisms document the existence of pre-disposing factors, which influence acute phase reaction as well as immuno-competence in sepsis. Both genes and gender will play an important role in the future to identify patients at risk and potentially, to design a specific and individualized immuno-therapies.

  20. Neonatal sepsis

    PubMed Central

    Shah, Birju A; Padbury, James F

    2014-01-01

    Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW <1500 g). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter α inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount. PMID:24185532

  1. IMPACT OF SEPSIS CLASSIFICATION AND MULTIDRUG RESISTANCE STATUS ON OUTCOME AMONG PATIENTS TREATED WITH APPROPRIATE THERAPY

    PubMed Central

    Burnham, Jason P.; Lane, Michael A.; Kollef, Marin H.

    2015-01-01

    Objective To assess the impact of sepsis classification and multidrug resistance status on outcome in patients receiving appropriate initial antibiotic therapy. Design A retrospective cohort study. Setting Barnes-Jewish Hospital, a 1250-bed teaching hospital. Patients Individuals with Enterobacteriaceae sepsis, severe sepsis, and septic shock that received appropriate initial antimicrobial therapy between June 2009 and December 2013. Interventions Clinical outcomes were compared according to multidrug resistance status, sepsis classification, demographics, severity of illness, comorbidities, and antimicrobial treatment. Measurements and Main Results We identified 510 patients with Enterobacteriaceae bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients (13.1%) were non-survivors. Mortality increased significantly with increasing severity of sepsis (3.5%, 9.9%, and 28.6%, for sepsis, severe sepsis, and septic shock, respectively, p<0.05). Time to antimicrobial therapy was not significantly associated with outcome. APACHE II was more predictive of mortality than age-adjusted Charlson comorbidity index. Multidrug resistance status did not result in excess mortality. Length of intensive care unit and hospital stay increased with more severe sepsis. In multivariate logistic regression analysis, African-American race, sepsis severity, APACHE II score, solid organ cancer, cirrhosis, and transfer from an outside hospital were all predictors of mortality. Conclusions Our results support sepsis severity, but not multidrug resistance status as being an important predictor of death when all patients receive appropriate initial antibiotic therapy. Future sepsis trials should attempt to provide appropriate antimicrobial therapy and take sepsis severity into careful account when determining outcomes. PMID:25855900

  2. The Outcome of Polymicrobial Sepsis is Independent of T and B Cells

    PubMed Central

    Bosmann, Markus; Russkamp, Norman F.; Patel, Vinay R.; Zetoune, Firas S.; Sarma, J. Vidya; Ward, Peter A.

    2011-01-01

    The contribution of the adaptive and innate immune systems to the pathogenesis and outcome of sepsis remains a fundamental yet controversial question. Here, we use mice lacking the recombination activating gene-1 (Rag-1) to study the role of T and B cells in sepsis after cecal ligation and puncture (CLP). Spleens of Rag-1−/− mice were atrophic and completely devoid of CD3+ T cells and CD19+ B cells. Wildtype mice and Rag-1−/− mice (both on a C57BL/6J background) underwent CLP or sham surgery. Both wildtype and Rag-1−/− mice developed clinical signs of sepsis within the first day after CLP. This included severe hypothermia as measured by a decrease in body surface temperature and organ dysfunction as detected by plasma increases in BUN and LDH levels. Survival curves of wildtype and Rag-1−/− mice after CLP were superimposable, with 35% survival in the wildtype group and 27% survival in the Rag-1−/− group, respectively (not significant, P=0.875). Using multiplex bead-based assays, the mediator concentrations for 23 cytokines and chemokines were measured in plasma of wildtype and Rag-1−/− mice 8 h after CLP or sham surgery. Compared to sham surgery mice, the highest mediator levels were observed for G-CSF, KC, IL-6, MCP-1 and IL-10. Levels for most mediators were unaffected by the absence of T and B lymphocytes. Only the concentrations of IL-6 and IL-17 were found to be significantly lower in Rag-1−/− mice compared to wildtype mice. In conclusion, the absence of T and B cells in the CLP model employed does not appear to affect the acute outcome of severe sepsis. PMID:21701414

  3. Impact of Delayed Admission to the Intensive Care Unit from the Emergency Department upon Sepsis Outcomes and Sepsis Protocol Compliance

    PubMed Central

    Price, Lori Lyn; Andoh-Duku, Augustine; LaCamera, Peter

    2017-01-01

    Rationale. The impact of emergency department length of stay (EDLOS) upon sepsis outcomes needs clarification. We sought to better understand the relationship between EDLOS and both outcomes and protocol compliance in sepsis. Methods. We performed a retrospective observational study of septic patients admitted to the ICU from the ED between January 2012 and December 2015 in a single tertiary care teaching hospital. 287 patients with severe sepsis and septic shock were included. Study population was divided into patients with EDLOS < 6 hrs (early admission) versus ≥6 hours (delayed admission). We assessed the impact of EDLOS on hospital mortality, compliance with sepsis protocol, and resuscitation. Statistical significance was determined by chi-square test. Results. Of the 287 septic ED patients, 137 (47%) were admitted to the ICU in <6 hours. There was no significant in-hospital mortality difference between early and delayed admissions (p = 0.68). Both groups have similar compliance with the 3-hour protocol (p = 0.77). There was no significant difference in achieving optimal resuscitation within 12 hours (p = 0.35). Conclusion. We found that clinical outcomes were not significantly different between early and delayed ICU admissions. Additionally, EDLOS did not impact compliance with the sepsis protocol with the exception of repeat lactate draw. PMID:28409028

  4. Effects of honokiol on sepsis-induced acute kidney injury in an experimental model of sepsis in rats.

    PubMed

    Li, Nan; Xie, Hua; Li, Longkai; Wang, Jing; Fang, Ming; Yang, Ning; Lin, Hongli

    2014-08-01

    Acute kidney injury (AKI) is a severe complication of sepsis, which largely contributes to the high mortality rate of sepsis. Honokiol, a natural product isolated from Magnolia officinalis (Houpo), has been shown to exhibit anti-inflammatory and antioxidant properties. Here, we investigated the effects of honokiol on sepsis-associated AKI in rats subjected to cecal ligation and puncture (CLP). We found that the administration of honokiol improved the survival of septic rats. Periodic acid-Schiff stain revealed that the morphological changes of kidney tissues in CLP rats were restored after honokiol treatment. Furthermore, honokiol reduced CLP-induced oxidative stress and inflammatory cytokine production. The levels of nitric oxide (NO) and inducible NO synthetase (iNOS) were attenuated by honokiol in septic rats. Finally, honokiol inhibited CLP-induced activation of NF-κB signaling in CLP rats. Our findings suggest that honokiol might be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI.

  5. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

    PubMed Central

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  6. Changing Definitions of Sepsis

    PubMed Central

    Gül, Fethi; Arslantaş, Mustafa Kemal; Cinel, İsmail; Kumar, Anand

    2017-01-01

    Sepsis is one of the main causes of morbidity and mortality in critically ill patients despite the use of modern antibiotics and resuscitation therapies. Outcomes in sepsis have improved overall, probably because of an enhanced focus on early diagnosis and other improvements in supportive care, but mortality rates still remain unacceptably high. The diagnosis and definition of sepsis is a critical problem due to the heterogeneity of this disease process. Although it is apparent that much more needs to be done to advance our understanding, sepsis and related terms remain difficult to define. A 1991 consensus conference developed initial definitions that systemic inflammatory response syndrome (SIRS) to infection would be called sepsis. Definitions of sepsis and septic shock were revised in 2001 to incorporate the threshold values for organ damage. In early 2016, the new definitions of sepsis and septic shock have changed dramatically. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The consensus document describes organ dysfunction as an acute increase in total Sequential Organ Failure Assessment (SOFA) score two points consequently to the infection. A significant change in the new definitions is the elimination of any mention of SIRS. The Sepsis-3 Task Force also introduced a new bedside index, called the qSOFA, to identify outside of critical care units patients with suspected infection who are likely to develop sepsis. Recently updated the consensus definitions improved specificity compared with the previous descriptions. PMID:28752002

  7. Australian Staphylococcus aureus Sepsis Outcome Programme annual report, 2013.

    PubMed

    Coombs, Geoffrey W; Nimmo, Graeme R; Daly, Denise A; Le, Tam T; Pearson, Julie C; Tan, Hui-Leen; Robinson, James O; Collignon, Peter J; McLaws, Mary-Louise; Turnidge, John D

    2014-12-31

    From 1 January to 31 December 2013, around Australia 26 institutions around Australia participated in the Australian Staphylococcal Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2013 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, (with particular emphasis on susceptibility to methicillin) and to characterise the molecular epidemiology of the isolates. Overall 19.1% of the 2,010 SAB episodes were methicillin resistant, which is significantly higher than that reported in most European countries. Although the SAB 30-day all cause mortality appears to be decreasing in Australia, methicillin-resistant SAB associated mortality remains high (20.1%) and was significantly higher than methicillin-sensitive SAB associated mortality (13%) (P< 0.0001). With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin sensitive S. aureus remains rare. However, in addition to the ß-lactams, approximately 50% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 20% were resistant to co-trimoxazole, tetracycline and gentamicin. Linezolid, daptomycin and teicoplanin resistance was detected in a small number of S. aureus isolates. Resistance to vancomycin was not detected. Resistance was largely attributable to 2 healthcare associated MRSA clones; ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) has now become the predominant healthcare associated clone in Australia. Approximately 60% of methicillin-resistant SAB were due to community associated clones. Although polyclonal, almost 50% of community associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA) and ST1-IV [2B] (WA1). CA-MRSA, in particular the ST45-V [5C2&5] (WA84) clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and

  8. SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome

    PubMed Central

    Vachharajani, Vidula T.; Liu, Tiefu; Brown, Candice M.; Wang, Xianfeng; Buechler, Nancy L.; Wells, Jonathan David; Yoza, Barbara K.; McCall, Charles E.

    2014-01-01

    Mechanism-based sepsis treatments are unavailable, and their incidence is rising worldwide. Deaths occur during the early acute phase of hyperinflammation or subsequent postacute hypoinflammatory phase with sustained organ failure. The acute sepsis phase shifts rapidly, and multiple attempts to treat early excessive inflammation have uniformly failed. We reported in a sepsis cell model and human sepsis blood leukocytes that nuclear NAD+ sensor SIRT1 deacetylase remodels chromatin at specific gene sets to switch the acute-phase proinflammatory response to hypoinflammatory. Importantly, SIRT1 chromatin reprogramming is reversible, suggesting that inhibition of SIRT1 might reverse postacute-phase hypoinflammation. We tested this concept in septic mice, using the highly specific SIRT1 inhibitor EX-527, a small molecule that closes the NAD+ binding site of SIRT1. Strikingly, when administered 24 h after sepsis, all treated animals survived, whereas only 40% of untreated mice survived. EX-527 treatment reversed the inability of leukocytes to adhere at the small intestine MVI, reversed in vivo endotoxin tolerance, increased leukocyte accumulation in peritoneum, and improved peritoneal bacterial clearance. Mechanistically, the SIRT1 inhibitor restored repressed endothelial E-selectin and ICAM-1 expression and PSGL-1 expression on the neutrophils. Systemic benefits of EX-527 treatment included stabilized blood pressure, improved microvascular blood flow, and a shift toward proimmune macrophages in spleen and bone marrow. Our findings reveal that modifying the SIRT1 NAD+ axis may provide a novel way to treat sepsis in its hypoinflammatory phase. PMID:25001863

  9. Outcomes of Older Adults With Sepsis at Admission to an Intensive Care Unit.

    PubMed

    Rowe, Theresa; Araujo, Katy L B; Van Ness, Peter H; Pisani, Margaret A; Juthani-Mehta, Manisha

    2016-01-01

    Background.  Sepsis is a major cause of morbidity and mortality among older adults. The main goals of this study were to assess the association of sepsis at intensive care unit (ICU) admission with mortality and to identify predictors associated with increased mortality in older adults. Methods.  We conducted a prospective cohort study of 309 participants ≥60 years admitted to an ICU. Sepsis was defined as 2 of 4 systemic inflammatory response syndrome criteria plus a documented infection within 2 calendar days before or after admission. The main outcome measure was time to death within 1 year of ICU admission. Sepsis was evaluated as a predictor for mortality in a Cox proportional hazards model. Results.  Of 309 participants, 196 (63%) met the definition of sepsis. Among those admitted with and without sepsis, 75 (38%) vs 20 (18%) died within 1 month of ICU admission (P < .001) and 117 (60%) vs 48 (42%) died within 1 year (P < .001). When adjusting for baseline characteristics, sepsis had a significant impact on mortality (hazard ratio [HR] = 1.80; 95% confidence interval [CI], 1.28-2.52; P < .001); however, after adjusting for baseline characteristics and process covariates (antimicrobials and vasopressor use within 48 hours of admission), the impact of sepsis on mortality became nonsignificant (HR = 1.26; 95% CI, .87-1.84; P = .22). Conclusions.  The diagnosis of sepsis in older adults upon ICU admission was associated with an increase in mortality compared with those admitted without sepsis. After controlling for early use of antimicrobials and vasopressors for treatment, the association of sepsis with mortality was reduced.

  10. Outcomes of Older Adults With Sepsis at Admission to an Intensive Care Unit

    PubMed Central

    Rowe, Theresa; Araujo, Katy L. B.; Van Ness, Peter H.; Pisani, Margaret A.; Juthani-Mehta, Manisha

    2016-01-01

    Background. Sepsis is a major cause of morbidity and mortality among older adults. The main goals of this study were to assess the association of sepsis at intensive care unit (ICU) admission with mortality and to identify predictors associated with increased mortality in older adults. Methods. We conducted a prospective cohort study of 309 participants ≥60 years admitted to an ICU. Sepsis was defined as 2 of 4 systemic inflammatory response syndrome criteria plus a documented infection within 2 calendar days before or after admission. The main outcome measure was time to death within 1 year of ICU admission. Sepsis was evaluated as a predictor for mortality in a Cox proportional hazards model. Results. Of 309 participants, 196 (63%) met the definition of sepsis. Among those admitted with and without sepsis, 75 (38%) vs 20 (18%) died within 1 month of ICU admission (P < .001) and 117 (60%) vs 48 (42%) died within 1 year (P < .001). When adjusting for baseline characteristics, sepsis had a significant impact on mortality (hazard ratio [HR] = 1.80; 95% confidence interval [CI], 1.28–2.52; P < .001); however, after adjusting for baseline characteristics and process covariates (antimicrobials and vasopressor use within 48 hours of admission), the impact of sepsis on mortality became nonsignificant (HR = 1.26; 95% CI, .87–1.84; P = .22). Conclusions. The diagnosis of sepsis in older adults upon ICU admission was associated with an increase in mortality compared with those admitted without sepsis. After controlling for early use of antimicrobials and vasopressors for treatment, the association of sepsis with mortality was reduced. PMID:26925430

  11. Effect on extrapulmonary sepsis-induced acute lung injury by hemoperfusion with neutral microporous resin column.

    PubMed

    Huang, Zhao; Wang, Si-rong; Yang, Zi-li; Liu, Ji-yun

    2013-08-01

    The aim of this study was to investigate the effect of neutral microporous resin hemoperfusion on oxygenation improvement, removal of inflammatory cytokines in plasma and bronchoalveolar lavage, and mortality in acute lung injury induced by extrapulmonary sepsis. Forty-six patients with acute lung injury induced by extrapulmonary sepsis were randomized to HA type hemoperfusion treatment (N=25) or standard therapy (N=21). Those undergoing hemoperfusion treatment received HA330 hemoperfusion. We measured the plasma and bronchoalveolar lavage concentrations of TNF-α and IL-1, and the following parameters were compared between the control group and the hemoperfusion group on days 0, 3 and 7: lung injury measurements (arterial oxygen tension/fractional inspired oxygen ratio, lung injury score, chest X-ray score); interstitial edema of lung (extravascular lung water). Duration of mechanical ventilation, hospital, 28-day, and intensive care unit mortality were also observed. Patients treated with HA hemoperfusion showed a significant removal of plasma and bronchoalveolar lavage TNF-α and IL-1 over time while in the study. Patients in the HA group also demonstrated not only significant improvement of PaO2 /FiO2 , but also decreased Lung Injury Score and chest X-ray score at days 3 and 7. Furthermore, the measurements of the arterial oxygen tension/fractional inspired oxygen ratio, lung injury score and extravascular lung water (EVLWI) significantly correlated with and the concentration of cytokines in the plasma (all P<0.05). The HA hemoperfusion treatment group had a significant reduction in duration of mechanical ventilation, length of intensive care unit stay, and intensive care unit mortality. Significant removal of inflammatory cytokines from circulation and lung by hemoperfusion treatment using the HA type cartridge may contribute to the improvement of lung injury and intensive care unit outcome in extrapulmonary septic patients. © 2012 The Authors. Therapeutic

  12. Early traditional Chinese medicine bundle therapy for the prevention of sepsis acute gastrointestinal injury in elderly patients with severe sepsis

    PubMed Central

    Wang, Yifei; Zhang, Yunhua; Jiang, Ronglin

    2017-01-01

    This study aimed to study the effect of early traditional Chinese medicine bundle therapy on the prevention of sepsis-associated acute gastrointestinal injury (AGI). This was a multicenter, prospective, observational, non-randomized cohort study of 296 consecutive patients with severe sepsis during 2013/3 and 2014/11; 150 patients received standard treatments (controls) and 146 received traditional Chinese medicine bundle therapy (intervention group) (herbal decoction gavage based on syndrome differentiation, Chinese acupuncture, application of mirabilite, and defecation mixture). D-lactic acid, diamine oxidase, endotoxin, gastrin, motilin, and intra-abdominal pressure were measured. AGI was categorized into four levels. Compared with controls, D-lactic acid, diamine oxidase, endotoxin, gastrin, and intra-abdominal pressure in the intervention group were decreased, and motilin was increased on day 7. AGI incidence in the intervention group was lower than in controls. GIF scores of the intervention AGI II and III groups were lower than in controls. The APACHE II scores of the intervention AGI II, III, and IV groups were lower than in controls. Compared with controls, mechanical ventilation time and ICU stay in the intervention group were shorter, and 28-day overall and AGI-attributed mortality were lower. For elderly patients with severe sepsis, early traditional Chinese medicine bundle therapy could decrease AGI incidence and improve prognosis. PMID:28382954

  13. A Multidisciplinary Sepsis Program Enabled by a Two-Stage Clinical Decision Support System: Factors That Influence Patient Outcomes.

    PubMed

    Amland, Robert C; Haley, James M; Lyons, Jason J

    2016-11-01

    Sepsis is an inflammatory response triggered by infection, with risk of in-hospital mortality fueled by disease progression. Early recognition and intervention by multidisciplinary sepsis programs may reverse the inflammatory response among at-risk patient populations, potentially improving outcomes. This retrospective study of a sepsis program enabled by a 2-stage sepsis Clinical Decision Support (CDS) system sought to evaluate the program's impact, identify early indicators that may influence outcomes, and uncover opportunities for quality improvement. Data encompassed 16 527 adult hospitalizations from 2014 and 2015. Of 2108 non-intensive care unit patients screened-in by sepsis CDS, 97% patients were stratified by 177 providers. Risk of adverse outcome improved 30% from baseline to year end, with gains materializing and stabilizing at month 7 after sepsis program go-live. Early indicators likely to influence outcomes include patient age, recent hospitalization, electrolyte abnormalities, hypovolemic shock, hypoxemia, patient location when sepsis CDS activated, and specific alert patterns.

  14. Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome.

    PubMed

    Toner, Philip; McAuley, Danny Francis; Shyamsundar, Murali

    2015-10-23

    Sepsis is a common condition that is associated with significant morbidity, mortality and health-care cost. Pulmonary and non-pulmonary sepsis are common causes of the acute respiratory distress syndrome (ARDS). The mortality from ARDS remains high despite protective lung ventilation, and currently there are no specific pharmacotherapies to treat sepsis or ARDS. Sepsis and ARDS are characterised by activation of the inflammatory cascade. Although there is much focus on the study of the dysregulated inflammation and its suppression, the associated activation of the haemostatic system has been largely ignored until recently. There has been extensive interest in the role that platelet activation can have in the inflammatory response through induction, aggregation and activation of leucocytes and other platelets. Aspirin can modulate multiple pathogenic mechanisms implicated in the development of multiple organ dysfunction in sepsis and ARDS. This review will discuss the role of the platelet, the mechanisms of action of aspirin in sepsis and ARDS, and aspirin as a potential therapy in treating sepsis and ARDS.

  15. Baicalin Inhibits Renal Cell Apoptosis and Protects Against Acute Kidney Injury in Pediatric Sepsis

    PubMed Central

    Zhu, Yanping; Fu, Yanxia; Lin, Hairong

    2016-01-01

    Background Pediatric sepsis has high morbidity in children, may lead to acute kidney injury (AKI), and further aggravate the disease. Baicalin is a kind of flavonoid in Scutellaria baicalensis Georgi and has been reported to protect against several diseases, but its roles in septic AKI remain unclear. This study aimed to uncover the effects of baicalin in AKI during pediatric sepsis. Material/Methods Blood urea nitrogen (BUN) and serum creatinine (Cr) levels were detected in 50 pediatric patients, who underwent basic therapy with or without baicalin adjunctive therapy. Mouse sepsis models were constructed by cecal ligation and puncture (CLP) and treated with baicalin intragastrically, after which BUN and Cr examination, TUNEL apoptosis assay, and expression analyses of BAX and BCL2 were performed. Results Baicalin adjunctive therapy significantly decreased BUN and Cr levels in pediatric sepsis patients (P<0.05). CLP led to elevated BUN and Cr levels in the mouse model (P<0.01), indicating kidney injury accompanied by sepsis. Baicalin decreased BUN and Cr levels (P<0.05), and reduced the apoptotic cell percent in the renal tissue (P<0.05) of the CLP model. It inhibited BAX and promoted BCL2 in the renal tissue, which was consistent with cell apoptosis changes. Conclusions Baicalin is capable of suppressing renal cell apoptosis and protecting against AKI in pediatric sepsis. This study provides a potential adjunctive therapy for treating AKI in pediatric sepsis, and further research is necessary to reveal its deeper mechanisms. PMID:28013315

  16. Australian Enterococcal Sepsis Outcome Programme annual report, 2013.

    PubMed

    Coombs, Geoffrey W; Pearson, Julie C; Daly, Denise A; Le, Tam T; Robinson, James O; Gottlieb, Thomas; Howden, Benjamin P; Johnson, Paul D R; Bennett, Catherine M; Stinear, Timothy P; Turnidge, John D

    2014-12-31

    From 1 January to 31 December 2013, 26 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2013 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 826 unique episodes of bacteraemia investigated, 94.6% were caused by either E. faecalis (56.1%) or E. faecium (38.5%). Ampicillin resistance was not detected in E. faecalis but was detected in over 90% of E. faecium. Vancomycin non-susceptibility was reported in 0.2% and 40.9% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Overall, 41.6% of E. faecium harboured vanA or vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium isolates consisted of 81 pulsed-field gel electrophoresis pulsotypes of which 72.3% were classified into 14 major pulsotypes containing five or more isolates. Multilocus sequence typing grouped the 14 major pulsotypes into clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. Of the 2 predominant sequence types, ST203 (80 isolates) was identified across Australia and ST555 (40 isolates) was isolated primarily in the western and central regions (Northern Territory, South Australia and Western Australia) respectively. In conclusion, the AESOP 2013 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanB E. faecium, which have limited treatment options.

  17. Characteristics and outcomes of culture-negative versus culture-positive severe sepsis

    PubMed Central

    2013-01-01

    Introduction Culture-negative sepsis is a common but relatively understudied condition. The aim of this study was to compare the characteristics and outcomes of culture-negative versus culture-positive severe sepsis. Methods This was a prospective observational cohort study of 1001 patients who were admitted to the medical intensive care unit (ICU) of a university hospital from 2004 to 2009 with severe sepsis. Patients with documented fungal, viral, and parasitic infections were excluded. Results There were 415 culture-negative patients (41.5%) and 586 culture-positive patients (58.5%). Gram-positive bacteria were isolated in 257 patients, and gram-negative bacteria in 390 patients. Culture-negative patients were more often women and had fewer comorbidities, less tachycardia, higher blood pressure, lower procalcitonin levels, lower Acute Physiology and Chronic Health Evaluation II (median 25.0 (interquartile range 19.0 to 32.0) versus 27.0 (21.0 to 33.0), P = 0.001) and Sequential Organ Failure Assessment scores, less cardiovascular, central nervous system, and coagulation failures, and less need for vasoactive agents than culture-positive patients. The lungs were a more common site of infection, while urinary tract, soft tissue and skin infections, infective endocarditis and primary bacteremia were less common in culture-negative than in culture-positive patients. Culture-negative patients had a shorter duration of hospital stay (12 days (7.0 to 21.0) versus 15.0 (7.0 to27.0), P = 0.02) and lower ICU mortality than culture-positive patients. Hospital mortality was lower in the culture-negative group (35.9%) than in the culture-positive group (44.0%, P = 0.01), the culture-positive subgroup, which received early appropriate antibiotics (41.9%, P = 0.11), and the culture-positive subgroup, which did not (55.5%, P < 0.001). After adjusting for covariates, culture positivity was not independently associated with mortality on multivariable analysis. Conclusions

  18. Effect of aphasia on acute stroke outcomes.

    PubMed

    Boehme, Amelia K; Martin-Schild, Sheryl; Marshall, Randolph S; Lazar, Ronald M

    2016-11-29

    To determine the independent effects of aphasia on outcomes during acute stroke admission, controlling for total NIH Stroke Scale (NIHSS) scores and loss of consciousness. Data from the Tulane Stroke Registry were used from July 2008 to December 2014 for patient demographics, NIHSS scores, length of stay (LOS), complications (sepsis, deep vein thrombosis), and discharge modified Rankin Scale (mRS) score. Aphasia was defined as a score >1 on question 9 on the NIHSS on admission and hemiparesis as >1 on questions 5 or 6. Among 1,847 patients, 866 (46%) had aphasia on admission. Adjusting for NIHSS score and inpatient complications, those with aphasia had a 1.22 day longer LOS than those without aphasia, whereas those with hemiparesis (n = 1,225) did not have any increased LOS compared to those without hemiparesis. Those with aphasia had greater odds of having a complication (odds ratio [OR] 1.44, confidence interval [CI] 1.07-1.93, p = 0.0174) than those without aphasia, which was equivalent to those having hemiparesis (OR 1.47, CI 1.09-1.99, p = 0.0137). Controlling for NIHSS scores, aphasia patients had higher odds of discharge mRS 3-6 (OR 1.42 vs 1.15). Aphasia is independently associated with increased LOS and complications during the acute stroke admission, adding $2.16 billion annually to US acute stroke care. The presence of aphasia was more likely to produce a poor functional outcome than hemiparesis. These data suggest that further research is necessary to determine whether establishing adaptive communication skills can mitigate its consequences in the acute stroke setting. © 2016 American Academy of Neurology.

  19. Impact of Prehospital Care on Outcomes in Sepsis: A Systematic Review

    PubMed Central

    Smyth, Michael A; Brace-McDonnell, Samantha J; Perkins, Gavin D

    2016-01-01

    Introduction Sepsis is a common and potentially life-threatening response to an infection. International treatment guidelines for sepsis advocate that treatment be initiated at the earliest possible opportunity. It is not yet clear if very early intervention by ambulance clinicians prior to arrival at hospital leads to improved clinical outcomes among sepsis patients. Methoda We systematically searched the electronic databases MEDLINE, EMBASE, CINAHL, the Cochrane Library and PubMed up to June 2015. In addition, subject experts were contacted. We adopted the GRADE (grading recommendations assessment, development and evaluation) methodology to conduct the review and follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations to report findings. Results Nine studies met the eligibility criteria – one study was a randomized controlled trial while the remaining studies were observational in nature. There was considerable variation in the methodological approaches adopted and outcome measures reported across the studies. Because of these differences, the studies did not answer a unique research question and meta-analysis was not appropriate. A narrative approach to data synthesis was adopted. Conclusion There is little robust evidence addressing the impact of prehospital interventions on outcomes in sepsis. That which is available is of low quality and indicates that prehospital interventions have limited impact on outcomes in sepsis beyond improving process outcomes and expediting the patient’s passage through the emergency care pathway. Evidence indicating that prehospital antibiotic therapy and fluid resuscitation improve patient outcomes is currently lacking. PMID:27429693

  20. Serum metabolomics identifies citrulline as a predictor of adverse outcomes in an equine model of gut-derived sepsis.

    PubMed

    Steelman, Samantha M; Johnson, Philip; Jackson, Amy; Schulze, James; Chowdhary, Bhanu P

    2014-05-15

    Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the Lmn group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in Lmn samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis.

  1. Clinico-microbiological profile and outcomes of nosocomial sepsis in an Indian tertiary care hospital--a prospective cohort study.

    PubMed

    Saravu, Kavitha; Prasad, Madhura; Eshwara, Vandana Kalwaje; Mukhopadhyay, Chiranjay

    2015-07-01

    Nosocomial infections are linked to rising morbidity and mortality worldwide. We sought to investigate the pattern of nosocomial sepsis, device usage, risk factors for mortality and the antimicrobial resistance pattern of the causative organisms in medical intensive care units (ICUs) in an Indian tertiary care hospital. We conducted a single-centre based prospective cohort study in four medical ICUs and patients who developed features of sepsis 48 hours after admission to the ICUs were included. Patients' demographics, indwelling device usage, microbiological culture reports, drug resistance patterns and the outcomes were recorded. The Acute Physiology and Chronic Health Evaluation (APACHE) III score and the relative risk of variables contributing towards non recovery were calculated. Pneumonia (49%) was the commonest nosocomial infection resulting in sepsis, followed by urosepsis (21.8%), bloodstream infection (BSI) (10.3%) and catheter-related bloodstream infection (CRBSI) (5%). Sixty three percent of the Acinetobacter baumannii and 64.4% of the Pseudomonas aeruginosa were multidrug-resistant (MDR). Seventy percent of the Klebsiella pneumoniae were extended spectrum beta-lactamase producers and 7.4% were resistant to carbapenems. Forty three percent of the Staphylococcus aureus were methicillin-resistant S. aureus. Resistance to carbapenems was 35.2% in this study. High APACHE III scores (P = 0.006 by unpaired t-test) and chronic kidney disease (P = 0.023) were significantly associated with non-recovery. A high degree of multidrug resistance was observed among both Gram-positive and -negative organisms in nosocomial sepsis patients. Carbapenem resistance was a common occurrence. Chronic kidney disease and high APACHE III scores were significantly associated with non-recovery. Male gender and sepsis leading to cardiovascular failure were the independent predictors of mortality.

  2. Glycyrrhizic Acid Prevents Sepsis-Induced Acute Lung Injury and Mortality in Rats

    PubMed Central

    Zhao, Hongyu; Zhao, Min; Wang, Yu; Li, Fengchun; Zhang, Zhigang

    2015-01-01

    Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. However, the effects of GA on sepsis-induced acute lung injury (ALI) have not been determined. Tthe aim of this study was to investigate the molecular mechanism involved in the effects of GA against sepsis-induced ALI in rats. We found that GA alleviated sepsis-induced ALI through improvements in various pathological changes, as well as decreases in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid, and a significant increase in the survival rate of treated rats. Additionally, GA markedly inhibited sepsis-induced pulmonary inflammatory responses. Moreover, we found that treatment with GA inhibited oxidative stress damage and apoptosis in lung tissue induced by ALI. Finally, GA treatment significantly inhibited NF-κ B, JNK and P38 MAPK activation. Our data indicate that GA has a protective effect against sepsis-induced ALI by inhibiting the inflammatory response, damage from oxidative stress, and apoptosis via inactivation of NF-κB and MAPK signaling pathways, providing a molecular basis for a new medical treatment for sepsis-induced ALI. PMID:26385569

  3. Glycyrrhizic Acid Prevents Sepsis-Induced Acute Lung Injury and Mortality in Rats.

    PubMed

    Zhao, Hongyu; Zhao, Min; Wang, Yu; Li, Fengchun; Zhang, Zhigang

    2016-02-01

    Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. However, the effects of GA on sepsis-induced acute lung injury (ALI) have not been determined. Tthe aim of this study was to investigate the molecular mechanism involved in the effects of GA against sepsis-induced ALI in rats. We found that GA alleviated sepsis-induced ALI through improvements in various pathological changes, as well as decreases in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid, and a significant increase in the survival rate of treated rats. Additionally, GA markedly inhibited sepsis-induced pulmonary inflammatory responses. Moreover, we found that treatment with GA inhibited oxidative stress damage and apoptosis in lung tissue induced by ALI. Finally, GA treatment significantly inhibited NF-κ B, JNK and P38 MAPK activation. Our data indicate that GA has a protective effect against sepsis-induced ALI by inhibiting the inflammatory response, damage from oxidative stress, and apoptosis via inactivation of NF-κB and MAPK signaling pathways, providing a molecular basis for a new medical treatment for sepsis-induced ALI.

  4. First Report of Acute Cholecystitis with Sepsis Caused by Cellulomonas denverensis▿

    PubMed Central

    Ohtaki, Hirofumi; Ohkusu, Kiyofumi; Sawamura, Haruki; Ohta, Hirotoshi; Inoue, Rina; Iwasa, Junpei; Ito, Hiroyasu; Murakami, Nobuo; Ezaki, Takayuki; Moriwaki, Hisataka; Seishima, Mitsuru

    2009-01-01

    Cellulomonas denverensis is a small and thin gram-positive rod-shaped bacterium that was proposed as a new species in 2005. Here we report a female case of acute cholecystitis and sepsis in which C. denverensis was determined to be causative. PMID:19656981

  5. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study

    PubMed Central

    Davenport, Emma E; Burnham, Katie L; Radhakrishnan, Jayachandran; Humburg, Peter; Hutton, Paula; Mills, Tara C; Rautanen, Anna; Gordon, Anthony C; Garrard, Christopher; Hill, Adrian V S; Hinds, Charles J; Knight, Julian C

    2016-01-01

    Summary Background Effective targeted therapy for sepsis requires an understanding of the heterogeneity in the individual host response to infection. We investigated this heterogeneity by defining interindividual variation in the transcriptome of patients with sepsis and related this to outcome and genetic diversity. Methods We assayed peripheral blood leucocyte global gene expression for a prospective discovery cohort of 265 adult patients admitted to UK intensive care units with sepsis due to community-acquired pneumonia and evidence of organ dysfunction. We then validated our findings in a replication cohort consisting of a further 106 patients. We mapped genomic determinants of variation in gene transcription between patients as expression quantitative trait loci (eQTL). Findings We discovered that following admission to intensive care, transcriptomic analysis of peripheral blood leucocytes defines two distinct sepsis response signatures (SRS1 and SRS2). The presence of SRS1 (detected in 108 [41%] patients in discovery cohort) identifies individuals with an immunosuppressed phenotype that included features of endotoxin tolerance, T-cell exhaustion, and downregulation of human leucocyte antigen (HLA) class II. SRS1 was associated with higher 14 day mortality than was SRS2 (discovery cohort hazard ratio (HR) 2·4, 95% CI 1·3–4·5, p=0·005; validation cohort HR 2·8, 95% CI 1·5–5·1, p=0·0007). We found that a predictive set of seven genes enabled the classification of patients as SRS1 or SRS2. We identified cis-acting and trans-acting eQTL for key immune and metabolic response genes and sepsis response networks. Sepsis eQTL were enriched in endotoxin-induced epigenetic marks and modulated the individual host response to sepsis, including effects specific to SRS group. We identified regulatory genetic variants involving key mediators of gene networks implicated in the hypoxic response and the switch to glycolysis that occurs in sepsis, including HIF1α and

  6. Outcome and functional prognosis of pelvic sepsis after ileal pouch-anal anastomosis in patients with ulcerative colitis.

    PubMed

    Ide, Shozo; Araki, Toshimitsu; Okita, Yoshiki; Kawamura, Mikio; Toiyama, Yuji; Kobayashi, Minako; Ohi, Masaki; Tanaka, Koji; Inoue, Yasuhiro; Uchida, Keiichi; Mohri, Yasuhiko; Kusunoki, Masato

    2017-03-01

    Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure for ulcerative colitis, but pouch failure or pelvic sepsis still occurs in some patients. We conducted this study to investigate the cause of pouch failure and evaluate defecatory function after pelvic sepsis. A total of 234 patients who underwent restorative proctocolectomy were enrolled. We analyzed the cause of pouch failure, as well as defecatory function and manometric outcomes, with and without the complication of pelvic sepsis. Pelvic sepsis developed in 29 (12.3%) of the 234 patients who underwent restorative proctocolectomy (pelvic sepsis group). The pelvic sepsis led to pouch failure in two of these patients (as a vaginal fistula in one and ileo-anal anastomotic leakage in one). Of the remaining majority of patients who did not suffer pelvic sepsis (control group), nine suffered pouch failure (as vaginal fistula in four, perianal abscess in two, pouch-spinal marrow fistula in one, and chronic pouchitis in two). There were no significant differences in defecatory function or manometric outcomes between the two groups. In the pelvic sepsis group, stool frequency was significantly correlated with white blood cell count (P = 0.01) and the duration until onset of pelvic sepsis (P < 0.01). Pelvic sepsis after restorative proctocolectomy for ulcerative colitis does not affect defecatory and manometric function, but control of the inflammation caused by pelvic sepsis is integral for defecatory function.

  7. Jack of all trades: pleiotropy and the application of chemically modified tetracycline-3 in sepsis and the acute respiratory distress syndrome (ARDS).

    PubMed

    Roy, Shreyas K; Kendrick, Daniel; Sadowitz, Benjamin D; Gatto, Louis; Snyder, Kathleen; Satalin, Joshua M; Golub, Lorne M; Nieman, Gary

    2011-12-01

    Sepsis is a disease process that has humbled the medical profession for centuries with its resistance to therapy, relentless mortality, and pathophysiologic complexity. Despite 30 years of aggressive, concerted, well-resourced efforts the biomedical community has been unable to reduce the mortality of sepsis from 30%, nor the mortality of septic shock from greater than 50%. In the last decade only one new drug for sepsis has been brought to the market, drotrecogin alfa-activated (Xigris™), and the success of this drug has been limited by patient safety issues. Clearly a new agent is desperately needed. The advent of recombinant human immune modulators held promise but the outcomes of clinical trials using biologics that target single immune mediators have been disappointing. The complex pathophysiology of the systemic inflammatory response syndrome (SIRS) is self-amplifying and redundant at multiple levels. In this review we argue that perhaps pharmacologic therapy for sepsis will only be successful if it addresses this pathophysiologic complexity; the drug would have to be pleiotropic, working on many components of the inflammatory cascade at once. In this context, therapy that targets any single inflammatory mediator will not adequately address the complexity of SIRS. We propose that chemically modified tetracycline-3, CMT-3 (or COL-3), a non-antimicrobial modified tetracycline with pleiotropic anti-inflammatory properties, is an excellent agent for the management of sepsis and its associated complication of the acute respiratory distress syndrome (ARDS). The purpose of this review is threefold: (1) to examine the shortcomings of current approaches to treatment of sepsis and ARDS in light of their pathophysiology, (2) to explore the application of COL-3 in ARDS and sepsis, and finally (3) to elucidate the mechanisms of COL-3 that may have potential therapeutic benefit in ARDS and sepsis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Acute lung injury and fibrosis in a baboon model of Escherichia coli sepsis.

    PubMed

    Keshari, Ravi S; Silasi-Mansat, Robert; Zhu, Hua; Popescu, Narcis I; Peer, Glenn; Chaaban, Hala; Lambris, John D; Polf, Holly; Lupu, Cristina; Kinasewitz, Gary; Lupu, Florea

    2014-02-01

    Sepsis-induced inflammation of the lung leads to acute respiratory distress syndrome (ARDS), which may trigger persistent fibrosis. The pathology of ARDS is complex and poorly understood, and the therapeutic approaches are limited. We used a baboon model of Escherichia coli sepsis that mimics the complexity of human disease to study the pathophysiology of ARDS. We performed extensive biochemical, histological, and functional analyses to characterize the disease progression and the long-term effects of sepsis on the lung structure and function. Similar to humans, sepsis-induced ARDS in baboons displays an early inflammatory exudative phase, with extensive necrosis. This is followed by a regenerative phase dominated by proliferation of type 2 epithelial cells, expression of epithelial-to-mesenchymal transition markers, myofibroblast migration and proliferation, and collagen synthesis. Baboons that survived sepsis showed persistent inflammation and collagen deposition 6-27 months after the acute episodes. Long-term survivors had almost double the amount of collagen in the lung as compared with age-matched control animals. Immunostaining for procollagens showed persistent active collagen synthesis within the fibroblastic foci and interalveolar septa. Fibroblasts expressed markers of transforming growth factor-β and platelet-derived growth factor signaling, suggesting their potential role as mediators of myofibroblast migration and proliferation, and collagen deposition. In parallel, up-regulation of the inhibitors of extracellular proteases supports a deregulated matrix remodeling that may contribute to fibrosis. The primate model of sepsis-induced ARDS mimics the disease progression in humans, including chronic inflammation and long-lasting fibrosis. This model helps our understanding of the pathophysiology of fibrosis and the testing of new therapies.

  9. Enrichment of the Lung Microbiome with Gut Bacteria in Sepsis and the Acute Respiratory Distress Syndrome

    PubMed Central

    Dickson, Robert P.; Singer, Benjamin H.; Newstead, Michael W.; Falkowski, Nicole R.; Erb-Downward, John R.; Standiford, Theodore J.; Huffnagle, Gary B.

    2016-01-01

    SUMMARY Sepsis and the acute respiratory distress syndrome (ARDS) are major causes of mortality without targeted therapies. Although many experimental and clinical observations have implicated gut microbiota in the pathogenesis of these diseases, culture-based studies have failed to demonstrate translocation of bacteria to the lungs in critically ill patients. Here we report culture-independent evidence that the lung microbiome is enriched with gut bacteria both in a murine model of sepsis and in humans with established ARDS. Following experimental sepsis, lung communities were dominated by viable gut-associated bacteria. Ecologic analysis identified the lower gastrointestinal tract, rather than the upper respiratory tract, as the likely source community of post-sepsis lung bacteria. In bronchoalveolar lavage fluid from humans with ARDS, gut-specific bacteria (Bacteroides spp.) were common and abundant, undetected by culture, and correlated with the intensity of systemic inflammation. Alveolar TNF-α, a key mediator of alveolar inflammation in ARDS, was significantly correlated with altered lung microbiota. Our results demonstrate that the lung microbiome is enriched with gut-associated bacteria in sepsis and ARDS, potentially representing a shared mechanism of pathogenesis in these common and lethal diseases. PMID:27670109

  10. A CXCL2 polymorphism is associated with better outcomes in patients with severe sepsis.

    PubMed

    Villar, Jesús; Pérez-Méndez, Lina; Flores, Carlos; Maca-Meyer, Nicole; Espinosa, Elena; Muriel, Arturo; Sangüesa, Rubén; Blanco, Jesús; Muros, Mercedes; Kacmarek, Robert M

    2007-10-01

    Several studies have implicated the CXCL2 chemokine as a mediator in the development of sepsis. We hypothesized that a tandem repeat polymorphism (AC)n in the CXCL2 gene, previously associated with susceptibility to severe sepsis, contributes to morbidity and mortality in severe sepsis. Prospective, observational, genetic study of septic patients. A network of Spanish postsurgical and critical care units. A total of 183 critically ill patients fulfilling the International Sepsis Criteria for severe sepsis. None. Patients were classified into three groups according to the presence of compound 24 +/- 1 (AC) repeat genotypes: homozygote 24 +/- 1 carriers (HC group), heterozygote 24 +/- 1 carriers (HTC), and non 24 +/- 1 carriers (NC group). Mortality, development of acute respiratory distress syndrome, and number of failing organs were determined for each group. Overall mortality was 46.4%. HC patients had a lower mortality (39.9%) than HTC (52.2%) and NC (72.7%) patients (trend test p = .018). This difference remained significant when using a multiple logistic regression analysis (p = .035). The presence of population stratification was ruled out, since 20 independent genomic control markers demonstrated homogeneity among groups. An exploratory analysis of the effect of acute respiratory distress syndrome on mortality showed a relative risk of 2.60 in the HC group (p = .0004), while in the nonhomozygote carriers (NHC) group the relative risk was 3.34 (p = .0001). Our data suggest that a tandem repeat polymorphism (AC)n at position -665 in the CXCL2 gene may be an independent predictor of mortality for severe sepsis. Additional studies are needed to confirm these results. (C) 2007 Lippincott Williams & Wilkins, Inc.

  11. Management and outcomes of severe dengue patients presenting with sepsis in a tropical country.

    PubMed

    Teparrukkul, Prapit; Hantrakun, Viriya; Day, Nicholas P J; West, T Eoin; Limmathurotsakul, Direk

    2017-01-01

    Dengue is a common cause of infection in adults in tropical countries. Sepsis is a syndrome of systemic manifestations induced by infection of any organisms; including bacterial, fungal and viral agents. Here, we investigated the diagnosis, management and outcomes of dengue patients presenting with sepsis in a prospective study of community-acquired sepsis in Thailand. From June to December 2015, 874 adult patients (age≥18 years) with suspected or documented community-acquired infection, with ≥3 diagnostic criteria for sepsis according to the Surviving Sepsis Campaign 2012, and within 24 hours of admission were evaluated. Serum was stored and later tested for dengue PCR assays. A total of 126 patients had dengue PCR assays positive (2 DENV-1, 12 DENV-2, 24 DENV-3 and 88 DENV-4), and 5 of them (4%) died. We found that attending physicians suspected dengue infection on admission in 84 patients (67%), and recorded dengue infection as the final diagnosis in 96 patients (76%). Four of five fatal cases were diagnosed and treated as septic shock not due to dengue. In multivariable analysis, there was a trend showing that age≥60 years, hypoxemia and misdiagnosis of dengue by attending physicians were associated with 28-day mortality. A number of adult patients who died of dengue are misdiagnosed as severe sepsis and septic shock. Diagnosis of dengue based on clinical features alone is difficult. Rapid diagnostic tests for dengue may need to be routinely used in adult patients presenting with sepsis and septic shock in tropical countries. This approach could improve diagnosis and management of those patients.

  12. Chromobacterium Violaceum Sepsis: Rethinking Conventional Therapy to Improve Outcome

    PubMed Central

    Richard, Kathleen R.; Lovvorn, Joshua J.; Oliver, Sara E.; Ross, Shannon A.; Benner, Kim W.; Kong, Michele Y.F.

    2015-01-01

    Patient: Male, 11 Final Diagnosis: Chromobacterium violaceum infection Symptoms: Abscess • fever • rash Medication: — Clinical Procedure: ECMO Specialty: Critical Care Medicine Objective: Rare disease Background: Chromobacterium violaceum (C. violaceum) is a facultative anaerobic gram-negative bacterium found in soil and water, especially in tropical and subtropical areas. Although infection in humans is rare, it is associated with significant morbidity. The bacterium is known for its resistance to multiple antimicrobials, and the possibility of relapse and reinfection. Presence of bacteremia, disseminated infection, and ineffective antimicrobial agents are predictors of mortality. Case Report: We report the case of a previously healthy 11-year-old male with C. violaceum sepsis who was exposed to stagnant water. He presented with severe septic shock and developed multi-organ system failure. Initial presumptive diagnosis was staphylococcal infection secondary to presence of skin abscesses resulting in antibiotic coverage with vancomycin, clindamycin, nafcillin and ceftriaxone. He also had multiple lung and liver abscesses. Once C. violaceum was identified, he received meropenem and ciprofloxacin, and was later discharged on ertapenem and trimethoprim-sulfamethoxazole (TMP-SMX) to complete a total of six months of antibiotics. He was diagnosed with chronic granulomatous disease (CGD) and is currently on prophylactic TMP-SMX and itraconazole. He has not had any relapses since his initial presentation. Conclusions: This case highlights the importance of considering C. violaceum as a relevant human pathogen, and considering it early in temperate regions, particularly in cases of fulminant sepsis associated with multi-organ abscesses. Once C. violaceum is identified, appropriate antimicrobial therapy should be started promptly, and sufficient duration of treatment is necessary for successful therapy. PMID:26477750

  13. Epidemiology and Outcome of Severe Sepsis and Septic Shock in Surgical Intensive Care Units in Northern Taiwan.

    PubMed

    Huang, Chun-Ta; Tsai, Yi-Ju; Tsai, Pi-Ru; Yu, Chong-Jen; Ko, Wen-Je

    2015-11-01

    Severe sepsis remains the leading cause of mortality in the critically ill. Local epidemiological studies on sepsis are of paramount importance to increase our knowledge about sepsis features and to improve patient care and prognosis.Adult patients (≥20 years) admitted to the surgical intensive care units with severe sepsis or septic shock from 2009 to 2010 were retrospectively retrieved and analyzed. The primary outcome of interest was 28-day mortality.Of 7795 admissions, 536 (6.9%) patients had severe sepsis. The most common sites of infection were the respiratory tract (38%) and abdomen (33%). Gram-negative bacteria, particularly Klebsiella pneumoniae (8.6%) and Escherichia coli (6.0%), were the major infecting micro-organisms, responsible for approximately two-thirds of the severe sepsis episodes. The overall 28-day mortality rate was 61%, and a higher sequential organ failure assessment score and the use of mechanical ventilation were independently associated with a worse outcome.Admissions with severe sepsis are not uncommon and are associated with substantial 28-day mortality in surgical intensive care units in northern Taiwan. Establishment and optimization of each institutional sepsis care standard to improve the outcome of sepsis are warranted.

  14. Epidemiology and outcome of sepsis syndromes in Italian ICUs: a muticentre, observational cohort study in the region of Piedmont.

    PubMed

    Sakr, Y; Elia, C; Mascia, L; Barberis, B; Cardellino, S; Livigni, S; Fiore, G; Filippini, C; Ranieri, V M

    2013-09-01

    Sepsis is an important cause of mortality and morbidity in the intensive care unit (ICU). We performed a study to describe the epidemiology of sepsis syndromes in patients admitted to ICUs of the Piedmont region. In this prospective, multicentre, observational study, all 3902 patients admitted to a network of 24 ICUs from 17 hospitals during a 180 day period (April 3-September 29, 2006) were included. Patients were followed from the first day of admission until death or ICU discharge. The incidence of sepsis during the ICU stay was 11.4% (N.=446), corresponding to an incidence of 25 cases/100,000 inhabitants/year; 141 (31.6%) patients had only sepsis, 160 patients had severe sepsis (35.9%) and 145 patients (32.5%) had septic shock In 227 patients (50.9%), sepsis was observed within 48 hours after admission to the ICU, and 219 patients (49.1%) developed ICU-acquired sepsis. The main sources of infection were the lungs, abdomen, and urinary tract. ICU mortality was higher (41.3 vs. 17.3%, P<0.0001) and the median ICU length of stay longer (15 vs. 2 days, P<0.0001) in patients with sepsis than in those without sepsis. The mortality rate increased with the severity of sepsis. ICU-acquired sepsis was associated with higher ICU mortality rates than sepsis occurring within 48 hours of ICU admission (49.8 vs. 33.0%, P<0.0001). Sepsis is a common occurrence in critically ill patients. Our data underscore the regional variability in the epidemiology and outcome of sepsis syndromes and may be useful to guide appropriate resource allocation.

  15. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

    PubMed

    Mithal, Leena B; Palac, Hannah L; Yogev, Ram; Ernst, Linda M; Mestan, Karen K

    2017-01-01

    Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

  16. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants

    PubMed Central

    Palac, Hannah L.; Yogev, Ram; Ernst, Linda M.; Mestan, Karen K.

    2017-01-01

    Background Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. Methods In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. Results cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants. Conclusion This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and

  17. Positive blood culture is not associated with increased mortality in patients with sepsis-induced acute respiratory distress syndrome.

    PubMed

    Yang, Szu-Chun; Liao, Kuang-Ming; Chen, Chang-Wen; Lin, Wei-Chieh

    2013-11-01

    Previous studies have demonstrated that positive blood culture could contribute to poorer outcomes in patients with pneumonia. However, the impact of positive blood culture on the outcomes of patients with sepsis-induced acute respiratory distress syndrome (ARDS) has not been evaluated. An observational study that prospectively screened 4861 patients admitted to medical or surgical intensive care units (ICUs) of a tertiary referral centre was performed. Among 4861 admitted patients, 146 diagnosed with sepsis-induced ARDS were enrolled (mean age: 66.1 years). Lower PaO2 /FiO2 , decreased respiratory system compliance, and higher lung injury scores (LIS) on the day of ARDS diagnosis were associated with positive blood cultures (n = 68) rather than negative blood cultures (n = 78). There was no relationship between positive blood culture and in-hospital mortality. Kaplan-Meier estimates also revealed that positive blood culture was not associated with 60-day mortality but with an increased length of stay in the hospital and in the ICU (P = 0.007 and P = 0.016, respectively). Using multivariate logistic regression, higher LIS was independently associated with positive blood culture. In addition, chronic pulmonary disease, lower platelet count, higher LIS, and the development of shock on the diagnosis of ARDS, were independent risk factors for in-hospital mortality. This study suggests that the presence of positive blood culture is not associated with increased mortality; however, the mean durations of hospital and ICU stays in patients with sepsis-induced ARDS are increased. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  18. Sepsis Prevalence and Outcome on the General Wards and Emergency Departments in Wales: Results of a Multi-Centre, Observational, Point Prevalence Study

    PubMed Central

    Ellis, Gemma; Morgan, Paul; Kopczynska, Maja; Dhadda, Amrit; Mann, Charlotte; Donoghue, Danielle; Rollason, Sarah; Brownlow, Emma; Hill, Francesca; Carr, Grace; Turley, Hannah; Hassall, James; Lloyd, James; Davies, Llywela; Atkinson, Michael; Jones, Molly; Jones, Nerys; Martin, Rhodri; Ibrahim, Yousef; Hall, Judith E.

    2016-01-01

    Data on sepsis prevalence on the general wards is lacking on the UK and in the developed world. We conducted a multicentre, prospective, observational study of the prevalence of patients with sepsis or severe sepsis on the general wards and Emergency Departments (ED) in Wales. During the 24-hour study period all patients with NEWS≥3 were screened for presence of 2 or more SIRS criteria. To be eligible for inclusion, patients had to have a high clinical suspicion of an infection, together with a systemic inflammatory response (sepsis) and evidence of acute organ dysfunction and/or shock (severe sepsis). There were 5317 in-patients in the 24-hour study period. Data were returned on 1198 digital data collection forms on patients with NEWS≥3 of which 87 were removed, leaving 1111 for analysis. 146 patients had sepsis and 144 patients had severe sepsis. Combined prevalence of sepsis and severe sepsis was 5.5% amongst all in-patients. Patients with sepsis had significantly higher NEWS scores (3 IQR 3–4 for non-sepsis and 4 IQR 3–6 for sepsis patients, respectively). Common organ dysfunctions in severe sepsis were hypoxia (47%), hypoperfusion (40%) and acute kidney injury (25%). Mortality at 90 days was 31% with a median (IQR) hospital free stay of 78 (36–85) days. Screening for sepsis, referral to Critical Care and completion of Sepsis 6 bundle was low: 26%, 16% and 12% in the sepsis group. Multivariable logistic regression analysis identified higher National Early Warning Score, diabetes, COPD, heart failure, malignancy and current or previous smoking habits as independent variables suggesting the diagnosis of sepsis. We observed that sepsis is more prevalent in the general ward and ED than previously suggested before and that screening and effective treatment for sepsis and severe sepsis is far from being operationalized in this environment, leading to high 90 days mortality. PMID:27907062

  19. Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects

    PubMed Central

    Yasuda, Hideo; Yuen, Peter S.T.; Hu, Xuzhen; Zhou, Hua; Star, Robert A.

    2008-01-01

    Acute kidney injury (AKI) occurs in about half of patients in septic shock and the mortality of AKI with sepsis is extremely high. An effective therapeutic intervention is urgently required. Statins are HMG-CoA reductase inhibitors that also have pleiotropic actions. They have been reported to increase survival of septic or infectious patients. But the effect of simvastatin, a widely used statin, on sepsis-induced AKI is unknown. The effects of simvastatin and TNF-alpha neutralizing antibody were studied in a clinically relevant model of sepsis-induced AKI using cecal ligation and puncture (CLP) in elderly mice. Simvastatin siginificantly improved CLP-induced mortality and AKI. Simvastatin attenuated CLP-induced tubular damage and reversed CLP-induced reduction of intrarenal microvascular perfusion and renal tubular hypoxia at 24 hours. Simvastatin also restored towards normal CLP-induced renal vascular protein leak and serum TNF-alpha. Neither delayed simvastatin therapy nor TNF-alpha neutralizing antibody improved CLP-induced AKI. Simvastatin improved sepsis-induced AKI by direct effects on the renal vasculature, reversal of tubular hypoxia, and had a systemic anti-inflammatory effect. PMID:16557230

  20. Renal assist device and treatment of sepsis-induced acute kidney injury in intensive care units.

    PubMed

    Issa, Naim; Messer, Jennifer; Paganini, Emil P

    2007-01-01

    Acute kidney injury (AKI) is a frequent and serious complication of sepsis in ICU patients and is associated with a very high mortality. Despite the advent of sophisticated renal replacement therapies (RRT) employing high-dose hemofiltration and high-flux membranes, mortality and morbidity from sepsis-induced AKI remained high. Moreover, these dialytic modalities could not substitute for the important functions of renal tubular cells in decreasing sepsis-induced AKI biological dysregulations. The results from the in vitro and preclinical animal model studies were very intriguing and led to the development of a bioartificial kidney consisting of a renal tubule assist device containing human proximal tubular cells (RAD) added in tandem to a continuous venovenous hemofiltration circuit. The results from the phase I safety trial and the recent phase II clinical trial showed that the RAD not only can replace many of the indispensable biological kidney functions, but also modify the natural history of sepsis-induced AKI by ameliorating patient survival.

  1. Alkaline phosphatase as a treatment of sepsis-associated acute kidney injury.

    PubMed

    Peters, Esther; van Elsas, Andrea; Heemskerk, Suzanne; Jonk, Luigi; van der Hoeven, Johannes; Arend, Jacques; Masereeuw, Rosalinde; Pickkers, Peter

    2013-01-01

    Currently there are no pharmacological therapies licensed to treat sepsis-associated acute kidney injury (AKI). Considering the high incidence and mortality of sepsis-associated AKI, there is an urgent medical need to develop effective pharmacological interventions. Two phase II clinical trials recently demonstrated beneficial effects of the enzyme alkaline phosphatase (AP). In critically ill patients with sepsis-associated AKI, treatment with AP reduced the urinary excretion of tubular injury biomarkers and plasma markers of inflammation, which was associated with improvement of renal function. The dephosphorylating enzyme, AP, is endogenously present in the renal proximal tubule apical membrane but becomes depleted during ischemia-induced AKI, thereby possibly contributing to further renal damage. The exact mechanism of action of AP in AKI is unknown, but might be related to detoxification of circulating lipopolysaccharide and other proinflammatory mediators that lose their proinflammatory effects after dephosphorylation. Alternatively, tissue damage associated with systemic inflammation might be attenuated by an AP-mediated effect on adenosine metabolism. Adenosine is a signaling molecule that has been shown to protect the body from inflammation-induced tissue injury, which is derived through dephosphorylation of ATP. In this Perspectives article, we discuss the clinical activity of AP and its putative molecular modes of action, and we speculate on its use to treat and possibly prevent sepsis-associated AKI.

  2. Mitochondrial Function in Sepsis

    PubMed Central

    Arulkumaran, Nishkantha; Deutschman, Clifford S.; Pinsky, Michael R.; Zuckerbraun, Brian; Schumacker, Paul T.; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A.

    2015-01-01

    Mitochondria are an essential part of the cellular infrastructure, being the primary site for high energy adenosine triphosphate (ATP) production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered and end organ dysfunction not only common but predictive of long term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used as both a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide. PMID:26871665

  3. Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis.

    PubMed

    Ware, Lorraine B; Magarik, Jordan A; Wickersham, Nancy; Cunningham, Gary; Rice, Todd W; Christman, Brian W; Wheeler, Arthur P; Bernard, Gordon R; Summar, Marshall L

    2013-01-17

    The role of nitric oxide synthase (NOS) in the pathophysiology of acute respiratory distress syndrome (ARDS) is not well understood. Inducible NOS is upregulated during physiologic stress; however, if NOS substrate is insufficient then NOS can uncouple and switch from NO generation to production of damaging peroxynitrites. We hypothesized that NOS substrate levels are low in patients with severe sepsis and that low levels of the NOS substrate citrulline would be associated with end organ damage including ARDS in severe sepsis. Plasma citrulline, arginine and ornithine levels and nitrate/nitrite were measured at baseline in 135 patients with severe sepsis. ARDS was diagnosed by consensus definitions. Plasma citrulline levels were below normal in all patients (median 9.2 uM, IQR 5.2 - 14.4) and were significantly lower in ARDS compared to the no ARDS group (6.0 (3.3 - 10.4) vs. 10.1 (6.2 - 16.6), P = 0.002). The rate of ARDS was 50% in the lowest citrulline quartile compared to 15% in the highest citrulline quartile (P = 0.002). In multivariable analyses, citrulline levels were associated with ARDS even after adjustment for covariates including severity of illness. In severe sepsis, levels of the NOS substrate citrulline are low and are associated with ARDS. Low NOS substrate levels have been shown in other disease states to lead to NOS uncoupling and oxidative injury suggesting a potential mechanism for the association between low citrulline and ARDS. Further studies are needed to determine whether citrulline supplementation could prevent the development of ARDS in patients with severe sepsis and to determine its role in NOS coupling and function.

  4. Biomarkers of lung epithelial injury and inflammation distinguish severe sepsis patients with acute respiratory distress syndrome.

    PubMed

    Ware, Lorraine B; Koyama, Tatsuki; Zhao, Zhiguo; Janz, David R; Wickersham, Nancy; Bernard, Gordon R; May, Addison K; Calfee, Carolyn S; Matthay, Michael A

    2013-10-24

    Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis. This was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS. Using the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days. Abnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury.

  5. Type 2 Deiodinase and Host Responses of Sepsis and Acute Lung Injury

    PubMed Central

    Ma, Shwu-Fan; Xie, Lishi; Pino-Yanes, Maria; Sammani, Saad; Wade, Michael S.; Letsiou, Eleftheria; Siegler, Jessica; Wang, Ting; Infusino, Giovanni; Kittles, Rick A.; Flores, Carlos; Zhou, Tong; Prabhakar, Bellur S.; Moreno-Vinasco, Liliana; Villar, Jesus; Jacobson, Jeffrey R.; Dudek, Steven M.

    2011-01-01

    The role of thyroid hormone metabolism in clinical outcomes of the critically ill remains unclear. Using preclinical models of acute lung injury (ALI), we assessed the gene and protein expression of type 2 deiodinase (DIO2), a key driver for synthesis of biologically active triiodothyronine, and addressed potential association of DIO2 genetic variants with ALI in a multiethnic cohort. DIO2 gene and protein expression levels in murine lung were validated by microarrays and immunoblotting. Lung injury was assessed by levels of bronchoalveolar lavage protein and leukocytes. Single-nucleotide polymorphisms were genotyped and ALI susceptibility association assessed. Significant increases in both DIO2 gene and D2 protein expression were observed in lung tissues from murine ALI models (LPS- and ventilator-induced lung injury), with expression directly increasing with the extent of lung injury. Mice with reduced levels of DIO2 expression (by silencing RNA) demonstrated reduced thyroxine levels in plasma and increased lung injury (increased bronchoalveolar lavage protein and leukocytes), suggesting a protective role for DIO2 in ALI. The G (Ala) allele of the Thr92Ala coding single-nucleotide polymorphism (rs225014) was protective in severe sepsis and severe sepsis–associated ALI after adjustments for age, sex, and genetic ancestry in a logistic regression model in European Americans. Our studies indicate that DIO2 is a novel ALI candidate gene, the nonsynonymous Thr92Ala coding variant of which confers ALI protection. Increased DIO2 expression may dampen the ALI inflammatory response, thereby strengthening the premise that thyroid hormone metabolism is intimately linked to the integrated response to inflammatory injury in critically ill patients. PMID:21685153

  6. Body temperature control in sepsis-induced acute lung injury.

    PubMed

    Wang, Giueng-Chueng; Chi, Wei-Ming; Perng, Wan-Cherng; Huang, Kun-Lun

    2003-12-31

    Body temperature is precisely regulated to maintain homeostasis in homeothermic animals. Although it remains unproved whether change of body temperature constitutes a beneficial or a detrimental component of the septic response, temperature control should be an important entity in septic experiments. We investigated the effect of body temperature control on the lipopolysaccharide (LPS)-induced lung injury. Acute lung injury in rats was induced by intratracheal spray of LPS and body temperature was either clamped at 37 degrees C for 5 hours or not controlled. The severity of lung injury was evaluated at the end of the experiment. Intratracheal administration of aerosolized LPS caused a persistent decline in body temperature and a significant lung injury as indicated by an elevation of protein-concentration and LDH activity in the bronchoalveolar lavage (BAL) fluid and wet/dry weight (W/D) ratio of lungs. Administration of LPS also caused neutrophil sequestration and lipid peroxidation in the lung tissue as indicated by increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) production, respectively. Control of body temperature at 37 degrees C after LPS (LPS/BT37, n = 11) significantly reduced acute lung injury as evidenced by decreases in BAL fluid protein concentration (983 +/- 189 vs. 1403 +/- 155 mg/L) and LDH activity (56 +/- 10 vs. 123 +/- 17 deltamAbs/min) compared with the LPS group (n = 11). Although the W/D ratio of lung and MDA level were lower in the rats received temperature control compared with those received LPS only, the differences were not statistically significant. Our results demonstrated that intratracheal administration of aerosolized LPS induced a hypothermic response and acute lung injury in rats and controlling body temperature at a normal range may alleviate the LPS-induced lung injury.

  7. The Role of Obesity in Sepsis Outcome among Critically Ill Patients: A Retrospective Cohort Analysis.

    PubMed

    Papadimitriou-Olivgeris, Matthaios; Aretha, Diamanto; Zotou, Anastasia; Koutsileou, Kyriaki; Zbouki, Aikaterini; Lefkaditi, Aikaterini; Sklavou, Christina; Marangos, Markos; Fligou, Fotini

    2016-01-01

    Background. The objective of this study was to assess the correlation between sepsis, obesity, and mortality of patients admitted to an Intensive Care Unit (ICU). Subjects and Methods. Data of all patients admitted to the ICU of a tertiary hospital during a 28-month period were retrospectively analyzed and included in the study. Results. Of 834 patients included, 163 (19.5%) were obese, while 25 (3.0%) were morbidly obese. Number of comorbidities (P < 0.001), bloodstream infection (P  0.033), and carbapenemase-producing Klebsiella pneumoniae colonization during ICU stay (P  0.005) were significantly associated with obesity, while nonobese patients suffered more frequently from spontaneous intracranial hemorrhage (P  0.038). Total ICU mortality was 22.5%. Increased mortality among obese ICU patients was observed. Sepsis was the main condition of admission for which obese patients had statistically lower survival than normal weight subjects (76.3% versus 43.7%; P  0.001). Mortality of septic patients upon admission was independently associated with SOFA score upon ICU admission (P  0.003), obesity (P  0.014), pneumonia (P  0.038), and development of septic shock (P  0.015). Conclusions. Our study revealed that sepsis upon ICU admission is adversely influenced by obesity but further studies are needed in order to assess the role of obesity in sepsis outcome.

  8. The Role of Obesity in Sepsis Outcome among Critically Ill Patients: A Retrospective Cohort Analysis

    PubMed Central

    Papadimitriou-Olivgeris, Matthaios; Zotou, Anastasia; Koutsileou, Kyriaki; Zbouki, Aikaterini; Lefkaditi, Aikaterini; Sklavou, Christina; Marangos, Markos; Fligou, Fotini

    2016-01-01

    Background. The objective of this study was to assess the correlation between sepsis, obesity, and mortality of patients admitted to an Intensive Care Unit (ICU). Subjects and Methods. Data of all patients admitted to the ICU of a tertiary hospital during a 28-month period were retrospectively analyzed and included in the study. Results. Of 834 patients included, 163 (19.5%) were obese, while 25 (3.0%) were morbidly obese. Number of comorbidities (P < 0.001), bloodstream infection (P  0.033), and carbapenemase-producing Klebsiella pneumoniae colonization during ICU stay (P  0.005) were significantly associated with obesity, while nonobese patients suffered more frequently from spontaneous intracranial hemorrhage (P  0.038). Total ICU mortality was 22.5%. Increased mortality among obese ICU patients was observed. Sepsis was the main condition of admission for which obese patients had statistically lower survival than normal weight subjects (76.3% versus 43.7%; P  0.001). Mortality of septic patients upon admission was independently associated with SOFA score upon ICU admission (P  0.003), obesity (P  0.014), pneumonia (P  0.038), and development of septic shock (P  0.015). Conclusions. Our study revealed that sepsis upon ICU admission is adversely influenced by obesity but further studies are needed in order to assess the role of obesity in sepsis outcome. PMID:27777948

  9. Use of reactive hyperemia - peripheral arterial tonometry and circulating biological markers to predict outcomes in sepsis

    PubMed Central

    Nobre, Vandack; Ataíde, Thiago Bragança; Brant, Luisa Caldeira; Oliveira, Clara Rodrigues; Rodrigues, Lucas Vieira; Ribeiro, Antonio Luiz Pinho; Lopes, Fernanda Barbosa; Saraiva, Ivan Euclides; Andrade, Marcus Vinícius

    2016-01-01

    Objective To evaluate the usefulness and prognostic value of reactive hyperemia - peripheral arterial tonometry in patients with sepsis. Moreover, we investigated the association of reactive hyperemia - peripheral arterial tonometry results with serum levels of certain inflammatory molecules. Methods Prospective study, conducted in an 18-bed mixed intensive care unit for adults. The exclusion criteria included severe immunosuppression or antibiotic therapy initiated more than 48 hours before assessment. We measured the reactive hyperemia - peripheral arterial tonometry on inclusion (day 1) and on day 3. Interleukin-6, interleukin-10, high-mobility group box 1 protein and soluble ST2 levels were measured in the blood obtained upon inclusion. Results Seventeen of the 79 patients (21.6%) enrolled were determined to have reactive hyperemia - peripheral arterial tonometry signals considered technically unreliable and were excluded from the study. Thus, 62 patients were included in the final analysis, and they underwent a total of 95 reactive hyperemia - peripheral arterial tonometry exams within the first 48 hours after inclusion. The mean age was 51.5 (SD: 18.9), and 49 (62%) of the patients were male. Reactive hyperemia indexes from days 1 and 3 were not associated with vasopressor need, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, or 28-day mortality. Among the patients who died, compared with survivors, there was a significant increase in the day 3 reactive hyperemia index compared with day 1 (p = 0.045). There was a weak negative correlation between the day 1 reactive hyperemia - peripheral arterial tonometry index and the levels of high-mobility group box 1 protein (r = -0.287). Conclusion Technical difficulties and the lack of clear associations between the exam results and clinical severity or outcomes strongly limits the utility of reactive hyperemia - peripheral arterial tonometry in septic patients

  10. Use of reactive hyperemia - peripheral arterial tonometry and circulating biological markers to predict outcomes in sepsis.

    PubMed

    Nobre, Vandack; Ataíde, Thiago Bragança; Brant, Luisa Caldeira; Oliveira, Clara Rodrigues; Rodrigues, Lucas Vieira; Ribeiro, Antonio Luiz Pinho; Lopes, Fernanda Barbosa; Saraiva, Ivan Euclides; Andrade, Marcus Vinícius

    2016-01-01

    To evaluate the usefulness and prognostic value of reactive hyperemia - peripheral arterial tonometry in patients with sepsis. Moreover, we investigated the association of reactive hyperemia - peripheral arterial tonometry results with serum levels of certain inflammatory molecules. Prospective study, conducted in an 18-bed mixed intensive care unit for adults. The exclusion criteria included severe immunosuppression or antibiotic therapy initiated more than 48 hours before assessment. We measured the reactive hyperemia - peripheral arterial tonometry on inclusion (day 1) and on day 3. Interleukin-6, interleukin-10, high-mobility group box 1 protein and soluble ST2 levels were measured in the blood obtained upon inclusion. Seventeen of the 79 patients (21.6%) enrolled were determined to have reactive hyperemia - peripheral arterial tonometry signals considered technically unreliable and were excluded from the study. Thus, 62 patients were included in the final analysis, and they underwent a total of 95 reactive hyperemia - peripheral arterial tonometry exams within the first 48 hours after inclusion. The mean age was 51.5 (SD: 18.9), and 49 (62%) of the patients were male. Reactive hyperemia indexes from days 1 and 3 were not associated with vasopressor need, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, or 28-day mortality. Among the patients who died, compared with survivors, there was a significant increase in the day 3 reactive hyperemia index compared with day 1 (p = 0.045). There was a weak negative correlation between the day 1 reactive hyperemia - peripheral arterial tonometry index and the levels of high-mobility group box 1 protein (r = -0.287). Technical difficulties and the lack of clear associations between the exam results and clinical severity or outcomes strongly limits the utility of reactive hyperemia - peripheral arterial tonometry in septic patients admitted to the intensive care unit.

  11. Polymyxin B hemoperfusion prevents acute kidney injury in sepsis model.

    PubMed

    Mitaka, Chieko; Masuda, Takahiro; Kido, Koji; Uchida, Tokujiro; Abe, Shinya; Miyasho, Taku; Tomita, Makoto; Inada, Eiichi

    2016-03-01

    Direct hemoperfusion with a polymyxin B-immobilized column (PMX-DHP) adsorbs endotoxin and has been used for the treatment of septic shock. Yet, the mechanisms by which PMX-DHP acts on acute kidney injury are only partially understood. Rats were anesthetized, tracheostomized, and placed on mechanical ventilation. The animals were randomized to three groups: a cecal ligation and puncture (CLP) + dummy-DHP group (n = 10), a CLP + PMX-DHP group (n = 10), and a sham group (n = 4). Four hours after CLP, a dummy-DHP or PMX-DHP was performed for 1 h. The heart rate, mean arterial pressure, arterial blood gases, and plasma concentrations of creatinine, lactate, potassium, interleukin (IL)-6, and IL-10 were measured at 0 h and 8 h. Eight hours after CLP, the kidney was harvested, and histopathologic examination was performed. The expressions of cleaved poly (ADP-ribose) polymerase (PARP) and nuclear factor (NF)-κB p65 were examined by immunohistochemistry. A terminal deoxynucleotide transferase dUTP nick-end labeling assay was performed to detect apoptotic nuclei in kidney sections. PMX-DHP maintained hemodynamics and the acid-base balance and significantly (P < 0.05) decreased the plasma concentrations of lactate, creatinine, potassium, IL-6, and IL-10 compared with dummy-DHP. PMX-DHP significantly (P < 0.001) attenuated the expressions of cleaved PARP and NF-κB p65 in renal tubular cells and renal tubular cell apoptosis compared with dummy-DHP. These findings suggest that PMX-DHP may protect against acute kidney injury not only by inhibiting the NF-κB signaling pathway but also by preventing renal tubular cell apoptosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Clinical role of serum pre-B cell colony-enhancing factor in ventilated patients with sepsis and acute respiratory distress syndrome.

    PubMed

    Lee, Kwangha; Huh, Jin Won; Lim, Chae-Man; Koh, Younsuck; Hong, Sang-Bum

    2013-10-01

    We measured serum levels of pre-B cell colony-enhancing factor (PBEF), which has been suggested as a novel biomarker of sepsis and acute respiratory distress syndrome (ARDS), and evaluated its use as a prognostic biomarker. PBEF was measured in 104 adult ventilated patients who were diagnosed with sepsis upon admission using an enzyme-linked immunosorbent assay. The mean age of our patients was 62.9 ± 12.1 y, and 62 (59.6%) patients were male. The median PBEF level was 5.4 ng/ml (range 1.1-150.7 ng/ml). Non-survivors (n = 57) demonstrated significantly higher PBEF levels than survivors (18.7 ± 34.5 vs 6.9 ± 6.1 ng/ml; p = 0.022). Most particularly, patients with PBEF levels ≥ 10.4 ng/ml (n = 27) demonstrated higher hospital mortality than patients with PBEF levels < 10.4 ng/ml (n = 77) (74.1% vs. 48.1%; p = 0.025). Univariate logistic analysis determined PBEF ≥ 10.4 ng/ml to be an independent factor associated with hospital survival (hazard ratio = 0.324, 95% confidence interval = 0.123-0.854; p = 0.023). Among patients with sepsis-induced ARDS (n = 59), non-survivors (n = 35) demonstrated significantly higher PBEF levels than survivors (n = 24), but not interleukin-6 (IL-6) levels. Our findings indicate that high PBEF is associated with poor clinical outcomes in ventilated patients with sepsis and sepsis-induced ARDS. Serum PBEF might be a better predictor of mortality than IL-6 in patients with sepsis-induced ARDS.

  13. Ulinastatin is a novel candidate drug for sepsis and secondary acute lung injury, evidence from an optimized CLP rat model.

    PubMed

    Wang, Ning; Liu, Xin; Zheng, Xinchuan; Cao, Hongwei; Wei, Guo; Zhu, Yuanfeng; Fan, Shijun; Zhou, Hong; Zheng, Jiang

    2013-11-01

    Ulinastatin is a potent multivalent serine protease inhibitor, which was recently found with therapeutic potentials in treating sepsis, and the most life-threatening complication of critically ill population. However, the pharmacological features and possible mechanisms need to be further elucidated in reliable and clinical relevant sepsis models. As known, sepsis induced by surgery of cecal ligation and puncture (CLP) is widely accepted as the gold standard animal model, but the inconsistency of outcomes is the most obvious problem. In the present experiments, we reported an improved rat CLP model with much more consistent outcomes using self-made three edged puncture needles in our lab. Results from this optimized model revealed that ulinastatin improved survivals of CLP rats, attenuated proinflammatory response and prevented systemic disorder and organ dysfunction. Ulinastatin was also found to be effective in ameliorating sepsis-related ALI, a syndrome most frequent and fatal in sepsis. The molecular mechanism investigation showed that ulinastatin's protection against ALI was probably related to the down-regulation of NF-κB activity and inhibition of TNF-α, IL-6 and elastase expressions in the lung tissue. In conclusion, based on a successful establishment of optimized rat CLP model ulinastatin is proved to be an effective candidate for sepsis treatment, due to its anti-inflammation and anti-protease activities that ameliorate systemic disorders, prevent organ injuries and thus improve the survival outcomes of sepsis in animals.

  14. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain.

    PubMed

    Ferrer, Ricard; Artigas, Antonio; Levy, Mitchell M; Blanco, Jesús; González-Díaz, Gumersindo; Garnacho-Montero, José; Ibáñez, Jordi; Palencia, Eduardo; Quintana, Manuel; de la Torre-Prados, María Victoria

    2008-05-21

    Concern exists that current guidelines for care of patients with severe sepsis and septic shock are followed variably, possibly due to a lack of adequate education. To determine whether a national educational program based on the Surviving Sepsis Campaign guidelines affected processes of care and hospital mortality for severe sepsis. Before and after design in 59 medical-surgical intensive care units (ICUs) located throughout Spain. All ICU patients were screened daily and enrolled if they fulfilled severe sepsis or septic shock criteria. A total of 854 patients were enrolled in the preintervention period (November-December 2005), 1465 patients during the postintervention period (March-June 2006), and 247 patients during the long-term follow-up period 1 year later (November-December 2006) in a subset of 23 ICUs. The educational program consisted of training physicians and nursing staff from the emergency department, wards, and ICU in the definition, recognition, and treatment of severe sepsis and septic shock as outlined in the guidelines. Treatment was organized in 2 bundles: a resuscitation bundle (6 tasks to begin immediately and be accomplished within 6 hours) and a management bundle (4 tasks to be completed within 24 hours). Hospital mortality, differences in adherence to the bundles' process-of-care variables, ICU mortality, 28-day mortality, hospital length of stay, and ICU length of stay. Patients included before and after the intervention were similar in terms of age, sex, and Acute Physiology and Chronic Health Evaluation II score. At baseline, only 3 process-of-care measurements (blood cultures before antibiotics, early administration of broad-spectrum antibiotics, and mechanical ventilation with adequate inspiratory plateau pressure) we had compliance rates higher than 50%. Patients in the postintervention cohort had a lower risk of hospital mortality (44.0% vs 39.7%; P = .04). The compliance with process-of-care variables also improved after the

  15. Liver proteomics for therapeutic drug discovery: inhibition of the cyclophilin receptor CD147 attenuates sepsis-induced acute renal failure

    PubMed Central

    Dear, James W.; Leelahavanichkul, Asada; Aponte, Angel; Hu, Xuzhen; Constant, Stephanie L.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

    2008-01-01

    Objective Sepsis-induced multi-organ failure continues to have a high mortality. The liver is an organ central to the disease pathogenesis. The objective of this study was to identify the liver proteins that change in abundance with sepsis and, therefore, identify new drug targets. Design Proteomic discovery study and drug target validation Setting Research institute laboratory Subjects Three month old C57BL/6 mice Interventions We used a mouse model of sepsis based on cecal ligation and puncture (CLP) but with fluid and antibiotic resuscitation. Liver proteins that changed in abundance were identified by difference in-gel electrophoresis (DIGE). We compared liver proteins from 6 hr post-CLP to sham-operated mice (‘early proteins’) and 24 hr post-CLP with 6 hr post-CLP (‘late proteins’). Proteins that changed in abundance were identified by tandem mass spectrometry. We then inhibited the receptor for one protein and determined the effect on sepsis-induced organ dysfunction. Results The liver proteins that changed in abundance after sepsis had a range of functions such as acute phase proteins, coagulation, ER stress, oxidative stress, apoptosis, mitochondrial proteins and nitric oxide metabolism. We found that cyclophilin increased in abundance after CLP. When the receptor for this protein, CD147, was inhibited sepsis-induced renal dysfunction was reduced. There was also a significant reduction in serum cytokine production when CD147 was inhibited. Conclusion By applying proteomics to a clinically relevant mouse model of sepsis we identified a number of novel proteins that changed in abundance. The inhibition of the receptor for one of these proteins, cyclophilin, attenuated sepsis-induced acute renal failure. The application of proteomics to sepsis research can facilitate the discovery of new therapeutic targets. PMID:17944020

  16. Alkaline phosphatase: a possible treatment for sepsis-associated acute kidney injury in critically ill patients.

    PubMed

    Peters, Esther; Heemskerk, Suzanne; Masereeuw, Rosalinde; Pickkers, Peter

    2014-06-01

    Acute kidney injury (AKI) is a common disease in the intensive care unit and accounts for high morbidity and mortality. Sepsis, the predominant cause of AKI in this setting, involves a complex pathogenesis in which renal inflammation and hypoxia are believed to play an important role. A new therapy should be aimed at targeting both these processes, and the enzyme alkaline phosphatase, with its dual mode of action, might be a promising candidate. First, alkaline phosphatase is able to reduce inflammation through dephosphorylation and thereby detoxification of endotoxin (lipopolysaccharide), which is an important mediator of sepsis. Second, adenosine triphosphate, released during cellular stress caused by inflammation and hypoxia, has detrimental effects but can be converted by alkaline phosphatase into adenosine with anti-inflammatory and tissue-protective effects. These postulated beneficial effects of alkaline phosphatase have been confirmed in animal experiments and two phase 2a clinical trials showing that kidney function improved in critically ill patients with sepsis-associated AKI. Because renal inflammation and hypoxia also are observed commonly in AKI induced by other causes, it would be of interest to investigate the therapeutic effect of alkaline phosphatase in these nephropathies as well.

  17. [Bacillus cereus sepsis and subarachnoid hemorrhage following consolidation chemotherapy for acute myelogenous leukemia].

    PubMed

    Kawatani, Eri; Kishikawa, Yuki; Sankoda, Chikahiro; Kuwahara, Nobuo; Mori, Daisuke; Osoegawa, Kouichi; Matsuishi, Eijo; Gondo, Hisashi

    2009-04-01

    A 64-year-old man with acute myelogenous leukemia (FAB classification, M7) in remission received consolidation chemotherapy with mitoxantrone/cytosine arabinoside. WBC counts decreased to 0/microl on day 14, and fever (39.3 degrees C) and epigastralgia developed on day 15. Cefozopran was instituted for febrile neutropenia; however, on day 16, he was found to be in cardiac arrest. CT scan on day 16 revealed subarachnoid hemorrhage. Gram-positive rods were isolated from blood cultures on day 15, and were later identified as B.cereus. He recovered transiently, but eventually died on day 19. Postmortem examination demonstrated many colonies of B. cereus in the cerebrum, cerebellum, lung, and liver. Hepatocyte necrosis was also observed in the liver. Bacterial aneurysms or septic emboli were not identified in the arachnoid vessels, but necrosis of cerebral vessels was prominent, which was considered to be the cause of subarachnoid hemorrhage. Fatal subarachnoid hemorrhage has been reported to be associated with B. cereus sepsis, which developed at nadir following chemotherapy for leukemia patients. Because of the aggressive clinical course of B. cereus sepsis, including the risk for subarachnoid hemorrhage, early treatment with effective antibiotics for B. cereus sepsis would be important in the management of leukemia patients after chemotherapy.

  18. Genetic Determinants and Ethnic Disparities in Sepsis-associated Acute Lung Injury

    PubMed Central

    Barnes, Kathleen C.

    2005-01-01

    Acute lung injury (ALI) is a common and devastating illness that occurs in the context of sepsis and other systemic inflammatory disorders. In systemic illnesses like sepsis, only a subset of patients develops ALI even when pathologic stimuli are apparently equivalent, suggesting that there are genetic features that may influence its onset. Considerable obstacles in defining the exact nature of the pathogenesis of ALI include substantial phenotypic variance, incomplete penetrance, complex gene–environment interactions and a strong potential for locus heterogeneity. Moreover, ALI arises in a critically ill population with diverse precipitating factors and appropriate controls that best match the reference population have not been agreed upon. The sporadic nature of ALI precludes conventional approaches such as linkage mapping for the elucidation of candidate genes, but tremendous progress has been made in combining robust, genomic tools such as high-throughput, expression profiling with case-control association studies in well characterized populations. Similar to trends observed in common, complex traits such as hypertension and diabetes, some of these studies have highlighted differences in allelic variant frequencies between European American and African American ALI patients for novel genes which may explain, in part, the complex interplay between ethnicity, sepsis and the development of ALI. In trying to understand the basis for contemporary differences in allelic frequency, which may lead to differences in susceptibility, the potential role of positive selection for genetic variants in ancestral populations is considered. PMID:16222037

  19. Appropriate antibiotic dosing in severe sepsis and acute renal failure: factors to consider.

    PubMed

    González de Molina, Francisco Javier; Ferrer, Ricard

    2011-08-01

    Severe sepsis and septic shock cause considerable morbidity and mortality. Early appropriate empiric broad-spectrum antibiotics and advanced resuscitation therapy are the cornerstones of treatment for these conditions. In prescribing an antibiotic regimen in septic patients with acute renal failure treated with continuous renal replacement therapy, several factors should be considered: pharmacokinetics, weight, residual renal function, hepatic function, mode of renal replacement therapy (membrane and surface area, sieving coefficient, effluent and dialysate rate, and blood flow rate), severity of illness, microorganism, minimum inhibitory concentration, and others. Studies that determine the serum antibiotic concentrations are very useful in establishing the correct dosage in critical patients.

  20. Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis?

    PubMed Central

    Wernly, Bernhard; Lichtenauer, Michael; Franz, Marcus; Kabisch, Bjoern; Muessig, Johanna; Masyuk, Maryna; Kelm, Malte; Hoppe, Uta C.; Jung, Christian

    2016-01-01

    Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58–77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004–1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075–1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998–1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra-ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient

  1. Circulating high sensitivity troponin T in severe sepsis and septic shock: distribution, associated factors, and relation to outcome

    PubMed Central

    Røsjø, Helge; Varpula, Marjut; Hagve, Tor-Arne; Karlsson, Sari; Ruokonen, Esko; Pettilä, Ville

    2010-01-01

    Purpose To assess the clinical utility of a recently developed highly sensitive cardiac troponin T (hs-cTnT) assay for providing prognostic information on patients with sepsis. Methods cTnT levels were measured by the novel hs-cTnT assay at two time points (inclusion and 72 h thereafter) in a subgroup of patients from the FINNSEPSIS study and associations with clinical outcomes were examined. Results for the hs-cTnT assay were compared to those of the established fourth-generation cTnT assay. Results cTnT measured by the fourth-generation and hs-cTnT assay was detectable in 124 (60%) and 207 (100%) patients, respectively, on inclusion in this study. hs-cTnT levels on inclusion correlated with several indices of risk in sepsis, including the simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores. The level of hs-cTnT on inclusion was higher in hospital non-survivors (n = 47) than survivors (n = 160) (median 0.054 [Q1–3, 0.022–0.227] versus 0.035 [0.015–0.111] μg/L, P = 0.047), but hs-cTnT level was not an independent predictor of in-hospital mortality. hs-cTnT levels on inclusion were also higher in patients with septic shock during the hospitalization (0.044 [0.024–0.171] versus 0.033 [0.012–0.103] μg/L, P = 0.03), while this was not the case for the fourth-generation cTnT assay or NT-proBNP levels. Conclusions Circulating hs-cTnT is present in patients with severe sepsis and septic shock, associates with disease severity and survival, but does not add to SAPS II score for prediction of mortality. hs-cTnT measurement could still have a role in sepsis as an early marker of shock. Electronic supplementary material The online version of this article (doi:10.1007/s00134-010-2051-x) contains supplementary material, which is available to authorized users. PMID:20938765

  2. Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis.

    PubMed

    Cardinal-Fernández, Pablo; Ferruelo, Antonio; El-Assar, Mariam; Santiago, Catalina; Gómez-Gallego, Félix; Martín-Pellicer, Ana; Frutos-Vivar, Fernando; Peñuelas, Oscar; Nin, Nicolás; Esteban, Andrés; Lorente, José A

    2013-03-01

    The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis. Patients older than 18 years admitted to the intensive care unit (ICU) with the diagnosis of severe sepsis were prospectively included. A blood sample was drawn on the first day of ICU admission, and DNA was extracted. We genotyped the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene (polymerase chain reaction) and the following single-nucleotide polymorphisms (TaqMan SNP genotyping assay): tumor necrosis factor α -376 G/A, -308 G/A, and -238 G/A; interleukin 8 -251 T/A; pre-B cell colony-enhancing factor -1001 G/T; and vascular endothelial growth factor +405 C/G and +936 C/T. Polymorphisms were selected based on reports on their association with ARDS. Variables associated in univariate analysis (P < 0.1) with the diagnosis of ARDS were included in a multiple logistic regression analysis. We studied 149 patients, of whom 35 presented ARDS. Variables included in the maximal multivariate model were male sex, chronic alcoholism, use of ACE inhibitors or angiotensin-receptor blockers, Simplified Acute Physiology Score II score, serum glucose concentration at ICU admission, and the presence of the allele D of the ACE gene. After adjustment for those variables, the presence of the allele D of the ACE gene (odds ratio, 4.75; 95% confidence interval, 1.02-22.20; P = 0.048) was significantly associated with the diagnosis of ARDS. The presence of the allele D of the ACE gene is associated with ARDS in patients with severe sepsis.

  3. Early activation of pro-fibrotic WNT5A in sepsis-induced acute lung injury.

    PubMed

    Villar, Jesús; Cabrera-Benítez, Nuria E; Ramos-Nuez, Angela; Flores, Carlos; García-Hernández, Sonia; Valladares, Francisco; López-Aguilar, Josefina; Blanch, Lluís; Slutsky, Arthur S

    2014-10-21

    The mechanisms of lung repair and fibrosis in the acute respiratory distress syndrome (ARDS) are poorly known. Since the role of WNT/β-catenin signaling appears to be central to lung healing and fibrosis, we hypothesized that this pathway is activated very early in the lungs after sepsis. We tested our hypothesis using a three-step experimental design: (1) in vitro lung cell injury model with human bronchial epithelial BEAS-2B and lung fibroblasts (MRC-5) cells exposed to endotoxin for 18 hours; (2) an animal model of sepsis-induced ARDS induced by cecal ligation and perforation, and (3) lung biopsies from patients who died within the first 24 hours of septic ARDS. We examined changes in protein levels of target genes involved in the Wnt pathway, including WNT5A, non-phospho (Ser33/37/Thr41) β-catenin, matrix metalloproteinase-7 (MMP7), cyclin D1, and vascular endothelial growth factor (VEGF) by Western blotting and immunohistochemistry. Finally, we validated the main gene targets of this pathway in experimental animals and human lungs. Protein levels of WNT5A, non-phospho (Ser33/37/Thr41) β-catenin, total β-catenin, MMP7, cyclin D1, and VEGF increased after endotoxin stimulation in BEAS-2B and MRC-5 cells. Lungs from septic animals and from septic humans demonstrated acute lung inflammation, collagen deposition, and marked increase of WNT5A and MMP7 protein levels. Our findings suggest that the WNT/β-catenin signaling pathway is activated very early in sepsis-induced ARDS and could play an important role in lung repair and fibrosis. Modulation of this pathway might represent a potential target for treatment for septic and ARDS patients.

  4. Kallistatin protects against sepsis-related acute lung injury via inhibiting inflammation and apoptosis.

    PubMed

    Lin, Wei-Chieh; Chen, Chang-Wen; Huang, Yu-Wen; Chao, Lee; Chao, Julie; Lin, Yee-Shin; Lin, Chiou-Feng

    2015-07-22

    Kallistatin, an endogenous plasma protein, exhibits pleiotropic properties in inhibiting inflammation, oxidative stress and apoptosis, as evidenced in various animal models and cultured cells. Here, we demonstrate that kallistatin levels were positively correlated with the concentration of total protein in bronchoalveolar lavage fluids (BALF) from patients with sepsis-related acute respiratory distress syndrome (ARDS), indicating a compensatory mechanism. Lower ratio of kallistatin to total protein in BALF showed a significant trend toward elevated neutrophil counts (P = 0.002) in BALF and increased mortality (P = 0.046). In lipopolysaccharide (LPS)-treated mice, expression of human kallistatin in lung by gene transfer with human kallistatin-encoding plasmid ameliorated acute lung injury (ALI) and reduced cytokine/chemokine levels in BALF. These mice exhibited attenuated lung epithelial apoptosis and decreased Fas/FasL expression compared to the control mice. Mouse survival was improved by kallistatin gene transfer or recombinant human kallistatin treatment after LPS challenge. In LPS-stimulated A549 human lung epithelial cells, kallistatin attenuated apoptosis, down-regulated Fas/FasL signaling, suppressed intracellular reactive oxygen species (ROS) and inhibited ROS-mediated NF-κB activation and inflammation. Furthermore, LPS-induced apoptosis was blocked by antioxidant N-acetylcysteine or NF-κB inhibitor via down-regulating Fas expression. These findings suggest the therapeutic potential of kallistatin for sepsis-related ALI/ARDS.

  5. Extracorporeal blood therapy in sepsis and acute respiratory distress syndrome: the "purifying dream".

    PubMed

    Xu, Xuefeng; Dai, Huaping; Jia, Chun'e; Wang, Chen

    2014-01-01

    To discuss the rationale, hypothesis, modality of extracorporeal blood purification (EBP) techniques for the critically ill animal models or patients, and to summarize the experimental and clinical studies with inconsistent data which explored the EBP's efficacy in the areas of critical care medicine. Articles referred in this review were collected from the database of PubMed published in English up to June 2014. We had done a literature search by using the term "(sepsis OR acute lung injury OR acute respiratory distress syndrome) AND (extracorporeal blood purification OR hemofiltration OR hemoperfusion OR plasma exchange OR plasmapheresis OR adsorpiton)". Related original or review articles were included and carefully analyzed. Acute cellular and humoral immune disturbances occur in both sepsis and acute respiratory distress syndrome (ARDS). Treatments aimed at targeting one single pro-/anti-inflammatory mediator have largely failed with no proven clinical benefits. Such failure shifts the therapeutic rationale to the nonspecific, broad-spectrum methods for modulating the over-activated inflammatory and anti-inflammatory response. Therefore, EBP techniques have become the potential weapons with high promise for removing the circulating pro-/anti-inflammatory mediators and promoting immune reconstitution. Over the years, multiple extracorporeal techniques for the critically ill animal models or patients have been developed, including hemofiltration (HF), high-volume hemofiltration (HVHF), high-cutoff hemofiltration (HCO-HF), hemo-perfusion or -adsorption (HP/HA), coupled plasma filtration adsorption (CPFA), and plasma exchange (PE). These previous studies showed that EBP therapy was feasible and safe for the critically ill animal models or patients. However, data on their efficacy (especially on the clinical benefits, such as mortality) were inconsistent. It is not now to conclude that EBP intervention can purify septic or ARDS patients with high clinical efficacy

  6. Renal outcome after vancomycin treatment and renal replacement therapy in patients with severe sepsis and septic shock: a retrospective study.

    PubMed

    Otto, Gordon P; Sossdorf, Maik; Breuel, Hannes; Schlattmann, Peter; Bayer, Ole; Claus, Ralf A; Riedemann, Niels C; Busch, Martin

    2014-08-01

    Acute kidney injury during systemic infections is common; however, renal outcome is poorly investigated. The increase of multiresistant pathogens leads to the use of potential nephrotoxic antibiotics as vancomycin. We investigated the impact of vancomycin and renal replacement therapy (RRT) for renal recovery during sepsis. This is a retrospective data analysis of 1159 patients with severe sepsis or septic shock. Logistic regression models were performed. In total, 390 (33.6%) patients required RRT during intensive care unit (ICU) stay; 233 (20.1%), at discharge. Admission estimated glomerular filtration rate (eGFR) predicted the need of RRT during stay (odds ratio [OR] 0.969 [0.959-0.979] per increase of 1 mL/min, P<.001) and the prolonged need of RRT at ICU discharge (OR 0.979 [0.967-0.990], P<.001). Survivors without any RRT showed an improvement of eGFR at discharge, whereas patients after RRT did not (7.1 vs 0.8 mL/[min 1.73 m2], P<.001). The use (OR 1.648 [1.067-2.546], P<.05) and duration of vancomycin treatment (OR 1.043 [1.004-1.084] per each additional treatment day, P<.05) were predictors for ongoing RRT at discharge. Estimated GFR at ICU admission predicts renal outcome, whereas the use of vancomycin increases the probability of a prolonged need for RRT at discharge from ICU. The use of alternative antibiotics for certain patients, indicated by eGFR at admission, might be considered. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Understanding brain dysfunction in sepsis

    PubMed Central

    2013-01-01

    Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors. PMID:23718252

  8. Ketamine attenuates sepsis-induced acute lung injury via regulation of HMGB1-RAGE pathways.

    PubMed

    Li, Kehan; Yang, Jianxue; Han, Xuechang

    2016-05-01

    High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play important roles in the development of sepsis-induced acute lung injury (ALI). Ketamine is considered to confer protective effects on ALI during sepsis. In this study, we investigated the effects of ketamine on HMGB1-RAGE activation in a rat model of sepsis-induced ALI. ALI was induced in wild type (WT) and RAGE deficient (RAGE(-/-)) rats by cecal ligation and puncture (CLP) or HMGB1 to mimic sepsis-induced ALI. Rats were randomly divided to six groups: sham-operation+normal saline (NS, 10 mL/kg), sham-operation+ketamine (10 mg/kg), CLP/HMGB1+NS (10 mL/kg), CLP/HMGB1+ketamine (5 mg/kg), CLP/HMGB1+ketamine (7.5 mg/kg), and CLP/HMGB1+ketamine (10 mg/kg) groups. NS and ketamine were administered at 3 and 12 h after CLP/HMGB1 via intraperitoneal injection. Pathological changes of lung, inflammatory cell counts, expression of HMGB1 and RAGE, and concentrations of various inflammatory mediators in bronchoalveolar lavage fluids (BALF) and lung tissue were then assessed. Nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in the lung were also evaluated. CLP/HMGB1 increased the wet to dry weight ratio and myeloperoxidase activity in lung, the number of total cells, neutrophils, and macrophages in the BALF, and inflammatory mediators in the BALF and lung tissues. Moreover, expression of HMGB1 and RAGE in lung tissues was increased after CLP. Ketamine inhibited all the above effects. It also inhibited the activation of IκB-α, NF-κB p65, and MAPK. Ketamine protects rats against HMGB1-RAGE activation in a rat model of sepsis-induced ALI. These effects may partially result from reductions in NF-κB and MAPK. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  9. AP214, an analogue of α-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality

    PubMed Central

    Doi, Kent; Hu, Xuzhen; Yuen, Peter S.T.; Leelahavanichkul, Asada; Yasuda, Hideo; Kim, Soo Mi; Schnermann, Jürgen; Jonassen, Thomas E.N.; Frøkiær, Jørgen; Nielsen, Søren; Star, Robert A.

    2008-01-01

    Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. α-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new α-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 hr after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-α and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-κB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis. PMID:18354376

  10. Patterns of gene expression in peripheral blood mononuclear cells and outcomes from patients with sepsis secondary to community acquired pneumonia.

    PubMed

    Severino, Patricia; Silva, Eliézer; Baggio-Zappia, Giovana Lotici; Brunialti, Milena Karina Coló; Nucci, Laura Alejandra; Rigato, Otelo; da Silva, Ismael Dale Cotrim Guerreiro; Machado, Flávia Ribeiro; Salomao, Reinaldo

    2014-01-01

    Mechanisms governing the inflammatory response during sepsis have been shown to be complex, involving cross-talk between diverse signaling pathways. Current knowledge regarding the mechanisms underlying sepsis provides an incomplete picture of the syndrome, justifying additional efforts to understand this condition. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis. In this study, we investigate whole-genome expression profiles in mononuclear cells from survivors (n = 5) and non-survivors (n = 5) of sepsis. To circumvent the heterogeneity of septic patients, only patients admitted with sepsis caused by community-acquired pneumonia were included. Blood samples were collected at the time of sepsis diagnosis and seven days later to evaluate the role of biological processes or genes possibly involved in patient recovery. Principal Components Analysis (PCA) profiling discriminated between patients with early sepsis and healthy individuals. Genes with differential expression were grouped according to Gene Ontology, and most genes related to immune defense were up-regulated in septic patients. Additionally, PCA in the early stage was able to distinguish survivors from non-survivors. Differences in oxidative phosphorylation seem to be associated with clinical outcome because significant differences in the expression profile of genes related to mitochondrial electron transport chain (ETC) I-V were observed between survivors and non-survivors at the time of patient enrollment. Global gene expression profiles after seven days of sepsis progression seem to reproduce, to a certain extent, patterns collected at the time of diagnosis. Gene expression profiles comparing admission and follow-up samples differed between survivors and non-survivors, with decreased expression of genes related to immune functions in non-survivors. In conclusion, genes related to host defense and inflammatory response

  11. Outcome prediction in sepsis: Speckle tracking echocardiography based assessment of myocardial function

    PubMed Central

    2014-01-01

    Introduction Speckle tracking echocardiography (STE) is a relatively novel and sensitive method for assessing ventricular function and may unmask myocardial dysfunction not appreciated with conventional echocardiography. The association of ventricular dysfunction and prognosis in sepsis is unclear. We sought to evaluate frequency and prognostic value of biventricular function, assessed by STE in patients with severe sepsis or septic shock. Methods Over an eighteen-month period, sixty patients were prospectively imaged by transthoracic echocardiography within 24 hours of meeting severe sepsis criteria. Myocardial function assessment included conventional measures and STE. Association with mortality was assessed over 12 months. Results Mortality was 33% at 30 days (n = 20) and 48% at 6 months (n = 29). 32% of patients had right ventricle (RV) dysfunction based on conventional assessment compared to 72% assessed with STE. 33% of patients had left ventricle (LV) dysfunction based on ejection fraction compared to 69% assessed with STE. RV free wall longitudinal strain was moderately associated with six-month mortality (OR 1.1, 95% confidence interval, CI, 1.02-1.26, p = 0.02, area under the curve, AUC, 0.68). No other conventional echocardiography or STE method was associated with survival. After adjustment (for example, for mechanical ventilation) severe RV free wall longitudinal strain impairment remained associated with six-month mortality. Conclusion STE may unmask systolic dysfunction not seen with conventional echocardiography. RV dysfunction unmasked by STE, especially when severe, was associated with high mortality in patients with severe sepsis or septic shock. LV dysfunction was not associated with survival outcomes. PMID:25015102

  12. Sepsis may not be a risk factor for mortality in patients with acute kidney injury treated with continuous renal replacement therapy.

    PubMed

    Nagata, Isao; Uchino, Shigehiko; Tokuhira, Natsuko; Ohnuma, Tetsu; Namba, Yoshitomo; Katayama, Shinshu; Kawarazaki, Hiroo; Toki, Noriyoshi; Takeda, Kenta; Yasuda, Hideto; Izawa, Junichi; Uji, Makiko

    2015-10-01

    We aimed to study the clinical characteristics, courses, and outcomes of critically ill patients with septic acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) in comparison with nonseptic AKI treated with CRRT. This is a multicenter retrospective observational study conducted in 14 Japanese intensive care units in 2010. All adult patients with severe AKI treated with CRRT were eligible (n = 343), and information on patient characteristics, variables at CRRT initiation, CRRT settings, and outcomes was collected. Patients were categorized into the septic AKI group and the nonseptic AKI group according to contributing factors to AKI. Approximately half of study patients (48.7%) had sepsis/septic shock as a contributing factor to AKI, and patients with septic AKI treated with CRRT had more serious clinical conditions than patients with nonseptic AKI. However, no significant difference was observed in intensive care unit mortality (48.5% vs 43.8%; P = .44) and hospital mortality (61.1% vs 56.3%; P = .42) between patients with septic and nonseptic AKIs treated with CRRT. Furthermore, sepsis was associated with lower hospital mortality (odds ratio, 0.378; P = .012) in multivariable regression analysis. Sepsis may not be a risk factor for mortality in patients with AKI whose condition has become severe enough to require CRRT. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Dental sepsis.

    PubMed

    Mueller, P O; Lowder, M Q

    1998-08-01

    Dental sepsis or periapical abscess formation constitutes a large percentage of dental conditions that afflict horses. Dental sepsis occurs when the pulp chamber of the tooth is exposed to the oral cavity or external environment, allowing bacterial localization with resulting infection. Although acute, primary, septic pulpitis in horses is rare, dental sepsis often results from colonization of the pulp chamber with pathogenic bacteria secondary to maleruption or impaction of teeth with secondary alveolar bone lysis, primary fractures of the tooth, mandible, or maxilla, periodontal disease, or infundibular necrosis. The sequela to pulpal infection are extensions into the periradicular tissues and mandibular or maxillary periapical abscess formation.

  14. Urinary exosomal activating transcriptional factor 3 as the early diagnostic biomarker for sepsis-induced acute kidney injury.

    PubMed

    Panich, Tanaporn; Chancharoenthana, Wiwat; Somparn, Poorichaya; Issara-Amphorn, Jiraphorn; Hirankarn, Nattiya; Leelahavanichkul, Asada

    2017-01-07

    An early sepsis-induced acute kidney injury (sepsis-AKI) biomarker is currently in needed. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a candidate of sepsis-AKI biomarker but with different cut-point values. Urinary exosomal activating transcriptional factor 3 (uATF3) has been mentioned as an interesting biomarker. We conducted experiments in mice and a prospective, multicenter study in patients as a proof of concept that urine exosome is an interesting biomarker. An early expression of ATF3 in kidney of CD-1 mice at 6 h after cecal ligation and puncture implied the possibility of uATF3 as an early sepsis-AKI biomarker. Increase serum creatinine (Scr) ≥0.3 mg/dL from the baseline was used as an AKI diagnosis and urine was analyzed for uATF3 and uNGAL. Patients with baseline Scr at admission ≥1.5 mg/dL were excluded. The analysis showed higher Scr, uNGAL and uATF3 in patients with sepsis-AKI in comparison with patients with sepsis-non-AKI and healthy volunteers. A fair correlation, r(2) = 0.47, between uATF3 and uNGAL was showed in sepsis-AKI group with Scr ≥2 mg/dL. To see if uATF3 could be an early sepsis-AKI biomarker, urine sample was collected daily during the first week of the admission. In sepsis-AKI and sepsis-non-AKI groups, uNGAL were 367 ± 43 ng/mL and 183 ± 23 ng/mL, respectively; and uATF3 were 19 ± 4 ng/mL and 1.4 ± 0.8 ng/mL, respectively. With the mean value of uNGAL and uATF3 in sepsis AKI as a cut-off level, AUROC of uNGAL and uATF3 were 64% (95% CI 0.54 to 0.74) and 84% (95% CI 0.77 to 0.91), respectively. Urine exosome is an interesting source of urine biomarker and uATF3 is an interesting sepsis-AKI biomarker.

  15. An extended leukocyte differential count (16 types of circulating leukocytes) using the CytoDiff flow cytometric system can provide information for the discrimination of sepsis severity and prediction of outcome in sepsis patients.

    PubMed

    Park, Sang Hyuk; Park, Borae G; Park, Chan-Jeoung; Kim, Sue; Kim, Duck-Hee; Jang, Seongsoo; Hong, Suk-Kyung; Chi, Hyun-Sook

    2014-07-01

    The Beckman Coulter CytoDiff flow cytometric system (Beckman Coulter, Miami, FL) was recently developed for performing leukocyte differential counts in up to 16 leukocyte subpopulations. We compared these leukocyte subpopulation levels among patients with three stages of sepsis (uncomplicated sepsis, severe sepsis, septic shock), especially focused on the discrimination of complicated sepsis from uncomplicated sepsis. We examined a total of 181 samples with sepsis who were admitted to the surgical intensive care unit. In addition, we examined samples obtained from 60 normal healthy volunteers. Both the proportions and absolute numbers of each cell type in the four groups were obtained using the CytoDiff flow cytometric system and compared. Mature neutrophils and immature granulocytes failed to discriminate patients with complicated sepsis from those with uncomplicated sepsis although their absolute numbers were increased compared with normal controls. In contrast, almost all lymphocyte subpopulations and CD16(-) monocytes decreased significantly in patients with complicated sepsis compared with uncomplicated sepsis. Among them, only B lymphocytes showed independent ability to discriminate two groups. Both B lymphocytes and CD16(-) monocytes possessed a significant adverse prognostic impact on overall survival when their absolute numbers decreased. Almost all lymphocyte subpopulations and CD16(-) monocytes decrease in size with increasing sepsis severity. Among them, only B lymphocytes showed independent ability to discriminate patients with complicated sepsis from those with uncomplicated sepsis. Both B lymphocytes and CD16 (-) monocytes show a significant adverse prognostic impact on overall survival outcomes in sepsis patients when their absolute numbers are decreased. Copyright © 2013 Clinical Cytometry Society.

  16. Stimulation of Brain AMP-Activated Protein Kinase Attenuates Inflammation and Acute Lung Injury in Sepsis

    PubMed Central

    Mulchandani, Nikhil; Yang, Weng-Lang; Khan, Mohammad Moshahid; Zhang, Fangming; Marambaud, Philippe; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2015-01-01

    Sepsis and septic shock are enormous public health problems with astronomical financial repercussions on health systems worldwide. The central nervous system (CNS) is closely intertwined in the septic process but the underlying mechanism is still obscure. AMP-activated protein kinase (AMPK) is a ubiquitous energy sensor enzyme and plays a key role in regulation of energy homeostasis and cell survival. In this study, we hypothesized that activation of AMPK in the brain would attenuate inflammatory responses in sepsis, particularly in the lungs. Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV. The septic mice treated with AICAR exhibited elevated phosphorylation of AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle. Similarly, the expressions of TNF-α, IL-1β, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced. Moreover, histological findings in the lungs showed improvement of morphologic features and reduction of apoptosis with AICAR treatment. We further found that the beneficial effects of AICAR on septic mice were diminished in AMPKα2 deficient mice, showing that AMPK mediates these effects. In conclusion, our findings reveal a new functional role of activating AMPK in the CNS to attenuate inflammatory responses and acute lung injury in sepsis. PMID:26252187

  17. Combination therapy with ampicillin and azithromycin improved outcomes in a mouse model of group B streptococcal sepsis.

    PubMed

    Upadhyay, Kirtikumar; Hiregoudar, Basu; Meals, Elizabeth; English, Boyce Keith; Talati, Ajay J

    2017-01-01

    Evidence suggests that β-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a β-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation. TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end. GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005). Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.

  18. Sepsis-induced acute lung injury (ALI) is milder in diabetic rats and correlates with impaired NFkB activation.

    PubMed

    Filgueiras, Luciano R; Martins, Joilson O; Serezani, Carlos H; Capelozzi, Vera L; Montes, Marlise B A; Jancar, Sonia

    2012-01-01

    Acute lung injury (ALI) develops in response to a direct insult to the lung or secondarily to a systemic inflammatory response, such as sepsis. There is clinical evidence that the incidence and severity of ALI induced by direct insult are lower in diabetics. In the present study we investigated whether the same occurs in ALI secondarily to sepsis and the molecular mechanisms involved. Diabetes was induced in male Wistar rats by alloxan and sepsis by caecal ligation and puncture surgery (CLP). Six hours later, the lungs were examined for oedema and cell infiltration in bronchoalveolar lavage. Alveolar macrophages (AMs) were cultured in vitro for analysis of IκB and p65 subunit of NFκB phosphorylation and MyD88 and SOCS-1 mRNA. Diabetic rats were more susceptible to sepsis than non-diabetics. In non-diabetic rats, the lung presented oedema, leukocyte infiltration and increased COX2 expression. In diabetic rats these inflammatory events were significantly less intense. To understand why diabetic rats despite being more susceptible to sepsis develop milder ALI, we examined the NFκB activation in AMs of animals with sepsis. Whereas in non-diabetic rats the phosphorylation of IκB and p65 subunit occurred after 6 h of sepsis induction, this did not occur in diabetics. Moreover, in AMs from diabetic rats the expression of MyD88 mRNA was lower and that of SOCS-1 mRNA was increased compared with AMs from non-diabetic rats. These results show that ALI secondary to sepsis is milder in diabetic rats and this correlates with impaired activation of NFκB, increased SOCS-1 and decreased MyD88 mRNA.

  19. The effect of Lactobacillus bacteria supplement on sepsis and its complications in patients with acute burns.

    PubMed

    Koren, Lior; Gurfinkel, Reuven; Glezinger, Ronen; Perry, Zvi Howard; Lev-Ari, Sandra; Rosenberg, Lior

    2007-08-01

    Sepsis as a result of bacterial translocation from the gastrointestinal tract (GIT) is a known associate of morbidity and mortality in patients with severe burns. This translocation is influenced by the GIT flora. Oral consumption of Lactobacillus bacteria was previously shown to reduce translocation. We conducted a retrospective cohort study on a series of 56 patients with burns admitted to Soroka University Medical Center in Beer-Sheva, Israel. Those 56 patients included 28 who were given lactobacillus supplements and 28 who were not. The parameters that were compared between the groups evaluated the level of sepsis and its complications. The parameters of morbidity during hospitalization were significantly higher in the treatment group; however, their mortality was lower. That difference in mortality between the groups was not significant as a whole (p=0.071), but it was significant in the subgroup analysis of 41-70% total body surface area burned. In that subgroup there were zero cases of death in the treatment group versus five cases in the control group (p=0.005). Our findings suggest that in acute burns, lactobacillus bacteria food additives may be clinically beneficial in patients with total burned body surface area of 41-70%.

  20. Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome.

    PubMed

    Carcillo, Joseph A; Halstead, E Scott; Hall, Mark W; Nguyen, Trung C; Reeder, Ron; Aneja, Rajesh; Shakoory, Bita; Simon, Dennis

    2017-06-01

    We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes. Tertiary children's hospital PICU. One hundred consecutive severe sepsis admissions. Clinical data were recorded daily, and blood was collected twice weekly. Multiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002). Our approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

  1. Fast Versus Slow Recruitment Maneuver at Different Degrees of Acute Lung Inflammation Induced by Experimental Sepsis.

    PubMed

    Santos, Raquel S; Moraes, Lillian; Samary, Cynthia S; Santos, Cíntia L; Ramos, Maíra B A; Vasconcellos, Ana P; Horta, Lucas F; Morales, Marcelo M; Capelozzi, Vera L; Garcia, Cristiane S N B; Marini, John J; Gama de Abreu, Marcelo; Pelosi, Paolo; Silva, Pedro L; Rocco, Patricia R M

    2016-04-01

    Large tidal volume (VT) breaths or "recruitment maneuvers" (RMs) are used commonly to open collapsed lungs, but their effectiveness may depend on how the RM is delivered. We hypothesized that a stepped approach to RM delivery ("slow" RM) compared with a nonstepped ("fast" RM), when followed by decremental positive end-expiratory pressure (PEEP) titration to lowest dynamic elastance, would (1) yield a more homogeneous inflation of the lungs, thus reducing the PEEP obtained during post-RM titration; (2) produce less lung morphofunctional injury, regardless of the severity of sepsis-induced acute lung inflammation; and (3) result in less biological damage in severe, but not in moderate, acute lung inflammation. Sepsis was induced by cecal ligation and puncture surgery in 51 Wistar rats. After 48 hours, animals were anesthetized, mechanically ventilated (VT = 6 mL/kg), and stratified by PO2/fraction of inspired oxygen ratio into moderate (≥300) and severe (<300) acute lung inflammation groups. Each group was then subdivided randomly into 3 subgroups: (1) nonrecruited; (2) RM with continuous positive airway pressure (30 cm H2O for 30 seconds; CPAPRM or fast RM); and (3) RM with stepwise airway pressure increase (5 cm H2O/step, 8.5 seconds/step, 6 steps, 51 seconds; STEPRM or slow RM), with a maximum pressure hold for 10 seconds. All animals underwent decremental PEEP titration to determine the level of PEEP required to optimize dynamic compliance after RM and were then ventilated for 60 minutes with VT = 6 mL/kg, respiratory rate = 80 bpm, fraction of inspired oxygen = 0.4, and the newly adjusted PEEP for each animal. Respiratory mechanics, hemodynamics, and arterial blood gases were measured before and at the end of 60-minute mechanical ventilation. Lung histology and biological markers of inflammation and damage inflicted to endothelial cells were evaluated at the end of the 60-minute mechanical ventilation. Respiratory system mean airway pressure was lower in

  2. Successfully treated severe obstetric sepsis and acute respiratory distress syndrome with extracorporeal membrane oxygenation.

    PubMed

    Benetis, Rimantas; Nadisauskiene, Ruta; Sirvinskas, Edmundas; Lenkutis, Tadas; Siudikas, Adakrius; Kadusauskaitė, Vytaute; Railaitė, Dalia; Sukovas, Arturas; Abraitis, Vytautas

    2016-05-01

    We report a unique clinical case about an 18-year-old woman, immediately post-partum after an urgent C-section, who survived severe sepsis, acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) and was successfully treated with 11 different antibiotics, massive blood transfusions and repetitive surgeries and was on extracorporeal membrane oxygenation (ECMO) support for 22 days. Although, ECMO is a time-limited procedure and most manufacturers do not advise more than 14 days of use, the situation for this patient was life-threatening and ECMO, despite the dangerous risks listed above, was the only way to win time for the lungs to recover and for treatment of the underlying disease, while maintaining adequate oxygenation and circulation. Fortunately, the condition of this woman was stabilized and she achieved complete physical recovery, despite minor neurological deficit in the fingers of her right hand. © The Author(s) 2015.

  3. The relationship between plasma cholesterol, amino acids and acute phase proteins in sepsis.

    PubMed

    Chiarla, C; Giovannini, I; Siegel, J H

    2004-08-01

    The purpose of the study was to correlate degree of hypocholesterolemia to changes in plasma levels of amino acids and other metabolic variables in severely injured septic patients. Measurements included plasma cholesterol, full amino-acidograms, acute phase proteins, complementary variables and blood cell counts. The Fischer plasma molar amino acid ratio (leucine+isoleucine+valine)/(phenylalanine+tyrosine) was calculated. Plasma cholesterol for all measurements (n=145) was 3.1+/-1.1 mmol/L and, upon entry in the study, it was correlated inversely with sepsis severity score (p<0.05). Along the clinical course, changes in cholesterol were clearly paralleled by opposite changes in C-reactive protein, which was the best correlate of cholesterol (r2=0.70, p<0.0001). Furthermore cholesterol was inversely related to phenylalanine, fibrinogen, lactate and white blood cell count, and directly to the Fischer molar amino acid ratio, cystathionine, methionine, glycine and transferrin (r2 between 0.36 and 0.15, p<0.0001 for all). Within this pattern of correlations, cholesterol was also directly related to alkaline phosphatase, which accounted for the effect of cholestasis, when present. For any given value of the other variables, cholesterol increased significantly with increase in alkaline phosphatase (p<0.0001). C-reactive protein (CRP, mg/dl) and alkaline phosphatase (ALKPH, U/L) together in the same regression explained 79% of the variability of cholesterol (CHOL, mmol/L): CHOL=5.90-0.74[Log(e)CRP]+0.004[ALKPH]; multiple r2=0.79, p<0.0001. Inclusion in this regression of other variables did not increase the r2. By using only amino acid variables, the best fit was provided by a regression including the Fischer ratio and cystathionine, which explained 55% of the variability of cholesterol (multiple r2=0.55 p<0.0001), and this result was not improved by the inclusion of other amino acids. These data show that severity of hypocholesterolemia in sepsis is quantifiably related

  4. Early-age-related changes in proteostasis augment immunopathogenesis of sepsis and acute lung injury.

    PubMed

    Bodas, Manish; Min, Taehong; Vij, Neeraj

    2010-11-15

    The decline of proteasomal activity is known to be associated with the age-related disorders but the early events involved in this process are not apparent. To address this, we investigated the early-age-related (pediatric vs. adult) mechanisms that augment immunopathogenesis of sepsis and acute lung injury. The 3-weeks (pediatric) and 6-months (adult) old C57BL/6 mice were selected as the study groups. Mice were subjected to 1×20 cecal ligation and puncture (CLP) mediated sepsis or intratracheal Psuedomonas aeruginosa (Pa)-LPS induced acute lung injury (ALI).We observed a significant increase in basal levels of pro-inflammatory cytokine, IL-6 and neutrophil activity marker, myeloperoxidase (MPO) in the adult mice compared to the pediatric indicating the age-related constitutive increase in inflammatory response. Next, we found that age-related decrease in PSMB6 (proteasomal subunit) expression in adult mice results in accumulation of ubiquitinated proteins that triggers the unfolded protein response (UPR). We identified that Pa-LPS induced activation of UPR modifier, p97/VCP (valosin-containing protein) in the adult mice lungs correlates with increase in Pa-LPS induced NFκB levels. Moreover, we observed a constitutive increase in p-eIF2α indicating a protective ER stress response to accumulation of ubiquitinated-proteins. We used MG-132 treatment of HBE cells as an in vitro model to standardize the efficacy of salubrinal (inhibitor of eIF2α de-phosphorylation) in controlling the accumulation of ubiquitinated proteins and the NFκB levels. Finally, we evaluated the therapeutic efficacy of salubrinal to correct proteostasis-imbalance in the adult mice based on its ability to control CLP induced IL-6 secretion or recruitment of pro-inflammatory cells. Our data demonstrate the critical role of early-age-related proteostasis-imbalance as a novel mechanism that augments the NFκB mediated inflammation in sepsis and ALI. Moreover, our data suggest the therapeutic

  5. Early-Age-Related Changes in Proteostasis Augment Immunopathogenesis of Sepsis and Acute Lung Injury

    PubMed Central

    Bodas, Manish; Min, Taehong; Vij, Neeraj

    2010-01-01

    Background The decline of proteasomal activity is known to be associated with the age-related disorders but the early events involved in this process are not apparent. To address this, we investigated the early-age-related (pediatric vs. adult) mechanisms that augment immunopathogenesis of sepsis and acute lung injury. Methodology/Principal Findings The 3-weeks (pediatric) and 6-months (adult) old C57BL/6 mice were selected as the study groups. Mice were subjected to 1×20 cecal ligation and puncture (CLP) mediated sepsis or intratracheal Psuedomonas aeruginosa (Pa)-LPS induced acute lung injury (ALI).We observed a significant increase in basal levels of pro-inflammatory cytokine, IL-6 and neutrophil activity marker, myeloperoxidase (MPO) in the adult mice compared to the pediatric indicating the age-related constitutive increase in inflammatory response. Next, we found that age-related decrease in PSMB6 (proteasomal subunit) expression in adult mice results in accumulation of ubiquitinated proteins that triggers the unfolded protein response (UPR). We identified that Pa-LPS induced activation of UPR modifier, p97/VCP (valosin-containing protein) in the adult mice lungs correlates with increase in Pa-LPS induced NFκB levels. Moreover, we observed a constitutive increase in p-eIF2α indicating a protective ER stress response to accumulation of ubiquitinated-proteins. We used MG-132 treatment of HBE cells as an in vitro model to standardize the efficacy of salubrinal (inhibitor of eIF2α de-phosphorylation) in controlling the accumulation of ubiquitinated proteins and the NFκB levels. Finally, we evaluated the therapeutic efficacy of salubrinal to correct proteostasis-imbalance in the adult mice based on its ability to control CLP induced IL-6 secretion or recruitment of pro-inflammatory cells. Conclusions/Significance Our data demonstrate the critical role of early-age-related proteostasis-imbalance as a novel mechanism that augments the NFκB mediated

  6. SPECTRUM OF DISEASE AND OUTCOME OF PRIMARY AMPUTATION FOR DIABETIC FOOT SEPSIS.

    PubMed

    Cheddie, S; Manneh, C; Zulu, H

    2017-09-01

    Guillotine amputation for diabetic foot sepsis followed by an elective refashioning of the stump is regarded as standard practice. Primary amputation is associated with higher reamputation rates. A prospective cohort study of 85 patients who underwent surgery for diabetic foot sepsis from 2014 to 2016 at Madadeni Provincial Hospital, KwaZulu-Natal was done. Ethical approval was granted. The Wagner classification (Wag) was used to classify disease severity. Outcome measures included length of hospital stay, mortality and re-amputation rates. Of the 85 patients, females (n=45) accounted for 53% of admissions. The mean age was 61 years (range: 29 to 80 years). The majority of patients were African, n=75 (88%). Only 1 patient presented with diabetic ketoacidosis and 18 (21%) presented with renal failure. Most patients presented with advanced disease: [Wag 5, n=66 (78%); Wag 4, n=12 (14%); Wag 3, n=5 (6%); Wag 2, n=2 (2%)]. The levels of vascular occlusion included aortoiliac disease n=2 (2%), femoro-popliteal disease n=18 (21%), tibio-peroneal disease n=65 (76%). Radiographic features included normal findings n=60 (71%); gas gangrene n=11 (13%), osteitis n=8 (9%). The following amputations were done: AKA, n=29 (34%); BKA, n=39 (46%); TMA, n=8 (9%); Toe-ectomy, n=5 (6%) and Debridement, n=4 (5%). The re-amputation rate to above knee amputation was n= 3/39 (8%). All AKA stumps healed well. The overall in-hospital mortality was n=5 (6%) and mean length of hospital stay was 7.8 days ±3.83. The majority of patients presented with advanced disease requiring a major amputation. A definitive one stage primary amputation is a safe and effective procedure for diabetic foot sepsis and is associated with a low re-amputation rate, length of hospital stay and mortality. A guillotine amputation should be reserved for physiologically unstable patients.

  7. Early Increase of Plasma Homocysteine in Sepsis Patients with Poor Outcome

    PubMed Central

    Ploder, Martin; Kurz, Katharina; Spittler, Andreas; Neurauter, Gabriele; Roth, Erich; Fuchs, Dietmar

    2010-01-01

    Moderate hyperhomocysteinemia is a well-established coronary risk factor that develops when dietary supply with folate and/or vitamin B12 is inadequate. Recently, stimulated peripheral blood mononuclear cells were shown to produce homocysteine. Thus, the stimulated immune system may contribute to moderate hyperhomocysteinemia during certain diseases. Because multiple trauma and sepsis are accompanied by often strong inflammatory responses, we investigated whether hyperhomocysteinemia may develop in patients. Total homocysteine and cysteine concentrations were measured in 83 plasma specimens from 18 patients (14 men, 4 women; 15 posttrauma with sepsis and 3 with sepsis alone) every third day of follow-up. Finally results were compared with concentrations of cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6, the immune activation marker neopterin and the extent of tryptophan degradation as indicated by the kynurenine-to-tryptophan ratio (kyn/trp). Compared with baseline, average total homocysteine (P < 0.05, d 4–d 10) and cysteine (P < 0.05, d 7–d 13) concentrations increased during follow-up of patients. However, only the increase of homocysteine was related to the survival status: total homocysteine was significantly higher in nonsurvivors (P < 0.05, d 4 and d 10) than in survivors, whereas cysteine concentrations increased in both subgroups. Homocysteine correlated with kyn/trp but not with neopterin concentrations. Increase of total homocysteine is common in patients after trauma with unfavorable outcome. Because all patients received standardized enteral nutrition after the end of hypodynamic shock, inconsistent vitamin supply is unlikely to be the reason for hyperhomocysteinemia in some of the patients; rather, it is associated with a stronger proinflammatory response. Certainly, the number of patients in our study is still small and results can only be regarded as preliminary. PMID:20386870

  8. Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in d-galactose-induced aging rats

    PubMed Central

    Liu, Chao; Hu, Jie; Mao, Zhi; Kang, Hongjun; Liu, Hui; Fu, Wanlei; Lv, Yangfan; Zhou, Feihu

    2017-01-01

    Background Recently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis. Objective To investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats. Methods Twelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model. Results The mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, P<0.05 at 12 h and 24 h post-CLP). The rate of severe AKI (RIFLE-F) at 24 h post-CLP was 43% for both the control and L d-gal groups and 80% for the H d-gal group. Conclusion High-dose- d-gal-induced aging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose- d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients. PMID:28408808

  9. Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in d-galactose-induced aging rats.

    PubMed

    Liu, Chao; Hu, Jie; Mao, Zhi; Kang, Hongjun; Liu, Hui; Fu, Wanlei; Lv, Yangfan; Zhou, Feihu

    2017-01-01

    Recently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis. To investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats. Twelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model. The mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, P<0.05 at 12 h and 24 h post-CLP). The rate of severe AKI (RIFLE-F) at 24 h post-CLP was 43% for both the control and L d-gal groups and 80% for the H d-gal group. High-dose- d-gal-induced aging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose- d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients.

  10. Diabetes and sepsis outcomes--it is not all bad news.

    PubMed

    Yende, Sachin; van der Poll, Tom

    2009-01-01

    Patients with diabetes mellitus have an increased risk of developing infections and sepsis. In this issue of Critical Care Esper and colleagues report on a large survey, involving 12.5 million sepsis cases, that examined the impact of pre-existing diabetes on organ dysfunction during sepsis. Their main conclusion was that diabetes patients, relative to non-diabetics, were less likely to develop respiratory failure and more likely to develop renal failure during the course of sepsis.

  11. Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis

    PubMed Central

    Chen, Jiao; Li, Xiaozhong; Bai, Zhenjiang; Fang, Fang; Hua, Jun; Li, Ying; Pan, Jian; Wang, Jian; Feng, Xing; Li, Yanhong

    2016-01-01

    Objective To evaluate whether early and acquired daily fluid overload (FO), as well as fluctuations in fluid accumulation, were associated with adverse outcomes in critically ill children with severe sepsis. Methods This study enrolled 202 children in a pediatric intensive care unit (PICU) with severe sepsis. Early fluid overload was defined as ≥5% fluid accumulation occurring in the first 24 hours of PICU admission. The maximum daily fluid accumulation ≥5% occurring during the next 6 days in patients with at least 48 hours of PICU stay was defined as PICU-acquired daily fluid overload. The fluctuation in fluid accumulation was calculated as the difference between the maximum and the minimum daily fluid accumulation obtained during the first 7 days after admission. Results Of the 202 patients, 61 (30.2%) died during PICU stay. Among all patients, 41 (20.3%) experienced early fluid overload, including 9 with a FO ≥10%. Among patients with at least 48 hours of PICU stay (n = 154), 36 (23.4%) developed PICU-acquired daily fluid overload, including 2 with a FO ≥10%. Both early fluid overload (AOR = 1.20; 95% CI 1.08–1.33; P = 0.001; n = 202) and PICU-acquired daily fluid overload (AOR = 5.47 per log increase; 95% CI 1.15–25.96; P = 0.032; n = 154) were independent risk factors associated with mortality after adjusting for age, illness severity, etc. However, fluctuations in fluid accumulation were not associated with mortality after adjustment. Length of PICU stay increased with greater fluctuations in fluid accumulation in all patients with at least 48 hours of PICU stay (FO <5%, 5%-10% vs. ≥10%: 4 [3–8], 7 [4–11] vs. 10 [6–16] days; P <0.001; n = 154) and in survivors (4 [3–8], 7 [5–11] vs. 10 [5–15] days; P <0.001; n = 121). Early fluid overload achieved an area under-the-receiver-operating-characteristic curve of 0.74 (95% CI 0.65–0.82; P <0.001; n = 202) for predicting mortality in patients with severe sepsis, with a sensitivity of 67

  12. ACUTE PHASE DEATHS FROM MURINE POLYMICROBIAL SEPSIS ARE CHARACTERIZED BY INNATE IMMUNE SUPPRESSION RATHER THAN EXHAUSTION1

    PubMed Central

    Chiswick, Evan L.; Mella, Juan R.; Bernardo, John; Remick, Daniel

    2015-01-01

    Sepsis, a leading cause of death in the U.S., has poorly understood mechanisms of mortality. To address this, our model of Cecal Ligation and Puncture (CLP) induced sepsis stratifies mice as predicted to Live (Live-P) or Die (Die-P) based on plasma IL-6. Six hours post-CLP, both Live-P and Die-P groups have equivalent peritoneal bacterial colony forming units and recruitment of phagocytes. By 24hr, however, Die-P mice have increased bacterial burden, despite increased neutrophil recruitment, suggesting Die-P phagocytes have impaired bacterial killing. Peritoneal cells were used to study multiple bactericidal processes: bacterial killing, Reactive Oxygen Species (ROS) generation, and phagocytosis. Total phagocytosis and intra-phagosomal processes were determined with triple-labeled E.coli, covalently labeled with ROS and pH sensitive probes, and an ROS/pH insensitive probe for normalization. While similar proportions of Live-P and Die-P phagocytes responded to exogenous stimuli, Die-P phagocytes showed marked deficits in all parameters measured, thus suggesting immunosuppression rather than exhaustion. This contradicts the prevailing sepsis paradigm that acute phase sepsis deaths (<5 days) result from excessive inflammation, whereas chronic phase deaths (>5 days) are characterized by insufficient inflammation and immunosuppression. These data suggest that suppression of cellular innate immunity in sepsis occurs within the first six hours. PMID:26371253

  13. Circulating endothelial progenitor cells may predict outcomes in adult patients with severe sepsis in the emergency department.

    PubMed

    Kung, Chia-Te; Su, Chih-Min; Chen, Chao Tung; Cheng, Hsien-Hung; Chang, Meng-Wei; Hung, Chih-Wei; Hung, Shin-Chiang; Chang, Wen-Neng; Tsai, Nai-Wen; Wang, Hung-Chen; Su, Yu-Jih; Huang, Chin-Cheng; Lin, Wei-Che; Cheng, Ben-Chung; Chang, Ya-Ting; Lu, Cheng-Hsien

    2016-04-01

    Dysfunctional and decreased numbers of endothelial progenitor cells (EPCs) may play an essential role in the initiation of organ dysfunction caused by severe sepsis. We evaluated the role of serial circulating EPCs in outcomes of patients with severe sepsis. In total, 101 adult patients with severe sepsis and septic shock were evaluated. Circulating levels of EPCs (CD133(+)/CD34(+) and KDR(+)/CD34(+) cells) were determined at different time points. The levels of CD133(+)/CD34(+) and KDR(+)/CD34(+) EPCs were significantly higher in the severe sepsis group than in the healthy controls. Levels of CD133(+)/CD34(+) EPCs were significantly higher in the mortality group than in the survival group on day 1 of admission (p<0.05), but decreased significantly with time among non-survivors (p<0.05), and were lowest on day 4 at the emergency department. The Sequential Organ Failure Assessment score and number of CD133(+)/CD34(+) EPCs on admission were independently associated with in-hospital mortality. The level of CD133(+)/CD34(+) EPCs on admission is independently associated with in-hospital mortality, and the trend of a sharp decrease in the number of EPCs is related to outcomes in patients with severe sepsis. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A Valuable Tool in Predicting Poor Outcome due to Sepsis in Pediatric Intensive Care Unit: Tp-e/QT Ratio.

    PubMed

    Ozdemir, Rahmi; Isguder, Rana; Kucuk, Mehmet; Karadeniz, Cem; Ceylan, Gokhan; Katipoglu, Nagehan; Yilmazer, Murat Muhtar; Yozgat, Yilmaz; Mese, Timur; Agin, Hasan

    2016-10-01

    To assess the feasibility of 12-lead electrocardiographic (ECG) measures such as P wave dispersion (PWd), QT interval, QT dispersion (QTd), Tp-e interval, Tp-e/QT and Tp-e/QTc ratio in predicting poor outcome in patients diagnosed with sepsis in pediatric intensive care unit (PICU). Ninety-three patients diagnosed with sepsis, severe sepsis or septic shock and 103 age- and sex-matched healthy children were enrolled into the study. PWd, QT interval, QTd, Tp-e interval and Tp-e/QT, Tp-e/QTc ratios were obtained from a 12-lead electrocardiogram. PWd, QTd, Tp-e interval and Tp-e/QT, Tp-e/QTc ratios were significantly higher in septic patients compared with the controls. During the study period, 41 patients had died. In multivariate logistic regression analyses, only Tp-e/QT ratio was found to be an independent predictor of mortality. The ECG measurements can predict the poor outcome in patients with sepsis. The Tp-e/QT ratio may be a valuable tool in predicting mortality for patients with sepsis in the PICU. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. The international PROGRESS registry of patients with severe sepsis: drotrecogin alfa (activated) use and patient outcomes

    PubMed Central

    Martin, Greg; Brunkhorst, Frank M; Janes, Jonathan M; Reinhart, Konrad; Sundin, David P; Garnett, Kassandra; Beale, Richard

    2009-01-01

    Introduction Since the launch of drotrecogin alfa activated (DrotAA), institutions and individual countries have published data on its use in clinical practice, based on audit or registry data. These studies were limited in size and geographic locale and included patients with greater disease severity and higher mortality than those in clinical trials. The purpose of this study was to compare baseline characteristics and clinical outcomes (using appropriate statistical adjustments) of patients treated or not treated with DrotAA from the international PROGRESS (Promoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis. Methods PROGRESS was a global, non-interventional, multi-center, prospective, observational study of patients having a diagnosis of severe sepsis treated in intensive care units at a participating institution. All treatment modalities were as per standard of care at the participating institutions. Baseline characteristics and hospital mortality were analyzed and regression techniques used to develop propensity and outcome models adjusted for baseline imbalances between groups. Results Overall, 14,543 patients from 37 countries were enrolled and 12,492 had complete data for analysis. Germany was the highest enrolling country (1,810; 14.5%) and the US had the most DrotAA patients (206, 23.3%); 882 (7%) overall received DrotAA therapy. DrotAA-treated patients were younger (median age 58 vs. 61 years), had greater organ dysfunction (cardiovascular: 90% vs. 74%; respiratory: 90% vs. 81%; renal: 60% vs. 45%; metabolic: 63% versus 42%; 3 or more organ dysfunctions: 84% vs. 67%) and had a higher median APACHE II score (26 vs. 23, all with P < 0.001). Although in-hospital mortality was similar for DrotAA and non-DrotAA-treated patients (49.6% vs. 49.7%, respectively), after adjusting for imbalances, patients receiving DrotAA had a 28% (0.60 to 0.86, 95% Confidence Intervals) reduction in the odds of death and a relative risk

  16. Effect of sepsis and systemic inflammatory response syndrome on neonatal hearing screening outcomes following gentamicin exposure.

    PubMed

    Cross, Campbell P; Liao, Selena; Urdang, Zachary D; Srikanth, Priya; Garinis, Angela C; Steyger, Peter S

    2015-11-01

    . Combining subjects with either vancomycin or furosemide overlap with gentamicin treatment yielded an almost significant risk ratio (RR=1.77, p=0.05) compared to the rest of the cohort. We report an increased risk of referral with DPOAE screening for those receiving ≥4 days of intravenous gentamicin administration that may contribute to the greater prevalence of hearing loss in NICU graduates. We propose an expanded prospective study to gather a larger cohort of subjects, identifying those with sepsis or neonatal SIRS, to increase the statistical power of this study design. Subsequent studies also need to obtain follow-up diagnostic audiological data to verify whether the outcomes of DPOAE screening, in addition to the standard AABR screen, is a reliable predictor of permanent hearing loss following gentamicin exposure in the NICU. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors

    PubMed Central

    Hamzić-Mehmedbašić, Aida; Rašić, Senija; Balavac, Merima; Rebić, Damir; Delić-Šarac, Marina; Durak-Nalbantić, Azra

    2016-01-01

    Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome. PMID:27471736

  18. Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime?

    PubMed Central

    Zhao, Yunzhao; Han, Gang; Li, Weiqin; Huang, Qian; Tong, Zhihui; Li, Jieshou

    2012-01-01

    Background The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction. Objective This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored. Methods Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups. Results Within the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845–0.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications. Conclusions Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care

  19. Septic versus non-septic acute kidney injury in critically ill patients: characteristics and clinical outcomes

    PubMed Central

    Cruz, Marília Galvão; Dantas, João Gabriel Athayde de Oliveira; Levi, Talita Machado; Rocha, Mário de Seixas; de Souza, Sérgio Pinto; Boa-Sorte, Ney; de Moura, Carlos Geraldo Guerreiro; Cruz, Constança Margarida Sampaio

    2014-01-01

    Objective This study aimed to describe and compare the characteristics and clinical outcomes of patients with septic and non-septic acute kidney injury. Methods This study evaluated an open cohort of 117 critically ill patients with acute kidney injury who were consecutively admitted to an intensive care unit, excluding patients with a history of advanced-stage chronic kidney disease, kidney transplantation, hospitalization or death in a period shorter than 24 hours. The presence of sepsis and in-hospital death were the exposure and primary variables in this study, respectively. A confounding analysis was performed using logistic regression. Results No significant differences were found between the mean ages of the groups with septic and non-septic acute kidney injury [65.30±21.27 years versus 66.35±12.82 years, respectively; p=0.75]. In the septic and non-septic acute kidney injury groups, a predominance of females (57.4% versus 52.4%, respectively; p=0.49) and Afro-descendants (81.5% versus 76.2%, respectively; p=0.49) was observed. Compared with the non-septic patients, the patients with sepsis had a higher mean Acute Physiology and Chronic Health Evaluation II score [21.73±7.26 versus 15.75±5.98; p<0.001)] and a higher mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart failure (p<0.001) were more common in the non-septic patients. Septic acute kidney injury was associated with a greater number of patients who required dialysis (p=0.001) and a greater number of deaths (p<0.001); however, renal function recovery was more common in this group (p=0.01). Sepsis (OR: 3.88; 95%CI: 1.51-10.00) and an Acute Physiology and Chronic Health Evaluation II score >18.5 (OR: 9.77; 95%CI: 3.73-25.58) were associated with death in the multivariate analysis. Conclusion Sepsis was an independent predictor of death. Significant differences were found between the characteristics and clinical outcomes of patients with septic versus non-septic acute kidney

  20. Pediatric sepsis: challenges and adjunctive therapies.

    PubMed

    Hanna, William; Wong, Hector R

    2013-04-01

    Sepsis remains an important challenge in pediatric critical care medicine. This review provides an appraisal of adjunctive therapies for sepsis and highlights opportunities for meeting selected challenges in the field. Future clinical studies should address long-term and functional outcomes as well as acute outcomes. Potential adjunctive therapies such as corticosteroids, hemofiltration, hemoadsorption, and plasmapheresis may have important roles, but still require formal and more rigorous testing by way of clinical trials. Finally, the design of future clinical trials should consider novel approaches for stratifying outcome risks as a means of improving the risk-to-benefit ratio of experimental therapies. Published by Elsevier Inc.

  1. Pediatric sepsis: challenges and adjunctive therapies

    PubMed Central

    Hanna, William; Wong, Hector R.

    2012-01-01

    SYNOPSIS Sepsis remains an important challenge in pediatric critical care medicine. The current review intends to provide an appraisal of adjunctive therapies for sepsis and to highlight opportunities for meeting selected challenges in the field. Future clinical studies should address long-term and functional outcomes, as well as acute outcomes. Potential adjunctive therapies such as corticosteroids, hemofiltration, hemoadsorption, and plasmapheresis may have important roles, but still require formal and more rigorous testing by way of clinical trials. Finally, the design of future clinical trials should consider novel approaches for stratifying outcome risks as a means of improving the risk to benefit ratio of experimental therapies. PMID:23537672

  2. The outcomes of children with pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference.

    PubMed

    Quasney, Michael W; López-Fernández, Yolanda M; Santschi, Miriam; Watson, R Scott

    2015-06-01

    To provide additional details and evidence behind the recommendations for outcomes assessment of patients with pediatric acute respiratory distress syndrome from the Pediatric Acute Lung Injury Consensus Conference. Consensus conference of experts in pediatric acute lung injury. A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. The outcomes subgroup comprised four experts. When published data were lacking, a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the topics related to pediatric acute respiratory distress syndrome, seven of which related to outcomes after pediatric acute respiratory distress syndrome. All seven recommendations had strong agreement. Children with acute respiratory distress syndrome continue to have a high mortality, specifically, in relation to certain comorbidities and etiologies related to pediatric acute respiratory distress syndrome. Comorbid conditions, such as an immunocompromised state, increase the risk of mortality even further. Likewise, certain etiologies, such as non-pulmonary sepsis, also place children at a higher risk of mortality. Significant long-term effects were reported in adult survivors of acute respiratory distress syndrome: diminished lung function and exercise tolerance, reduced quality of life, and diminished neurocognitive function. Little knowledge of long-term outcomes exists in children who survive pediatric acute respiratory distress syndrome. Characterization of the longer term consequences of pediatric acute respiratory distress syndrome in children is vital to help identify opportunities for improved therapeutic and rehabilitative strategies that will lessen the long-term burden of pediatric acute

  3. Biology of sepsis: its relevance to pediatric nephrology.

    PubMed

    Blatt, Neal B; Srinivasan, Sushant; Mottes, Theresa; Shanley, Maureen M; Shanley, Thomas P

    2014-12-01

    Because of its multi-organ involvement, the syndrome of sepsis provides clinical challenges to a wide variety of health care providers. While multi-organ dysfunction triggered by sepsis requires general supportive critical care provided by intensivists, the impact of sepsis on renal function and the ability of renal replacement therapies to modulate its biologic consequences provide a significant opportunity for pediatric nephrologists and related care providers to impact outcomes. In this review, we aim to highlight newer areas of understanding of the pathobiology of sepsis with special emphasis on those aspects of particular interest to pediatric nephrology. As such, we aim to: (1) review the definition of sepsis and discuss advances in our mechanistic understanding of sepsis; (2) review current hypotheses regarding sepsis-induced acute kidney injury (AKI) and describe its epidemiology based on evolving definitions of AKI; (3) review the impact of renal failure on the immune system, highlighting the sepsis risk in this cohort and strategies that might minimize this risk; (4) review how renal replacement therapeutic strategies may impact sepsis-induced AKI outcomes. By focusing the review on these specific areas, we have omitted other important areas of the biology of sepsis and additional interactions with renal function from this discussion; however, we have aimed to provide a comprehensive list of references that provide contemporary reviews of these additional areas.

  4. Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial

    PubMed Central

    2014-01-01

    Introduction Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT). Methods This is a retrospective, case–control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment. Results Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 μg/L (median 3.4 to 45.2) and 10.8 μg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65). Conclusions In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification. PMID:24393424

  5. Predictive ability of circulating osteoprotegerin as a novel biomarker for early detection of acute kidney injury induced by sepsis.

    PubMed

    Schaalan, Mona; Mohamed, Waleed

    2017-06-01

    Though significant progress has been made towards new diagnostic approaches for early detection of acute kidney injury (AKI) induced by different factors, there is still an urgent demand for a more specific and predictive biomarker for each type. The aim of this study is to unravel the potential diagnostic utility of circulating osteoprotegerin (OPG) in septic patients who developed AKI in the ICU, compared to cystatin C (a renal function maker) and KIM-1 (a kidney damage marker). Eighty patients (male = 43, female = 37) with ages ranging from 42 to 46 years and with sepsis, 40 of whom developed AKI, and 30 healthy controls were enrolled in this prospective study. Results revealed significant progressive elevation of OPG, along with cystatin C and KIM-1, among sepsis, severe sepsis, and sepsis-AKI patients. The progression of OPG levels paralleled the deterioration of kidney and endothelial functions from sepsis to sepsis-AKI, revealed as progressively increased levels of serum E-selectin (15.3%), endothelin-1 (ET-1) (19.6%), and decreased nitric oxide (NO) (29.7%), associated with elevations of TNF-α (25.5%) and TGF-β (18%). Their comparative prognostic validity of sepsis-AKI was assessed using ROC analysis, which revealed that OPG, KIM-1, and cystatin C showed similar AUCs (0.827-0.83) but with different sensitivities, viz., 84%, 88%, and 92%, respectively. Although cystatin showed 82% specificity, OPG showed a higher, similar specificity to KIM-1 of 85%, indicating its potential function as a marker of renal damage such as KIM-1. This study revealed a significant elevation of circulating OPG in septic patients with different levels of severity and those who progressed to AKI. Moreover, OPG showed a significant correlation to KIM-1 and cystatin, as well as conventional renal, inflammatory, and endothelial markers. Having a similar specificity to KIM-1, as evidenced by the ROC analysis, OPG has the potential to serve as a reliable biomarker of kidney damage

  6. Improving outcomes of acute myocarditis in children.

    PubMed

    Di Filippo, Sylvie

    2016-01-01

    Acute viral myocarditis may impair prognosis in children of all ages. Its true incidence is underestimated because of heterogeneity of presentation and outcome. Patients may either recover or progress to chronic cardiomyopathy or death. Improving short-term and long-term prognosis is challenging but can probably be achieved by new diagnostic techniques and novel targeted therapies. The objectives of this review are: (1) to detail the current state of knowledge of the pathophysiological mechanisms of acute myocarditis; (2) to provide an update on diagnostic tools such as magnetic resonance imaging and endomyocardial biopsy; and (3) to present new insights in therapeutic strategies, targeted therapies and management of fulminant cases. Options for improving outcomes in acute myocarditis in the pediatric population are discussed.

  7. The characteristics and impact of source of infection on sepsis-related ICU outcomes.

    PubMed

    Jeganathan, Niranjan; Yau, Stephen; Ahuja, Neha; Otu, Dara; Stein, Brian; Fogg, Louis; Balk, Robert

    2017-10-01

    Source of infection is an independent predictor of sepsis-related mortality. To date, studies have failed to evaluate differences in septic patients based on the source of infection. Retrospective study of all patients with sepsis admitted to the ICU of a university hospital within a 12month time period. Sepsis due to intravascular device and multiple sources had the highest number of positive blood cultures and microbiology whereas lung and abdominal sepsis had the least. The observed hospital mortality was highest for sepsis due to multiple sources and unknown cause, and was lowest when due to abdominal, genitourinary (GU) or skin/soft tissue. Patients with sepsis due to lungs, unknown and multiple sources had the highest rates of multi-organ failure, whereas those with sepsis due to GU and skin/soft tissue had the lowest rates. Those with multisource sepsis had a significantly higher median ICU length of stay and hospital cost. There are significant differences in patient characteristics, microbiology positivity, organs affected, mortality, length of stay and cost based on the source of sepsis. These differences should be considered in future studies to be able to deliver personalized care. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Nonactivated Protein C in the Treatment of Neonatal Sepsis: A Retrospective Analysis of Outcome.

    PubMed

    Lauterbach, Ryszard; Wilk, Barbara; Bocheńska, Agata; Hurkała, Joanna; Radziszewska, Renata

    2016-09-01

    Previously, we found that plasma protein C (PC) activity ≤10% significantly increased the probability of the occurrence of death during neonatal sepsis. Accordingly, if the activity of plasma PC declined during the course of sepsis to ≤10%, we administered a nonactivated PC zymogen to increase a PC activity. The aim of that retrospective analysis was to explore treatment effects of PC zymogen supplementation in septic infants, with plasma PC activity ≤10%. A database was used to locate 85 newborns treated with PC from among 458 analyzed infants with confirmed sepsis. The median birth weight and gestational age of treated infants were, respectively, 1010.0 g and 29 weeks. In 47 infants, early-onset sepsis developed, whereas in 38 neonates, late-onset sepsis was recognized. PC was given as a single dose of 200 IU/kg. Among 458 septic patients, death occurred in 19 newborns (4.2%), exclusively in infants with plasma PC activity ≤10%. In 15 infants, death occurred in the course of early-onset sepsis and 4 newborns died of late-onset sepsis (early-onset sepsis vs. late-onset sepsis; P = 0.036; χ with the Yates correction). An increased risk of death in septic neonates with plasma PC activity ≤10% suggests the necessity for its evaluation and possibility of supplementation of PC zymogen.

  9. Risk of Acute Stroke After Hospitalization for Sepsis: A Case-Crossover Study.

    PubMed

    Boehme, Amelia K; Ranawat, Purnima; Luna, Jorge; Kamel, Hooman; Elkind, Mitchell S V

    2017-03-01

    Infections have been found to increase the risk of stroke over the short term. We hypothesized that stroke risk would be highest shortly after a sepsis hospitalization, but that the risk would decrease, yet remain up to 1 year after sepsis. This case-crossover analysis utilized data obtained from the California State Inpatient Database of the Healthcare Cost and Utilization Project. All stroke admissions were included. Exposure was defined as hospitalization for sepsis or septicemia 180, 90, 30, or 15 days before stroke (risk period) or similar time intervals exactly 1 or 2 years before stroke (control period). Conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between sepsis/septicemia and ischemic or hemorrhagic stroke. Ischemic (n=37 377) and hemorrhagic (n=12 817) strokes that occurred in 2009 were extracted where 3188 (8.5%) ischemic and 1101 (8.6%) hemorrhagic stroke patients had sepsis. Sepsis within 15 days before the stroke placed patients at the highest risk of ischemic (OR, 28.36; 95% CI, 20.02-40.10) and hemorrhagic stroke (OR, 12.10; 95% CI, 7.54-19.42); however, although the risk decreased, it remained elevated 181 to 365 days after sepsis for ischemic (OR, 2.59; 95% CI, 2.20-3.06) and hemorrhagic (OR, 3.92; 95% CI 3.29-4.69) strokes. There was an interaction with age (P=0.0006); risk of developing an ischemic stroke within 180 days of hospitalization for sepsis increased 18% with each 10-year decrease in age. Risk of stroke is high after sepsis, and this risk persists for up to a year. Younger sepsis patients have a particularly increased risk of stroke after sepsis. © 2017 American Heart Association, Inc.

  10. Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury

    PubMed Central

    Zhao, Wen-Yu; Zhang, Lei; Sui, Ming-Xing; Zhu, You-Hua; Zeng, Li

    2016-01-01

    Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD+ dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model. SIRT3 deletion increased the CLP-induced upregulation of the NLRP3 inflammasome and apoptosis-associated speck-like protein, resulting in the activation of oxidative stress, increased production of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and the enhancement of apoptosis, and these effects were reversed by antioxidant NAC. Our results suggest that SIRT3 plays a protective role against mitochondrial damage in the kidney by attenuating ROS production, inhibiting the NRLP3 inflammasome, attenuating oxidative stress, and downregulating IL-1β and IL-18. PMID:27620507

  11. Pathophysiologic and clinical correlates of hypophosphatemia and the relationship with sepsis and outcome in postoperative patients after hepatectomy.

    PubMed

    Giovannini, Ivo; Chiarla, Carlo; Nuzzo, Gennaro

    2002-08-01

    Hypophosphatemia in critically ill and postoperative (p.o.) patients is a multifactorial event, and is also related to severity of illness. This study was conducted to assess pathophysiologic correlates of hypophosphatemia and the simultaneous relationship with clinical events after hepatectomy. A total of 333 measurements were obtained in 59 patients: these were performed preoperatively and at p.o. days 1, 3, and 7 in all patients, and subsequently, until recovery or death, only in those with complications. Measurements included plasma phosphate together with a large number of additional blood chemistries, taking into account primary and associated diseases, events associated with the operation, doses of parenteral substrates, occurrence of sepsis or other p.o. complications, outcome, and a consistent set of complementary variables. Plasma phosphate decreased at p.o. days 1 and 3 (P < 0.001) and retumed to a level close to baseline at p.o. day 7. Regression analysis showed that phosphate was related simultaneously to patient age (inversely), levels of creatinine and potassium (directly), and dose of parenteral amino acids (inversely; P < 0.001 for all). Independently of covariation with these variables, there was a decrement in phosphate at p.o. days 1 and 3 that was related specifically to p.o. condition; this decrement had a general component common to all patients, an additional component related to duration of previous hepatic ischemia at surgery, and a further component predictive of the subsequent development of complications (in most cases, sepsis). Plasma phosphate at p.o. day 1 was related inversely to APACHE II score (r2 = 0.4, P < 0.001), and levels lower than 1.5 mg/dL were associated with an almost 4-fold increase in the rate of complications compared with cases with higher phosphate (P < 0.001). The best single variable bridging early evidence of hypophosphatemia to subsequent development of complications was plasma cholesterol, which fell

  12. The Immunomodulatory and Therapeutic Effects of Mesenchymal Stromal Cells for Acute Lung Injury and Sepsis.

    PubMed

    Ho, Mirabelle S H; Mei, Shirley H J; Stewart, Duncan J

    2015-11-01

    It is increasingly recognized that immunomodulation represents an important mechanism underlying the benefits of many stem cell therapies, rather than the classical paradigm of transdifferentiation and cell replacement. In the former paradigm, the beneficial effects of cell therapy result from paracrine mechanism(s) and/or cell-cell interaction as opposed to direct engraftment and repair of diseased tissue and/or dysfunctional organs. Depending on the cell type used, components of the secretome, including microRNA (miRNA) and extracellular vesicles, may be able to either activate or suppress the immune system even without direct immune cell contact. Mesenchymal stromal cells (MSCs), also referred to as mesenchymal stem cells, are found not only in the bone marrow, but also in a wide variety of organs and tissues. In addition to any direct stem cell activities, MSCs were the first stem cells recognized to modulate immune response, and therefore they will be the focus of this review. Specifically, MSCs appear to be able to effectively attenuate acute and protracted inflammation via interactions with components of both innate and adaptive immune systems. To date, this capacity has been exploited in a large number of preclinical studies and MSC immunomodulatory therapy has been attempted with various degrees of success in a relatively large number of clinical trials. Here, we will explore the various mechanism employed by MSCs to effect immunosuppression as well as review the current status of its use to treat excessive inflammation in the context of acute lung injury (ALI) and sepsis in both preclinical and clinical settings.

  13. Aetiology, antimicrobial therapy and outcome of patients with community acquired severe sepsis: a prospective study in a Norwegian university hospital.

    PubMed

    Nygård, Siri Tandberg; Langeland, Nina; Flaatten, Hans K; Fanebust, Rune; Haugen, Oddbjørn; Skrede, Steinar

    2014-03-04

    Severe sepsis is recognized as an inflammatory response causing organ dysfunction in patients with infection. Antimicrobial therapy is the mainstay of treatment. There is an ongoing demand for local surveillance of sepsis aetiology and monitoring of empirical treatment recommendations. The present study was established to describe the characteristics, quality of handling and outcome of patients with severe sepsis admitted to a Norwegian university hospital. A one year prospective, observational study of adult community acquired case-defined severe sepsis was undertaken. Demographics, focus of infection, microbiological findings, timing and adequacy of empirical antimicrobial agents were recorded. Clinical diagnostic practice was evaluated. Differences between categorical groups were analysed with Pearson's chi-squared test. Predictors of in-hospital mortality were identified in a multivariate stepwise backward logistic regression model. In total 220 patients were identified, yielding an estimated annual incidence of 0.5/1000 inhabitants. The focus of infection was established at admission in 69%. Respiratory tract infection was present in 52%, while genitourinary, soft tissue and abdominal infections each were found in 12-14%. Microbiological aetiology was identified in 61%; most prevalent were Streptococcus pneumoniae, Escherichia coli and Staphylococcus aureus. Independent predictors of in-hospital mortality were malignancy, cardiovascular disease, endocarditis, abdominal infections, undefined microbiological aetiology, delay in administration of empirical antimicrobial agents ≥ 6 hours and use of inadequate antimicrobial agents. In patients ≥ 75 years, antimicrobial therapy was less in compliance with current recommendations and more delayed. Community acquired severe sepsis is common. Initial clinical aetiology is often revised. Compliance with recommendations for empirical antimicrobial treatment is lowest in elderly patients. Our results emphasizes that

  14. Preadmission Oral Corticosteroids Are Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Adults With Sepsis.

    PubMed

    McKown, Andrew C; McGuinn, Erin M; Ware, Lorraine B; Wang, Li; Janz, David R; Rice, Todd W; Semler, Matthew W

    2017-05-01

    To determine the association between preadmission oral corticosteroid receipt and the development of acute respiratory distress syndrome in critically ill patients with sepsis. Retrospective observational study. Medical, surgical, trauma, and cardiovascular ICUs of an academic medical center. A total of 1,080 critically ill patients with sepsis. None. The unadjusted occurrence rate of acute respiratory distress syndrome within 96 hours of ICU admission was 35% among patients who had received oral corticosteroids compared with 42% among those who had not (p = 0.107). In a multivariable analysis controlling for prespecified confounders, preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome in the 96 hours after ICU admission (odds ratio, 0.53; 95% CI, 0.33-0.84; p = 0.008), a finding that persisted in multiple sensitivity analyses. The median daily dose of oral corticosteroids among the 165 patients receiving oral corticosteroids, in prednisone equivalents, was 10 mg (interquartile range, 5-30 mg). Higher doses of preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome (odds ratio for 30 mg of prednisone compared with 5 mg 0.53; 95% CI, 0.32-0.86). In multivariable analyses, preadmission oral corticosteroids were not associated with in-hospital mortality (odds ratio, 1.41; 95% CI, 0.87-2.28; p = 0.164), ICU length of stay (odds ratio, 0.90; 95% CI, 0.63-1.30; p = 0.585), or ventilator-free days (odds ratio, 1.06; 95% CI, 0.71-1.57; p = 0.783). Among ICU patients with sepsis, preadmission oral corticosteroids were independently associated with a lower incidence of early acute respiratory distress syndrome.

  15. Protective Effects of Cucurbitacin B on Acute Lung Injury Induced by Sepsis in Rats

    PubMed Central

    Hua, Shu; Liu, Xing; Lv, Shuguang; Wang, Zhifang

    2017-01-01

    Background The aim of this study was to investigate the protective effects of cucurbitacin B (CuB) on sepsis-induced acute lung injury (ALI) in rats. Material/Methods An ALI model was made by cecal ligation and puncture (CLP) in SD rats. Rats were randomly divided into 5 groups (n=15 per group): animals undergoing a sham CLP (sham group); animals undergoing CLP (CLP control group); animals undergoing CLP and treated with CuB at 1 mg/kg of body weight (bw) (low-dose CuB [L-CuB] group), animals undergoing CuB at 2 mg/kg of bw (mid-dose CuB [M-CuB] group); and animals undergoing CuB at 5 mg/kg of bw (high-dose CuB [H-CuB] group). Samples of blood and lung tissue were harvested at different time points (6, 12, and 24 hour post-CLP surgery) for the detection of indicators which represented ALI. Five rats were respectively sacrificed at each time point. Pathological changes of lung tissue were observed by H&E staining. Another 50 rats were distributed into the same five groups to record the 72 hour survival rates. Results Treatment with CuB significantly increased the blood gas PaO2 levels and decreased lung wet/dry (W/D) ratio (p<0.05). It significantly reduced protein concentration, accumulation of the inflammatory cells, and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), (p<0.05), in the bronchoalveolar lavage fluid (BALF). Pulmonary pathological damage and survival rates at 72 hours were found to be effectively improved by CuB. In addition, CuB performed its pulmonary protection effects in a dose-depended manner. Conclusions CuB can effectively improve the pulmonary gas exchange function, reduce pulmonary edema, and inhibit the inflammatory response in the lung, revealing that CuB may serve as a potential therapeutic strategy for sepsis-induced ALI. PMID:28315572

  16. Management of sepsis during MARS treatment in acute on chronic liver failure.

    PubMed

    Novelli, G; Morabito, V; Pugliese, F; Ferretti, G; Novelli, S; Ianni, S; Lai, Q; Rossi, M; Berloco, P B

    2011-05-01

    The aim of our study was a 30-day follow-up of the use of early detection of endotoxin by the endotoxin activity assay (EAA) for patients with acute liver failure superimposed on chronic liver disease (AoCLF) and treated with polymyxin-B hemoperfusion-based (PMX-DHP) treatment and albumin dialysis in the molecular adsorbent recirculating system (MARS). From February 2008 to July 2010, we evaluated 10 AoCLF patients experiencing systemic inflammatory response syndrome (SIRS) in association with suspected infection and an EAA-positive test (>0.60). These patients awaiting liver transplantation (OLT) showed similar Model End-Stage Liver Disease (MELD) scores (range, 19-25) and encephalopathy grade ≤ 2. Five patients received therapy to remove endotoxins with PMX-DHP with MARS treatment for liver failure (group A); the other 5 patients received MARS treatment only (group B). Two PMX-DHP treatments were performed in 4 group A patients (average EA=0.66 [range, 0.61-0.70]) and 3 treatments for 1 patient (EA=0.92). All 5 subjects underwent an average of 4 MARS treatments (range, 3-5). At the end of therapy, the median EA level was 0.42 (range, 0.37-0.48). As reported in the literature, we achieved a significant improvement in liver and kidney functions using MARS. Measurements of lactate, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were significantly improved among patients treated with the extracorporeal therapies. At 30 days of observation, all 5 patients treated with MARS plus PMX-DHP are alive. In group B, a mean of 7.5 MRAS treatments were performed. We observed an improvement in hemodynamic and liver functions with reduced levels of proinflammatory cytokines and lactates in 4 patients. One patient showed no improvement in clinical status with the development of sepsis and subsequent multiorgan failure after 24 days. The possibility of an early diagnosis using the EAA in AoCLF patients could prevent the progression of the sepsis cascade. The use of PMX

  17. Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury.

    PubMed

    Acosta-Herrera, Marialbert; Lorenzo-Diaz, Fabian; Pino-Yanes, Maria; Corrales, Almudena; Valladares, Francisco; Klassert, Tilman E; Valladares, Basilio; Slevogt, Hortense; Ma, Shwu-Fan; Villar, Jesus; Flores, Carlos

    2015-01-01

    Acute lung injury (ALI) is a severe inflammatory process of the lung. The only proven life-saving support is mechanical ventilation (MV) using low tidal volumes (LVT) plus moderate to high levels of positive end-expiratory pressure (PEEP). However, it is currently unknown how they exert the protective effects. To identify the molecular mechanisms modulated by protective MV, this study reports transcriptomic analyses based on microarray and microRNA sequencing in lung tissues from a clinically relevant animal model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP) in male Sprague-Dawley rats. At 24 hours post-CLP, septic animals were randomized to three ventilatory strategies: spontaneous breathing, LVT (6 ml/kg) plus 10 cmH2O PEEP and high tidal volume (HVT, 20 ml/kg) plus 2 cmH2O PEEP. Healthy, non-septic, non-ventilated animals served as controls. After 4 hours of ventilation, lung samples were obtained for histological examination and gene expression analysis using microarray and microRNA sequencing. Validations were assessed using parallel analyses on existing publicly available genome-wide association study findings and transcriptomic human data. The catalogue of deregulated processes differed among experimental groups. The 'response to microorganisms' was the most prominent biological process in septic, non-ventilated and in HVT animals. Unexpectedly, the 'neuron projection morphogenesis' process was one of the most significantly deregulated in LVT. Further support for the key role of the latter process was obtained by microRNA studies, as four species targeting many of its genes (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) were found deregulated. Additional analyses revealed 'VEGF signaling' as a central underlying response mechanism to all the septic groups (spontaneously breathing or mechanically ventilated). Based on this data, we conclude that a co-deregulation of 'VEGF signaling' along with 'neuron projection morphogenesis

  18. Acute lung inflammation in Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice: a comparative study.

    PubMed

    Kumar, Vijay; Chhibber, Sanjay

    2011-10-01

    Lungs play an important role in the body's defense against a variety of pathogens, but this network of immune system-mediated defense can be deregulated during acute pulmonary infections. The present study compares acute lung inflammation occurring during Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice. Pneumonia was induced by intranasal instillation of bacteria (10(4) cfu), while sepsis was developed by placing the fibrin-thrombin clot containing known amount of bacteria (10(2) cfu) into the peritoneal cavity of animals. Mice with sepsis showed 100% mortality within five post-infection days, whereas all the animals with pneumonia survived. In animals suffering from K. pneumoniae B5055-induced pneumonia, all the inflammatory parameters (TNF-α, IL-1α, MPO, MDA, and NO) were found to be maximum till third post-infection day, after that, a decline was observed, whereas in septic animals, all the above-mentioned markers of inflammation kept on increasing. Histopathological study showed presence of alternatively activated alveolar macrophages (or foam cells) in lungs of mice with pneumonia after third post-infection day, which might have contributed to the induction of resolution of inflammation, but no such observation was made in lungs of septic mice. Hence, during pneumonia, controlled activation of macrophages may lead to resolution of inflammation.

  19. Acute kidney injury in elderly intensive care patients from a developing country: clinical features and outcome

    PubMed Central

    Yokota, Laís Gabriela; Sampaio, Beatriz Motta; Rocha, Erica; Balbi, André Luís; Ponce, Daniela

    2017-01-01

    Aim The elderly are at high risk of acute kidney injury (AKI) because of structural and functional degeneration over time and with the aging of the population, the demand for intensive care unit (ICU) admission for older patients has risen recently. However, data from developing countries are scarce. This study aimed to describe the incidence of AKI in elderly patients admitted to ICU from a developing country, to determine the most frequent etiologies for renal impairment and identify its risk factors and outcome. Methods All patients admitted to the ICU at a Brazilian teaching hospital for 12 consecutive months were followed prospectively from the time of admission until ICU discharge. Elderly was defined as aged >60 years and AKI was defined according to the Kidney Disease Improving Global Outcomes 2012 criteria. Multivariable logistic regression was used to adjust confounding and selection bias. Results Two hundred elderly patients were included in the study. AKI incidence was 27% and the main etiology was sepsis (48.1%). At logistic regression, baseline creatinine (odds ratio [OR]=5.17, p<0.0001), Acute Physiology and Chronic Health Evaluation (APACHE) II (OR=1.20, p<0.0001), sepsis (OR=2.96, p<0.0001), and longer ICU stay (OR=1.68, p<0.0001) were associated with AKI in elderly patients. Baseline creatinine (OR=1.97, p=0.018), APACHE II (OR=1.29, p<0.0001), sepsis (OR=1.87, p<0.0001), and AKI severity (OR=2.57, p=0.027) were identified as predictors of death. Conclusion AKI was frequent in elderly patients admitted to ICU from a developing country, and it was identified as a risk factor for death. Sepsis was an important risk factor for both AKI and mortality, similar to developed countries and in younger populations. PMID:28210101

  20. Acute kidney injury in elderly intensive care patients from a developing country: clinical features and outcome.

    PubMed

    Yokota, Laís Gabriela; Sampaio, Beatriz Motta; Rocha, Erica; Balbi, André Luís; Ponce, Daniela

    2017-01-01

    The elderly are at high risk of acute kidney injury (AKI) because of structural and functional degeneration over time and with the aging of the population, the demand for intensive care unit (ICU) admission for older patients has risen recently. However, data from developing countries are scarce. This study aimed to describe the incidence of AKI in elderly patients admitted to ICU from a developing country, to determine the most frequent etiologies for renal impairment and identify its risk factors and outcome. All patients admitted to the ICU at a Brazilian teaching hospital for 12 consecutive months were followed prospectively from the time of admission until ICU discharge. Elderly was defined as aged >60 years and AKI was defined according to the Kidney Disease Improving Global Outcomes 2012 criteria. Multivariable logistic regression was used to adjust confounding and selection bias. Two hundred elderly patients were included in the study. AKI incidence was 27% and the main etiology was sepsis (48.1%). At logistic regression, baseline creatinine (odds ratio [OR]=5.17, p<0.0001), Acute Physiology and Chronic Health Evaluation (APACHE) II (OR=1.20, p<0.0001), sepsis (OR=2.96, p<0.0001), and longer ICU stay (OR=1.68, p<0.0001) were associated with AKI in elderly patients. Baseline creatinine (OR=1.97, p=0.018), APACHE II (OR=1.29, p<0.0001), sepsis (OR=1.87, p<0.0001), and AKI severity (OR=2.57, p=0.027) were identified as predictors of death. AKI was frequent in elderly patients admitted to ICU from a developing country, and it was identified as a risk factor for death. Sepsis was an important risk factor for both AKI and mortality, similar to developed countries and in younger populations.

  1. Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

    PubMed Central

    Peng, Qian-Yi; Zou, Yu; Zhang, Li-Na; Ai, Mei-Lin; Liu, Wei; Ai, Yu-Hang

    2016-01-01

    Background: Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality. Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI, and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization. The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI. Methods: Septic rat models were established by cecal ligation and puncture (CLP). Rats were divided into the sham group, the CLP group, and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group. Nicotinamide adenine dinucleotide (NAD+), cADPR, CD38, and intracellular Ca2+ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor (TNF)-α, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities were measured. Results: NAD+, cADPR, CD38, and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca2+ levels (P = 0.007), attenuated lung histological injury (P = 0.023), reduced TNF-α and MDA levels (P < 0.001 and P = 0.002, respectively) and recovered SOD activity (P = 0.031) in the lungs of septic rats. Conclusions: The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI. PMID:27411462

  2. Epidemiology and outcomes of acute encephalitis.

    PubMed

    Venkatesan, Arun

    2015-06-01

    This review seeks to describe recent advances in the epidemiology, outcomes, and prognostic factors in acute encephalitis. Infectious causes continue to account for the largest proportion of encephalitis cases in which a cause is identified, although autoimmune causes are increasingly recognized. Type-A gamma-aminobutyric acid (GABAa) receptor antibodies have been recently identified in encephalitis with refractory seizures, whereas the roles of antibodies to the glycine receptor and dipeptidyl peptidase-like protein 6 have been defined in progressive encephalomyelitis with rigidity and myoclonus. Recent findings in the US cases of encephalomyelitis presenting with acute flaccid paralysis raise the possibility that enterovirus D68, a common respiratory pathogen, may cause central nervous system disease. Mortality from acute encephalitis occurs in about 10% of cases, with a large proportion of survivors suffering from cognitive or physical disability. In addition to delay in institution of appropriate antiviral or immune therapy, several potentially reversible factors associated with poor prognosis have been identified, including cerebral edema, status epilepticus, and thrombocytopenia. Encephalitis imposes a significant worldwide health burden and is associated with poor outcomes. Supportive treatment and early institution of therapy may improve outcomes. Careful neurocognitive assessment of survivors of encephalitis is needed to better define long-term outcomes.

  3. Immune profiles and clinical outcomes between sepsis patients with or without active cancer requiring admission to intensive care units

    PubMed Central

    Lin, Chiung-Yu; Huang, Kuo-Tung; Kao, Hsu-Ching; Fang, Ying-Tang; Huang, Chi-Han; Chang, Ya-Ting; Wang, Yi-His; Wang, Chin-Chou

    2017-01-01

    Background Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis. It would be interesting to see if immune status was different in severe sepsis patients with or without active cancer. The aim of this study was to assess the differences in immune profiles, and clinical outcomes between severe sepsis patients with or without cancer admitted to ICU. Methods A combined retrospective and prospective observational study from a cohort of adult sepsis patients admitted to three medical ICUs at Kaohsiung Chang Gung Memorial Hospital in Taiwan between August 2013 and June 2016. Results Of the 2744 patients admitted to the ICU, 532 patients with sepsis were included. Patients were divided into those with or without active cancer according to their medical history. Of the 532 patients, 95 (17.9%) patients had active cancer, and 437 (82.1%) patients had no active cancer history. Patients with active cancer were younger (p = 0.001) and were less likely to have diabetes mellitus (p < 0.001), hypertension (p < 0.001), coronary artery disease (p = 0.004), chronic obstructive pulmonary disease (p = 0.002) or stroke (p = 0.002) compared to patients without active cancer. Patients with active cancer also exhibited higher baseline lactate levels (p = 0.038), and higher baseline plasma interleukin (IL)-10 levels (p = 0.040), higher trend of granulocyte colony-stimulating factor (G-CSF) (p = 0.004) compared to patients without active cancer. The 14-day, 28-day and 90-day mortality rates were higher for patients with active cancer than those

  4. Immune profiles and clinical outcomes between sepsis patients with or without active cancer requiring admission to intensive care units.

    PubMed

    Fang, Wen-Feng; Chen, Yu-Mu; Lin, Chiung-Yu; Huang, Kuo-Tung; Kao, Hsu-Ching; Fang, Ying-Tang; Huang, Chi-Han; Chang, Ya-Ting; Wang, Yi-His; Wang, Chin-Chou; Lin, Meng-Chih

    2017-01-01

    Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis. It would be interesting to see if immune status was different in severe sepsis patients with or without active cancer. The aim of this study was to assess the differences in immune profiles, and clinical outcomes between severe sepsis patients with or without cancer admitted to ICU. A combined retrospective and prospective observational study from a cohort of adult sepsis patients admitted to three medical ICUs at Kaohsiung Chang Gung Memorial Hospital in Taiwan between August 2013 and June 2016. Of the 2744 patients admitted to the ICU, 532 patients with sepsis were included. Patients were divided into those with or without active cancer according to their medical history. Of the 532 patients, 95 (17.9%) patients had active cancer, and 437 (82.1%) patients had no active cancer history. Patients with active cancer were younger (p = 0.001) and were less likely to have diabetes mellitus (p < 0.001), hypertension (p < 0.001), coronary artery disease (p = 0.004), chronic obstructive pulmonary disease (p = 0.002) or stroke (p = 0.002) compared to patients without active cancer. Patients with active cancer also exhibited higher baseline lactate levels (p = 0.038), and higher baseline plasma interleukin (IL)-10 levels (p = 0.040), higher trend of granulocyte colony-stimulating factor (G-CSF) (p = 0.004) compared to patients without active cancer. The 14-day, 28-day and 90-day mortality rates were higher for patients with active cancer than those without active cancer (P

  5. The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome.

    PubMed

    Dorward, David A; Felton, Jennifer M; Robb, Calum T; Craven, Thomas; Kipari, Tiina; Walsh, Timothy S; Haslett, Christopher; Kefala, Kallirroi; Rossi, Adriano G; Lucas, Christopher D

    2017-02-01

    Acute respiratory distress syndrome (ARDS) is a neutrophil-dominant disorder with no effective pharmacological therapies. While the cyclin-dependent kinase inhibitor AT7519 induces neutrophil apoptosis to promote inflammation resolution in preclinical models of lung inflammation, its potential efficacy in ARDS has not been examined. Untreated peripheral blood sepsis-related ARDS neutrophils demonstrated prolonged survival after 20 hours in vitro culture. AT7519 was able to override this phenotype to induce apoptosis in ARDS neutrophils with reduced expression of the pro-survival protein Mcl-1. We demonstrate the first pharmacological compound to induce neutrophil apoptosis in sepsis-related ARDS, highlighting cyclin-dependent kinase inhibitors as potential novel therapeutic agents. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome

    PubMed Central

    Felton, Jennifer M; Robb, Calum T; Craven, Thomas; Kipari, Tiina; Walsh, Timothy S; Haslett, Christopher; Kefala, Kallirroi; Rossi, Adriano G; Lucas, Christopher D

    2017-01-01

    Acute respiratory distress syndrome (ARDS) is a neutrophil-dominant disorder with no effective pharmacological therapies. While the cyclin-dependent kinase inhibitor AT7519 induces neutrophil apoptosis to promote inflammation resolution in preclinical models of lung inflammation, its potential efficacy in ARDS has not been examined. Untreated peripheral blood sepsis-related ARDS neutrophils demonstrated prolonged survival after 20 hours in vitro culture. AT7519 was able to override this phenotype to induce apoptosis in ARDS neutrophils with reduced expression of the pro-survival protein Mcl-1. We demonstrate the first pharmacological compound to induce neutrophil apoptosis in sepsis-related ARDS, highlighting cyclin-dependent kinase inhibitors as potential novel therapeutic agents. PMID:27965411

  7. Neonatal sepsis

    MedlinePlus

    ... better the outcome. Possible Complications Complications may include: Disability Death When to Contact a Medical Professional Seek medical help right away for an infant that shows symptoms of neonatal sepsis. Prevention Pregnant women may need preventive antibiotics if they have: Chorioamnionitis ...

  8. The impact of serial lactate monitoring on emergency department resuscitation interventions and clinical outcomes in severe sepsis and septic shock: an observational cohort study.

    PubMed

    Dettmer, Matthew; Holthaus, Christopher V; Fuller, Brian M

    2015-01-01

    Monitoring in the setting of critical illness must be linked to beneficial therapy to affect clinical outcome. Elevated serum lactate is associated with an increase in mortality in emergency department (ED) patients with severe sepsis and septic shock. The reduction of lactate levels toward normal during acute resuscitation is associated with improved clinical outcomes. The majority of data demonstrating the interventions used to achieve a reduction in lactate levels and the associated clinical outcomes have been obtained during protocolized randomized trials. We therefore conducted a retrospective observational cohort study of 243 adult patients with severe sepsis and septic shock to assess the interventions associated with nonprotocolized serial lactate monitoring and to assess clinical outcomes. A multivariable model was used to assess outcome differences between the serial lactate (SL) and no serial lactate (NL) cohorts. The SL group received more crystalloid resuscitation (3.6 L vs. 2.5 L; P < 0.01), central venous oxygen saturation monitoring (30% vs. 12%; P < 0.01), and central venous pressure monitoring (23.5% vs. 11.8%; P = 0.02). By day 28, a total of 31 patients in the SL group (23.5%) and 44 in the NL group (39.6%) had died. Multivariable logistic regression analysis demonstrated that the lack of serial lactate monitoring was independently associated with mortality (adjusted odds ratio, 2.09; 95% confidence interval [CI], 1.12 - 3.89; P = 0.02). The SL group also showed greater improvement in 24-h Sequential Organ Failure Assessment scores (1.16 vs. 0.19; P = 0.03), decreased intensive care unit length of stay in days (4.6 vs. 6.0; P = 0.04), and more ventilator-free (19.9 vs. 16; P = 0.05) and vasopressor-free (21.6 vs. 17.9; P = 0.02) days. In the setting of routine clinical care, serial lactate monitoring is associated with an increase in crystalloid administration, resuscitation interventions, and improved clinical outcomes in ED patients with

  9. Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis.

    PubMed

    Zilberberg, Marya D; Nathanson, Brian H; Sulham, Kate; Fan, Weihong; Shorr, Andrew F

    2017-04-17

    Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. We conducted a retrospective cohort study in Premier Perspective database (2009-2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/-15.3 vs. 69.1+/-15.9 years, p < 0.001), and more likely to be African-American (19.7% vs. 14.0%, p < 0.001) than those with non-CRE. Both chronic (Charlson score 2.0+/-2.0 vs. 1.9+/-2.1, p = 0.009) and acute (by day 2: ICU 56.3% vs. 30.4%, p < 0.001, and mechanical ventilation 35.8% vs. 11.7%, p < 0.001) illness burdens were higher among CRE than non-CRE subjects, respectively. CRE patients were 3× more likely to receive IET than non-CRE (46.5% vs. 11.8%, p < 0.001). In a regression model CRE was a strong predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence interval 3.5 to 4.5, p < 0.001). In turn, IET was associated with an adjusted rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of 5.2 days (95% confidence interval 4.8, 5.6, p < 0.001) LOS and $10,312 (95% confidence interval $9497, $11,126, p < 0

  10. Epidemiology and outcome of Staphylococcus aureus bloodstream infection and sepsis in a Norwegian county 1996-2011: an observational study.

    PubMed

    Paulsen, Julie; Mehl, Arne; Askim, Åsa; Solligård, Erik; Åsvold, Bjørn Olav; Damås, Jan Kristian

    2015-03-04

    Staphylococcus aureus is one of the most common and lethal causes of bloodstream infection and the incidence is increasing. We carried out a prospective observational study of patients with Staphylococcus aureus bloodstream infection and sepsis in Nord-Trøndelag county in Norway from 1996-2011. The main outcome of interest was all-cause mortality within 30 and 90 days. Positive blood cultures were registered prospectively by the microbiology laboratory and clinical variables were retrospectively registered from patients' hospital records. The severity of sepsis was assigned according to the 2001 International Sepsis Definition Conference criteria. The association between clinical characteristics and mortality was studied using logistic regression analysis, and adjusted 30- and 90-day mortality risks were estimated. Among 373 patients, the median age was 74 years and 60.3% were male. 0.8% of the patients were diagnosed with MRSA. 29.8% of the patients developed severe sepsis and 12.9% developed septic shock. The all-cause mortality was 14.5%, 27.3% and 36.2% at 7, 30 and 90 days, respectively. Compared to patients with sepsis without organ failure (Mortality risk 13.3%, 95% CI 7.5-16.3%), the 30-day mortality risk was 3-fold higher among those with severe sepsis (39.9%, 95% CI 29.5-48.5%) and more than 4-fold higher for those with septic shock (57.3%, 95% CI 42.5-72.2%). The 30-day all-cause mortality varied by focus of infection, with the highest 30-day mortality risk among those with a pulmonary focus (42.4%, 95% CI 26.0-58.5%) and unknown focus of infection (38.7%, 95% CI 27.5-48.2%). The mortality risk did not differ between the first and second halves of the study period with a 30-day mortality risk of 27.3%, (95% CI 18.1-33.1%) for 1996-2003 versus 27.4% (95% CI 19.4-31.4%) for 2004-2011. The same pattern was seen for 90-day mortality risk. Staphylococcus aureus bloodstream infection carries a high case fatality rate, especially among those with severe

  11. Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity: a prospective observational cohort study.

    PubMed

    Mansur, Ashham; Steinau, Maximilian; Popov, Aron Frederik; Ghadimi, Michael; Beissbarth, Tim; Bauer, Martin; Hinz, José

    2015-06-01

    Previous investigations have presumed a potential therapeutic effect of statin therapy in patients with acute respiratory distress syndrome (ARDS). Statins are expected to attenuate inflammation in the lungs of patients with ARDS due to their anti-inflammatory effects. Clinical investigations of the role of statin therapy have revealed contradictory results. This study aimed to investigate whether pretreatment and continuous therapy with statins in patients with sepsis-associated ARDS are associated with 28-day survival according to disease severity (mild, moderate, or severe). Patients with sepsis-associated ARDS from the surgical intensive care were enrolled in this prospective observational investigation. ARDS was classified into three groups (mild, moderate, and severe); 28-day mortality was recorded as the primary outcome variable and organ failure was recorded as secondary outcome variable. Sequential Organ Failure Assessment scores and the requirements for organ support were evaluated throughout the observational period to assess organ failure. 404 patients with sepsis-associated ARDS were enrolled in this investigation. The distribution of the ARDS subgroups was 13 %, 59 %, and 28 % for mild, moderate, and severe disease, respectively. Statin therapy improved 28-day survival exclusively in the patients with severe ARDS compared with patients without statin therapy (88.5 % and 62.5 %, respectively; P = 0.0193). To exclude the effects of several confounders, we performed multivariate Cox regression analysis, which showed that statin therapy remained a significant covariate for mortality (hazard ratio, 5.46; 95 % CI, 1.38-21.70; P = 0.0156). Moreover, after carrying a propensity score-matching in the severe ARDS cohort, Kaplan-Meier survival analysis confirmed the improved 28-day survival among patients with statin therapy (P = 0.0205). Patients with severe ARDS who received statin therapy had significantly more vasopressor-free days compared with those

  12. Outcome of Pediatric Acute Myeloid Leukemia Patients Receiving Intensive Care in the United States

    PubMed Central

    Maude, Shannon L.; Fitzgerald, Julie C.; Fisher, Brian T.; Li, Yimei; Huang, Yuan-Shung; Torp, Kari; Seif, Alix E.; Kavcic, Marko; Walker, Dana M.; Leckerman, Kateri H.; Kilbaugh, Todd J.; Rheingold, Susan R.; Sung, Lillian; Zaoutis, Theoklis E.; Berg, Robert A.; Nadkarni, Vinay M.; Thomas, Neal J.; Aplenc, Richard

    2015-01-01

    Objective Children with acute myeloid leukemia are at risk for sepsis and organ failure. Outcomes associated with intensive care support have not been studied in a large pediatric acute myeloid leukemia population. Our objective was to determine hospital mortality of pediatric acute myeloid leukemia patients requiring intensive care. Design Retrospective cohort study of children hospitalized between 1999 and 2010. Use of intensive care was defined by utilization of specific procedures and resources. The primary endpoint was hospital mortality. Setting Forty-three children’s hospitals contributing data to the Pediatric Health Information System database. Patients Patients who are newly diagnosed with acute myeloid leukemia and who are 28 days through 18 years old (n = 1, 673) hospitalized any time from initial diagnosis through 9 months following diagnosis or until stem cell transplant. A reference cohort of all nononcology pediatric admissions using the same intensive care resources in the same time period (n = 242,192 admissions) was also studied. Interventions None. Measurements and Main Results One-third of pediatric patients with acute myeloid leukemia (553 of 1,673) required intensive care during a hospitalization within 9 months of diagnosis. Among intensive care admissions, mortality was higher in the acute myeloid leukemia cohort compared with the nononcology cohort (18.6% vs 6.5%; odds ratio, 3.23; 95% CI, 2.64–3.94). However, when sepsis was present, mortality was not significantly different between cohorts (21.9% vs 19.5%; odds ratio, 1.17; 95% CI, 0.89–1.53). Mortality was consistently higher for each type of organ failure in the acute myeloid leukemia cohort versus the nononcology cohort; however, mortality did not exceed 40% unless there were four or more organ failures in the admission. Mortality for admissions requiring intensive care decreased over time for both cohorts (23.7% in 1999–2003 vs 16.4% in 2004–2010 in the acute myeloid

  13. Outcome of pediatric acute myeloid leukemia patients receiving intensive care in the United States.

    PubMed

    Maude, Shannon L; Fitzgerald, Julie C; Fisher, Brian T; Li, Yimei; Huang, Yuan-Shung; Torp, Kari; Seif, Alix E; Kavcic, Marko; Walker, Dana M; Leckerman, Kateri H; Kilbaugh, Todd J; Rheingold, Susan R; Sung, Lillian; Zaoutis, Theoklis E; Berg, Robert A; Nadkarni, Vinay M; Thomas, Neal J; Aplenc, Richard

    2014-02-01

    Children with acute myeloid leukemia are at risk for sepsis and organ failure. Outcomes associated with intensive care support have not been studied in a large pediatric acute myeloid leukemia population. Our objective was to determine hospital mortality of pediatric acute myeloid leukemia patients requiring intensive care. Retrospective cohort study of children hospitalized between 1999 and 2010. Use of intensive care was defined by utilization of specific procedures and resources. The primary endpoint was hospital mortality. Forty-three children's hospitals contributing data to the Pediatric Health Information System database. Patients who are newly diagnosed with acute myeloid leukemia and who are 28 days through 18 years old (n = 1,673) hospitalized any time from initial diagnosis through 9 months following diagnosis or until stem cell transplant. A reference cohort of all nononcology pediatric admissions using the same intensive care resources in the same time period (n = 242,192 admissions) was also studied. None. One-third of pediatric patients with acute myeloid leukemia (553 of 1,673) required intensive care during a hospitalization within 9 months of diagnosis. Among intensive care admissions, mortality was higher in the acute myeloid leukemia cohort compared with the nononcology cohort (18.6% vs 6.5%; odds ratio, 3.23; 95% CI, 2.64-3.94). However, when sepsis was present, mortality was not significantly different between cohorts (21.9% vs 19.5%; odds ratio, 1.17; 95% CI, 0.89-1.53). Mortality was consistently higher for each type of organ failure in the acute myeloid leukemia cohort versus the nononcology cohort; however, mortality did not exceed 40% unless there were four or more organ failures in the admission. Mortality for admissions requiring intensive care decreased over time for both cohorts (23.7% in 1999-2003 vs 16.4% in 2004-2010 in the acute myeloid leukemia cohort, p = 0.0367; and 7.5% in 1999-2003 vs 6.5% in 2004-2010 in the nononcology

  14. Targeting Abl kinases to regulate vascular leak during sepsis and acute respiratory distress syndrome.

    PubMed

    Rizzo, Alicia N; Aman, Jurjan; van Nieuw Amerongen, Geerten P; Dudek, Steven M

    2015-05-01

    The vascular endothelium separates circulating fluid and inflammatory cells from the surrounding tissues. Vascular leak occurs in response to wide-spread inflammatory processes, such as sepsis and acute respiratory distress syndrome, because of the formation of gaps between endothelial cells. Although these disorders are leading causes of mortality in the intensive care unit, no medical therapies exist to restore endothelial cell barrier function. Recent evidence highlights a key role for the Abl family of nonreceptor tyrosine kinases in regulating vascular barrier integrity. These kinases have well-described roles in cancer progression and neuronal morphogenesis, but their functions in the vasculature have remained enigmatic until recently. The Abl family kinases, c-Abl (Abl1) and Abl related gene (Arg, Abl2), phosphorylate several cytoskeletal effectors that mediate vascular permeability, including nonmuscle myosin light chain kinase, cortactin, vinculin, and β-catenin. They also regulate cell-cell and cell-matrix junction dynamics, and the formation of actin-based cellular protrusions in multiple cell types. In addition, both c-Abl and Arg are activated by hyperoxia and contribute to oxidant-induced endothelial cell injury. These numerous roles of Abl kinases in endothelial cells and the current clinical usage of imatinib and other Abl kinase inhibitors have spurred recent interest in repurposing these drugs for the treatment of vascular barrier dysfunction. This review will describe the structure and function of Abl kinases with an emphasis on their roles in mediating vascular barrier integrity. We will also provide a critical evaluation of the potential for exploiting Abl kinase inhibition as a novel therapy for inflammatory vascular leak syndromes. © 2015 American Heart Association, Inc.

  15. Protective Role of Liriodendrin in Sepsis-Induced Acute Lung Injury.

    PubMed

    Yang, Lei; Li, Dihua; Zhuo, Yuzhen; Zhang, Shukun; Wang, Ximo; Gao, Hongwei

    2016-10-01

    In current study, we investigated the role of liriodendrin, a constituent isolated from Sargentodoxa cuneata (Oliv.) Rehd. Et Wils (Sargentodoxaceae), in cecal ligation and puncture (CLP)-induced acute lung inflammatory response and injury (ALI). The inflammatory mediator levels in bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay (ELISA). Pathologic changes in lung tissues were evaluated via pathological section with hematoxylin and eosin (H&E) staining. To investigate the mechanism whereby liriodendrin regulates lung inflammation, the phosphorylation of the NF-kB (p65) and expression of vascular endothelial growth factor (VEGF) were determined by western blot assay. We show that liriodendrin treatment significantly improved the survival rate of mice with CLP-induced sepsis. Pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration were markedly decreased by liriodendrin. In addition, liriodendrin decreased the production of the proinflammatory mediators including (TNF-α, IL-1β, MCP-1, and IL-6) in lung tissues. Vascular permeability and lung myeloperoxidase (MPO) accumulation in the liriodendrin-treated mice were substantially reduced. Moreover, liriodendrin treatment significantly suppressed the expression of VEGF and activation of NF-kB in the lung. We further show that liriodendrin significantly reduced the production of proinflammatory mediators and downregulated NF-kB signaling in LPS-stimulated RAW 264.7 macrophage cells. Moreover, liriodendrin prevented the generation of reactive oxygen species (ROS) by upregulating the expression of SIRT1 in RAW 264.7 cells. These findings provide a novel theoretical basis for the possible application of liriodendrin in clinic.

  16. Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis

    PubMed Central

    2014-01-01

    Background Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission. Methods This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission. Results Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001). Conclusions The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes. PMID:24593040

  17. Australian Group on Antimicrobial Resistance Australian Staphylococcus aureus Sepsis Outcome Programme annual report, 2014.

    PubMed

    Coombs, Geoffrey W; Daley, Denise A; Thin Lee, Yung; Pearson, Julie C; Robinson, J Owen; Nimmo, Graeme R; Collignon, Peter; Howden, Benjamin P; Bell, Jan M; Turnidge, John D

    2016-06-30

    From 1 January to 31 December 2014, 27 institutions around Australia participated in the Australian Staphylococcal Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2014 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to methicillin and to characterise the molecular epidemiology of the isolates. Overall, 18.8% of the 2,206 SAB episodes were methicillin resistant, which was significantly higher than that reported in most European countries. The 30-day all-cause mortality associated with methicillin-resistant SAB was 23.4%, which was significantly higher than the 14.4% mortality associated with methicillin-sensitive SAB (P <0.0001). With the exception of the beta-lactams and erythromycin, antimicrobial resistance in methicillin-sensitive S. aureus remains rare. However in addition to the beta-lactams, approximately 50‰ of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 15% were resistant to co-trimoxazole, tetracycline and gentamicin. When applying the European Committee on Antimicrobial Susceptibility Testing breakpoints, teicoplanin resistance was detected in 2 S. aureus isolates. Resistance was not detected for vancomycin or linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to 2 healthcare-associated MRSA clones; ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) has become the predominant healthcare associated clone in Australia. Sixty per cent of methicillin-resistant SAB were due to community-associated (CA) clones. Although polyclonal, almost 44% of community-associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA) and ST1-IV [2B] (WA1). CA-MRSA, in particular the ST45-V [5C2&5] (WA84) clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin

  18. Utility of cytokine, adhesion molecule and acute phase proteins in early diagnosis of neonatal sepsis

    PubMed Central

    Fattah, M. A.; Omer, Al Fadhil A.; Asaif, S.; Manlulu, R.; Karar, T.; Ahmed, A.; Aljada, A.; Saleh, Ayman M.; Qureshi, Shoeb; Nasr, A.

    2017-01-01

    Background and Aim: Neonatal infection, including bacterial sepsis, is a major health care issue with an annual global mortality in excess of one million lives. Therefore, this study aimed to evaluate the potential diagnostic value of C-reactive protein (CRP), E-selectin, procalcitonin (PCT), interleukins-6 (IL-6), and tumor necrosis factor-α (TNF-α) both independently and in combination for the diagnosis of neonatal sepsis in its earliest stages. Materials and Methods: A total of 320 subjects were included in this study. A prospective cross-sectional study was conducted among neonates admitted to Neonatal Intensive Care Unit at King Abdulaziz Medical City, Riyadh, KSA during January 2013 to August 2015, the study based on three study groups categorized according to clinical symptoms and blood culture result. Study groups include healthy control neonates (n = 80), clinical sepsis (CS) group (n = 80) with clinical signs of sepsis but their blood culture was negative, and sepsis group with clinical signs of sepsis and their blood culture was positive. Results: The study observed significant difference in plasma levels of CRP, IL-6, TNF-α, E-selectin, and PCT in patients group when compared with control group (P < 0.001). Furthermore, the levels are significantly different between patient groups including CS and neonatal sepsis group. Moreover, result observed significant difference in CRP and IL-6 in early onset sepsis (EOS) when compared with late onset sepsis (LOS) neonates (P < 0.001 and 0.01), respectively, while there were no significant difference in TNF-α, E-selectin, and PCT between EOS and LOS (P = 0.44, 0.27 and 0.24), respectively. Regarding biomarkers accuracy, the result showed that CRP has the best diagnostic accuracy with cutoff value of 3.6 ng/ml (sensitivity 78% and specificity of 70%). The best combination is shown with CRP and IL-6 in which sensitivity increased to 89% and specificity to 79%. Conclusion: It was concluded that infected new

  19. Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis.

    PubMed

    Ginde, Adit A; Blatchford, Patrick J; Trzeciak, Stephen; Hollander, Judd E; Birkhahn, Robert; Otero, Ronny; Osborn, Tiffany M; Moretti, Eugene; Nguyen, H Bryant; Gunnerson, Kyle J; Milzman, David; Gaieski, David F; Goyal, Munish; Cairns, Charles B; Rivers, Emanuel P; Shapiro, Nathan I

    2014-08-01

    The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed-chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase-associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)-measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 - 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.

  20. Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis

    PubMed Central

    Ginde, Adit A.; Blatchford, Patrick J.; Trzeciak, Stephen; Hollander, Judd E.; Birkhahn, Robert; Otero, Ronny; Osborn, Tiffany M.; Moretti, Eugene; Nguyen, H. Bryant; Gunnerson, Kyle J.; Milzman, David; Gaieski, David F.; Goyal, Munish; Cairns, Charles B.; Rivers, Emanuel P.; Shapiro, Nathan I.

    2014-01-01

    Objective To evaluate age-related differences in inflammation biomarkers during the first 72 hours of hospitalization for sepsis. Methods This was a secondary analysis of a prospective observational cohort of adult patients (n=855) from ten, urban, academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. We analyzed six inflammation-related biomarkers—chemokine (CC-motif) ligand-23 (CCL-23); C-reactive protein (CRP); interleukin-1 receptor antagonist (IL-1ra); neutrophil gelatinase-associated lipocalin (NGAL); peptidoglycan recognition protein (PGRP); and tumor necrosis factor receptor-1a (TNFR-1a)—measured at presentation and 3, 6, 12, 24, 48, or 72 hours later. Results The median age was 56 (IQR 43–72) years and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18–34 years had severe sepsis or septic shock compared to 71% for those aged ≥65 years (p<0.001). In longitudinal models adjusting for demographics, co-morbidities, and infection source, older age was associated with higher baseline values for CCL-23, IL-1ra, NGAL, and TNFR-1a (all p<0.05). However, older adults had higher mean values during the entire 72-hour period only for NGAL and TNFR-1a, and higher final 72-hour values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Conclusion While older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 hours of hospitalization. PMID:24978893

  1. Serum adhesion molecules as outcome predictors in adult severe sepsis patients requiring mechanical ventilation in the emergency department.

    PubMed

    Kung, Chia-Te; Su, Chih-Min; Chang, Hsueh-Wen; Cheng, Hsien-Hung; Hsiao, Sheng-Yuan; Tsai, Tsung-Cheng; Chang, Wen-Neng; Tsai, Nai-Wen; Wang, Hung-Chen; Su, Yu-Jih; Huang, Chin-Cheng; Lin, Wei-Che; Cheng, Ben-Chung; Chang, Ya-Ting; Chiang, Yi-Fang; Lu, Cheng-Hsien

    2014-10-01

    Serum adhesion molecules play a pivotal role in the pathogenesis of sepsis syndrome. This study aimed to evaluate the prognostic value of serum adhesion molecules in patients with severe sepsis and mechanical ventilation (MV) at the emergency department. Eighty-seven consecutive patients with severe sepsis, including 35 with MV, were evaluated. Serum samples were collected for analysis of serum adhesion molecules. The patients' clinical and laboratory data on admission were also recorded. The maximum 24-h APACHE II and 24-h SOFA scores were significantly higher in the severe sepsis patients requiring MV than in patients without MV (p=0.02 and p<0.001). Mortality rate was significantly higher in severe sepsis patients requiring MV than in patients without MV (40% [14/35] vs. 9.6% [5/52], p=0.001). Both VCAM-1 level (p=0.03) and lactate concentration (p=0.04) on admission had significant differences between survivors and non-survivors in patients requiring MV. In the logistic regression model, only VCAM-1 level (p=0.049) was independently predictive of mortality. By correlation analysis, lactate concentration significantly correlated with the mean VCAM-1 level on admission (γ=0.484, p=0.004). The area under the ROC curve for VCAM-1 level was 0.747 (p=0.02, 95% CI: 0.576-0.918). The cut-off value of VCAM-1 level for predicting hospital mortality in severe sepsis patients receiving MV was 1870ng/mL, with 77% sensitivity and 71% specificity; then the likelihood ratio equals 2.7. In this study, VCAM-1 level is a more powerful outcome predictor of hospital mortality in severe sepsis patients requiring MV than lactate concentration and other conventional parameters on admission. This suggests that increased plasma VCAM-1 concentration may be useful in identifying who are at risk of hospital mortality among severely septic patients requiring MV. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  2. Chronic antiplatelet therapy is not associated with alterations in the presentation, outcome, or host response biomarkers during sepsis: a propensity-matched analysis.

    PubMed

    Wiewel, Maryse A; de Stoppelaar, Sacha F; van Vught, Lonneke A; Frencken, Jos F; Hoogendijk, Arie J; Klein Klouwenberg, Peter M C; Horn, Janneke; Bonten, Marc J; Zwinderman, Aeilko H; Cremer, Olaf L; Schultz, Marcus J; van der Poll, Tom

    2016-03-01

    Sepsis is a major health burden worldwide. Preclinical investigations in animals and retrospective studies in patients have suggested that inhibition of platelets may improve the outcome of sepsis. In this study we investigated whether chronic antiplatelet therapy impacts on the presentation and outcome of sepsis, and the host response. We performed a prospective observational study in 972 patients admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in the Netherlands between January 2011 and July 2013. Of them, 267 patients (27.5%) were on antiplatelet therapy (95.9% acetylsalicylic acid) before admission. To account for differential likelihoods of receiving antiplatelet therapy, a propensity score was constructed, including variables associated with use of antiplatelet therapy. Cox proportional hazards regression was used to estimate the association of antiplatelet therapy with mortality. Antiplatelet therapy was not associated with sepsis severity at presentation, the primary source of infection, causative pathogens, the development of organ failure or shock during ICU stay, or mortality up to 90 days after admission, in either unmatched or propensity-matched analyses. Antiplatelet therapy did not modify the values of 19 biomarkers providing insight into hallmark host responses to sepsis, including activation of the coagulation system, the vascular endothelium, the cytokine network, and renal function, during the first 4 days after ICU admission. Pre-existing antiplatelet therapy is not associated with alterations in the presentation or outcome of sepsis, or the host response.

  3. Improving documentation and coding for acute organ dysfunction biases estimates of changing sepsis severity and burden: a retrospective study.

    PubMed

    Rhee, Chanu; Murphy, Michael V; Li, Lingling; Platt, Richard; Klompas, Michael

    2015-09-14

    Claims-based analyses report that the incidence of sepsis-associated organ dysfunction is increasing. We examined whether coding practices for acute organ dysfunction are changing over time and if so, whether this is biasing estimates of rising severe sepsis incidence and severity. We assessed trends from 2005 to 2013 in the annual sensitivity and incidence of discharge ICD-9-CM codes for organ dysfunction (shock, respiratory failure, acute kidney failure, acidosis, hepatitis, coagulopathy, and thrombocytopenia) relative to standardized clinical criteria (use of vasopressors/inotropes, mechanical ventilation for ≥ 2 consecutive days, rise in baseline creatinine, low pH, elevated transaminases or bilirubin, abnormal international normalized ratio or low fibrinogen, and decline in platelets). We studied all adult patients with suspected infection (defined by ≥ 1 blood culture order) at two US academic hospitals. Acute organ dysfunction codes were present in 57,273 of 191,695 (29.9%) hospitalizations with suspected infection, most commonly acute kidney failure (60.2% of cases) and respiratory failure (28.9%). The sensitivity of all organ dysfunction codes except thrombocytopenia increased significantly over time. This was most pronounced for acute kidney failure codes, which increased in sensitivity from 59.3% in 2005 to 87.5% in 2013 relative to a fixed definition for changes in creatinine (p = 0.019 for linear trend). Acute kidney failure codes were increasingly assigned to patients with smaller creatinine changes: the average peak creatinine change associated with a code was 1.99 mg/dL in 2005 versus 1.49 mg/dL in 2013 (p <0.001 for linear decline). The mean number of dysfunctional organs in patients with suspected infection increased from 0.32 to 0.59 using discharge codes versus 0.69 to 0.79 using clinical criteria (p < 0.001 for both trends and comparison of the two trends). The annual incidence of hospitalizations with suspected infection and any

  4. Beneficial effects of Red Light-Emitting Diode treatment in experimental model of acute lung injury induced by sepsis.

    PubMed

    Costa, Silvia Goes; Barioni, Éric Diego; Ignácio, Aline; Albuquerque, Juliana; Câmara, Niels Olsen Saraiva; Pavani, Christiane; Vitoretti, Luana Beatriz; Damazo, Amílcar Sabino; Farsky, Sandra Helena Poliselli; Lino-Dos-Santos-Franco, Adriana

    2017-10-04

    Sepsis is a severe disease with a high mortality index and it is responsible for the development of acute lung injury (ALI). We evaluated the effects of light-emitting diode (LED) on ALI induced by sepsis. Balb-c mice were injected with lipopolysaccharide or saline and then irradiated or not with red LED on their tracheas and lungs for 150 s, 2 and 6 h after LPS injections. The parameters were investigated 24 h after the LPS injections. Red LED treatment reduced neutrophil influx and the levels of interleukins 1β, 17 A and, tumor necrosis factor-α; in addition to enhanced levels of interferon γ in the bronchoalveolar fluid. Moreover, red LED treatment enhanced the RNAm levels of IL-10 and IFN-γ. It also partially reduced the elevated oxidative burst and enhanced apoptosis, but it did not alter the translocation of nuclear factor κB, the expression of toll-like receptor 4 (TLR4), as well as, oedema or mucus production in their lung tissues. Together, our data has shown the beneficial effects of short treatment with LED on ALI that are caused by gram negative bacterial infections. It is suggested that LED applications are an inexpensive and non-invasive additional treatment for sepsis.

  5. Concise Review: Mesenchymal Stromal Cell‐Based Approaches for the Treatment of Acute Respiratory Distress and Sepsis Syndromes

    PubMed Central

    Soeder, Yorick; Dahlke, Marc H.

    2017-01-01

    Abstract Despite extensive research on candidate pharmacological treatments and a significant and increasing prevalence, sepsis syndrome, and acute respiratory distress syndrome (ARDS) remain areas of unmet clinical need. Preclinical studies examining mesenchymal stromal cell (MSCs) based‐therapies have provided compelling evidence of potential benefit; however, the precise mechanism by which MSCs exert a therapeutic influence, and whether MSC application is efficacious in humans, remains unknown. Detailed evaluation of the limited number of human trials so far completed is further hampered as a result of variations in trial design and biomarker selection. This review provides a concise summary of current preclinical and clinical knowledge of MSCs as a cell therapy for sepsis syndrome and ARDS. The challenges of modeling such heterogeneous and rapidly progressive disease states are considered and we discuss how lessons from previous studies of pharmacological treatments for sepsis syndrome and ARDS might be used to inform and refine the design of the next generation of MSC clinical trials. Stem Cells Translational Medicine 2017;6:1141–1151 PMID:28186706

  6. Glycyrrhizic acid pretreatment prevents sepsis-induced acute kidney injury via suppressing inflammation, apoptosis and oxidative stress.

    PubMed

    Zhao, Hongyu; Liu, Zhenning; Shen, Haitao; Jin, Shuai; Zhang, Shun

    2016-06-15

    Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. The aim of our study was to investigate the molecular mechanism involved in the protective effects of GA in lipopolysaccharide (LPS) stimulated rat mesangial cells (HBZY-1) and septic rats. Sepsis model was established by injection of 5mg/kg LPS in rats or incubation with 1μg/ml LPS for 24h in HBZY-1 cells. A variety of molecular biological experiments were carried out to assess the effects of GA on inflammation, apoptosis, and oxidative stress. First we found that GA alleviated sepsis-induced kidney injury in vivo. Furthermore, GA suppressed inflammatory response in vivo and in vitro. Additionally, GA inhibited cell apoptosis and the changes in expressions of apoptosis related proteins induced by LPS. Moreover, GA markedly inhibited oxidative stress induced by LPS via activation of ERK signaling pathway. Finally GA could inhibit the activation of NF-κ B induced by LPS. Our present study indicates that GA has a protective effect against sepsis-induced inflammatory response, apoptosis, and oxidative stress damage, which provides a molecular basis for a new medical treatment of septic acute kidney injury.

  7. Toward Smarter Lumping and Smarter Splitting: Rethinking Strategies for Sepsis and Acute Respiratory Distress Syndrome Clinical Trial Design.

    PubMed

    Prescott, Hallie C; Calfee, Carolyn S; Thompson, B Taylor; Angus, Derek C; Liu, Vincent X

    2016-07-15

    Both quality improvement and clinical research efforts over the past few decades have focused on consensus definition of sepsis and acute respiratory distress syndrome (ARDS). Although clinical definitions based on readily available clinical data have advanced recognition and timely use of broad supportive treatments, they likely hinder the identification of more targeted therapies that manipulate select biological mechanisms underlying critical illness. Sepsis and ARDS are by definition heterogeneous, and patients vary in both their underlying biology and their severity of illness. We have long been able to identify subtypes of sepsis and ARDS that confer different prognoses. The key is that we are now on the verge of identifying subtypes that may confer different response to therapy. In this perspective, inspired by a 2015 American Thoracic Society International Conference Symposium entitled "Lumpers and Splitters: Phenotyping in Critical Illness," we highlight promising approaches to uncovering patient subtypes that may predict treatment responsiveness and not just differences in prognosis. We then discuss how this information can be leveraged to improve the success and translatability of clinical trials by using predictive enrichment and other design strategies. Last, we discuss the challenges and limitations to identifying biomarkers and endotypes and incorporating them into routine clinical practice.

  8. Neurological sequelae of healthcare-associated sepsis in very-low-birthweight infants: Umbrella review and evidence-based outcome tree.

    PubMed

    Haller, Sebastian; Deindl, Philipp; Cassini, Alessandro; Suetens, Carl; Zingg, Walter; Abu Sin, Muna; Velasco, Edward; Weiss, Bettina; Ducomble, Tanja; Sixtensson, Madlen; Eckmanns, Tim; Harder, Thomas

    2016-01-01

    Sepsis is a frequent cause of death in very-low-birthweight infants and often results in neurological impairment. Its attributable risk of sequelae has not been systematically assessed. To establish an outcome tree for mapping the burden of neonatal sepsis, we performed systematic literature searches to identify systematic reviews addressing sequelae of neonatal sepsis. We included cohort studies and performed meta-analyses of attributable risks. Evidence quality was assessed using GRADE. Two systematic reviews met inclusion criteria. The first included nine cohort studies with 5,620 participants and five outcomes (neurodevelopmental impairment, cerebral palsy, vision impairment, hearing impairment, death). Pooled risk differences varied between 4% (95% confidence interval (CI):2-10) and 13% (95% CI:5-20). From the second review we analysed four studies with 472 infants. Positive predictive value of neurodevelopmental impairment for later cognitive impairment ranged between 67% (95% CI:22-96) and 83% (95% CI:36-100). Neonatal sepsis increases risk of permanent neurological impairment. Effect size varies by outcome, with evidence quality being low to very low. Data were used to construct an outcome tree for neonatal sepsis. Attributable risk estimates for sequelae following neonatal sepsis are suitable for burden estimation and may serve as outcome parameters in interventional studies.

  9. Association between regulatory T cell activity and sepsis and outcome of severely burned patients: a prospective, observational study

    PubMed Central

    2010-01-01

    Introduction To investigate the significance of changes in regulatory T cells (Tregs) activity and its relationship with sepsis, as well as outcome of patients with major burns. Methods The periphery blood samples of 106 patients were collected on post-burn days 1, 3, 7, 14, and 21. Tregs were isolated and their phenotypes (cytotoxic T-lymphocyte-associated antigen 4 and forkhead/winged helix transcription factor p3) were analyzed by flow cytometry, and the contents of cytokines (interleukin-10 and transforming growth factor-β1) released into supernatants by Tregs were also determined by enzyme-linked immunosorbent assay kits. Gene expressions of cytokines were assessed by real-time quantitative polymerase chain reaction. Results Expressions of Tregs phenotypes and gene/protein expression of cytokines were all elevated after burn, and there were obvious differences among patients with various burn sizes. They were also higher in septic patients than those without sepsis. Among septic patients, the expressions of Tregs phenotypes and the levels of cytokines were markedly lower in the survival group than those in patients with fatal outcome. Conclusions Severe burn injury per se could lead to the changes in Tregs activities. Elevated levels of cytokines produced by Tregs and activation markers on Tregs surface might play an important role in the pathogenesis of sepsis and mortality in burned patients. PMID:20064232

  10. The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population.

    PubMed

    Ma, Guoda; Wang, Haiyang; Mo, Guixi; Cui, Lili; Li, You; Shao, Yiming; Liu, Xin; Xie, Yuliu; Li, Jia; Fu, Jiawu; Tao, Hua; Zhao, Bin; Zhang, Liangqing; Li, Keshen

    2014-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P = 0.622 for genotype; P = 0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P = 0.014 for allele and P = 0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P = 0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P < 0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

  11. The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population

    PubMed Central

    Ma, Guoda; Wang, Haiyang; Mo, Guixi; Cui, Lili; Li, You; Shao, Yiming; Liu, Xin; Xie, Yuliu; Li, Jia; Fu, Jiawu; Tao, Hua; Zhao, Bin; Zhang, Liangqing; Li, Keshen

    2014-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P = 0.622 for genotype; P = 0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P = 0.014 for allele and P = 0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P = 0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P < 0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis. PMID:25152754

  12. Sepsis Patients with First and Second-Hit Infections Show Different Outcomes Depending on the Causative Organism

    PubMed Central

    Morgan, Matt P.; Szakmany, Tamas; Power, Sarah G.; Olaniyi, Patrick; Hall, Judith E.; Rowan, Kathy; Eberl, Matthias

    2016-01-01

    Objective: With improving rates of initial survival in severe sepsis, second-hit infections that occur following resolution of the primary insult carry an increasing burden of morbidity. However, despite the clinical relevance of these infections, no data are available on differential outcomes in patients with first and second-hit infections depending on the nature of the causative organism. This study aims to explore any differences in these subgroups. Design: In a retrospective, observational cohort study, the United Kingdom Intensive Care National Audit & Research Centre (ICNARC) database was used to explore the outcomes of patient with first-hit infections leading to sepsis, and sepsis patients with second-hit infections grouped according to the Gram status of the causative organism. Setting: General critical care units in England, Wales, and Northern Ireland participating in the ICNARC programme between 1 January, 2007 and 30 June, 2012. Patients: Patient groups analyzed included 2119 patients with and 1319 patients without sepsis who developed an intensive care unit acquired infection in blood. Subgroups included patients with trauma, emergency neurosurgery, elective surgery, and cardiogenic shock. Measurements and main results: Gram-negative organisms were associated with poorer outcomes in first-hit infections. The 90-day mortality of patients who developed a Gram-negative infection was 43.6% following elective surgery and 27.9% following trauma. This compared with a mortality of 25.6 and 20.6%, respectively, in Gram-positive infections. Unexpectedly, an inverse relationship between Gram status and mortality was observed in second-hit infections. Patients with an initial diagnosis of sepsis who developed secondary infections caused by Gram-negative organisms had a 90-day mortality of 40.4%, compared with 43.6% in Gram-positive infections. Conclusions: Our study identifies a fundamental difference in patient outcomes between first-hit and second

  13. Serum Neutrophil Gelatinase-Associated Lipocalin in Infants and Children with Sepsis-Related Conditions with or without Acute Renal Dysfunction

    PubMed Central

    Afify, Mohammed Farouk M.; Maher, Sheren Esam; Ibrahim, Nora Mohamed; El-Hamied, Waleed Mahamoud Abd

    2016-01-01

    PURPOSE To validate serum neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for acute kidney injury (AKI) in sepsis-related conditions and its predictive and prognostic values. PATIENTS AND METHODS This study included 65 patients, who were clinically evaluated for sepsis, severe sepsis, or septic shock, and 20 apparently healthy served as controls. Patients were divided into two groups: Group I (AKI-sepsis): 65 newly admitted patients diagnosed as sepsis, who were further divided into three subgroups according to the severity: systemic inflammatory response syndrome, severe sepsis, and septic shock, and Group II (control group): 20 apparently healthy subjects matched for age and sex, serum creatinine and serum NGAL concentrations were estimated initially within 24 hours of admission and after 72 hours of admission in all patients and control groups. RESULTS Serum NGAL increased significantly with increasing severity of renal impairment. Receiver-operating characteristic analysis suggested that serum NGAL cutoff value of 40 ng/mL within the first 24 hours of admission is highly specific and sensitive for predicting AKI, with sensitivity of 90.9% and specificity of 75.8%. CONCLUSION We concluded that early measurement of serum NGAL level in sepsis can serve as a clinically useful marker for early prediction of AKI and for grading of its severity. PMID:27547045

  14. Neuromuscular electrical stimulation acutely mobilizes endothelial progenitor cells in critically ill patients with sepsis.

    PubMed

    Stefanou, Christos; Karatzanos, Eleftherios; Mitsiou, Georgios; Psarra, Katerina; Angelopoulos, Epameinondas; Dimopoulos, Stavros; Gerovasili, Vasiliki; Boviatsis, Efstathios; Routsi, Christina; Nanas, Serafeim

    2016-12-01

    Endothelial progenitor cells (EPCs) have been suggested to constitute a restoration index of the disturbed endothelium in ICU patients. Neuromuscular electric stimulation (NMES) is increasingly employed in ICU to prevent comorbidities such as ICU-acquired weakness, which is related to endothelial dysfunction. The role of NMES to mobilize EPCs has not been investigated yet. The purpose of this study was to explore the NMES-induced effects on mobilization of EPCs in septic ICU patients. Thirty-two septic mechanically ventilated patients (mean ± SD, age 58 ± 14 years) were randomized to one of the two 30-min NMES protocols of different characteristics: a high-frequency (75 Hz, 6 s on-21 s off) or a medium-frequency (45 Hz, 5 s on-12 s off) protocol both applied at maximally tolerated intensity. Blood was sampled before and immediately after the NMES sessions. Different EPCs subpopulations were quantified by cytometry markers CD34(+)/CD133(+)/CD45(-), CD34(+)/CD133(+)/CD45(-)/VEGFR2 (+) and CD34(+)/CD45(-)/VEGFR2 (+). Overall, CD34(+)/CD133(+)/CD45(-) EPCs increased from 13.5 ± 10.2 to 20.8 ± 16.9 and CD34(+)/CD133(+)/CD45(-)/VEGFR2 (+) EPCs from 3.8 ± 5.2 to 6.4 ± 8.5 cells/10(6) enucleated cells (mean ± SD, p < 0.05). CD34(+)/CD45(-)/VEGFR2 (+) EPCs also increased from 16.5 ± 14.5 to 23.8 ± 19.2 cells/10(6) enucleated cells (mean ± SD, p < 0.05). EPCs mobilization was not affected by NMES protocol and sepsis severity (p > 0.05), while it was related to corticosteroids administration (p < 0.05). NMES acutely mobilized endothelial progenitor cells, measures of the endothelial restoration potential, in septic ICU patients.

  15. Procalcitonin as a marker of sepsis and outcome in patients with neurotrauma: an observation study

    PubMed Central

    2013-01-01

    Background Procalcitonin (PCT) is a reliable biomarker of sepsis and infection. The level of PCT associated with sepsis and infection in patients with traumatic brain injury is currently unknown. The purpose of this study was to investigate the value of PCT and C-reactive protein (CRP) as diagnostic markers of sepsis and to evaluate the prognostic value of these markers related to the severity of injury, sepsis and mortality. Methods 105 adult patients with neurotrauma were enrolled in this study from June 2011 to February 2013. PCT and CRP were measured at admission and 2, 3, 5 and 7 days after admission. The sepsis criteria established by American College of Chest Physicians /Society of Critical Care Medicine Consensus Conference were used to identify patients. Injury Severity Score (ISS) and Glasgow Coma Score (GCS) were used to assess the severity of the injury. All these patients were monitored for 28 days. Results At admission, the median level of PCT was consistent with the severity of brain injury as follows: mild 0.08 ng/ml (0.05 - 0.13), moderate 0.25 ng/ml (0.11 - 0.55) and severe 0.31 ng/ml (0.17 - 0.79), but the range of CRP levels varied greatly within the given severity of brain injury. Seventy-one (67.6%) patients developed sepsis. The initial levels of PCT at admission were statistically higher in patients with sepsis, compared with patients with systemic inflammatory response syndrome (SIRS), but there were no differences in the initial concentration of CRP between sepsis and SIRS. After adjusting for these parameters, multivariate logistic regression analysis revealed that PCT was an independent risk factor for septic complications (p < 0.05). The areas under the ROCs at admission for the prediction of mortality were 0.76 (p < 0.05) and 0.733 for PCT and CRP, respectively. Conclusions Increased levels of PCT during the course of the ICU stay could be an important indicator for the early diagnosis of sepsis after neurotrauma. In

  16. Sepsis-related acute respiratory distress syndrome in children with cancer: the respiratory dynamics of a devastating condition.

    PubMed

    Arduini, Rodrigo Genaro; Araujo, Orlei Ribeiro de; Silva, Dafne Cardoso Bourguignon da; Senerchia, Andreza Almeida; Petrilli, Antonio Sergio

    2016-01-01

    To evaluate the clinical course and respiratory parameters of mechanically ventilated children with cancer suffering from sepsis-related acute respiratory distress syndrome. This 2-year prospective, longitudinal, observational cohort study enrolled 29 children and adolescents. Clinical data, measurements of blood gases and ventilation parameters were collected at four different time points. Fluctuations between measurements as well as differences in estimated means were analyzed by linear mixed models in which death within 28 days from the onset of acute respiratory distress syndrome was the primary endpoint. There were 17 deaths within 28 days of acute respiratory distress syndrome onset and another 7 between 29 - 60 days. Only 5 patients survived for more than 60 days. Nine (31%) patients died as a direct consequence of refractory hypoxemia, and the others died of multiple organ failure and catecholamine-refractory shock. In 66% of the measurements, the tidal volume required to obtain oxygen saturation equal to or above 90% was greater than 7mL/kg. The estimated means of dynamic compliance were low and were similar for survivors and non-survivors but with a negative slope between the first and final measurements, accompanied by a negative slope of the tidal volume for non-survivors. Non-survivors were significantly more hypoxemic, with PaO2/FiO2 ratios showing lower estimated means and a negative slope along the four measurements. Peak, expiratory and mean airway pressures showed positive slopes in the non-survivors, who also had more metabolic acidosis. In most of our children with cancer, sepsis and acute respiratory distress syndrome progressed with deteriorating ventilation indexes and escalating organic dysfunction, making this triad nearly fatal in children.

  17. Sepsis-related acute respiratory distress syndrome in children with cancer: the respiratory dynamics of a devastating condition

    PubMed Central

    Arduini, Rodrigo Genaro; de Araujo, Orlei Ribeiro; da Silva, Dafne Cardoso Bourguignon; Senerchia, Andreza Almeida; Petrilli, Antonio Sergio

    2016-01-01

    Objective To evaluate the clinical course and respiratory parameters of mechanically ventilated children with cancer suffering from sepsis-related acute respiratory distress syndrome. Methods This 2-year prospective, longitudinal, observational cohort study enrolled 29 children and adolescents. Clinical data, measurements of blood gases and ventilation parameters were collected at four different time points. Fluctuations between measurements as well as differences in estimated means were analyzed by linear mixed models in which death within 28 days from the onset of acute respiratory distress syndrome was the primary endpoint. Results There were 17 deaths within 28 days of acute respiratory distress syndrome onset and another 7 between 29 - 60 days. Only 5 patients survived for more than 60 days. Nine (31%) patients died as a direct consequence of refractory hypoxemia, and the others died of multiple organ failure and catecholamine-refractory shock. In 66% of the measurements, the tidal volume required to obtain oxygen saturation equal to or above 90% was greater than 7mL/kg. The estimated means of dynamic compliance were low and were similar for survivors and non-survivors but with a negative slope between the first and final measurements, accompanied by a negative slope of the tidal volume for non-survivors. Non-survivors were significantly more hypoxemic, with PaO2/FiO2 ratios showing lower estimated means and a negative slope along the four measurements. Peak, expiratory and mean airway pressures showed positive slopes in the non-survivors, who also had more metabolic acidosis. Conclusions In most of our children with cancer, sepsis and acute respiratory distress syndrome progressed with deteriorating ventilation indexes and escalating organic dysfunction, making this triad nearly fatal in children. PMID:28099641

  18. Heat Shock Protein A12B Protects Vascular Endothelial Cells Against Sepsis-Induced Acute Lung Injury in Mice.

    PubMed

    Chen, Yi; Wang, Lei; Kang, Qiuxiang; Zhang, Xu; Yu, Guifang; Wan, Xiaojian; Wang, Jiafeng; Zhu, Keming

    2017-01-01

    Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI) during sepsis. Heat shock protein A12B (HSPA12B) is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15): a sham operation group, a cecal ligation and puncture (CLP) group, a HSPA12B siRNA-CLP group and a negative control (NC) siRNA-CLP group. The mice were treated by nasal inhalation of 2-OMe-modified HSPA12B siRNA or NC siRNA. Sepsis was induced by CLP. Samples were harvested 24 and 48 hours post-CLP surgery. Pathological changes and scoring of lung tissue samples were monitored using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6) and myeloperoxidase activity in bronchoalveolar lavage fluid were analyzed by ELISA. Pulmonary edema was assessed using a wet-to-dry weight ratio. Neutrophils and alveolar macrophages were counted using flow cytometry. Pulmonary endothelial cell apoptosis was detected by TUNEL staining. Expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blot analysis. In addition, 7-day survival was recorded. For in vitro experiments, human umbilical vein endothelial cells were pre-transfected with HSPA12B siRNA or pIRES2-EGFP-HSPA12B-Flag plasmid and treated with lipopolysaccharide; subsequently, the expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blotting. Nasal inhalation of nano-polymer-encapsulated HSPA12B siRNA specifically downregulated mRNA and protein expression levels of HSPA12B in lung tissues. The administration of HSPA12B siRNA aggravated lung pathological injury, upregulated pro-inflammatory cytokine (e.g., IL-1β, TNF-α, and IL-6) expression, and

  19. Outcome of acute fulminant myocarditis in children

    PubMed Central

    Amabile, N; Fraisse, A; Bouvenot, J; Chetaille, P; Ovaert, C

    2006-01-01

    Objectives To highlight clinical features and outcome of acute fulminant myocarditis (AFM) in children. Methods Diagnostic criteria were (1) the presence of severe and acute heart failure; (2) left ventricular dysfunction on echocardiography; (3) recent history of viral illness; and (4) no history of cardiomyopathy. Results Eleven children were included between 1998 and 2003, at a median age of 1 (0 to 9) year. Their mean left ventricular ejection fraction (LVEF) was 22 (SD 9)% at presentation. A virus was identified in five patients: human parvovirus B19 (n  =  2), Epstein–Barr (n  =  1), varicella zoster (n  =  1), and coxsackie (n = 1). The median intensive care unit course was 13 (2–34) days. Intravenous inotropic support was required by nine patients and eight were mechanically ventilated. All patients received corticosteroid, associated with intravenous immunoglobulin in seven. Five patients experienced cardiocirculatory arrest that was successfully resuscitated in four. At a median follow up of 58.7 (33.8–83.1) months, the 10 survivors are asymptomatic with normalised LVEF. Conclusion Despite a severe presentation, the outcome of AFM is favourable. Aggressive symptomatic management is warranted and heart transplantation should be considered only when maximal supportive therapy does not lead to improvement. PMID:16449512

  20. Diminished neutrophil extracellular trap (NET) formation is a novel innate immune deficiency induced by acute ethanol exposure in polymicrobial sepsis, which can be rescued by CXCL1.

    PubMed

    Jin, Liliang; Batra, Sanjay; Jeyaseelan, Samithamby

    2017-09-18

    Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that acute alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines. Thus, we assessed whether acute ethanol challenge via gavage diminishes antibacterial host defense in a sepsis model using cecal ligation and puncture (CLP) and whether this immunosuppression can be rescued by exogenous CXCL1. We found acute alcohol intoxication augments mortality and enhances bacterial growth in mice following CLP. Ethanol exposure impairs critical antibacterial functions of mouse and human neutrophils including reactive oxygen species production, neutrophil extracellular trap (NET) formation, and NET-mediated killing in response to both Gram-negative (E. coli) and Gram-positive (Staphylococcus aureus) pathogens. As compared with WT (C57Bl/6) mice, CXCL1 knockout mice display early mortality following acute alcohol exposure followed by CLP. Recombinant CXCL1 (rCXCL1) in acute alcohol challenged CLP mice increases survival, enhances bacterial clearance, improves neutrophil recruitment, and enhances NET formation (NETosis). Recombinant CXCL1 (rCXCL1) administration also augments bacterial killing by alcohol-treated and E. coli- and S. aureus-infected neutrophils. Taken together, our data unveils novel mechanisms underlying acute alcohol-induced dysregulation of the immune responses in polymicrobial sepsis, and CXCL1 is a critical mediator to rescue alcohol-induced immune dysregulation in polymicrobial sepsis.

  1. Serum sPD-L1, Upregulated in Sepsis, May Reflect Disease Severity and Clinical Outcomes in Septic Patients.

    PubMed

    Liu, M; Zhang, X; Chen, H; Wang, G; Zhang, J; Dong, P; Liu, Y; An, S; Wang, L

    2017-01-01

    We aimed to find the correlation between serum sPD-L1 (soluble programmed cell death L-1 ligand) and sepsis. Totally 91 consecutive patients with sepsis were performed in a 15-bed medical intensive care unit (ICU) of the second affiliated hospital, Xi'an Jiaotong University in Xi'an, China, between February 2015 and May 2016. Healthy controls (HC) consisted of 29 healthy volunteer. Baseline demographic data were recorded. Blood samples were collected through an indwelling central venous or by peripheral venipuncture. Serum sPD-L1 and sPD-1 levels were determined with enzyme-linked immunosorbent assay kits (Elabscience Biotechnology Co. Ltd, Wuhan, China). SPSS19.0 software (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. Kaplan-Meier survival analysis and Cox regression analysis were also performed. Serum sPD-L1 levels and sPD-1 levels were significantly increased in septic patients compared with HC (P = 0.000). Serum sPD-L1 levels were significantly increased in non-survivors compared with survivors (P < 0.05), but there was no statistically difference on serum sPD-1 levels between non-survivors and survivors (P > 0.05). Serum sPD-L1 levels were correlated with absolute lymphocyte (ALC), platelets and SOFA scores. Serum sPD-L1/sPD-1 levels were negatively correlated with ALC and platelets, and SOFA scores. The prognostic accuracy of the sPD-L1 level to predict 28-day mortality was similar to that of the APACHE-II scores and SOFA scores. Cox regression analysis showed that sPD-L1 was an independent prognostic factor. Serum sPD-L1 is upregulated in sepsis and may reflect disease severity and clinical outcomes in patients. Serum sPD-L1 may be an independent prognostic factor for sepsis.

  2. SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

    PubMed

    Gregoric, Pavle; Pavle, Gregoric; Sijacki, Ana; Ana, Sijacki; Stankovic, Sanja; Sanja, Stankovic; Radenkovic, Dejan; Dejan, Radenkovic; Ivancevic, Nenad; Nenad, Ivancevic; Karamarkovic, Aleksandar; Aleksandar, Karamarkovic; Popovic, Nada; Nada, Popovic; Karadzic, Borivoje; Borivoje, Karadzic; Stijak, Lazar; Stefanovic, Branislav; Branislav, Stefanovic; Milosevic, Zoran; Zoran, Milosević; Bajec, Djordje; Djordje, Bajec

    2010-01-01

    Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.

  3. A prospective observational study assessing the outcome of Sepsis in intensive care unit of a tertiary care hospital, Peshawar

    PubMed Central

    Ullah, Arslan Rahat; Hussain, Arshad; Ali, Iftikhar; Samad, Abdul; Ali Shah, Syed Tajammul; Yousef, Muhammad; Khan, Tahir Mehmood

    2016-01-01

    Objective: The current study aims to explore the factors associated with outcome among patients with severe sepsis and septic shock admitted to the intensive care unit, Northwest General Hospital and Research Centre, Peshawar, Pakistan. Methods: A prospective observational study was carried out at intensive care unit of our hospital from February 2014 to October 2015. Data was collected using a structured format and statistical analysis was done using SPSS version 20®. Regression model was applied to identify the factors contributing to the outcome of severe sepsis and septic shock. P-value less than 0.05 was considered statistically significant. Results: Majority of the patients meeting the criteria of this study were male 147 (54.9%) with a mean age of 54.8. The most common source of sepsis was lung infections (42.2%) followed by urinary tract infections (18.7%), soft tissue infections (6.3%) abdominal infections (6%) and in 6.3% patients the source remained unknown. Further analysis has revealed that increase in number of days of hospitalization was observed to be slightly associated with the outcome of the treatment (1.086 [1.002 – 1.178], 0.046). Moreover, the risk of mortality was the higher among the patients with septic shock 22.161[10.055 – 48.840], and having respiratory, kidney and central nervous system complications. Overall it is seen that septic shock alone was found responsible to cause death among 32.0% of the patients (Model 1: R2 0.32, p=0.000), and upon involvement of the organ complications the risk of mortality was observed to 42.0%. Conclusion: Chances of recovery were poor among the patients with septic shock. Moreover, those patients having respiratory and urinary tract infection are least likely to survive. PMID:27375715

  4. Bloodstream infections and sepsis in Greece: over-time change of epidemiology and impact of de-escalation on final outcome

    PubMed Central

    2014-01-01

    Background Choice of empirically prescribed antimicrobials for sepsis management depends on epidemiological factors. The epidemiology of sepsis in Greece was studied in two large-periods. Methods Sepsis due to bloodstream infections (BSI) from July 2006 until March 2013 was recorded in a multicenter study in 46 departments. Patients were divided into sepsis admitted in the emergencies and hospitalized in the general ward (GW) and sepsis developing after admission in the Intensive Care Unit (ICU). The primary endpoints were the changes of epidemiology and the factors related with BSIs by multidrug-resistant (MDR) pathogens; the secondary endpoint was the impact of de-escalation on antimicrobial therapy. Results 754 patients were studied; 378 from 2006–2009 and 376 from 2010–2013. Major differences were recorded between periods in the GW. They involved increase of: sepsis severity; the incidence of underlying diseases; the incidence of polymicrobial infections; the emergence of Klebsiella pneumoniae as a pathogen; and mortality. Factors independently related with BSI by MDR pathogens were chronic hemofiltration, intake of antibiotics the last three months and residence into long-term care facilities. De-escalation in BSIs by fully susceptible Gram-negatives did not affect final outcome. Similar epidemiological differences were not found in the ICU; MDR Gram-negatives predominated in both periods. Conclusions The epidemiology of sepsis in Greece differs in the GW and in the ICU. De-escalation in the GW is a safe strategy. PMID:24885072

  5. Neonatal sepsis at Muhimbili National Hospital, Dar es Salaam, Tanzania; aetiology, antimicrobial sensitivity pattern and clinical outcome.

    PubMed

    Mhada, Tumaini V; Fredrick, Francis; Matee, Mecky I; Massawe, Augustine

    2012-10-24

    Neonatal sepsis contributes significantly to morbidity and mortality among young infants. The aetiological agents as well as their susceptibility to antimicrobial agents are dynamic. This study determined aetiology, antimicrobial susceptibility and clinical outcome of neonatal sepsis at Muhimbili National Hospital. Three hundred and thirty neonates admitted at the Muhimbili National Hospital neonatal ward between October, 2009 and January, 2010 were recruited. Standardized questionnaires were used to obtain demographic and clinical information. Blood and pus samples were cultured on MacConkey, blood and chocolate agars and bacteria were identified based on characteristic morphology, gram stain appearance and standard commercially prepared biochemical tests. Antimicrobial sensitivity testing was performed for ampicillin, cloxacillin, gentamicin, amikacin, cefuroxime and ceftriaxone on Mueller Hinton agar using the Kirby Bauer diffusion method. Culture proven sepsis was noted in 24% (74/330) of the study participants. Isolated bacterial pathogens were predominantly Staphylococcus aureus, Klebsiella spp and Escherichia coli. Klebsiella spp 32.7% (17/52) was the predominant blood culture isolate in neonates aged below seven days while Staphylococcus aureus 54.5% (12/22) was commonest among those aged above seven days. Staphylococcus aureus was the predominant pus swabs isolate for both neonates aged 0-6 days 42.2% (98/232) and 7-28 days 52.3% (34/65). Resistance of blood culture isolates was high to ampicillin 81.1% (60/74) and cloxacillin 78.4% (58/74), moderate to ceftriaxone 14.9% (11/74) and cefuroxime 18.9% (14/74), and low to amikacin 1.3% (1/74). Isolates from swabs had high resistance to ampicillin 89.9% (267/297) and cloxacillin 85.2 (253/297), moderate resistance to ceftriaxone 38.0% (113/297) and cefuroxime 36.0% (107/297), and low resistance to amikacin 4.7% (14/297). Sepsis was higher in neonates with fever and hypothermia (p=0.02), skin pustules (p<0

  6. Characteristics and Outcomes of HIV-Infected Patients With Severe Sepsis: Continued Risk in the Post-Highly Active Antiretroviral Therapy Era.

    PubMed

    Cribbs, Sushma K; Tse, Caroline; Andrews, Joel; Shenvi, Neeta; Martin, Greg S

    2015-08-01

    Although highly active antiretroviral therapy has led to improved survival in HIV-infected individuals, outcomes for HIV-infected patients with sepsis in the post-highly active antiretroviral therapy era are conflicting. Access to highly active antiretroviral therapy and healthcare disparities continue to affect outcomes. We hypothesized that HIV-infected patients with severe sepsis would have worse outcomes compared with their HIV-uninfected counterparts in a large safety-net hospital where access to healthcare is low and delivery of critical care is delayed. Secondary analysis of an ongoing prospective observational study between 2006 and 2010. Three adult ICUs (medical ICU, surgical ICU, and neurologic ICU) at Grady Memorial Hospital, Atlanta, GA. Adult patients with severe sepsis in the ICU. Baseline patient characteristics and clinical outcomes were collected. HIV-infected and HIV-uninfected patients with sepsis were compared using t tests, chi-square tests, and logistic regression; p values less than 0.05 indicated significance. Of 1,095 patients with severe sepsis enrolled, 165 (15%) were positive for HIV, with a median CD4 count of 41 (8-167). Twenty-two percent of HIV-infected patients were on highly active antiretroviral therapy prior to admission, and 80% had a CD4 count less than 200. HIV-infected patients had a greater hospital mortality (50% vs 38%; p < 0.01). HIV infection (odds ratio = 1.78; p = 0.005) was an independent predictor of mortality by multivariate regression modeling after adjusting for age, history of pneumonia, history of hospital-acquired infection, and history of sepsis. HIV-infected patients with severe sepsis continue to suffer worse outcomes compared with HIV-uninfected patients in a large urban safety-net hospital caring for patients with limited access to medical care. Further studies need to be done to investigate the effect of socioeconomic status and mitigate healthcare disparities among critically ill HIV-infected patients.

  7. Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile.

    PubMed

    Wang, Min; Yan, Jingjun; He, Xingxing; Zhong, Qiang; Zhan, Chengye; Li, Shusheng

    2016-04-18

    Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways associated with sepsis-related ARDS based on a public microarray dataset and to further explore the molecular mechanism of ARDS. A total of 122 up-regulated DEGs and 91 down-regulated differentially expressed genes (DEGs) were obtained. The up- and down-regulated DEGs were mainly involved in functions like mitotic cell cycle and pathway like cell cycle. Protein-protein interaction network of ARDS analysis revealed 20 hub genes including cyclin B1 (CCNB1), cyclin B2 (CCNB2) and topoisomerase II alpha (TOP2A). A total of seven transcription factors including forkhead box protein M1 (FOXM1) and 30 target genes were revealed in the transcription factor-target gene regulation network. Furthermore, co-cited genes including CCNB2-CCNB1 were revealed in literature mining for the relations ARDS related genes. Pathways like mitotic cell cycle were closed related with the development of ARDS. Genes including CCNB1, CCNB2 and TOP2A, as well as transcription factors like FOXM1 might be used as the novel gene therapy targets for sepsis related ARDS.

  8. Biomarker and Drug Target Discovery Using Proteomics in a New Rat Model of Sepsis-Induced Acute Renal Failure

    PubMed Central

    Holly, Mikaela K.; Dear, James W.; Hu, Xuzhen; Schechter, Alan N.; Gladwin, Mark T.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

    2008-01-01

    Background Sepsis is one of the common causes of acute renal failure (ARF). The objective of this study was to identify new biomarkers and therapeutic targets. We present a new rat model of sepsis-induced ARF based on cecal ligation and puncture (CLP). We used this model to find urinary proteins which may be potential biomarkers and/or drug targets. Methods Aged rats were treated with fluids and antibiotics after CLP. Urinary proteins from septic rats without ARF and urinary proteins from septic rats with ARF were compared by difference in-gel electrophoresis (DIGE). Results CLP surgery elevated IL-6 and IL-10 serum cytokines and blood nitrite compared with sham-operated rats. However there was a range of serum creatinine values at 24 hrs (0.4–2.3 mg/dL) and only 24% developed ARF. Histology confirmed renal injury in these rats. 49% of rats did not develop ARF. Rats without ARF also had less liver injury. The mortality rate at 24 hrs was 27% but was increased by housing the post-surgery rats in metabolic cages. Creatinine clearance and urine output 2–8 hours after CLP was significantly reduced in rats which died within 24 hours. Using DIGE we identified changes in a number of urinary proteins including albumin, brush-border enzymes (eg., meprin-1-alpha) and serine protease inhibitors. The meprin-1-alpha inhibitor actinonin prevented ARF in aged mice. Conclusion In summary we describe a new rat model of sepsis-induced ARF which has a heterogeneous response similar to humans. This model allowed us to use DIGE to find changes in urinary proteins and this approach identified a potential biomarker and drug target – meprin-1-alpha. PMID:16760904

  9. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study.

    PubMed

    Levy, Mitchell M; Artigas, Antonio; Phillips, Gary S; Rhodes, Andrew; Beale, Richard; Osborn, Tiffany; Vincent, Jean-Louis; Townsend, Sean; Lemeshow, Stanley; Dellinger, R Phillip

    2012-12-01

    Mortality from severe sepsis and septic shock differs across continents, countries, and regions. We aimed to use data from the Surviving Sepsis Campaign (SSC) to compare models of care and outcomes for patients with severe sepsis and septic shock in the USA and Europe. The SSC was introduced into more than 200 sites in Europe and the USA. All patients identified with severe sepsis and septic shock in emergency departments or hospital wards and admitted to intensive care units (ICUs), and those with sepsis in ICUs were entered into the SSC database. Patients entered into the database from its launch in January, 2005, through January, 2010, in units with at least 20 patients and 3 months of enrolment of patients were included in this analysis. Patients included in the cohort were limited to those entered in the first 4 years at every site. We used random-effects logistic regression to estimate the hospital mortality odds ratio (OR) for Europe relative to the USA. We used random-effects linear regression to find the relation between lengths of stay in hospital and ICU and geographic region. 25 375 patients were included in the cohort. The USA included 107 sites with 18 766 (74%) patients, and Europe included 79 hospital sites with 6609 (26%) patients. In the USA, 12 218 (65·1%) were admitted to the ICU from the emergency department whereas in Europe, 3405 (51·5%) were admitted from the wards. The median stay on the hospital wards before ICU admission was longer in Europe than in the USA (1·0 vs 0·1 days, difference 0·9, 95% CI 0·8-0·9). Raw hospital mortality was higher in Europe than in the USA (41·1%vs 28·3%, difference 12·8, 95% CI 11·5-14·7). The median length of stay in ICU (7·8 vs 4·2 days, 3·6, 3·3-3·7) and hospital (22·8 vs 10·5 days, 12·3, 11·9-12·8) was longer in Europe than in the USA. Adjusted mortality in Europe was not significantly higher than that in the USA (32·3%vs 31·3%, 1·0, -1·7 to 3·7, p=0·468). Complete compliance

  10. Salidroside ameliorates sepsis-induced acute lung injury and mortality via downregulating NF-κB and HMGB1 pathways through the upregulation of SIRT1.

    PubMed

    Lan, Kuo-Cheng; Chao, Sung-Chuan; Wu, Hsiao-Yi; Chiang, Chia-Lien; Wang, Ching-Chia; Liu, Shing-Hwa; Weng, Te-I

    2017-09-20

    Sepsis is a life-threatening medical condition. Salidroside, a substance isolated from Rhodiola rosea, possesses antioxidant and anti-inflammatory properties. The effect and mechanism of salidroside on sepsis-induced acute lung injury still remains to be well clarified. Here, we investigated the effect and mechanism of salidroside on septic mouse models and explored the role of salidroside-upregulated SIRT1. Salidroside inhibited the inflammatory responses and HMGB1 productions in bacterial lipopolysaccharide (LPS)-treated macrophages and mice. Salidroside could also reverse the decreased SIRT1 protein expression in LPS-treated macrophages and mice. Salidroside also alleviated the sepsis-induced lung edema, lipid peroxidation, and histopathological changes and the mortality, and improved the lung PaO2/FiO2 ratio in cecal ligation and puncture (CLP)-induced septic mice. Salidroside significantly decreased the serum TNF-α, IL-6, NO, and HMGB1 productions, pulmonary inducible NO synthase (iNOS) and phosphorylated NF-κB-p65 protein expressions, and pulmonary HMGB1 nuclear translocation in CLP septic mice. Moreover, sepsis decreased the SIRT1 protein expression in the lungs of CLP septic mice. Salidroside significantly upregulated the SIRT1 expression and inhibited the inflammatory responses in CLP septic mouse lungs. These results suggest that salidroside protects against sepsis-induced acute lung injury and mortality, which might be through the SIRT1-mediated repression of NF-κB activation and HMGB1 nucleocytoplasmic translocation.

  11. Blockage of glycolysis by targeting PFKFB3 alleviates sepsis-related acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells.

    PubMed

    Gong, Yuanqi; Lan, Haibing; Yu, Zhihong; Wang, Meng; Wang, Shu; Chen, Yu; Rao, Haiwei; Li, Jingying; Sheng, Zhiyong; Shao, Jianghua

    2017-09-16

    Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP. The mice treated with the 3PO ameliorated the survival rate, histopathological changes, lung inflammation, lactate increased and lung apoptosis of mice with CLP-induced sepsis. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) resulted in cell apoptosis, inflammatory cytokine production, enhanced glycolytic flux and reactive oxygen species (ROS) increased. While these changes were attenuated by 3PO treatment. Sequentially, treatment of A549 cells with lactate caused cell apoptosis and enhancement of ROS. Pretreatment with N-acetylcysteine (NAC) significantly lowered LPS and lactate-induced the generation of ROS and cell apoptosis in A549 cells. Therefore, these results indicate that anaerobic glycolysis may be an important contributor in cell apoptosis of sepsis-related ALI. Moreover, LPS specifically induces apoptotic insults to A549 cell through lactate-mediated enhancement of ROS. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Pharmacological targets in the renal peritubular microenvironment: implications for therapy for sepsis-induced acute kidney injury

    PubMed Central

    Mayeux, Philip R.; MacMillan-Crow, Lee Ann

    2012-01-01

    One of the most frequent and serious complications to develop in septic patients is acute kidney injury (AKI), a disorder characterized by a rapid failure of the kidneys to adequately filter the blood, regulate ion and water balance, and generate urine. AKI greatly worsens the already poor prognosis of sepsis and increases cost of care. To date, therapies have been mostly supportive; consequently there has been little change in the mortality rates over the last decade. This is due, at least in part, to the delay in establishing clinical evidence of an infection and the associated presence of the systemic inflammatory response syndrome and thus, a delay in initiating therapy. A second reason is a lack of understanding regarding the mechanisms leading to renal injury, which has hindered the development of more targeted therapies. In this review, we summarize recent studies, which have examined the development of renal injury during sepsis and propose how changes in the peritubular capillary microenvironment lead to and then perpetuate microcirculatory failure and tubular epithelial cell injury. We also discuss a number of potential therapeutic targets in the renal peritubular microenvironment, which may prevent or lessen injury and/or promote recovery. PMID:22274552

  13. Maternal, fetal and renal outcomes of pregnancy-associated acute kidney injury requiring dialysis.

    PubMed

    Krishna, A; Singh, R; Prasad, N; Gupta, A; Bhadauria, D; Kaul, A; Sharma, R K; Kapoor, D

    2015-01-01

    Pregnancy-associated acute kidney injury (PAKI) is encountered frequently in developing countries. We evaluated the maternal, fetal and renal outcomes in women with PAKI who needed at least one session of dialysis. Of the total of 98 cases (mean age 28.85 ± 5.13 years; mean parity 2.65 ± 1.28) of PAKI, the most common cause of PAKI was postabortal sepsis. Eighteen patients died; those with oligoanuria, sepsis and central nervous system (CNS) involvement were at greater risk of mortality. The relative risk (RR) of neonatal mortality was lower after with full-term delivery (RR: 0.17, 95% confidence interval (CI): 0.03-0.96, P = 0.02) compared to preterm delivery. Of the 80 surviving patients, 60 (75%) patients achieved complete recovery of renal function at the end of 3 months; and of the remaining 14 had presumed (n = 4) or, biopsy-proven (n = 10) acute patchy cortical necrosis. The RR of non-recovery of renal function was high (RR: 24.7, 95% CI: 3.4- 179.5) in patients who did not recover at 6 weeks. Of the 14 patients with cortical necrosis, 3 (21.42%) became independent of dialysis at 6 months. PAKI patients should be watched for dialysis independency for 6 months.

  14. Association between recurrence of acute kidney injury and mortality in intensive care unit patients with severe sepsis.

    PubMed

    Rodrigo, Emilio; Suberviola, Borja; Santibáñez, Miguel; Belmar, Lara; Castellanos, Álvaro; Heras, Milagros; Rodríguez-Borregán, Juan Carlos; de Francisco, Angel Luis Martín; Ronco, Claudio

    2017-01-01

    Acute kidney injury (AKI) occurs in more than half critically ill patients admitted in intensive care units (ICU) and increases the mortality risk. The main cause of AKI in ICU is sepsis. AKI severity and other related variables such as recurrence of AKI episodes may influence mortality risk. While AKI recurrence after hospital discharge has been recently related to an increased risk of mortality, little is known about the rate and consequences of AKI recurrence during the ICU stay. Our hypothesis is that AKI recurrence during ICU stay in septic patients may be associated to a higher mortality risk. We prospectively enrolled all (405) adult patients admitted to the ICU of our hospital with the diagnosis of severe sepsis/septic shock for a period of 30 months. Serum creatinine was measured daily. 'In-ICU AKI recurrence' was defined as a new spontaneous rise of ≥0.3 mg/dl within 48 h from the lowest serum creatinine after the previous AKI episode. Excluding 5 patients who suffered the AKI after the initial admission to ICU, 331 patients out of the 400 patients (82.8%) developed at least one AKI while they remained in the ICU. Among them, 79 (19.8%) developed ≥2 AKI episodes. Excluding 69 patients without AKI, in-hospital (adjusted HR = 2.48, 95% CI 1.47-4.19), 90-day (adjusted HR = 2.54, 95% CI 1.55-4.16) and end of follow-up (adjusted HR = 1.97, 95% CI 1.36-2.84) mortality rates were significantly higher in patients with recurrent AKI, independently of sex, age, mechanical ventilation necessity, APACHE score, baseline estimated glomerular filtration rate, complete recovery and KDIGO stage. AKI recurred in about 20% of ICU patients after a first episode of sepsis-related AKI. This recurrence increases the mortality rate independently of sepsis severity and of the KDIGO stage of the initial AKI episode. ICU physicians must be aware of the risks related to AKI recurrence while multiple episodes of AKI should be highlighted in electronic medical

  15. Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children.

    PubMed

    López-Fernández, Yolanda; Azagra, Amelia Martínez-de; de la Oliva, Pedro; Modesto, Vicent; Sánchez, Juan I; Parrilla, Julio; Arroyo, María José; Reyes, Susana Beatriz; Pons-Ódena, Martí; López-Herce, Jesús; Fernández, Rosa Lidia; Kacmarek, Robert M; Villar, Jesús

    2012-12-01

    The incidence and outcome of the acute respiratory distress syndrome in children are not well-known, especially under current ventilatory practices. The goal of this study was to determine the incidence, etiology, and outcome of acute respiratory distress syndrome in the pediatric population in the setting of lung protective ventilation. A 1-yr, prospective, multicenter, observational study in 12 geographical areas of Spain (serving a population of 3.77 million ≤ 15 yrs of age) covered by 21 pediatric intensive care units. All consecutive pediatric patients receiving invasive mechanical ventilation and meeting American-European Consensus Criteria for acute respiratory distress syndrome. None. Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 146 mechanically ventilated patients fulfilled the acute respiratory distress syndrome definition, representing a incidence of 3.9/100,000 population ≤ 15 yrs of age/yr. Pneumonia and sepsis were the most common causes of acute respiratory distress syndrome. At the time of meeting acute respiratory distress syndrome criteria, mean PaO2/FIO2 was 99 mm Hg ± 41 mm Hg, mean tidal volume was 7.6 mL/kg ± 1.8 mL/kg predicted body weight, mean plateau pressure was 27 cm H2O ± 6 cm H2O, and mean positive end-expiratory pressure was 8.9 cm ± 2.9 cm H2O. Overall pediatric intensive care unit and hospital mortality were 26% (95% confidence interval 19.6-33.7) and 27.4% (95% confidence interval 20.8-35.1), respectively. At 24 hrs, after the assessment of oxygenation under standard ventilatory settings, 118 (80.8%) patients continued to meet acute respiratory distress syndrome criteria (PaO2/FIO2 104 mm Hg ± 36 mm Hg; pediatric intensive care units mortality 30.5%), whereas 28 patients (19.2%) had a PaO2/FIO2 >200 mm Hg (pediatric intensive care units mortality 7.1%) (p = .014). This is the largest study to estimate prospectively the pediatric population-based acute

  16. Sepsis biomarkers: a review

    PubMed Central

    2010-01-01

    Introduction Biomarkers can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy. Methods We used an electronic search of the PubMed database using the key words "sepsis" and "biomarker" to identify clinical and experimental studies which evaluated a biomarker in sepsis. Results The search retrieved 3370 references covering 178 different biomarkers. Conclusions Many biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been tested clinically, primarily as prognostic markers in sepsis; relatively few have been used for diagnosis. None has sufficient specificity or sensitivity to be routinely employed in clinical practice. PCT and CRP have been most widely used, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome. PMID:20144219

  17. Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients With Sepsis

    PubMed Central

    Honore, Patrick M.; Nguyen, H. Bryant; Gong, Michelle; Chawla, Lakhmir S.; Bagshaw, Sean M.; Artigas, Antonio; Shi, Jing; Joannes-Boyau, Olivier; Vincent, Jean-Louis

    2016-01-01

    Objectives: To examine the performance of the urinary biomarker panel tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with sepsis at ICU admission. To investigate the effect of nonrenal organ dysfunction on tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in this population. Method: In this ancillary analysis, we included patients with sepsis who were enrolled in either of two trials including 39 ICUs across Europe and North America. The primary endpoint was moderate-severe acute kidney injury (equivalent to Kidney Disease Improving Global Outcome stage 2–3) within 12 hours of enrollment. We assessed biomarker performance by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values at three cutoffs: 0.3, 1.0, and 2.0 (ng/mL)2/1,000. We also calculated nonrenal Sequential Organ Failure Assessment scores for each patient on enrollment and compared tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 results in patients with and without acute kidney injury and across nonrenal Sequential Organ Failure Assessment scores. Finally, we constructed a clinical model for acute kidney injury in this population and compared the performance of the model with and without tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7. Results: We included 232 patients in the analysis and 40 (17%) developed acute kidney injury. We observed significantly higher urine tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with acute kidney injury than without acute kidney injury in both patients with low and high nonrenal Sequential Organ Failure Assessment scores (p < 0.001). The area under the receiver operating characteristic curve (95% CI) of tissue inhibitor of metalloproteinase-2 and insulin

  18. Quadratic function between arterial partial oxygen pressure and mortality risk in sepsis patients: an interaction with simplified acute physiology score.

    PubMed

    Zhang, Zhongheng; Ji, Xuqing

    2016-10-13

    Oxygen therapy is widely used in emergency and critical care settings, while there is little evidence on its real therapeutic effect. The study aimed to explore the impact of arterial oxygen partial pressure (PaO2) on clinical outcomes in patients with sepsis. A large clinical database was employed for the study. Subjects meeting the diagnostic criteria of sepsis were eligible for the study. All measurements of PaO2 were extracted. The primary endpoint was death from any causes during hospital stay. Survey data analysis was performed by using individual ICU admission as the primary sampling unit. Quadratic function was assumed for PaO2 and its interaction with other covariates were explored. A total of 199,125 PaO2 samples were identified for 11,002 ICU admissions. Each ICU stay comprised 18 PaO2 samples in average. The fitted multivariable model supported our hypothesis that the effect of PaO2 on mortality risk was in quadratic form. There was significant interaction between PaO2 and SAPS-I (p = 0.007). Furthermore, the main effect of PaO2 on SOFA score was nonlinear. The study shows that the effect of PaO2 on mortality risk is in quadratic function form, and there is significant interaction between PaO2 and severity of illness.

  19. Quadratic function between arterial partial oxygen pressure and mortality risk in sepsis patients: an interaction with simplified acute physiology score

    PubMed Central

    Zhang, Zhongheng; Ji, Xuqing

    2016-01-01

    Oxygen therapy is widely used in emergency and critical care settings, while there is little evidence on its real therapeutic effect. The study aimed to explore the impact of arterial oxygen partial pressure (PaO2) on clinical outcomes in patients with sepsis. A large clinical database was employed for the study. Subjects meeting the diagnostic criteria of sepsis were eligible for the study. All measurements of PaO2 were extracted. The primary endpoint was death from any causes during hospital stay. Survey data analysis was performed by using individual ICU admission as the primary sampling unit. Quadratic function was assumed for PaO2 and its interaction with other covariates were explored. A total of 199,125 PaO2 samples were identified for 11,002 ICU admissions. Each ICU stay comprised 18 PaO2 samples in average. The fitted multivariable model supported our hypothesis that the effect of PaO2 on mortality risk was in quadratic form. There was significant interaction between PaO2 and SAPS-I (p = 0.007). Furthermore, the main effect of PaO2 on SOFA score was nonlinear. The study shows that the effect of PaO2 on mortality risk is in quadratic function form, and there is significant interaction between PaO2 and severity of illness. PMID:27734905

  20. The Effects of Quercetin on Acute Lung Injury and Biomarkers of Inflammation and Oxidative Stress in the Rat Model of Sepsis.

    PubMed

    Gerin, Fethullah; Sener, Umit; Erman, Hayriye; Yilmaz, Ahsen; Aydin, Bayram; Armutcu, Ferah; Gurel, Ahmet

    2016-04-01

    Experimental studies indicate that sepsis causes remote organ injury although the molecular mechanism has not been clearly defined. In this report, the role of oxidative damage, and inflammation on lung injury, following sepsis model by cecal ligation and puncture, and the effects of quercetin, antioxidant, and anti-inflammatory flavonoid, in the lung tissue were investigated. In the present study, we found that administration of single-dose quercetin before cecal ligation and puncture procedure, while markedly diminishing the levels of YKL-40 and oxidant molecules (xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA)), increases the antioxidant enzymes levels. Quercetin is beneficial to acute lung injury by decreasing the levels of oxidative stress markers and increasing the antioxidant enzyme activities. Quercetin also causes a decrease in the serum levels of YKL-40 and periostin in the oxidative lung injury induced by the experimental sepsis model.

  1. Serum Uric Acid Levels and Outcomes After Acute Ischemic Stroke.

    PubMed

    Wang, Zhongchao; Lin, Yanlin; Liu, Yuxiu; Chen, Ying; Wang, Bin; Li, Changgui; Yan, Shengli; Wang, Yangang; Zhao, Wenjuan

    2016-04-01

    Previous studies assessing the association between serum uric acid levels and neurological outcome after acute ischemic stroke reported conflicting results. A systematic review and meta-analysis were conducted to assess the impact of serum uric acid levels on outcome after acute ischemic stroke. Pubmed, Embase, Web of Science, and Google scholar were searched through September 26, 2014 to identify eligible published or unpublished studies on the association between serum uric acid levels and outcome after acute ischemic stroke. Hazard ratio (HR) for poor outcome or mean differences of serum uric acid levels with 95% confidence intervals (95% CIs) were pooled using meta-analysis. The primary outcome was occurrence of poor outcomes, while the secondary outcome was the mean differences of serum uric acid levels in patients with good or poor outcomes. Ten eligible studies with a total of 8131 acute ischemic stroke patients were included into the meta-analysis. Compared with low serum uric acid level, high serum uric acid level was associated better outcome after acute ischemic stroke (HR = 0.77, 95% CI 0.68-0.88, P = 0.0001). Sensitivity analysis further identified the prognostic role of serum uric acid levels on outcome after acute ischemic stroke. Patients with good outcomes had a higher serum uric acid level compared with those with poor outcome (mean difference = 30.61 μmol/L, 95% CI 20.13-41.08, P < 0.00001). There was no obvious risk of publication bias in the meta-analysis. This meta-analysis supports that serum uric acid level has a protective effect on neurological outcome after acute ischemic stroke. High uric acid level at the onset is a biomarker of better prognosis in patients with acute ischemic stroke.

  2. A national quality improvement initiative for reducing harm and death from sepsis in Wales.

    PubMed

    Hancock, Chris

    2015-04-01

    The Rapid Response to Acute Illness (RRAILS) Programme is a quality and service improvement initiative which is participated in by all Welsh healthcare organisations including the Welsh Ambulance Service Trust (WAST) and Velindre Cancer Centre. The aims of the programme were and are: Implementing the National Early Warning Score (NEWS) as standard in all clinical areas in all 18 acute hospitals. Quantifying the incidence of sepsis and acute deterioration in the non Critical Care setting. Improving reliability of systems for identification, escalation and treatment of sepsis. Demonstrably improving outcomes from sepsis and other causes of acute deterioration. Clinical teams participated in learning sets at which they were trained in service improvement and human factors principles and then supported to implement 'bundles' of best evidence whilst measuring both processes and outcomes. All organisations have implemented standardised tools and operating procedures including NEWS, sepsis screening tools, Patient Status at A Glance (PSAG) boards, sepsis response bags and an antibiotic formulary. All organisations have demonstrated improvements in the reliability of detection and escalation of acute deterioration whilst many have started to demonstrate local improvements in outcomes. The collaborative learning set is an effective method for improving quality of sepsis care throughout a single healthcare economy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Evaluation of risk factors and development of acute kidney injury in aneurysmal subarachnoid hemorrhage, head injury, and severe sepsis/septic shock patients during ICU treatment.

    PubMed

    Kamar, Ceren; Ali, Achmet; Altun, Demet; Orhun, Günseli; Sabancı, Akın; Sencer, Altay; Akıncı, İbrahim Özkan

    2017-01-01

    There are few studies examining development of acute kidney injury (AKI) in the various types of patients in intensive care units (ICUs). Presently described is evaluation of risk factors and development of AKI in different groups of ICU patients. Present study was performed in 3 different ICUs. Development of AKI was measured using Acute Kidney Injury Network (AKIN) classification system. Total of 300 patients who were treated in trauma, neurosurgery, or general ICU departments (due to head injury, aneurysmal subarachnoid hemorrhage [aSAH], or severe sepsis/septic shock, respectively) were assessed for incidence, risk factors, and development of AKI. AKI did not develop in aSAH patients when evaluated based on serum creatinine level; however, it was observed in 5% of aSAH patients according to volume adjusted creatinine (VACr) level. AKI developed in 76% of sepsis group, and in 20% of head injury group, based on AKIN classification, according to both serum and VACr levels. Incidence of AKI was significantly higher in sepsis group (p<0.001). Only use of vasopressor was significantly related to AKI development in sepsis and head injury groups. Mortality rate was 8%, 22%, and 42% in aSAH, head injury, and sepsis groups, respectively. AKI development and vasopressor use were significantly related to mortality in sepsis group. Despite similar characteristics and risk factors, there were fewer instances of AKI in aSAH group. Hypertension or hydration therapy used to treat vasospasm and polyuria due to cerebral salt-wasting syndrome may prevent aSAH patients from developing AKI.

  4. Incidence, clinical features, and implications on outcomes of neonatal late-onset sepsis with concurrent infectious focus.

    PubMed

    Wu, I-Hsyuan; Tsai, Ming-Horng; Lai, Mei-Yin; Hsu, Lee-Fen; Chiang, Ming-Chou; Lien, Reyin; Fu, Ren-Huei; Huang, Hsuan-Rong; Chu, Shih-Ming; Hsu, Jen-Fu

    2017-07-03

    Neonatal bloodstream infection (BSI) is the most important cause of morbidity and mortality in the neonatal intensive care unit (NICU). Although most neonatal BSIs are primary bacteremia, some are associated with a focus of infection. This distinction is not well characterized. All patients with neonatal late-onset sepsis (LOS) between January 2006 and December 2013 were enrolled. LOS was categorized as a BSI with a concurrent focus of infection if LOS occurred before or within 24 h after the diagnosis of a specific infectious entity, and as "primary bacteremia" if no concurrent focus of infection was identified. Data concerning demographics, hospital course, microbiology, and outcomes were compared via univariate and multivariate analyses. Of 948 episodes of neonatal LOS, 781 (82.4%) were primary bacteremia, whereas 167 (17.6%) were associated with a known focus of infection, including meningitis (n = 51, 5.4%), ventilator-associated pneumonia (VAP) (n = 36, 3.8%), catheter-related bloodstream infections (n = 57, 6.0%), and necrotizing enterocolitis (NEC) (n = 21, 2.2%). The majority of NEC-associated BSIs were caused by gram-negative bacilli (85.7%). Group B streptococcus accounted for nearly one-third of all meningitis cases (29.4%). Although sepsis-attributable mortality was comparable between primary bacteremia and neonatal BSIs with a focus of infection, neonatal BSIs with meningitis, VAP, and NEC had significantly higher rates of infectious complications. The independent risk factors of sepsis-attributable mortality were infectious complications (Odds ratio [OR] 6.98; 95% confidence interval [CI] 3.64-13.39, P < 0.001); history of one or more than one previous episode(s) of BSI (OR 2.40 and 7.40; 95% CI 1.21-4.74 and 3.70-14.78, P = 0.012 and <0.001, respectively); and underlying secondary pulmonary hypertension in neonates (OR 4.77; 95% CI 1.91-11.96, P = 0.001). A considerable proportion of neonatal LOS can be associated with known

  5. The ScpC protease of Streptococcus pyogenes affects the outcome of sepsis in a murine model.

    PubMed

    Sjölinder, Hong; Lövkvist, Lena; Plant, Laura; Eriksson, Jens; Aro, Helena; Jones, Allison; Jonsson, Ann-Beth

    2008-09-01

    The ScpC protease of Streptococcus pyogenes degrades interleukin-8 (IL-8), a chemokine that mediates neutrophil transmigration and activation. The ability to degrade IL-8 differs dramatically among clinical isolates of S. pyogenes. Bacteria expressing ScpC overcome immune clearance by preventing the recruitment of neutrophils in soft tissue infection of mice. To study the role of ScpC in streptococcal sepsis, we generated an ScpC mutant that did not degrade IL-8 and thus failed to prevent the recruitment of immune cells as well as to cause disease after soft tissue infection. In a murine model of sepsis, challenge with the ScpC mutant resulted in more severe systemic disease with higher bacteremia levels and mortality than did challenge with the wild-type strain. As expected, the blood level of KC, the murine IL-8 homologue, increased in mice infected with the ScpC mutant. However, the elevated KC levels did not influence neutrophil numbers in blood, as it did in soft tissue, indicating that additional factors contributed to neutrophil transmigration in blood. In addition, the absence of ScpC increased tumor necrosis factor, IL-6, and C5a levels in blood, which contributed to disease severity. Thus, the ScpC mutant triggers high neutrophil infiltration but not lethal outcome after soft tissue infection, whereas intravenous infection leads to highly aggressive systemic disease.

  6. The Effect of Early Goal-Directed Therapy on Outcome in Adult Severe Sepsis and Septic Shock Patients: A Meta-Analysis of Randomized Clinical Trials.

    PubMed

    Xu, Jing-Yuan; Chen, Qi-Hong; Liu, Song-Qiao; Pan, Chun; Xu, Xiu-Ping; Han, Ji-Bin; Xie, Jian-Feng; Huang, Ying-Zi; Guo, Feng-Mei; Yang, Yi; Qiu, Hai-Bo

    2016-08-01

    Whether early goal-directed therapy (EGDT) improves outcome in severe sepsis and septic shock remains unclear. We performed a meta-analysis of existing clinical trials to examine whether EGDT improved outcome in the resuscitation of adult sepsis patients compared with control care. We searched for eligible studies using MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials, and Web of Science databases. Studies were eligible if they compared the effects of EGDT versus control care on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Data including mortality, sample size of the patients with severe sepsis and septic shock, and resuscitation end points were extracted. Data were analyzed using methods recommended by the Cochrane Collaboration Review Manager 4.2 software. Random errors were evaluated by trial sequential analysis (TSA). Nine studies compared EGDT with control care, and 5202 severe sepsis and septic shock patients were included. A nonsignificant trend toward reduction in the longest all-cause mortality was observed in the EGDT group compared with control care (relative risk, 0.89; 99% confidence interval, 0.74-1.07; P = 0.10). However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients (relative risk, 0.72; 99% confidence interval, 0.57-0.90; P = 0.0002). TSA indicated lack of firm evidence for a beneficial effect. In this meta-analysis, a nonsignificant trend toward reduction in the longest all-cause mortality in patients resuscitated with EGDT was noted. However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients. TSA indicated a lack of firm evidence for the results. More powered, randomized controlled trials are needed to determine the effects.

  7. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study.

    PubMed

    Kabbali, Nadia; Tachfouti, Nabil; Arrayhani, Mohammed; Harandou, Mustapha; Tagnaouti, Mounia; Bentata, Yassamine; Laouad, Inass; Ramdani, Benyounes; Bayahia, Rabia; Oualim, Zouhair; Houssaini, Tarik Sqalli

    2015-01-01

    Acute kidney injury (AKI) is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%). Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases), hemorrhagic shock (six cases) and septic events (five cases). We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6%) cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care.

  8. [Clinical study of early use of neuromuscular blocking agents in patients with severe sepsis and acute respiratory distress syndrome].

    PubMed

    Lyu, Guangyu; Wang, Xiaoyuan; Jiang, Wenfang; Cai, Tianbin; Zhang, Youhua

    2014-05-01

    To observe the clinical effects of early use of neuromuscular blocking agents (NMBA) in patients with severe sepsis and acute respiratory distress syndrome (ARDS). A prospective study was conducted. 96 patients with severe sepsis and ARDS admitted from July 2012 to September 2013 to intensive care unit (ICU) of Liuzhou People's Hospital in Guangxi Zhuang Autonomous Region were enrolled and divided into severe ARDS group (n=48) and moderate ARDS group (n=48) according to the Berlin definition of ARDS. Then patients in each group were randomly divided into treatment group (n=24) and control group (n=24). All patients with diagnosis in accordance with the 2008 international septic shock and severe sepsis treatment guidelines were provided with comprehensive treatment and mechanical ventilation on the basis of analgesia and sedation. The patients in treatment group were given a loading dose of vecuronium during mechanical ventilation, started with 0.1 mg/kg up to 0.05 mg×kg(-1)×h(-1) for continuous intravenous infusion for 24-48 hours. The acute physiology and chronic health evaluation II (APACHEII) score, sequential organ failure assessment (SOFA), arterial oxygenation index (PaO2/FiO2), central venous oxygen saturation (ScvO2), arterial blood lactate (Lac), C-reactive protein (CRP) levels of two groups were compared before treatment and 48 hours after treatment, and 21-day mortality rate was finally compared. In moderate or severe ARDS group, there were no statistically significant difference in APACHEII score, SOFA score, PaO2/FiO2, ScvO2, Lac and CRP before treatment between two groups. APACHEII score, SOFA score, PaO2/FiO2, ScvO2, and Lac 48 hours after treatment were significantly improved in severe ARDS group compared with control group (APACHEII score: 16.58±2.41 vs. 19.79±3.52, t=3.679, P=0.010; SOFA score: 12.04±2.17 vs. 14.75±3.26, t=3.385, P=0.010; PaO2/FiO2: 159.31±22.57 mmHg vs. 131.81±34.93 mmHg, t=3.239, P=0.020; ScvO2: 0.673±0.068 vs. 0.572±0

  9. Volume of fluids administered during resuscitation for severe sepsis and septic shock and the development of the acute respiratory distress syndrome.

    PubMed

    Chang, Dong W; Huynh, Richard; Sandoval, Eric; Han, Neung; Coil, Clinton J; Spellberg, Brad J

    2014-12-01

    The purpose of this study was to examine the association between the volume of intravenous (IV) fluids administered in the resuscitative phase of severe sepsis and septic shock and the development of the acute respiratory distress syndrome (ARDS). This was a retrospective cohort study of adult patients admitted with severe sepsis and septic shock at a large academic public hospital. The relationship between the volume of IV fluids administered and the development of ARDS was examined using multivariable logistic regression analysis. Among 296 patients hospitalized for severe sepsis and septic shock, 75 (25.3%) developed ARDS. After controlling for confounding variables, there was no significant association between the volume of IV fluids administered in the first 24 hours of hospitalization and the development of ARDS (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.95-1.18). Serum albumin (OR, 0.52; 95% CI, 0.31-0.87) and Acute Physiology and Chronic Health Evaluation II score (OR, 1.08; 95% CI, 1.04-1.13) on admission were the most informative covariates for the development of ARDS in the regression model. For patients hospitalized for severe sepsis and septic shock, fluid administration to improve end-organ perfusion should remain the top priority in early resuscitation despite the potential risk of inducing ARDS. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Etiology and outcomes of acute kidney injury in Chinese children: a prospective multicentre investigation

    PubMed Central

    2013-01-01

    Background The incidence of AKI appears to have increasing trend. Up to now, prospective, multi-center, large-sample epidemiological study done on pediatric AKI on aspects of epidemiological characteristics, causes and outcomes have not reported. It is necessary to develop prospective, multi-center, large-sample epidemiological study in our country on pediatric AKI. The aim of this study was to determine the clinical features, etiology, and outcomes of acute kidney injury (AKI) in Chinese children. Method Paediatric patients (≤18 years old) admitted to 27 hospitals (14 children’s hospitals and 13 general hospitals) affiliated with the Medical University were investigated. AKI was defined using the 2005 Acute Kidney Injury Network criteria. Results During the study period, 388,736 paediatric patients were admitted. From this total, AKI was diagnosed in 1,257 patients, 43 of whom died. The incidence and mortality of AKI was 0.32% and 3.4% respectively. The mean (± SD) age of patients was 48.4 ± 50.4 months. Among the 1,257 AKI paediatric patients, 632 were less than one year old. Among the AKI paediatric patients, 615 (48.9%) were in stage 1, 277 (22.0%) in stage 2, and 365 (29.0%) in stage 3. The most common causes of AKI were renal causes (57.52%), whereas postrenal (25.69%) and prerenal (14.96%) causes were the least common. The three most common causes of AKI according to individual etiological disease were urolithiasis (22.35%), of which exposure to melamine-contaminated milk accounted for the highest incidence (63.7%); acute glomerulonephritis (10.10%); and severe dehydration (7.48%). A total of 43 AKI patients (3.4%) died during their hospital stay; 15 (34.9%) of the 43 died as a result of sepsis. Conclusion Primary renal diseases are a major risk factor for paediatric AKI in China. In terms of specific etiological disease, urolithiasis (postrenal disease) was the leading cause of paediatric AKI in 2008, when the disease was linked to exposure to

  11. Short women with severe sepsis-related acute lung injury receive lung protective ventilation less frequently: an observational cohort study

    PubMed Central

    2011-01-01

    Introduction Lung protective ventilation (LPV) has been shown to improve survival and the duration of mechanical ventilation in acute lung injury (ALI) patients. Mortality of ALI may vary by gender, which could result from treatment variability. Whether gender is associated with the use of LPV is not known. Methods A total of 421 severe sepsis-related ALI subjects in the Consortium to Evaluate Lung Edema Genetics from seven teaching hospitals between 2002 and 2008 were included in our study. We evaluated patients' tidal volume, plateau pressure and arterial pH to determine whether patients received LPV during the first two days after developing ALI. The odds ratio of receiving LPV was estimated by a logistic regression model with robust and cluster options. Results Women had similar characteristics as men with the exception of lower height and higher illness severity, as measured by Acute Physiology and Chronic Health Evaluation (APACHE) II score. 225 (53%) of the subjects received LPV during the first two days after ALI onset; women received LPV less frequently than men (46% versus 59%, P < 0.001). However, after adjustment for height and severity of illness (APACHE II), there was no difference in exposure to LPV between men and women (P = 0.262). Conclusions Short people are less likely to receive LPV, which seems to explain the tendency of clinicians to adhere to LPV less strictly in women. Strategies to standardize application of LPV, independent of differences in height and severity of illness, are necessary. PMID:22044724

  12. THE ENDOTHELIUM IN SEPSIS

    PubMed Central

    Ince, Can; Mayeux, Philip R.; Nguyen, Trung; Gomez, Hernando; Kellum, John A.; Ospina-Tascón, Gustavo A.; Hernandez, Glenn; Murray, Patrick; De Backer, Daniel

    2017-01-01

    Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014. PMID:26871664

  13. THE ENDOTHELIUM IN SEPSIS.

    PubMed

    Ince, Can; Mayeux, Philip R; Nguyen, Trung; Gomez, Hernando; Kellum, John A; Ospina-Tascón, Gustavo A; Hernandez, Glenn; Murray, Patrick; De Backer, Daniel

    2016-03-01

    Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014.

  14. Functional promoter variants in sphingosine 1-phosphate receptor 3 associate with susceptibility to sepsis-associated acute respiratory distress syndrome

    PubMed Central

    Sun, Xiaoguang; Ma, Shwu-Fan; Wade, Michael S.; Acosta-Herrera, Marialbert; Villar, Jesús; Pino-Yanes, Maria; Zhou, Tong; Liu, Bin; Belvitch, Patrick; Moitra, Jaideep; Han, Yoo-Jeong; Machado, Roberto; Noth, Imre; Natarajan, Viswanathan; Dudek, Steven M.; Jacobson, Jeffrey R.; Flores, Carlos

    2013-01-01

    The genetic mechanisms underlying the susceptibility to acute respiratory distress syndrome (ARDS) are poorly understood. We previously demonstrated that sphingosine 1-phosphate (S1P) and the S1P receptor S1PR3 are intimately involved in lung inflammatory responses and vascular barrier regulation. Furthermore, plasma S1PR3 protein levels were shown to serve as a biomarker of severity in critically ill ARDS patients. This study explores the contribution of single nucleotide polymorphisms (SNPs) of the S1PR3 gene to sepsis-associated ARDS. S1PR3 SNPs were identified by sequencing the entire gene and tagging SNPs selected for case-control association analysis in African- and ED samples from Chicago, with independent replication in a European case-control study of Spanish individuals. Electrophoretic mobility shift assays, luciferase activity assays, and protein immunoassays were utilized to assess the functionality of associated SNPs. A total of 80 variants, including 29 novel SNPs, were identified. Because of limited sample size, conclusive findings could not be drawn in African-descent ARDS subjects; however, significant associations were found for two promoter SNPs (rs7022797 −1899T/G; rs11137480 −1785G/C), across two ED samples supporting the association of alleles −1899G and −1785C with decreased risk for sepsis-associated ARDS. In addition, these alleles significantly reduced transcription factor binding to the S1PR3 promoter; reduced S1PR3 promoter activity, a response particularly striking after TNF-α challenge; and were associated with lower plasma S1PR3 protein levels in ARDS patients. These highly functional studies support S1PR3 as a novel ARDS candidate gene and a potential target for individualized therapy. PMID:23911438

  15. Common variants of NFE2L2 gene predisposes to acute respiratory distress syndrome in patients with severe sepsis.

    PubMed

    Acosta-Herrera, Marialbert; Pino-Yanes, Maria; Blanco, Jesús; Ballesteros, Juan Carlos; Ambrós, Alfonso; Corrales, Almudena; Gandía, Francisco; Subirá, Carlés; Domínguez, David; Baluja, Aurora; Añón, José Manuel; Adalia, Ramón; Pérez-Méndez, Lina; Flores, Carlos; Villar, Jesus

    2015-06-16

    The purpose of this study was to investigate whether common variants across the nuclear factor erythroid 2-like 2 (NFE2L2) gene contribute to the development of the acute respiratory distress syndrome (ARDS) in patients with severe sepsis. NFE2L2 is involved in the response to oxidative stress, and it has been shown to be associated with the development of ARDS in trauma patients. We performed a case-control study of 321 patients fulfilling international criteria for severe sepsis and ARDS who were admitted to a Spanish network of post-surgical and critical care units, as well as 871 population-based controls. Six tagging single-nucleotide polymorphisms (SNPs) of NFE2L2 were genotyped, and, after further imputation of additional 34 SNPs, association testing with ARDS susceptibility was conducted using logistic regression analysis. After multiple testing adjustments, our analysis revealed 10 non-coding SNPs in tight linkage disequilibrium (0.75 ≤ r (2)  ≤ 1) that were associated with ARDS susceptibility as a single association signal. One of those SNPs (rs672961) was previously associated with trauma-induced ARDS and modified the promoter activity of the NFE2L2 gene, showing an odds ratio of 1.93 per T allele (95 % confidence interval, 1.17-3.18; p = 0.0089). Our findings support the involvement of NFE2L2 gene variants in ARDS susceptibility and reinforce further exploration of the role of oxidant stress response as a risk factor for ARDS in critically ill patients.

  16. Acute renal failure associated with liver disease in India: etiology and outcome.

    PubMed

    Sural, S; Sharma, R K; Gupta, A; Sharma, A P; Gulati, S

    2000-01-01

    Acute renal failure (ARF) associated with liver disease is a commonly encountered clinical problem of varied etiology and high mortality. We have prospectively analyzed patients with liver disease and ARF to determine the etiology, clinical spectrum, prognosis and factors affecting the outcome. Other than hepatorenal syndrome patients, out of 221 cases, 66 developed ARF secondary to various liver disease like cirrhosis (n = 29, mortality 8, risk factors-older age p < 0.01, grade III/IV encephalopathy p < 0.05), fulminant hepatic failure (n = 25, mortality 15, risk factor-prolonged prothrombin time p < 0.01), and obstructive jaundice (n = 12, mortality 7, risk factor-sepsis p < 0.01). In these three groups the factors leading to ARF were volume depletion (24), gastrointestinal bleed (28), sepsis (34), drugs (27) [aminoglycosides (9) and NSAID (18)] along with hyperbilirubinemia. Various types of ARF with contemporaneous liver injury were malaria (n = 37, mortality 15, risk factors-higher bilirubin p < 0.001, higher creatinine p < 0.05, anuria p < 0.05 and dialysis dependency p < 0.05), sepsis (n = 36, mortality 22, risk factors-age p < 0.001, higher bilirubin p < 0.01, oliguria p < 0.05), hypovolemia with ischemic hepatic injury (n = 14, mortality 5, risk factors-higher creatinine p < 0.05 and SGPT p < 0.01), acute pancreatitis (n = 12, mortality 4, risk factors-higher bilirubin p < 0.001, higher SGPT p < 0.01, dialysis dependency p < 0.05), rifampicin toxicity (n = 10, no mortality), paroxysmal nocturnal hemoglobinuria (n = 3, no mortality), CuSO4 poisoning (n = 3 mortality 2), post abortal (n = 11, mortality 6, risk factors higher creatinine p < 0.05 and SGPT p < 0.01), ARF following delivery including HELLP syndrome (n = 12, mortality 4, risk factors-higher bilirubin p < 0.01 and SGPT p < 0.01), and of uncertain etiology (n= 14 mortality 4). 133 patients (60.2%), required hemodialysis hemodialfiltration or peritoneal dialysis. ARF associated with liver disease is

  17. A patient cohort on long-term sequelae of sepsis survivors: study protocol of the Mid-German Sepsis Cohort.

    PubMed

    Scherag, André; Hartog, Christiane S; Fleischmann, Carolin; Ouart, Dominique; Hoffmann, Franziska; König, Christian; Kesselmeier, Miriam; Fiedler, Sandra; Philipp, Monique; Braune, Anke; Eichhorn, Cornelia; Gampe, Christin; Romeike, Heike; Reinhart, Konrad

    2017-08-23

    An increasing number of patients survive sepsis; however, we lack valid data on the long-term impact on morbidity from prospective observational studies. Therefore, we designed an observational cohort to quantify mid-term and long-term functional disabilities after intensive care unit (ICU)-treated sepsis. Ultimately, findings for the Mid-German Sepsis Cohort (MSC) will serve as basis for the implementation of follow-up structures for patients with sepsis and help to increase quality of care for sepsis survivors. All patients surviving ICU-treated sepsis are eligible and are recruited from five study centres in Germany (acute care hospital setting in Jena, Halle/Saale, Leipzig, Bad Berka, Erfurt; large long-term acute care hospital and rehabilitation setting in Klinik Bavaria Kreischa). Screening is performed by trained study nurses. Data are collected on ICU management of sepsis. On written informed consent provided by patients or proxies, follow-up is carried out by trained research staff at 3, 6 and 12 months and yearly thereafter. The primary outcome is functional disability as assessed by (instrumental) activities of daily living. Other outcomes cover domains like mortality, cognitive, emotional and physical impairment, and resource use. The estimated sample size of 3000 ICU survivors is calculated to allow detection of relevant changes in the primary outcome in sepsis survivors longitudinally. The study is conducted according to the current version of the Declaration of Helsinki and has been approved by four local/federal responsible institutional ethics committees and by the respective federal data protection commissioners. Results of MSC will be fed back to the patients and published in peer-reviewed journals. German Clinical Trials Registry DRKS00010050. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Trends in Sepsis and Infection Sources in the United States. A Population-Based Study

    PubMed Central

    Lagu, Tara; Lindenauer, Peter K.

    2015-01-01

    Rationale: Stakeholders seek to monitor processes and outcomes of care among patients with sepsis, but use of administrative data for sepsis surveillance is controversial. Prior studies using only principal diagnoses from claims data have shown a trend of rising sepsis incidence with falling infection incidence, implying that administrative data are inaccurate for sepsis surveillance. Objectives: Because a sepsis diagnosis often modifies an infection site diagnosis, we sought to investigate trends in sepsis and infection using both principal and secondary diagnoses in administrative data. Methods: This was a retrospective cohort study. We used data from the Nationwide Inpatient Sample years 2003 to 2009 to identify age-standardized, population-based trends in sepsis and infection using all available diagnosis codes. Infection sites were defined as bacteremia, pneumonia, urinary tract, skin/soft tissue, and gastrointestinal; codes for septicemia, sepsis, severe sepsis, and septic shock were used to identify “sepsis.” We identified patients with infection and mechanical ventilation to estimate incidence of severe sepsis without requiring specific claims for sepsis or acute organ failure. Measurements and Main Results: We identified 53.9 million adult infection hospitalizations during the years 2003 to 2009; average age was 63 years, 61% of patients were women, and 70% reported white race, 14% black, and 11% Hispanic ethnicity. Incidence of hospitalizations with an infection claim increased from 3,147/100,000 U.S. residents in 2003 to 3,480/100,000 in 2009 (11% increase), whereas hospitalizations with sepsis claims increased from 359/100,000 to 535/100,000 residents during the same time frame (49% increase); P = 0.009 between infection and sepsis trends. The proportion of infection hospitalizations with a sepsis claim increased from 7.5% in 2003 to 11.5% in 2009 (54% increase). The incidence of hospitalizations with both an infection and mechanical ventilation

  19. Trends in sepsis and infection sources in the United States. A population-based study.

    PubMed

    Walkey, Allan J; Lagu, Tara; Lindenauer, Peter K

    2015-02-01

    Stakeholders seek to monitor processes and outcomes of care among patients with sepsis, but use of administrative data for sepsis surveillance is controversial. Prior studies using only principal diagnoses from claims data have shown a trend of rising sepsis incidence with falling infection incidence, implying that administrative data are inaccurate for sepsis surveillance. Because a sepsis diagnosis often modifies an infection site diagnosis, we sought to investigate trends in sepsis and infection using both principal and secondary diagnoses in administrative data. This was a retrospective cohort study. We used data from the Nationwide Inpatient Sample years 2003 to 2009 to identify age-standardized, population-based trends in sepsis and infection using all available diagnosis codes. Infection sites were defined as bacteremia, pneumonia, urinary tract, skin/soft tissue, and gastrointestinal; codes for septicemia, sepsis, severe sepsis, and septic shock were used to identify "sepsis." We identified patients with infection and mechanical ventilation to estimate incidence of severe sepsis without requiring specific claims for sepsis or acute organ failure. We identified 53.9 million adult infection hospitalizations during the years 2003 to 2009; average age was 63 years, 61% of patients were women, and 70% reported white race, 14% black, and 11% Hispanic ethnicity. Incidence of hospitalizations with an infection claim increased from 3,147/100,000 U.S. residents in 2003 to 3,480/100,000 in 2009 (11% increase), whereas hospitalizations with sepsis claims increased from 359/100,000 to 535/100,000 residents during the same time frame (49% increase); P = 0.009 between infection and sepsis trends. The proportion of infection hospitalizations with a sepsis claim increased from 7.5% in 2003 to 11.5% in 2009 (54% increase). The incidence of hospitalizations with both an infection and mechanical ventilation claim during 2003 was 173/100,000 as compared with 251/100,000 in

  20. The role of the liver in sepsis.

    PubMed

    Yan, Jun; Li, Song; Li, Shulin

    2014-01-01

    Despite the progress made in the clinical management of sepsis, sepsis morbidity and mortality rates remain high. The inflammatory pathogenesis and organ injury leading to death from sepsis are not fully understood for vital organs, especially the liver. Only recently has the role of the liver in sepsis begun to be revealed. Pre-existing liver dysfunction is a risk factor for the progression of infection to sepsis. Liver dysfunction after sepsis is an independent risk factor for multiple organ dysfunction and sepsis-induced death. The liver works as a lymphoid organ in response to sepsis. Acting as a double-edged sword in sepsis, the liver-mediated immune response is responsible for clearing bacteria and toxins but also causes inflammation, immunosuppression, and organ damage. Attenuating liver injury and restoring liver function lowers morbidity and mortality rates in patients with sepsis. This review summarizes the central role of liver in the host immune response to sepsis and in clinical outcomes.

  1. Outcomes of fasciotomy in patients with crush-induced acute kidney injury after Bam earthquake.

    PubMed

    Safari, Saeed; Najafi, Iraj; Hosseini, Mostafa; Sanadgol, Houshang; Sharifi, Ali; Alavi Moghadam, Mostafa; Abdulvand, Ali; Rashid Farrokhi, Farin; Borumand, Behrooz

    2011-01-01

    INTRODUCTION. Fasciotomy may increase the morbidity and mortality in patients with crush-induced acute kidney injury (AKI), by creating an open wound, increasing the risk of bleeding, coagulopathy, and potentially fatal sepsis. This study evaluates the outcomes of fasciotomy in these patients after Bam earthquake in Iran. MATERIALS AND METHODS. We reviewed medical records of victims of Bam earthquake complicated with crush-induced AKI. Demographic, biochemical, and clinical data of patients who underwent fasciotomy were evaluated and compared with other patients with AKI. RESULTS. Fasciotomy was performed for 70 of 200 patients with crush-induced AKI (35.0%). There were no significant differences regarding sex, age, time under the rubble, and muscle enzymes level between these patients and those without fasciotomy. They did not experience higher rates of disseminated intravascular coagulopathy, sepsis, adult respiratory distress syndrome, amputation, and dialysis session. Neither did they have a longer hospitalization period or higher death rate. CONCLUSIONS. This study showed that fasciotomy did not have any deteriorating effect on morbidity and mortality of patients with crush-induced AKI after Bam earthquake.

  2. Presentation, management, and outcomes of sepsis in adults and children admitted to a rural Ugandan hospital: A prospective observational cohort study

    PubMed Central

    Tutaryebwa, Leonard K.; West, T. Eoin

    2017-01-01

    Objectives Limited data are available on sepsis in low-resource settings, particularly outside of urban referral centers. We conducted a prospective observational single-center cohort study in May 2013 to assess the presentation, management and outcomes of adult and pediatric patients admitted with sepsis to a community hospital in rural Uganda. Methods We consecutively screened all patients admitted to medical wards who met sepsis criteria. We evaluated eligible patients within 24 hours of presentation and 24–48 hours after admission, and followed them until hospital discharge. In addition to chart review, mental status evaluation, peripheral capillary oxygen saturation, and point-of-care venous whole blood lactate and glucose testing were performed. Results Of 56 eligible patients, we analyzed data on 51 (20 adults and 31 children). Median age was 8 years (IQR 2–23 years). Sepsis accounted for a quarter of all adult and pediatric medical ward admissions during the study period. HIV prevalence among adults was 30%. On enrollment, over half of patients had elevated point-of-care whole blood lactate, few were hypoglycemic or had altered mental status, and one third were hypoxic. Over 80% of patients received at least one antibiotic, all severely hypoxic patients received supplemental oxygen, and half of patients with elevated lactate received fluid resuscitation. The most common causes of sepsis were malaria and pneumonia. In-hospital mortality was 3.9%. Conclusions This study highlights the importance of sepsis among adult and pediatric patients admitted to a rural Ugandan hospital and underscores the need for continued research on sepsis in low resource settings. PMID:28199348

  3. Neurological and developmental outcome of neonatal jaundice and sepsis in rural Kenya.

    PubMed

    Gordon, Anne L; English, Michael; Tumaini Dzombo, J; Karisa, Mary; Newton, Charles R J C

    2005-11-01

    Neonatal jaundice (NJ) and sepsis are common causes of neonatal mortality in sub-Saharan Africa, but little is known about the long-term morbidity in this setting. This study aimed to describe the neurological and developmental sequelae of severe neonatal hyperbilirubinaemia and neonatal sepsis (NS) in a district hospital in rural Kenya. Twenty-three term infants with NJ [total serum bilirubin (TSB) >300 mumol/l] and 24 infants with a history of NS were identified from hospital records. These children were compared to 40 children from the community (CC) without neonatal problems. At ages 18-32 months, the children's neurological, motor and developmental status were assessed, and blood groups of the NJ and NS subjects and their mothers were determined. Ten (43%) of the NJ subjects were unable to sit and/or stand independently. The NJ subjects had significantly more neurological, motor and developmental difficulties and caused greater maternal concern than the CCs. Five (21%) of the NJ subjects had possible blood group incompatibility. The NS subjects had significantly more motor and eye-hand difficulties and maternal concerns expressed than the CCs. Severe NJ in term infants (of mainly non-haemolytic origin) was associated with a high prevalence of neurological and developmental sequelae at ages 18-32 months. The NS is also associated with neuro-developmental sequelae, but the pattern is different to those seen in NJ. Since NS is common in resource poor countries, this may be an important cause of neuro-developmental impairment in children living in this setting.

  4. Implementing sepsis bundles

    PubMed Central

    Jozwiak, Mathieu; Monnet, Xavier

    2016-01-01

    Sepsis bundles represent key elements of care regarding the diagnosis and treatment of patients with septic shock and allow ones to convert complex guidelines into meaningful changes in behavior. Sepsis bundles endorsed the early goal-directed therapy (EGDT) and their implementation resulted in an improved outcome of septic shock patients. They induced more consistent and timely application of evidence-based care and reduced practice variability. These benefits mainly depend on the compliance with sepsis bundles, highlighting the importance of dedicated performance improvement initiatives, such as multifaceted educational programs. Nevertheless, the interest of early goal directed therapy in septic shock patients compared to usual care has recently been questioned, leading to an update of sepsis bundles in 2015. These new sepsis bundles may also exhibit, as the previous bundles, some limits and pitfalls and the effects of their implementation still needs to be evaluated. PMID:27713890

  5. Pulmonary Infection Is an Independent Risk Factor for Long-Term Mortality and Quality of Life for Sepsis Patients

    PubMed Central

    He, Xiao-Li; Liao, Xue-Lian; Xie, Zhi-Chao; Han, Li; Yang, Xiao-Lei

    2016-01-01

    Background. Long-term outcomes (mortality and health-related quality of life) of sepsis have risen as important indicators for health care. Pulmonary infection and abdominal infection are the leading causes of sepsis. However, few researches about long-term outcomes focused on the origin of sepsis. Here we aim to study the clinical differences between pulmonary-sepsis and abdominal-sepsis and to investigate whether different infection foci were associated with long-term outcomes. Methods. Patients who survived after hospital discharge were followed up by telephone interview. Quality of life (QoL) was assessed using the EuroQol 5-dimension (EQ5D) questionnaire. Results. Four hundred and eighty-three sepsis patients were included, 272 (56.3%) had pulmonary-sepsis, and 180 (37.3%) had abdominal-sepsis. The overall ICU and one-year mortality rates of the cohort were 17.8% and 36.1%, respectively. Compared with abdominal-sepsis, pulmonary-sepsis patients had older age, higher APACHE II, higher ICU mortality (31.7% versus 12.6%), and one-year mortality (45.4% versus 24.4%), together with worse QoL. Age, septic shock, acute renal failure, fungus infection, anion gap, and pulmonary infection were predictors for one-year mortality and pulmonary infection was a risk factor for poor QoL. Conclusions. Pulmonary-sepsis showed worse outcome than abdominal-sepsis. Pulmonary infection is a risk factor for one-year mortality and QoL after sepsis. PMID:28050557

  6. The Effectiveness of Corticosteroid Usage in Complex Therapy for Severe Sepsis and Acute Respiratory Distress Syndrome in Cases of Severe Traumatic Brain Injury.

    PubMed

    Oliynyk, Oleksandr V; Pereviznyk, Bohdana O; Yemiashev, Oleh V; Shlifirchyk, Anna

    2016-01-01

    Severe traumatic brain injury (STBI) is an important issue in contemporary medicine and treatment strategies are still in need of improvement. The most dangerous complications of STBI are multiple organ failure and severe sepsis. As many as 80% of STBI patients with multiple organ failure have acute respiratory distress syndrome (ARDS). The need for better treatment strategies for STBI has led to investigations of the positive therapeutic effects of corticosteroids (CS). About 10 to 15 years ago research showed the inexpediency of CS in STBI therapy, but there were also contradictory findings showing their effectiveness. STBI is frequently followed by severe sepsis, which is not usually treated with CS. No scientific papers investigated the usage or non-usage of CS in patients with STBI followed by severe sepsis and ARDS. The aim of the study was to investigate the influence of CS usage on treatment results in patients with STBI followed by severe sepsis and ARDS. The study involved an analysis of the treatment results in 267 patients with STBI followed by severe sepsis and ARDS, who were treated with and without CS. The study showed that patients' mortality decreased 1.24 times with CS use (500 mg/day of Solu-Medrol® for three days, followed by dose reduction by one-half every 3 days). Patients who took CS survived longer than patients without this treatment. The duration mechanical ventilation was shorter in patients who were treated with CS compared to the other group. Further research into CS use is needed to improve treatment strategies for STBI followed by severe sepsis and ARDS.

  7. Landiolol hydrochloride ameliorates acute lung injury in a rat model of early sepsis through the suppression of elevated levels of pulmonary endothelin-1.

    PubMed

    Matsuishi, Yujiro; Jesmin, Subrina; Kawano, Satoru; Hideaki, Sakuramoto; Shimojo, Nobutake; Mowa, Chishimba Nathan; Akhtar, Shila; Zaedi, Sohel; Khatun, Tanzila; Tsunoda, Yoshiya; Kiwamoto, Takumi; Hizawa, Nobuyuki; Inoue, Yoshiaki; Mizutani, Taro

    2016-12-01

    Among the dysfunctions and pathologies associated with sepsis, the underlying molecular mechanisms of sepsis-induced acute lung injury (ALI) are poorly understood. Endothelin (ET)-1, a potent vasoconstrictor and pro-inflammatory peptide, is known to be involved in the pathogenesis of ALI in a rat model of sepsis. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting β-blocker, plays a crucial role in ameliorating and attenuating LPS-induced ALI through modulation of the ET-1 system. Male Wistar rats at 8weeks of age were administered with either saline or lipopolysaccharide (LPS) for three hours (3h) and some of the LPS-administered rats were continuously treated with landiolol for 3h. ALI was induced by LPS, including levels of both circulatory and pulmonary TNF-α and IL-6 but [PaO2] was significantly decreased. LPS also induced a significant increase in levels of pulmonary ET-1 and ET-A receptor, but levels of ET-B receptor, which has vasodilating effects, were remarkably diminished. Further, LPS administration upregulated the pulmonary expression of HIF-1α. Finally, the treatment of LPS-administered rats with landiolol for 3h ameliorated and prevented ALI, normalized the altered levels of pulmonary ET-1 and ET-A receptors. Landiolol also induced significant down-regulation of ET-B receptor in lung tissues in the early hours (phase) of sepsis. However, Landiolol treatment had no effect on the up-regulated inflammatory mediators (TNF-α, IL-6) in both plasma and lung tissues during sepsis, and expression of pulmonary HIF-1α also remained unchanged after landiolol treatment. Collectively, these data led us to conclude that landiolol may ameliorate sepsis-induced ALI via the pulmonary ET system. Copyright © 2016. Published by Elsevier Inc.

  8. Evidence for a causal link between sepsis and long-term mortality: a systematic review of epidemiologic studies.

    PubMed

    Shankar-Hari, Manu; Ambler, Michael; Mahalingasivam, Viyaasan; Jones, Andrew; Rowan, Kathryn; Rubenfeld, Gordon D

    2016-04-13

    In addition to acute hospital mortality, sepsis is associated with higher risk of death following hospital discharge. We assessed the strength of epidemiological evidence supporting a causal link between sepsis and mortality after hospital discharge by systematically evaluating the available literature for strength of association, bias, and techniques to address confounding. We searched Medline and Embase using the following 'mp' terms, MESH headings and combinations thereof - sepsis, septic shock, septicemia, outcome. Studies published since 1992 where one-year post-acute mortality in adult survivors of acute sepsis could be calculated were included. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms to assess risk of bias, confounding, and causality. The difference in proportion between cumulative one-year mortality and acute mortality was defined as post-acute mortality. Meta-analysis was done by sepsis definition categories with post-acute mortality as the primary outcome. The literature search identified 11,156 records, of which 59 studies met our inclusion criteria and 43 studies reported post-acute mortality. In patients who survived an index sepsis admission, the post-acute mortality was 16.1% (95% CI 14.1, 18.1%) with significant heterogeneity (p < 0.001), on random effects meta-analysis. In studies reporting non-sepsis control arm comparisons, sepsis was not consistently associated with a higher hazard ratio for post-acute mortality. The additional hazard associated with sepsis was greatest when compared to the general population. Older age, male sex, and presence of comorbidities were commonly reported independent predictors of post-acute mortality in sepsis survivors, challenging the causality relationship. Sensitivity analyses for post-acute mortality were consistent with primary analysis. Epidemiologic criteria for a causal relationship between sepsis and post-acute mortality were not

  9. Intestinal epithelium is more susceptible to cytopathic injury and altered permeability than the lung epithelium in the context of acute sepsis.

    PubMed

    Julian, Mark W; Bao, Shengying; Knoell, Daren L; Fahy, Ruairi J; Shao, Guohong; Crouser, Elliott D

    2011-10-01

    Mitochondrial morphology and function are altered in intestinal epithelia during endotoxemia. However, it is unclear whether mitochondrial abnormalities occur in lung epithelial cells during acute sepsis or whether mitochondrial dysfunction corresponds with altered epithelial barrier function. Thus, we hypothesized that the intestinal epithelium is more susceptible to mitochondrial injury than the lung epithelium during acute sepsis and that mitochondrial dysfunction precedes impaired barrier function. Using a resuscitated feline model of Escherichia coli-induced sepsis, lung and ileal tissues were harvested after 6 h for histological and mitochondrial ultrastructural analyses in septic (n = 6) and time-matched controls (n = 6). Human lung epithelial cells (HLEC) and Caco-2 monolayers (n = 5) were exposed to 'cytomix' (TNFα: 40 ng/ml, IL-1β: 20 ng/ml, IFNγ: 10 ng/ml) for 24-72 h, and measurements of transepithelial electrical resistance (TER), epithelial permeability and mitochondrial membrane potential (ΔΨ) were taken. Lung epithelial morphology, mitochondrial ultrastructure and pulmonary gas exchange were unaltered in septic animals compared to matching controls. While histologically intact, ileal epithelia demonstrated marked mitochondrial ultrastructural damage during sepsis. Caco-2 monolayers treated with cytomix showed a significant decrease in mitochondrial ΔΨ within 24 h, which was associated with a progressive reduction in TER and increased epithelial permeability over the subsequent 48 h. In contrast, mitochondrial ΔΨ and epithelial barrier functions were preserved in HLEC following cytomix. These findings indicate that intestinal epithelium is more susceptible to mitochondrial damage and dysfunction than the lung epithelium in the context of sepsis. Early alterations in mitochondrial function portend subsequent epithelial barrier dysfunction.

  10. Discovery of a New Inhibitor of Myeloid Differentiation 2 from Cinnamamide Derivatives with Anti-Inflammatory Activity in Sepsis and Acute Lung Injury.

    PubMed

    Chen, Gaozhi; Zhang, Yali; Liu, Xing; Fang, Qilu; Wang, Zhe; Fu, Lili; Liu, Zhiguo; Wang, Yi; Zhao, Yunjie; Li, Xiaokun; Liang, Guang

    2016-03-24

    Acute inflammatory diseases, including acute lung injury and sepsis, remain the most common life-threatening illness in intensive care units worldwide. Cinnamamide has been incorporated in several synthetic compounds with therapeutic potentials including anti-inflammatory properties. However, the possible mechanism and direct molecular target of cinnamamides for their anti-inflammatory effects were rarely investigated. In this study, we synthesized a series of cinnamamides and evaluated their anti-inflammatory activities. The most active compound, 2i, was found to block LPS-induced MD2/TLR4 pro-inflammatory signaling activation in vitro and to attenuate LPS-caused sepsis and acute lung injury in vivo. Mechanistically, we demonstrated that 2i exerts its anti-inflammatory effects by directly targeting and binding MD2 in Arg90 and Tyr102 residues and inhibiting MD2/TLR4 complex formation. Taken together, this work presents a novel MD2 inhibitor, 2i, which has the potential to be developed as a candidate for the treatment of sepsis, and provides a new lead structure for the development of anti-inflammatory agents targeting MD2.

  11. Long-term outcome and quality of life of patients treated in surgical intensive care: a comparison between sepsis and trauma

    PubMed Central

    Korošec Jagodič, Helena; Jagodič, Klemen; Podbregar, Matej

    2006-01-01

    Introduction Our aim was to determine long-term survival and quality of life of patients admitted to a surgical intensive care unit (ICU) because of sepsis or trauma. Methods This was an observational study conducted in an 11-bed, closed surgical ICU at a 860-bed teaching general hospital over a 1-year period (January 2003 to December 2003). Patients were divided into two groups according to admission diagnoses: group 1 included patients with sepsis; and group 2 included patients with trauma (polytrauma, multiple trauma, head injury, or spinal injury). Quality of life was assessed after 2 years following ICU admission using the EuroQol 5D questionnaire. Results A total of 164 patients (98 trauma patients and 66 patients with sepsis) were included in the study. Trauma patients were younger than patients with sepsis (53 ± 21 years versus 64 ± 13 years; P ≤ 0.001). There was no significant difference between groups in Acute Physiology and Chronic Health Evaluation II score or length of stay in the surgical SICU. Trauma patients stayed longer on the general ward (35 ± 44 days versus 17 ± 24 days; P < 001). Surgical ICU survival, in-hospital survival, and post-hospital and cumulative 2-year survival were lower in the sepsis group than in the trauma group (surgical ICU survival: 60% versus 74%; in-hospital survival: 42% versus 62%; post-hospital survival: 78% versus 92%; cumulative 2-year survival: 33% versus 57%; P < 0.05). There was no significant difference in quality of life in all five dimensions of the EuroQol 5D between groups: 60% of patients had signs of depression, almost 60% had problems in usual activities and 56% had pain. Conclusion Patients with sepsis treated in a surgical ICU have higher short-term and long-term mortality than do trauma patients. However, quality of life is reduced to the same level in both groups. PMID:16978417

  12. Construction and management of ARDS/sepsis registry with REDCap

    PubMed Central

    Pang, Xiaoqing; Kozlowski, Natascha; Wu, Sulong; Jiang, Mei; Huang, Yongbo; Mao, Pu; Liu, Xiaoqing; He, Weiqun; Huang, Chaoyi; Zhang, Haibo

    2014-01-01

    Objective The study aimed to construct and manage an acute respiratory distress syndrome (ARDS)/sepsis registry that can be used for data warehousing and clinical research. Methods The workflow methodology and software solution of research electronic data capture (REDCap) was used to construct the ARDS/sepsis registry. Clinical data from ARDS and sepsis patients registered to the intensive care unit (ICU) of our hospital formed the registry. These data were converted to the electronic case report form (eCRF) format used in REDCap by trained medical staff. Data validation, quality control, and database management were conducted to ensure data integrity. Results The clinical data of 67 patients registered to the ICU between June 2013 and December 2013 were analyzed. Of the 67 patients, 45 (67.2%) were classified as sepsis, 14 (20.9%) as ARDS, and eight (11.9%) as sepsis-associated ARDS. The patients’ information, comprising demographic characteristics, medical history, clinical interventions, daily assessment, clinical outcome, and follow-up data, was properly managed and safely stored in the ARDS/sepsis registry. Data efficiency was guaranteed by performing data collection and data entry twice weekly and every two weeks, respectively. Conclusions The ARDS/sepsis database that we constructed and manage with REDCap in the ICU can provide a solid foundation for translational research on the clinical data of interest, and a model for development of other medical registries in the future. PMID:25276372

  13. Neonatal sepsis: an old problem with new insights.

    PubMed

    Shah, Birju A; Padbury, James F

    2014-01-01

    Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW<1500 g). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter α inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount.

  14. Construction and management of ARDS/sepsis registry with REDCap.

    PubMed

    Pang, Xiaoqing; Kozlowski, Natascha; Wu, Sulong; Jiang, Mei; Huang, Yongbo; Mao, Pu; Liu, Xiaoqing; He, Weiqun; Huang, Chaoyi; Li, Yimin; Zhang, Haibo

    2014-09-01

    The study aimed to construct and manage an acute respiratory distress syndrome (ARDS)/sepsis registry that can be used for data warehousing and clinical research. The workflow methodology and software solution of research electronic data capture (REDCap) was used to construct the ARDS/sepsis registry. Clinical data from ARDS and sepsis patients registered to the intensive care unit (ICU) of our hospital formed the registry. These data were converted to the electronic case report form (eCRF) format used in REDCap by trained medical staff. Data validation, quality control, and database management were conducted to ensure data integrity. The clinical data of 67 patients registered to the ICU between June 2013 and December 2013 were analyzed. Of the 67 patients, 45 (67.2%) were classified as sepsis, 14 (20.9%) as ARDS, and eight (11.9%) as sepsis-associated ARDS. The patients' information, comprising demographic characteristics, medical history, clinical interventions, daily assessment, clinical outcome, and follow-up data, was properly managed and safely stored in the ARDS/sepsis registry. Data efficiency was guaranteed by performing data collection and data entry twice weekly and every two weeks, respectively. The ARDS/sepsis database that we constructed and manage with REDCap in the ICU can provide a solid foundation for translational research on the clinical data of interest, and a model for development of other medical registries in the future.

  15. Quality improvement in pediatric sepsis.

    PubMed

    Melendez, Elliot; Bachur, Richard

    2015-06-01

    Although there is abundant literature detailing the impact of quality improvement in adult sepsis, the pediatric literature is lacking. Despite consensus definitions for sepsis, which patients along the sepsis spectrum should receive aggressive management and the exact onset of sepsis ('time zero') are not clearly established. In the adult emergency department (ED), sepsis onset is defined as the time of entry into the ED; however, this definition cannot be applied to hospitalized patients or patients who evolve during their ED course. Since the time of sepsis onset will dictate the timeliness of subsequent process measures, the variable definitions in the literature make it difficult to generalize findings among prior studies. Despite the variation in defining time zero, aggressive fluid administration, timely antibiotics, and compliance with sepsis bundles have been shown to improve mortality and to reduce hospital and intensive care length of stay. In addition, early identification tools show promise in beginning to define sepsis onset and retrospective search tools may allow improved case finding of those children of concern for sepsis. Quality improvement in pediatric sepsis is evolving. As we continue to define quality measures, we must standardize the definition of sepsis onset. This definition should be applicable to any treatment venue to ensure measures can be evaluated across all settings. In addition, we must delineate which patients along the sepsis spectrum should be candidates for timely interventions and standardize other outcome measures beyond mortality.

  16. Sepsis in standard care: patients' characteristics, effectiveness of antimicrobial therapy and patient outcome--a cohort study.

    PubMed

    Ratzinger, Franz; Eichbichler, Katharina; Schuardt, Michael; Tsirkinidou, Irene; Mitteregger, Dieter; Haslacher, Helmuth; Perkmann, Thomas; Schmetterer, Klaus G; Doffner, Georg; Burgmann, Heinz

    2015-06-01

    Fast diagnosis and initiation of appropriate antibiotic therapy is pivotal for the survival of sepsis patients. However, most studies on suspected sepsis patients are conducted in the intensive care unit or in the emergency room setting, neglecting the standard care setting. This study evaluated sepsis risk factors, microbiological accurateness of the initial empiric antimicrobial therapy and its effect on hospital mortality in standard care patients. In this prospective observational cohort study, patients with clinically suspected sepsis meeting two or more SIRS criteria were screened on standard care wards. After hospital discharge, occurrence of an infection was assessed according to standardized criteria, and empirical antibiotic therapy was evaluated using antibiograms of recognized pathogens by expert review. Of the 2384 screened patients, 298 fulfilled two or more SIRS criteria. Among these were 28.2 % SIRS patients without infection, 46.3 % non-bacteremic/fungemic sepsis patients and 25.5 % bacteremic/fungemic sepsis patients. Occurrence of a malignant disease and chills were associated with a higher risk of patients having bacteremic/fungemic sepsis, whereas other described risk factors remained insignificant. In total, 91.1 % of suspected sepsis patients received empirical antimicrobial therapy, but 41.1 % of bacteremic sepsis patients received inappropriate therapy. Non-surviving bacteremic sepsis patients received a higher proportion of inappropriate therapy than those who survived (p = 0.022). A significant proportion of bacteremic sepsis patients receive inappropriate empiric antimicrobial therapy. Our results indicate that rapid availability of microbiological results is vital, since inappropriate antimicrobial therapy tended to increase the hospital mortality of sepsis patients.

  17. A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: outcomes at 2 years

    PubMed Central

    Marlow, Neil; Morris, Timothy; Brocklehurst, Peter; Carr, Robert; Cowan, Frances M; Patel, Nishma; Petrou, Stavros; Redshaw, Maggie E; Modi, Neena; Dore, Caroline

    2013-01-01

    Objective The authors performed a randomised trial in very preterm small-for-gestational age (SGA) babies to determine if prophylaxis with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). Despite increased neutrophil counts following GM-CSF, the authors reported no significant difference in neonatal sepsis-free survival. Patients and methods 280 babies born <31 weeks of gestation and SGA were entered into the trial. Outcome was determined at 2 years to determine neurodevelopmental and general health outcomes, including economic costs. Results The authors found no significant differences in health outcomes or health and social care costs between the trial groups. In the GM-CSF arm, 87 of 134 (65%) babies survived to 2 years without severe disability compared with 87 of 131 (66%) controls (RR: 1·0, 95% CI 0·8 to 1·2). Marginally, more children receiving GM-CSF were reported to have cough (RR 1·7, 95% CI 1·1 to 2·6) and had signs of chronic respiratory disease (Harrison's sulcus; RR 2·0, 95% CI 1·0 to 3·9) though this was not reflected in bronchodilator use or need for hospitalisation for respiratory disease. Overall, the rate of neurologic abnormality (7%–9%) was similar but mean overall developmental scores were lower than expected for gestational age. Conclusions The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse outcomes at 2 years of age. The apparent excess of developmental impairment in the entire PROGRAMS cohort, without corresponding increase in neurological abnormality, may represent diffuse brain injury attributable to intrauterine growth restriction. PMID:22542709

  18. Sepsis and septic shock

    PubMed Central

    Hotchkiss, Richard S.; Moldawer, Lyle L.; Opal, Steven M.; Reinhart, Konrad; Turnbull, Isaiah R.; Vincent, Jean-Louis

    2017-01-01

    For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15–25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30–50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental. PMID:28117397

  19. Prehospital Sepsis Care.

    PubMed

    Jones, Jerrilyn; Lawner, Benjamin J

    2017-02-01

    Prehospital care providers are tasked with the delivery of time-sensitive care, and emergency medical services (EMS) systems must match patients to appropriate clinical resources. Modern systems are uniquely positioned to recognize and treat patients with sepsis. Interventions such as administration of intravenous fluid and transporting patients to the appropriate level of definitive care are linked to improved patient outcomes. As EMS systems refine their protocols for the recognition and stabilization of patients with suspected or presumed sepsis, EMS providers need to be educated about the spectrum of sepsis-related presentations and treatment strategies need to be standardized.

  20. Mechanism of Tissue Remodeling in Sepsis-Induced Acute Lung Injury

    DTIC Science & Technology

    2005-04-01

    acute lung injury have been identified (e.g., infection, trauma ), little is known about the factors that control the tissue remodeling response. This...in fibroblasts. This suggests that the main player in this process is acetaldehyde . To test this, we exposed cells to acetaldehyde and found that this

  1. Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study

    PubMed Central

    2014-01-01

    Introduction Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome. Methods In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality. Results Median time to AT was 2.1 (IQR 0.8 – 6.0) hours and 3 hours (-0.1 – 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001). Conclusions A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality. PMID:24589043

  2. Pediatric Sepsis.

    PubMed

    Prusakowski, Melanie K; Chen, Audrey P

    2017-02-01

    Pediatric sepsis is distinct from adult sepsis in its definitions, clinical presentations, and management. Recognition of pediatric sepsis is complicated by the various pediatric-specific comorbidities that contribute to its mortality and the age- and development-specific vital sign and clinical parameters that obscure its recognition. This article outlines the clinical presentation and management of sepsis in neonates, infants, and children, and highlights some key populations who require specialized care.

  3. Sepsis and cytokines: current status.

    PubMed

    Blackwell, T S; Christman, J W

    1996-07-01

    Sepsis is a constellation of clinical signs and symptoms resulting from excessive systemic host inflammatory response to infection. This inflammatory response is largely mediated by cytokines, which are released into the systemic circulation. Plasma concentrations of specific cytokines, TNF alpha, IL-1 beta, IL-6 and IL-8 are frequently elevated in human sepsis and cytokine concentrations correlate with severity and outcome of sepsis. In addition to pro-inflammatory cytokines, soluble cytokine receptors, cytokine receptor antagonists and counter-inflammatory cytokines are also produced in large quantities in patients with sepsis; however, the specific role of these molecules in sepsis remains undefined. A complex interaction of cytokines and cytokine-neutralizing molecules probably determines the clinical presentation and course of sepsis. Intervening in this sequence of events to modify the host inflammatory responses may prove to be a beneficial treatment strategy for sepsis, but currently tested anticytokine therapies have been largely unsuccessful.

  4. Acute and long-term dysphagia in critically ill patients with severe sepsis: results of a prospective controlled observational study.

    PubMed

    Zielske, Joerg; Bohne, Silvia; Brunkhorst, Frank M; Axer, Hubertus; Guntinas-Lichius, Orlando

    2014-11-01

    Dysphagia is a major risk factor for morbidity and mortality in critically ill patients treated in intensive care units (ICUs). Structured otorhinolaryngological data on dysphagia in ICU survivors with severe sepsis are missing. In a prospective study, 30 ICU patients with severe sepsis and thirty without sepsis as control group were examined using bedside fiberoptic endoscopic evaluation of swallowing after 14 days in the ICU (T1) and 4 months after onset of critical illness (T2). Swallowing dysfunction was assessed using the Penetration-Aspiration Scale (PAS). The Functional Oral Intake Scale was applied to evaluate the diet needed. Primary endpoint was the burden of dysphagia defined as PAS score >5. At T1, 19 of 30 severe sepsis patients showed aspiration with a PAS score >5, compared to 7 of 30 in critically ill patients without severe sepsis (p = 0.002). Severe sepsis and tracheostomy were independent risk factors for severe dysphagia with aspiration (PAS > 5) at T1 (p = 0.042 and 0.006, respectively). 4-month mortality (T2) was 57 % in severe sepsis patients compared to 20 % in patients without severe sepsis (p = 0.006). At T2, more severe sepsis survivors were tracheostomy-dependent and needed more often tube or parenteral feeding (p = 0.014 and p = 0.040, respectively). Multivariate analysis revealed tracheostomy at T1 as independent risk factor for severe dysphagia at T2 (p = 0.030). Severe sepsis appears to be a relevant risk factor for long-term dysphagia. An otorhinolaryngological evaluation of dysphagia at ICU discharge is mandatory for survivors of severe critical illness to plan specific swallowing rehabilitation programs.

  5. Outcomes in patients with mixed phenotype acute leukemia in Morocco.

    PubMed

    Bachir, Fatima; Zerrouk, Jihane; Howard, Scott C; Graoui, Omar; Lahjouji, Ali; Hessissen, Leila; Bennani, Sanae; Quessar, Assmae; El Aouad, Rajae

    2014-08-01

    Mixed phenotype acute leukemia (MPAL) includes biphenotypic and bilineal types of leukemia, which constitute rare subtypes that require individualized therapy. Outcomes in Moroccan patients with MPAL are unknown. Among 1264 patients with acute leukemia, 20 were classified as having MPAL, including 17 with biphenotypic acute leukemia (1.3%) and 3 with bilineal leukemia (0.2%). There were 8 adults and 12 children. In 12 cases (60%), leukemic blasts expressed myeloid and T-lymphoid antigens, and, in 5 cases (25%), leukemic blasts expressed B lymphoid antigens plus myeloid antigens. Patients were initially treated on protocols for acute myeloid leukemia (n=4), acute lymphoblastic leukemia (ALL, n=14), or with palliative care (n=2). The probability of survival at 2 years in MPAL cases was 52%± 14%. Six of the 12 patients younger than 15 years remain alive versus 1 of 8 adult patients. Patients treated with ALL-directed therapy had significantly higher overall survival than those treated with acute myeloid leukemia-directed therapy (P=0.003). There was no association between the phenotypic characteristics and the clinical outcome (P=0.83). In conclusion, MPAL represents 1.5% of acute leukemia in Morocco. The prognosis is poor, but initial treatment with therapy directed toward ALL, improved supportive care, and the prevention of abandonment of therapy may improve outcomes in this subgroup of patients.

  6. T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis

    PubMed Central

    Anantha, R V; Mazzuca, D M; Xu, S X; Porcelli, S A; Fraser, D D; Martin, C M; Welch, I; Mele, T; Haeryfar, S M M; McCormick, J K

    2014-01-01

    Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNK T) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNK T cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNK T cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNK T cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNK T cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNK T cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis. PMID:24965554

  7. T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis.

    PubMed

    Anantha, R V; Mazzuca, D M; Xu, S X; Porcelli, S A; Fraser, D D; Martin, C M; Welch, I; Mele, T; Haeryfar, S M M; McCormick, J K

    2014-11-01

    Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNK T) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNK T cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNK T cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNK T cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNK T cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNK T cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis.

  8. Outcomes after treatment of acute aortic occlusion.

    PubMed

    de Varona Frolov, Serguei R; Acosta Silva, Marcela P; Volo Pérez, Guido; Fiuza Pérez, Maria D

    2015-11-01

    Acute aortic occlusion (AAO) is a rare disease with high morbidity and mortality. The aim of this study was to describe the results of surgical treatment of acute aortic occlusion and risk factors for mortality. Retrospective review of the clinical history of 29 patients diagnosed and operated on for AAO during 28 years. The following variables were analysed: age, sex, tabaco use, diabetes, chronic renal insufficiency, chronic heart failure, atrial fibrillation, arterial hypertension, symptoms, diagnosis and treatment, 30-day mortality and long-term survival. A univariant analysis was performed of variables related to mortality. Twenty-nine patients were included (18 male) with a mean age of 66,2 years. The aetiology was: embolism (EM) in 11 cases and Thrombosis (TR) in 18 cases. The surgical procedures performed included bilateral transfemoral thrombectomy (14 cases), aorto-bifemoral by-pass (8 cases), axilo uni/bifemoral by-pass (5 cases) and aortoiliac and renal tromboendarterectomy (2 cases). Morbidity included: renal failure (14 cases), mesenteric ischemia (4 cases), cardiac complications (7 cases), respiratory complications (5 cases) and loss of extremity (2 cases). The in-hospital mortality was 21% (EM 0%, TR 21%). The estimated survival at 1.3 and 5 years was 60, 50 and 44% respectively. Age (p=0.032), arterial hypertension (p=0.039) and aetiology of the AAO (p=0.039) were related to mortality. Acute aortic occlusion is a medical emergency with high mortality rates. Acute renal failure is the most common postoperative complication. Copyright © 2012 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study.

    PubMed

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu S G; Shahid, Abu S M S B; Shahunja, K M; Das, Sumon Kumar; Hossain, Md Iqbal; Ahmed, Tahmeed

    2015-01-01

    In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children. In this retrospective case-control study SAM children aged 0-59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline. The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons). We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children.

  10. Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study

    PubMed Central

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu S. G.; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Hossain, Md Iqbal; Ahmed, Tahmeed

    2015-01-01

    Background In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children. Methods In this retrospective case-control study SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline. Results The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons). Conclusion and Significance We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case

  11. Differences in Sepsis Treatment and Outcomes between Public and Private Hospitals in Brazil: A Multicenter Observational Study

    PubMed Central

    Conde, Katia Aparecida Pessoa; Silva, Eliezer; Silva, Carla Oliveira; Ferreira, Elaine; Freitas, Flavio Geraldo Rezende; Castro, Isac; Rea-Neto, Alvaro; Grion, Cintia Magalhaes Carvalho; Moura, Anselmo Dornas; Lobo, Suzana Margareth; Azevedo, Luciano Cesar Pontes; Machado, Flavia Ribeiro

    2013-01-01

    Background Previous studies showed higher sepsis mortality rates in Brazil compared to other developed or developing countries. Moreover, another trial demonstrated an increased mortality rate in public hospitals compared to private hospitals in Brazil. The reasons for these findings may include delayed recognition and inadequate treatment of sepsis in public facilities. We designed this study to evaluate the factors associated with mortality in septic patients admitted to intensive care units in a network of public and private institutions. Materials and Methods This study is a retrospective analysis of a prospective cohort of sepsis patients in 19 private and public institutions in Brazil. We analyzed data from the original database and collected additional data to assess compliance to the treatment guidelines and to determine the time from the onset of organ dysfunction and the sepsis diagnosis by the healthcare team. Results A total of 396 patients were analyzed. Patients in public hospitals were younger, had a greater number of dysfunctional organs at baseline and a lower chance to have sepsis diagnosed within two hours of the onset of organ dysfunction. Private hospitals had a better compliance to lactate and blood culture sampling and maintenance of glycemic control. The multivariate analysis showed that age, disease severity at baseline and being treated at a public hospital were independent risk factors for mortality. A delay in the sepsis diagnosis of longer than two hours was associated with mortality only in the public setting. Conclusions We confirmed a lower sepsis mortality rate in the private hospitals of this network. Being treated in a public hospital was an independent factor for mortality. Delayed recognition of sepsis was more frequent in public institutions and this might have been associated with a higher mortality. Improving sepsis recognition and early diagnosis may be important targets in public institutions. PMID:23762255

  12. Successful therapy of meningococcal sepsis in acute disseminated lupus erythematosus with plasmapheresis, immunosuppression, and antibiotics.

    PubMed

    Dobos, G J; Meske, S; Keller, E; Riegel, W; Vaith, P; Peter, H H; Schollmeyer, P

    1990-10-03

    A 17-year-old female with a 5-year history of disseminated lupus erythematosus has remained without immunosuppressive therapy for the last 3 years. She was admitted to the hospital for acute abdominal pain, generalized edema, and rapidly developing dyspnea and somnolence. Although all symptoms were consistent with active SLE, septicemia was suspected because of leukocytosis (20,000/microliters), greatly elevated C-reactive protein (45 mg/dl), and normal complement values (C3 0.74 g/l, C4 0.21 g/l). Directly after bacterial blood cultures were prepared, a combined treatment was instituted consisting of plasmapheresis (3 x 2.1 l against fresh frozen plasma), antibiotics, prednisolone, and cyclophosphamide following the last plasmapheresis. Within three days cerebral function returned to normal, edema improved, and CRP fell to 0.5 mg/dl. The blood cultures and pericardial effusion displayed meningococcal colonies.

  13. [Catheter associated Staphylococcus sciuri sepsis in a patient with acute myeloid leukemia].

    PubMed

    Koçoğlu, Esra; Karabay, Oğuz

    2006-10-01

    The coagulase-negative bacterial species Staphylococcus sciuri is widely distributed in the natural environment. Although principally found in animals, S. sciuri is occasionally isolated from human samples. In this paper, S. sciuri bacteremia which was associated with an indwelling catheter of a patient with acute myeloid leukemia (AML) and neutropenia was presented. An empirical intravenous antibiotic therapy (meropenem, vancomycin) was initiated with the preliminary diagnosis of febrile neutropenia and catheter infection. The catalase and oxidase positive, tube coagulase negative strain isolated from three of the concurrent blood cultures and intravenous catheter culture has been identified as S. sciuri. The isolate was found resistant to penicilin and oxacilline. This case has emphasized the importance of identification of coagulase-negative staphylococci isolated from the cultures of patients with haematological malignancy.

  14. Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

    PubMed Central

    2013-01-01

    part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome. PMID:23594407

  15. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

    PubMed Central

    SEPEHR, REYHANEH; AUDI, SAID H.; MALEKI, SEPIDEH; STANISZEWSKI, KEVIN; EIS, ANNIE L.; KONDURI, GIRIJA G.; RANJI, MAHSA

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure. PMID:24672581

  16. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS.

    PubMed

    Sepehr, Reyhaneh; Audi, Said H; Maleki, Sepideh; Staniszewski, Kevin; Eis, Annie L; Konduri, Girija G; Ranji, Mahsa

    2013-07-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

  17. Examining Outcomes of Acute Psychiatric Hospitalization among Children

    PubMed Central

    Tharayil, Priya R.; Sigrid, James; Morgan, Ronald; Freeman, Kimberly

    2013-01-01

    Within the past two decades, few studies have examined outcomes of acute psychiatric hospitalization among children, demonstrating change in emotional and behavioral functioning. A secondary analysis of pre-test/post-test data collected on 36 children was conducted, using the Target Symptom Rating (TSR). The TSR is a 13-item measure with two subscales – Emotional Problems and Behavioral Problems and was designed for evaluation of outcome among children and adolescents in acute inpatient psychiatric settings. Results of this study, its limitations, and the barriers encountered in the implementation of the TSR scale as part of routine clinical practice are discussed. PMID:23946699

  18. Value of Shock Index in prognosticating the short-term outcome of death for patients presenting with severe sepsis and septic shock in the emergency department.

    PubMed

    Yussof, Shah Jahan Mohd; Zakaria, Mohd Idzwan; Mohamed, Fatahul Laham; Bujang, Mohamad Adam; Lakshmanan, Sharmila; Asaari, Abu Hassan

    2012-08-01

    The importance of early recognition and treatment of sepsis and its effects on short-term survival outcome have long been recognized. Having reliable indicators and markers that would help prognosticate the survival of these patients is invaluable and would subsequently assist in the course of effective dynamic triaging and goal directed management. To determine the prognosticative value of Shock Index (SI), taken upon arrival to the emergency department and after 2 hours of resuscitation on the shortterm outcome of severe sepsis and septic shock patients. This is a retrospective observational study involving 50 patients admitted to the University of Malaya Medical Centre between June 2009 and June 2010 who have been diagnosed with either severe sepsis or septic shock. Patients were identified retrospectively from the details recorded in the registration book of the resuscitation room. 50 patients were selected for this pilot study. The population comprised 19 males (38%) and 31 females (62%). The median (min, max) age was 54.5 (17.0, 84.0) years. The number of severe sepsis and septic shock cases were 31 (62%), and 19 (38%) respectively. There were 17 (34%) cases of pneumonias, 13 (26%) cases of urological sepsis, 8 (16%) cases of gastro intestinal tract related infections and 12 (24%) cases of other infections. There were a total of 23 (46%) survivors and 27 (54%) deaths. The value of the shock index is defined as systolic blood pressure divided by heart rate was calculated. Shock Index on presentation to ED (SI 1) and after 2 hours of resuscitation in the ED (SI 2). The median, minimum and maximum variables were tested using Mann-Whitney U and Chi square analysis. The significant parameters were re-evaluated for sensitivity, specificity and cut-off points. ROC curves and AUC values were generated among these variables to assess prognostic utility for outcome. Amongst all 7 variables tested, 2 were tested to be significant (p: < 0.05). From the sensitivity

  19. Predictors of outcome in acute encephalitis

    PubMed Central

    Thakur, Kiran T.; Motta, Melissa; Asemota, Anthony O.; Kirsch, Hannah L.; Benavides, David R.; Schneider, Eric B.; McArthur, Justin C.; Geocadin, Romergryko G.

    2013-01-01

    Objective: To investigate predictors of outcome in patients with all-cause encephalitis receiving care in the intensive care unit. Methods: A retrospective analysis of encephalitis cases at The Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center was performed. Using multivariate logistic regression analysis, we examined mortality and predictors of good outcome (defined as modified Rankin Scale scores of 1–3) and poor outcome (scores 4 and 5) in those surviving to hospital discharge. Results: In our cohort of 103 patients, the median age was 52 years (interquartile range 26), 52 patients (50.49%) were male, 28 patients (27.18%) had viral encephalitis, 19 (18.45%) developed status epilepticus (SE), 15 (14.56%) had cerebral edema, and 19 (18.45%) died. In our multivariate logistic regression analysis, death was associated with cerebral edema (odds ratio [OR] 18.06, 95% confidence interval [CI] 3.14–103.92), SE (OR 8.16, 95% CI 1.55–43.10), and thrombocytopenia (OR 6.28, 95% CI 1.41–28.03). Endotracheal intubation requirement with ventilator support was highly correlated with death (95%). In addition, in those patients who survived, viral, nonviral, and unknown causes of encephalitis were less likely to have a poor outcome at hospital discharge compared with an autoimmune etiology (viral encephalitis: OR 0.09, 95% CI 0.01–0.57; nonviral encephalitis: OR 0.02, 95% CI 0.01–0.31; unknown etiology: OR 0.18, 95% CI 0.04–0.91). Conclusions: Our study suggests that predictors of death in patients with encephalitis comprise potentially reversible conditions including cerebral edema, SE, and thrombocytopenia. Further prospective studies are needed to determine whether aggressive management of these complications in patients with encephalitis improves outcome. PMID:23892708

  20. Predictors of outcome in acute encephalitis.

    PubMed

    Thakur, Kiran T; Motta, Melissa; Asemota, Anthony O; Kirsch, Hannah L; Benavides, David R; Schneider, Eric B; McArthur, Justin C; Geocadin, Romergryko G; Venkatesan, Arun

    2013-08-27

    To investigate predictors of outcome in patients with all-cause encephalitis receiving care in the intensive care unit. A retrospective analysis of encephalitis cases at The Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center was performed. Using multivariate logistic regression analysis, we examined mortality and predictors of good outcome (defined as modified Rankin Scale scores of 1-3) and poor outcome (scores 4 and 5) in those surviving to hospital discharge. In our cohort of 103 patients, the median age was 52 years (interquartile range 26), 52 patients (50.49%) were male, 28 patients (27.18%) had viral encephalitis, 19 (18.45%) developed status epilepticus (SE), 15 (14.56%) had cerebral edema, and 19 (18.45%) died. In our multivariate logistic regression analysis, death was associated with cerebral edema (odds ratio [OR] 18.06, 95% confidence interval [CI] 3.14-103.92), SE (OR 8.16, 95% CI 1.55-43.10), and thrombocytopenia (OR 6.28, 95% CI 1.41-28.03). Endotracheal intubation requirement with ventilator support was highly correlated with death (95%). In addition, in those patients who survived, viral, nonviral, and unknown causes of encephalitis were less likely to have a poor outcome at hospital discharge compared with an autoimmune etiology (viral encephalitis: OR 0.09, 95% CI 0.01-0.57; nonviral encephalitis: OR 0.02, 95% CI 0.01-0.31; unknown etiology: OR 0.18, 95% CI 0.04-0.91). Our study suggests that predictors of death in patients with encephalitis comprise potentially reversible conditions including cerebral edema, SE, and thrombocytopenia. Further prospective studies are needed to determine whether aggressive management of these complications in patients with encephalitis improves outcome.

  1. Long-term risk of mortality after acute kidney injury in patients with sepsis: a contemporary analysis

    PubMed Central

    2010-01-01

    Background Acute kidney injury (AKI) is associated with increased short-term mortality of septic patients; however, the exact influence of AKI on long-term mortality in such patients has not yet been determined. Methods We retrospectively evaluated the impact of AKI, defined by the "Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease" (RIFLE) classification based on creatinine criteria, on 2-year mortality in a cohort of 234 hospital surviving septic patients who had been hospitalized at the Infectious Disease Intensive Care Unit of our Hospital. Results Mean-follow-up was 21 ± 6.4 months. During this period, 32 patients (13.7%) died. At 6 months, 1 and 2 years of follow-up, the cumulative probability of death of patients with previous AKI was 8.3, 16.9 and 34.2%, respectively, as compared with 2.2, 6 and 8.9% in patients without previous AKI (log-rank, P < 0.0001). In the univariate analysis, age (hazard ratio 1.4, 95% CI 1.2-1.7, P < 0.0001), as well as pre-existing cardiovascular disease (hazard ratio 3.6, 95% CI 1.4-9.4, P = 0.009), illness severity as evaluated by nonrenal APACHE II (hazard ratio 1.3, 95% CI 1.1-1.6, P = 0.002), and previous AKI (hazard ratio 4.2, 95% CI 2.1-8.5, P < 0.0001) were associated with increased 2-year mortality, while gender, race, pre-existing hypertension, cirrhosis, HIV infection, neoplasm, and baseline glomerular filtration rate did not. In the multivariate analysis, however, only previous AKI (hazard ratio 3.2, 95% CI 1.6-6.5, P = 0.001) and age (hazard ratio 1.4, 95% CI 1.2-1.6, P < 0.0001) emerged as independent predictors of 2-year mortality. Conclusions Acute kidney injury had a negative impact on long-term mortality of patients with sepsis. PMID:20525222

  2. Could a protocol based on early goal-directed therapy improve outcomes in patients with severe sepsis and septic shock in the Intensive Care Unit setting?

    PubMed Central

    Wawrzeniak, Iuri Christmann; Loss, Sergio Henrique; Moraes, Maria Cristina Martins; De La Vega, Fabiane Lopes; Victorino, Josue Almeida

    2015-01-01

    Context: Sepsis is a disease with high incidence and mortality. Among the interventions of the resuscitation bundle, the early goal-directed therapy (EGDT) is recommended. Aims: The aim was to evaluate outcomes in patients with severe sepsis and septic shock using EGDT in real life compared with patients who did not undergo it in the Intensive Care Unit (ICU) setting. Settings and Design: retrospective and observational cohort study at tertiary hospital. Subjects and Methods: All the patients admitted to ICU were screened for severe sepsis or septic shock and included in a registry and followed. The patients were allocated in two groups according to submission or not to EGDT. Results: A total of 268 adult patients with severe sepsis or septic shock were included. EGDT was employed in 97/268 patients. The general mortality was higher in no early goal-directed therapy (no-EGDT) then in EGDT groups (49.7% vs. 37.1% [P = 0.04] in hospital and 40.4% vs. 29.9% [P = 0.08] in the ICU, respectively. The general length of stay [LOS] in the no-EGDT and EGDT groups was 45.0 ± 59.8 vs. 29.1 ± 30.1 days [P = 0.002] in hospital and 17.4 ± 19.4 vs. 9.1 ± 9.8 days [P < 0.001] in the ICU, respectively). Conclusions: Our study shows reduced mortality and LOS in patients submitted to EGDT in the ICU setting. A simplified EGDT without central venous oxygen saturation is an important tool for sepsis management. PMID:25810612

  3. RAGE deficiency attenuates the protective effect of Lidocaine against sepsis-induced acute lung injury.

    PubMed

    Zhang, Zhuo; Zhou, Jie; Liao, Changli; Li, Xiaobing; Liu, Minghua; Song, Daqiang; Jiang, Xian

    2017-04-01

    Lidocaine (Lido) is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of cecal ligation and puncture (CLP)-induced acute lung injury (ALI). The receptor for advanced glycation end product (RAGE) exerts pro-inflammatory effects by enhancing pro-inflammatory cytokine production. However, the precise mechanism by which Lido confers protection against ALI is not clear. ALI was induced in RAGE WT and RAGE knockout (KO) rats using cecal ligation and puncture (CLP) operations for 24 h. The results showed that Lido significantly inhibited CLP-induced lung inflammation and histopathological lung injury. Furthermore, Lido significantly reduced CLP-induced upregulation of HMGB1 and RAGE expression and activation of the NF-κB and MAPK signaling pathways. With the use of RAGE KO rats, we demonstrate here that RAGE deficiency attenuates the protective effect of Lido against CLP-induced lung inflammatory cell infiltration and histopathological lung injury. These results suggest that RAGE deficiency attenuates the protective effect of Lido against CLP-induced ALI by attenuating the pro-inflammatory cytokines production.

  4. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

    PubMed

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

    2017-03-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

  5. The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis

    PubMed Central

    Sterling, Sarah A.; Miller, W. Ryan; Pryor, Jason; Puskarich, Michael A.; Jones, Alan E.

    2015-01-01

    Objectives We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. Data Sources and Study Selection A comprehensive search was performed using a pre-defined protocol. Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to ED triage and/or shock recognition, and mortality. Exclusion criteria: immunosuppressed populations, review article, editorial, or non-human studies. Data Extraction Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of ED triage; 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds Ratios (OR) were calculated using a random effect model. The primary outcome was mortality. Data Synthesis 1123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from ED triage. Patients who received antibiotics more than 3 hours after ED triage (< 3 hours reference), had a pooled OR for mortality of 1.16 (0.92 to 1.46, p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hour reference) had a pooled OR for mortality of 1.46 (0.89 to 2.40, p = 0.13). There was no increased mortality in the pooled ORs for each hourly delay from <1 to >5 hours in antibiotic administration from severe sepsis/shock recognition. Conclusion Using the available pooled data we found no significant mortality benefit of administering antibiotics within 3 hours of ED triage or within 1 hour of shock recognition in severe sepsis and septic shock

  6. Sepsis-related hypertensive response: friend or foe?

    PubMed Central

    Saleh, Mohamed

    2014-01-01

    In daily practice acute arterial hypertension may occur during acute sepsis. No management guidelines concerning this issue figured in the latest sepsis campaign guidelines. Arterial hypertension occurring during sepsis could be an overlooked condition despite its potential haemodynamic harmful consequences. In this paper, a clinical study of acute hypertensive response related to sepsis is detailed. It shows that arterial hypertension, renal salt wasting and glomerular hyperfiltration can occur simultaneously during sepsis. Mechanisms and management options of sepsis-related arterial hypertensive response are also discussed. PMID:24855080

  7. Acute low dose of MK-801 prevents memory deficits without altering hippocampal DARPP-32 expression and BDNF levels in sepsis survivor rats.

    PubMed

    Cassol-Jr, Omar J; Comim, Clarissa M; Constantino, Larissa S; Rosa, Daniela V F; Mango, Luiz Alexandre V; Stertz, Laura; Kapczinski, Flávio; Romano-Silva, Marco A; Quevedo, João; Dal-Pizzol, Felipe

    2011-01-01

    Sepsis is characterized by an intense inflammatory reaction with potential neurotoxic effects in the central nervous system and damage to memory and learning ability. We assessed the effects of acute low dose of MK-801 on the memory impairment, hippocampal BDNF levels and DARPP-32 expression ten days after sepsis. Under anesthesia, male Wistar rats underwent either cecal ligation and perforation (CLP) or sham. Then, the animals received either a single systemic injection of MK-801 (0.025 mg/kg) or saline solution. Ten days after CLP, the animals were submitted to the step-down inhibitory avoidance and object recognition tests. Also, the hippocampal BDNF protein levels and DARPP-32 expression were evaluated. MK-801 prevented cognitive impairment, but did not affect the hippocampal BDNF levels. DARPP-32 expression was significantly different only in the animals submitted to sepsis that received MK-801 treatment. Thus, we demonstrated that a single low dose of MK-801 prevented memory impairment without altering hippocampal DARPP-32 expression and BDNF levels.

  8. Cold-inducible RNA-binding protein (CIRP) causes sepsis-associated acute lung injury via induction of endoplasmic reticulum stress

    PubMed Central

    Khan, Mohammad Moshahid; Yang, Weng-Lang; Brenner, Max; Bolognese, Alexandra Cerutti; Wang, Ping

    2017-01-01

    Cold-inducible RNA-binding protein (CIRP), released into the circulation during sepsis, causes lung injury via an as yet unknown mechanism. Since endoplasmic reticulum (ER) stress is associated with acute lung injury (ALI), we hypothesized that CIRP causes ALI via induction of ER stress. To test this hypothesis, we studied the lungs of wild-type (WT) and CIRP knockout (KO) mice at 20 h after induction of sepsis by cecal ligation and puncture (CLP). WT mice had significantly more severe ALI than CIRP KO mice. Lung ER stress markers (BiP, pIRE1α, sXBP1, CHOP, cleaved caspase-12) were increased in septic WT mice, but not in septic CIRP KO mice. Effector pathways downstream from ER stress – apoptosis, NF-κB (p65), proinflammatory cytokines (IL-6, IL-1β), neutrophil chemoattractants (MIP-2, KC), neutrophil infiltration (MPO activity), lipid peroxidation (4-HNE), and nitric oxide (iNOS) – were significantly increased in WT mice, but only mildly elevated in CIRP KO mice. ER stress markers were increased in the lungs of healthy WT mice treated with recombinant murine CIRP, but not in the lungs of TLR4 KO mice. This suggests CIRP directly induces ER stress via TLR4 activation. In summary, CIRP induces lung ER stress and downstream responses to cause sepsis-associated ALI. PMID:28128330

  9. Cold-inducible RNA-binding protein (CIRP) causes sepsis-associated acute lung injury via induction of endoplasmic reticulum stress.

    PubMed

    Khan, Mohammad Moshahid; Yang, Weng-Lang; Brenner, Max; Bolognese, Alexandra Cerutti; Wang, Ping

    2017-01-27

    Cold-inducible RNA-binding protein (CIRP), released into the circulation during sepsis, causes lung injury via an as yet unknown mechanism. Since endoplasmic reticulum (ER) stress is associated with acute lung injury (ALI), we hypothesized that CIRP causes ALI via induction of ER stress. To test this hypothesis, we studied the lungs of wild-type (WT) and CIRP knockout (KO) mice at 20 h after induction of sepsis by cecal ligation and puncture (CLP). WT mice had significantly more severe ALI than CIRP KO mice. Lung ER stress markers (BiP, pIRE1α, sXBP1, CHOP, cleaved caspase-12) were increased in septic WT mice, but not in septic CIRP KO mice. Effector pathways downstream from ER stress - apoptosis, NF-κB (p65), proinflammatory cytokines (IL-6, IL-1β), neutrophil chemoattractants (MIP-2, KC), neutrophil infiltration (MPO activity), lipid peroxidation (4-HNE), and nitric oxide (iNOS) - were significantly increased in WT mice, but only mildly elevated in CIRP KO mice. ER stress markers were increased in the lungs of healthy WT mice treated with recombinant murine CIRP, but not in the lungs of TLR4 KO mice. This suggests CIRP directly induces ER stress via TLR4 activation. In summary, CIRP induces lung ER stress and downstream responses to cause sepsis-associated ALI.

  10. Differentially expressed miRNAs in sepsis-induced acute kidney injury target oxidative stress and mitochondrial dysfunction pathways

    PubMed Central

    Ge, Qin-Min; Huang, Chun-Mei; Zhu, Xiang-Yang; Bian, Fan; Pan, Shu-Ming

    2017-01-01

    Objective To identify specific miRNAs involved in sepsis-induced AKI and to explore their targeting pathways. Methods The expression profiles of miRNAs in serum from patients with sepsis-induced AKI (n = 6), sepsis-non AKI (n = 6), and healthy volunteers (n = 3) were investigated by microarray assay and validated by quantitative PCR (qPCR). The targets of the differentially expressed miRNAs were predicted by Target Scan, mirbase and Miranda. Then the significant functions and involvement in signaling pathways of gene ontology (GO) and KEGG pathways were analyzed. Furthermore, eight miRNAs were randomly selected out of the differentially expressed miRNAs for further testing by qPCR. Results qPCR analysis confirmed that the expressions levels of hsa-miR-23a-3p, hsa-miR-4456, hsa-miR-142-5p, hsa-miR-22-3p and hsa-miR-191-5p were significantly lower in patients with sepsis compared with the healthy volunteers, while hsa-miR-4270, hsa-miR-4321, hsa-miR-3165 were higher in the sepsis patients. Statistically, miR-4321; miR-4270 were significantly upregulated in the sepsis-induced AKI compared with sepsis-non AKI, while only miR-4321 significantly overexpressed in the sepsis groups compared with control groups. GO analysis showed that biological processes regulated by the predicted target genes included diverse terms. They were related to kidney development, regulation of nitrogen compound metabolic process, regulation of cellular metabolic process, cellular response to oxidative stress, mitochondrial outer membrane permeabilization, etc. Pathway analysis showed that several significant pathways of the predicted target genes related to oxidative stress. miR-4321 was involved in regulating AKT1, mTOR and NOX5 expression while miR-4270 was involved in regulating PPARGC1A, AKT3, NOX5, PIK3C3, WNT1 expression. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in oxidative stress and mitochondrial dysfunction. Conclusion This study

  11. [Aerobic etiology of acute appendicitis in adults. Multicenter study of abdominal sepsis in Argentina].

    PubMed

    Scapellato, Pablo G; Pessacq, Pedro; Corso, Alejandra; Pasteran, Fernando; Rapoport, Melina; Vasen, Walter; Nemirovsky, Corina; Calmaggi, Aníbal

    2017-01-01

    Antibiotic treatment for acute appendicitis is empirically chosen, based on epidemiological information. Resistance rates are different between regions and there are limited data on the situation in Argentina. As a part of a multicenter, observational study of abdominal infections, we performed the analysis of adult patients diagnosed with appendicitis, enrolled in 16 centers of 5 provinces, between Jan/01/2014 and Jun/30/2015. The aim was to analyze the prevalent aerobic pathogens, their resistance rates and the antimicrobial prescription pattern. On a total of 131 appendicitis cases analyzed, we found 184 aerobic pathogens (1.4 bacteria/episode): Escherichia coli 106 (57.6%), Klebsiella spp 16 (8.7%), Pseudomonas aeruginosa 19 (10.3%), Enterobacter spp. 2 (1%), other Gram negative bacilli 5 (2.7%); Enterococcus spp. 16 (8.7%) and other Gram positive cocci 20 (10.9%). The resistance rate of E. coli and enterobacteria to ampicillin/sulbactam was greater than 34% and greater than 31% to ciprofloxacin. However, the resistance of enterobacteria to piperacillin/tazobactam was 4.8%, to ceftriaxone 9.5%, to amikacin 3.6% and 8.2% to gentamicin. No resistance to carbapenems was found. The choice of quinolones or ampicillin/sulbactam for the treatment of appendicitis should be discouraged in our context, due to the high rates of resistance found in this prevalent etiology. Aminoglycoside-based treatments should be considered, given the findings of high antibiotic susceptibility and their low impact on the induction of resistance.

  12. Nurse staffing and patient outcomes in Belgian acute hospitals

    PubMed Central

    Van den Heede, Koen; Sermeus, Walter; Diya, Luwis; Clarke, Sean P.; Lesaffre, Emmanuel; Vleugels, Arthur; Aiken, Linda H.

    2008-01-01

    Background Studies have linked nurse staffing levels (number and skill mix) to several nurse-sensitive patient outcomes. However, evidence from European countries has been limited. Objectives This study examines the association between nurse staffing levels (i.e. acuity-adjusted Nursing Hours per Patient Day, the proportion of registered nurses with a Bachelor’s degree) and 10 different patient outcomes potentially sensitive to nursing care. Design-setting-participants Cross-sectional analyses of linked data from the Belgian Nursing Minimum Dataset (general acute care and intensive care nursing units: n = 1403) and Belgian Hospital Discharge Dataset (general, orthopedic and vascular surgery patients: n = 260,923) of the year 2003 from all acute hospitals (n = 115). Methods Logistic regression analyses, estimated by using a Generalized Estimation Equation Model, were used to study the association between nurse staffing and patient outcomes. Results The mean acuity-adjusted Nursing Hours per Patient Day in Belgian hospitals was 2.62 (S.D. = 0.29). The variability in patient outcome rates between hospitals is considerable. The inter-quartile ranges for the 10 patient outcomes go from 0.35 for Deep Venous Thrombosis to 3.77 for failure-to-rescue. No significant association was found between the acuity-adjusted Nursing Hours per Patient Day, proportion of registered nurses with a Bachelor’s degree and the selected patient outcomes. Conclusion The absence of associations between hospital-level nurse staffing measures and patient outcomes should not be inferred as implying that nurse staffing does not have an impact on patient outcomes in Belgian hospitals. To better understand the dynamics of the nurse staffing and patient outcomes relationship in acute hospitals, further analyses (i.e. nursing unit level analyses) of these and other outcomes are recommended, in addition to inclusion of other study variables, including data about nursing practice environments in

  13. Cardiac Arrest in Acute Ischemic Stroke: Incidence, Predisposing Factors, and Clinical Outcomes.

    PubMed

    Joundi, Raed A; Rabinstein, Alejandro A; Nikneshan, Davar; Tu, Jack V; Fang, Jiming; Holloway, Robert; Saposnik, Gustavo

    2016-07-01

    Cardiac arrest is a devastating complication of acute ischemic stroke, but little is known about its incidence and characteristics. We studied a large ischemic stroke inpatient population and compared patients with and without cardiac arrest. We studied consecutive patients from the Ontario Stroke Registry who had an ischemic stroke between July 2003 and June 2008 at 11 tertiary care stroke centers in Ontario. Multivariable analyses were used to determine independent predictors of cardiac arrest and associated outcomes. Adjusted survival curves were computed, and hazard ratios for mortality at 30 days and 1 year were determined for cardiac arrest and other major outcomes. Among the 9019 patients with acute ischemic stroke, 352 had cardiac arrest, for an overall incidence of 3.9%. In a sensitivity analysis with palliative patients removed, the incidence of cardiac arrest was 2.5%. Independent predictors of cardiac arrest were as follows: older age, greater stroke severity, preadmission dependence, and a history of diabetes, myocardial infarction, congestive heart failure, and atrial fibrillation. Systemic complications associated with cardiac arrest were as follows: myocardial infarction, pulmonary embolism, sepsis, gastrointestinal hemorrhage, and pneumonia. Patients with cardiac arrest had higher disability at discharge, and a markedly increased 30-day mortality of 82.1% compared with 9.3% without cardiac arrest. Cardiac arrest had a high incidence and was associated with poor outcomes after ischemic stroke, including multiple medical complications and very high mortality. Predictors of cardiac arrest identified in this study could help risk stratify ischemic stroke patients for cardiac investigations and prolonged cardiac monitoring. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Treatment of sepsis and ARDS with extracorporeal membrane oxygenation and interventional lung assist membrane ventilator in a patient with acute lymphoblastic leukemia.

    PubMed

    Gorjup, Vojka; Fister, Misa; Noc, Marko; Rajic, Vladan; Ribaric, Suada Filekovic

    2012-07-01

    We report an 18-year-old ice skater with acute lymphoblast leukemia. She developed Staphylococcus epidermidis bacteremia, severe sepsis, septic shock, and ARDS following chemotherapy-induced severe bone marrow failure. She was successfully treated with extraordinary life support measures, which included extracorporeal membrane oxygenation, double lumen lung ventilation for management of hemoptysis, and lung assist membrane ventilation. After 57 days of ICU treatment and a year of rehabilitation, the patient has fully regained her functional status, is now finishing high school, and is ice skating again.

  15. Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia.

    PubMed

    Boztug, Heidrun; Mühlegger, Nora; Pötschger, Ulrike; Attarbaschi, Andishe; Peters, Christina; Mann, Georg; Dworzak, Michael

    2017-01-01

    Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children's Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of 98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p < 0.0001). In addition, there were significantly fewer episodes of febrile neutropenia in the teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity of infection seemed to be worse when no antibiotic prophylaxis had been administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs. 4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus isolates in surveillance cultures was noticed. Antibiotic prophylaxis with teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML patients. The possibility to administer teicoplanin on alternate days on an outpatient basis or at home could contribute to patient's quality of life and decrease health care costs.

  16. Update on pediatric sepsis: a review.

    PubMed

    Kawasaki, Tatsuya

    2017-01-01

    Sepsis is one of the leading causes of mortality among children worldwide. Unfortunately, however, reliable evidence was insufficient in pediatric sepsis and many aspects in clinical practice actually depend on expert consensus and some evidence in adult sepsis. More recent findings have given us deep insights into pediatric sepsis since the publication of the Surviving Sepsis Campaign guidelines 2012. New knowledge was added regarding the hemodynamic management and the timely use of antimicrobials. Quality improvement initiatives of pediatric "sepsis bundles" were reported to be successful in clinical outcomes by several centers. Moreover, a recently published global epidemiologic study (the SPROUT study) did not only reveal the demographics, therapeutic interventions, and prognostic outcomes but also elucidated the inappropriateness of the current definition of pediatric sepsis. With these updated knowledge, the management of pediatric sepsis would be expected to make further progress. In addition, it is meaningful that the fundamental data on which future research should be based were established through the SPROUT study.

  17. Using the number needed to treat to assess appropriate antimicrobial therapy as a determinant of outcome in severe sepsis and septic shock.

    PubMed

    Vazquez-Guillamet, Cristina; Scolari, Michael; Zilberberg, Marya D; Shorr, Andrew F; Micek, Scott T; Kollef, Marin

    2014-11-01

    To assess appropriate antimicrobial therapy as an outcome determinant in severe sepsis and septic shock using the number needed to treat. Single-center cohort study (January 2008 to December 2012). One thousand two hundred fifty-bed academic hospital. Two thousand five hundred ninety-four patients with positive blood culture. We retrospectively identified patients with severe sepsis or septic shock. Inappropriate antimicrobial treatment was defined as an antimicrobial regimen that lacked in vitro activity against the isolated pathogen. Information regarding demographics, severity of illness, comorbidities, microbiology, and antimicrobial treatment was recorded. Logistic regression was used to identify risk factors for hospital mortality and inappropriate treatment. Seven hundred eighty-seven patients (30.3%) were nonsurvivors. Inappropriate antimicrobial treatment had the greatest adjusted odds ratio for hospital mortality (adjusted odds ratio, 3.4; 95% CI, 2.8-4.1; p < 0.001). Multivariate logistic regression analysis identified resistance to cefepime, resistance to meropenem, presence of multidrug resistance, nonabdominal surgery, and prior antibiotic use as being independently associated with the administration of inappropriate antimicrobial treatment. For the entire cohort, the number needed to treat with appropriate antimicrobial therapy to prevent one patient death was 4.0 (95% CI, 3.7-4.3). The prevalence-adjusted pathogen-specific number needed to treat (PNNT) with appropriate antimicrobial therapy to prevent one patient death was lowest for multidrug-resistant bacteria (PNNT = 20) followed by Candida species (PNNT = 34), methicillin-resistant Staphylococcus aureus (PNNT = 38), Pseudomonas aeruginosa (PNNT = 38), Escherichia coli (PNNT = 40), and methicillin-susceptible S. aureus (PNNT = 47). Our results support the importance of appropriate antimicrobial treatment as a determinant of outcome in patients with severe sepsis and septic shock. Our analyses

  18. Sepsis and maternal mortality.

    PubMed

    Acosta, Colleen D; Knight, Marian

    2013-04-01

    Despite global progress towards reducing maternal mortality, sepsis remains a leading cause of preventable maternal death. This review focuses on current measurement challenges, trends, causes and efforts to curb maternal death from sepsis in high and low-income countries. Under-reporting using routine registration data, compounded by misclassification and unreported deaths, results in significant underestimation of the burden of maternal death from sepsis. In the UK and the Netherlands the recent increase in maternal death from sepsis is mainly attributed to an increase in invasive group A streptococcal infections. Susceptibility to infection may be complicated by modulation of maternal immune response and increasing rates of risk factors such as caesarean section and obesity. Failure to recognize severity of infection is a major universal risk factor. Standardized Surviving Sepsis Campaign (SSC) recommendations for management of severe maternal sepsis are continuing to be implemented worldwide; however, outcomes differ according to models of intensive care resourcing and use. The need for robust data with subsequent analyses is apparent. This will significantly increase our understanding of risk factors and their causal pathways, which are critical to informing effective treatment strategies in consideration of resource availability.

  19. Established and novel biomarkers of sepsis.

    PubMed

    Faix, James D

    2011-04-01

    The increased incidence of sepsis, a systemic response to infection that occurs in some patients, has stimulated interest in identifying infected patients who are at risk and intervening early. When this condition progresses to severe sepsis (characterized by organ dysfunction), mortality is high. Hospitals that have implemented recommendations of the Surviving Sepsis Campaign have seen a reduction in mortality rate for hospital-acquired severe sepsis. They may reduce this further by focusing on new approaches to diagnosing sepsis, especially at an early stage. Sepsis is a complicated syndrome with many physiological derangements and many emerging laboratory markers of sepsis have been proposed as adjuncts to clinical evaluation. The list includes cytokines, acute phase proteins, neutrophil activation markers, markers of abnormal coagulation and, recently, markers of suppression of both the innate and adaptive immune response. The perfect biomarker would accurately identify patients at risk of developing severe sepsis and then guide targeted therapy.

  20. Effects of fluid resuscitation with 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis*.

    PubMed

    Zhou, Feihu; Peng, Zhi-Yong; Bishop, Jeffery V; Cove, Matthew E; Singbartl, Kai; Kellum, John A

    2014-04-01

    To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Controlled laboratory experiment. University laboratory. Sixty adult, male Sprague-Dawley rats. We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals. Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury. Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short-term survival when compared with 0.9% saline in this experimental animal model of sepsis.

  1. Effects of Fluid Resuscitation With 0.9% Saline Versus a Balanced Electrolyte Solution on Acute Kidney Injury in a Rat Model of Sepsis*

    PubMed Central

    Zhou, Feihu; Peng, Zhi-Yong; Bishop, Jeffery V.; Cove, Matthew E.; Singbartl, Kai; Kellum, John A.

    2014-01-01

    Objective To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Design Controlled laboratory experiment. Setting University laboratory. Subjects Sixty adult, male Sprague-Dawley rats. Interventions We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals. Measurements and Main Results Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury. Conclusion Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short

  2. Neurologic complications of sepsis.

    PubMed

    Schmutzhard, E; Pfausler, B

    2017-01-01

    Over the past decades, the incidence of sepsis and resultant neurologic sequelae has increased, both in industrialized and low- or middle-income countries, by approximately 5% per year. Up to 300 patients per 100 000 population per year are reported to suffer from sepsis, severe sepsis, and septic shock. Mortality is up to 30%, depending on the precision of diagnostic criteria. The increasing incidence of sepsis is partially explained by demographic changes in society, with aging, increasing numbers of immunocompromised patients, dissemination of multiresistant pathogens, and greater availability of supportive medical care in both industrialized and middle-income countries. This results in more septic patients being admitted to intensive care units. Septic encephalopathy is a manifestation especially of severe sepsis and septic shock where the neurologist plays a crucial role in diagnosis and management. It is well known that timely treatment of sepsis improves outcome and that septic encephalopathy may precede other signs and symptoms. Particularly in the elderly and immunocompromised patient, the brain may be the first organ to show signs of failure. The neurologist diagnosing early septic encephalopathy may therefore contribute to the optimal management of septic patients. The brain is not only an organ failing in sepsis (a "sepsis victim" - as with other organs), but it also overwhelmingly influences all inflammatory processes on a variety of pathophysiologic levels, thus contributing to the initiation and propagation of septic processes. Therefore, the best possible pathophysiologic understanding of septic encephalopathy is essential for its management, and the earliest possible therapy is crucial to prevent the evolution of septic encephalopathy, brain failure, and poor prognosis.

  3. Predictors and Outcomes of Dysphagia Screening After Acute Ischemic Stroke.

    PubMed

    Joundi, Raed A; Martino, Rosemary; Saposnik, Gustavo; Giannakeas, Vasily; Fang, Jiming; Kapral, Moira K

    2017-04-01

    Guidelines advocate screening all acute stroke patients for dysphagia. However, limited data are available regarding how many and which patients are screened and how failing a swallowing screen affects patient outcomes. We sought to evaluate predictors of receiving dysphagia screening after acute ischemic stroke and outcomes after failing a screening test. We used the Ontario Stroke Registry from April 1, 2010, to March 31, 2013, to identify patients hospitalized with acute ischemic stroke and determine predictors of documented dysphagia screening and outcomes after failing the screening test, including pneumonia, disability, and death. Among 7171 patients, 6677 patients were eligible to receive dysphagia screening within 72 hours, yet 1280 (19.2%) patients did not undergo documented screening. Patients with mild strokes were significantly less likely than those with more severe strokes to have documented screening (adjusted odds ratio, 0.51; 95% confidence interval [CI], 0.41-0.64). Failing dysphagia screening was associated with poor outcomes, including pneumonia (adjusted odds ratio, 4.71; 95% CI, 3.43-6.47), severe disability (adjusted odds ratio, 5.19; 95% CI, 4.48-6.02), discharge to long-term care (adjusted odds ratio, 2.79; 95% CI, 2.11-3.79), and 1-year mortality (adjusted hazard ratio, 2.42; 95% CI, 2.09-2.80). Associations were maintained in patients with mild strokes. One in 5 patients with acute ischemic stroke did not have documented dysphagia screening, and patients with mild strokes were substantially less likely to have documented screening. Failing dysphagia screening was associated with poor outcomes, including in patients with mild strokes, highlighting the importance of dysphagia screening for all patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

  4. Neonatal sepsis.

    PubMed

    Stefanovic, Iva Mihatov

    2011-01-01

    Neonatal sepsis is the most common cause of neonatal deaths with high mortality despite treatment. Neonatal sepsis can be classified into two subtypes depending upon onset of symptoms. There are many factors that make neonates more susceptable to infection. Signs of sepsis in neonates are often non-specific and high degree of suspicion is needed for early diagnosis. Some laboratory parameters can be helpful for screening of neonates with neonatal sepsis, but none of it is specific and sensitive enough to be used singly. Diagnostic approach mostly focuses on history and review of non specific signs and symptoms. Antibiotic treatment is the mainstay of treatment and supportive care is equally important. The aim of this review is to give an overview of neonatal sepsis, including incidence, etiology, clinical picture, diagnostics and therapy.

  5. Presentation, management and outcome of acute sigmoid diverticulitis requiring hospitalization.

    PubMed

    Alvarez, Jose A; Baldonedo, Ricardo F; Bear, Isabel G; Otero, Jorge; Pire, Gerardo; Alvarez, Paloma; Jorge, Jose I

    2007-01-01

    This study was conducted to assess the presentation, management, and outcomes of patients with acute sigmoid diverticulitis requiring hospitalization. From 1986 to 2005, the medical records of 265 patients treated for acute sigmoid diverticulitis requiring hospitalization were retrospectively analyzed. Data were collected with regard to patient's demographics, clinical characteristics, presentations of acute diverticulitis, treatment, morbidity, and mortality. Only 47 patients (17.7%) had a previous diverticulitis episode. Of the 265 patients, 166 (62.6%) were managed without operation, and 99 (37.4%) underwent surgery. Overall and major morbidity in the whole series were 30.2 (80/265) and 15.5% (40/265), respectively; whereas among the patients with surgical management, were 72.7 (72/99), and 35.3% (35/99), respectively. Overall and postoperative mortality rates were 2.6 (7/265) and 6.1% (6/99), respectively. Older age, steroid use, perforation, and co-morbidities were significantly associated with unfavorable outcomes. It was concluded that surgery for acute sigmoid diverticulitis requiring hospitalization carries important morbidity and mortality. To achieve improvements in outcome, a selective therapeutic approach should be considered, choosing the best surgical procedure for each complication of diverticular disease. Copyright (c) 2007 S. Karger AG, Basel

  6. Clinical profile and outcome of acute respiratory failure.

    PubMed

    Karande, Sunil; Murkey, Rajneesh; Ahuja, Sanjeev; Kulkarni, Madhuri

    2003-11-01

    To examine the etiological factors, clinical features, treatment modalities and outcome of acute respiratory failure in children. This hospital-based prospective observational study was conducted over 15 months. Fifty children with acute respiratory failure, diagnosed by serial arterial blood gas analysis, were consecutively enrolled. Ventilation therapy was initiated when the FiO2 requirement went above 0.6. Pulmonary diseases accounted for majority (68%) of cases, followed by nervous system (12%); and cardiovascular and skeletal muscle system diseases (10%, each). Bronchopneumonia was the commonest cause of acute respiratory failure (11 cases). The majority of cases were in the age group 1 month to < 1 year (26 cases). The commonest signs were altered depth and pattern of respiration (100%), chest wall retractions (88%), flaring of alae nasae (88%), tachypnea (84%), tachycardia (82%), and irritability (64%). Cyanosis was noticed in only 26 (52%) cases. Thirty-six (72%) children required ventilation therapy. The overall mortality was 58%. The mortality was high (55.9% to 66.7%), irrespective of the primary system involved. Significantly higher mortality was associated with co-existent malnutrition (p<0.001), Type I failure (p=0.039) and ventilation therapy (p<0.0001). Acute respiratory failure has varied etiology and clinical manifestations, and a high mortality. Its outcome is independent of age of the child and the primary system involved. Malnutrition and Type I failure are factors associated with a poor outcome.

  7. Improving alcohol withdrawal outcomes in acute care.

    PubMed

    Melson, Jo; Kane, Michelle; Mooney, Ruth; Mcwilliams, James; Horton, Terry

    2014-01-01

    Excessive alcohol consumption is the nation's third leading cause of preventable deaths. If untreated, 6% of alcohol-dependent patients experience alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT), when they stop drinking. Without routine screening, patients often experience DT without warning. Reduce the incidence of alcohol withdrawal advancing to DT, restraint use, and transfers to the intensive care unit (ICU) in patients with DT. In October 2009, the alcohol withdrawal team instituted a care management guideline used by all disciplines, which included tools for screening, assessment, and symptom management. Data were obtained from existing datasets for three quarters before and four quarters after implementation. Follow-up data were analyzed and showed a great deal of variability in transfers to the ICU and restraint use. Percentage of patients who developed DT showed a downward trend. Incidence of alcohol withdrawal advancing to DT and, in patients with DT, restraint use and transfers to the ICU. Initial data revealed a decrease in percentage of patients with alcohol withdrawal who experienced DT (16.4%-12.9%). In patients with DT, restraint use decreased (60.4%-44.4%) and transfers to the ICU decreased (21.6%-15%). Follow-up data indicated a continued downward trend in patients with DT. Changes were not statistically significant. Restraint use and ICU transfers maintained postimplementation levels initially but returned to preimplementation levels by third quarter 2012. Early identification of patients for potential alcohol withdrawal followed by a standardized treatment protocol using symptom-triggered dosing improved alcohol withdrawal management and outcomes.

  8. Systemic endotoxin and gastric mucosal pH are the best parameters to predict lethal outcome in a porcine model of abdominal sepsis according to multivariate analysis.

    PubMed

    Strate, Tim; Schneider, Claus; Yekebas, Emre; Knoefel, Wolfram T; Bloechle, Christian; Izbicki, Jakob R

    2003-01-01

    This study was devised to identify sepsis-relevant parameters that early and reliably predict a lethal outcome in intra-abdominal sepsis. In 18 Duroc pigs, peritonitis was induced through standardized gastrotomy. Twelve hours later the defect was oversewn and the abdominal cavity lavaged thoroughly. Sepsis relevant parameters were measured before initiating therapy, and 30 min later animals were extubated and observed for a period of 6 days under adequate analgesia with free access to water and food. All parameters were correlated with survival postoperatively. In the treatment group, 7 out of 18 pigs (39%) died within the observation period. Endotoxin level at 30 min after initiation of therapy [17.9 EU/mL (+/- 12.1) vs. 110.9 EU/mL (+/- 21); p <.001] and Delta pHi [0.015 (+/- 0.011) vs. -0.039 (+/- 0.013); p =.016] were identified as the two parameters with highest predictive power regarding mortality in a multivariate analysis. In conclusion measurement of endotoxin and gastric tonometry should gain wider clinical application in septic patients.

  9. Factors affecting the visual outcome in acute central serous chorioretinopathy

    PubMed Central

    Islam, Qamar Ul; Farooq, Muhammad Asad; Mehboob, Mohammad Asim

    2017-01-01

    Objective: To determine the visual outcome in patients with acute Central serous chorioretinopathy (CSCR) and to analyze the association of clinical, angiographic and tomographic factors with final visual outcome in Pakistani population. Methods: This study was conducted at AFIO Rawalpindi and PNS Shifa Naval hospital Karachi from November 2011 to August 2016. Fifty five eyes of 53 patients with acute CSCR were included. All patients underwent a detailed ophthalmic examination including SD OCT imaging at baseline, One month and three month and FFA was performed at baseline. Primary outcome measures were measurement of initial and final BCVA and CFT. SPSS 13.0 was used for the analysis of data. Results: Mean age of study population was 36.66 ± 6.24 years. On OCT mean CFT at baseline was 467.49 ± 144.80 µm in affected eye, whereas mean CFT measurements at final follow up was 244.67 ± 32.99 µm (p <0.01). Presenting mean log MAR BCVA was 0.47 ± 0.25 and final mean log MAR BCVA was 0.18 ± 0.14 (p <0.01). Baseline BCVA showed statistically significant association with final BCVA (p=0.03). Conclusion: Presenting VA of 6/12 or better is associated with favorable visual outcome in patients with acute CSCR. PMID:28367162

  10. The role of whole blood impedance aggregometry and its utilisation in the diagnosis and prognosis of patients with systemic inflammatory response syndrome and sepsis in acute critical illness.

    PubMed

    Davies, Gareth R; Mills, Gavin M; Lawrence, Matthew; Battle, Ceri; Morris, Keith; Hawkins, Karl; Williams, Phylip Rhodri; Davidson, Simon; Thomas, Dafydd; Evans, Phillip Adrian

    2014-01-01

    To assess the prognostic and diagnostic value of whole blood impedance aggregometry in patients with sepsis and SIRS and to compare with whole blood parameters (platelet count, haemoglobin, haematocrit and white cell count). We performed an observational, prospective study in the acute setting. Platelet function was determined using whole blood impedance aggregometry (multiplate) on admission to the Emergency Department or Intensive Care Unit and at 6 and 24 hours post admission. Platelet count, haemoglobin, haematocrit and white cell count were also determined. 106 adult patients that met SIRS and sepsis criteria were included. Platelet aggregation was significantly reduced in patients with severe sepsis/septic shock when compared to SIRS/uncomplicated sepsis (ADP: 90.7±37.6 vs 61.4±40.6; p<0.001, Arachadonic Acid 99.9±48.3 vs 66.3±50.2; p = 0.001, Collagen 102.6±33.0 vs 79.1±38.8; p = 0.001; SD ± mean)). Furthermore platelet aggregation was significantly reduced in the 28 day mortality group when compared with the survival group (Arachadonic Acid 58.8±47.7 vs 91.1±50.9; p<0.05, Collagen 36.6±36.6 vs 98.0±35.1; p = 0.001; SD ± mean)). However haemoglobin, haematocrit and platelet count were more effective at distinguishing between subgroups and were equally effective indicators of prognosis. Significant positive correlations were observed between whole blood impedance aggregometry and platelet count (ADP 0.588 p<0.0001, Arachadonic Acid 0.611 p<0.0001, Collagen 0.599 p<0.0001 (Pearson correlation)). Reduced platelet aggregometry responses were not only significantly associated with morbidity and mortality in sepsis and SIRS patients, but also correlated with the different pathological groups. Whole blood aggregometry significantly correlated with platelet count, however, when we adjust for the different groups we investigated, the effect of platelet count appears to be non-significant.

  11. Epidemiology and outcome of sepsis in adult patients with Streptococcus pneumoniae infection in a Norwegian county 1993-2011: an observational study.

    PubMed

    Askim, Åsa; Mehl, Arne; Paulsen, Julie; DeWan, Andrew T; Vestrheim, Didrik F; Åsvold, Bjørn Olav; Damås, Jan Kristian; Solligård, Erik

    2016-05-23

    Invasive pneumococcal disease (IPD) is responsible for significant mortality and morbidity worldwide. There are however few longitudinal studies on the changes in case fatality rate of IPD in recent years. We carried out a prospective observational study of patients with IPD in Nord Trøndelag county in Norway from 1993 to 2011 to study the clinical variables and disease outcome. The main outcome was all-cause mortality after 30 and 90 days. Patients with positive blood cultures were registered prospectively by the microbiology laboratory and clinical variables were registered retrospectively from patients' hospital records. The severity of sepsis was assigned according to the 2001 International Sepsis Definition Conference criteria. The association between mortality and predictive factors was studied using a logistic regression model. The total number of patients was 414 with mean age of 67 years and 53 % were male. Comorbidity was assessed by the Charlson Comorbidity Index (CCI). A CCI-score of 0 was registered in 144 patients (34.8 %), whereas 190 had a score of 1-2 (45.9 %) and 80 (19.3 %) had a score ≥3. 68.8 % of the patients received appropriate antibiotics within the first 6 h. The 30-day mortality risk increased by age and was 3-fold higher for patients aged ≥80 years (24.9, 95 % CI 16.4-33.4 %) compared to patients aged <70 (8.0, 95 % CI 3.5-12.4 %). 110 patients, (26.6 %) had severe sepsis and 37 (8.9 %) had septic shock. The 30 day all-cause mortality risk for those with sepsis without organ failure was 5.4 % (95 % CI 2.7-8.0 %), 20.2 % (95 % CI 13.5-27.4 %) for those with severe sepsis and 35.0 % (95 % CI 21.6-49.0 %) for those with septic shock. The mortality risk did not differ between the first and the second halves of the study period with a 30-day mortality risk of 13.5 % (95 % CI 7.9-19.2 %) for 1993-2002 versus 11.8 % (95 % CI 8.2-15.3 %) for 2003-2011. IPD carries a high mortality despite early and appropriate

  12. Current epidemiology of sepsis in mainland China

    PubMed Central

    Liao, Xuelian; Du, Bin; Lu, Meizhu; Wu, Minming

    2016-01-01

    The disease burden of sepsis is a global issue. Most of the large-scale epidemiological investigations on sepsis have been carried out in developed countries. The population of 1.3 billion in mainland China accounts for approximately 1/5th of the whole world population. Thus, the knowledge of the incidence and mortality of sepsis in mainland China is vital before employing measures for its improvement. However, most of the epidemiological data of sepsis in mainland China was obtained from ICU settings, and thus lacks the population-based incidence and mortality of sepsis. In the present review, we summarized the limited literature encompassing the incidence, mortality, long-term outcome, and pathogens of sepsis in mainland China. Therefore, it might provide some valuable information regarding the sepsis disease burden and current issues in the management of sepsis in mainland China. PMID:27713882

  13. Acute salicylate poisoning: risk factors for severe outcome.

    PubMed

    Shively, Rachel M; Hoffman, Robert S; Manini, Alex F

    2017-03-01

    Salicylate poisoning remains a significant public health threat with more than 20,000 exposures reported annually in the United States. We aimed to establish early predictors of severe in-hospital outcomes in Emergency Department patients presenting with acute salicylate poisoning. This was a secondary data analysis of adult salicylate overdoses from a prospective cohort study of acute drug overdoses at two urban university teaching hospitals from 2009 to 2013. Patients were included based on confirmed salicylate ingestion and enrolled consecutively. Demographics, clinical parameters, treatment and disposition were collected from the medical record. Severe outcome was defined as a composite occurrence of acidemia (pH <7.3 or bicarbonate <16 mEq/L), hemodialysis, and/or death. Out of 1997 overdoses screened, 48 patients met inclusion/exclusion criteria. Patient characteristics were 43.8% male, median age 32 (range 18-87), mean initial salicylate concentration 28.1 mg/dL (SD 26.6), and 20.8% classified as severe outcome. Univariate analysis indicated that age, respiratory rate, lactate, coma, and the presence of co-ingestions were significantly associated with severe outcome, while initial salicylate concentration alone had no association. However, when adjusted for salicylate concentration, only age (OR 1.13; 95% CI 1.02-1.26) and respiratory rate (OR 1.29; 95% CI 1.02-1.63) were independent predictors. Additionally, lactate showed excellent test characteristics to predict severe outcome, with an optimal cutpoint of 2.25 mmol/L (78% sensitivity, 67% specificity). In adult Emergency Department patients with acute salicylate poisoning, independent predictors of severe outcome were older age and increased respiratory rate, as well as initial serum lactate, while initial salicylate concentration alone was not predictive.

  14. Long-term outcomes of acute kidney injury.

    PubMed

    Coca, Steven G

    2010-05-01

    The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI). Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available. AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

  15. Ampicillin Resistance and Outcome Differences in Acute Antepartum Pyelonephritis

    PubMed Central

    Greer, Laura G.; Roberts, Scott W.; Sheffield, Jeanne S.; Rogers, Vanessa L.; Hill, James B.; Mcintire, Donald D.; Wendel, George D.

    2008-01-01

    Objective. To measure the incidence of ampicillin-resistant uropathogens in acute antepartum pyelonephritis and to determine if patients with resistant organisms had different clinical outcomes. Study design. This was a secondary analysis of a prospective cohort study of pregnant women admitted with pyelonephritis, diagnosed by standard clinical and laboratory criteria. All patients received ampicillin and gentamicin. Results. We identified 440 cases of acute pyelonephritis. Seventy-two percent (316 cases) had urine cultures with identification of organism and antibiotic sensitivities. Fifty-one percent of uropathogens were ampicillin resistant. The patients with ampicillin-resistant organisms were more likely to be older and multiparous. There were no significant differences in hospital course (length of stay, days of antibiotics, ECU admission, or readmission). Patients with ampicillin-resistant organisms did not have higher complication rates (anemia, renal dysfunction, respiratory insufficiency, or preterm birth). Conclusion. A majority of uropathogens were ampicillin resistant, but no differences in outcomes were observed in these patients. PMID:18923674

  16. Stress hyperglycemia and acute ischemic stroke in-hospital outcome.

    PubMed

    Tziomalos, Konstantinos; Dimitriou, Panagiotis; Bouziana, Stella D; Spanou, Marianna; Kostaki, Stavroula; Angelopoulou, Stella-Maria; Papadopoulou, Maria; Giampatzis, Vasilios; Savopoulos, Christos; Hatzitolios, Apostolos I

    2017-02-01

    Stress hyperglycemia is frequent in patients with acute ischemic stroke. However, it is unclear whether stress hyperglycemia only reflects stroke severity or if it is directly associated with adverse outcome. We aimed to evaluate the prognostic significance of stress hyperglycemia in acute ischemic stroke. We prospectively studied 790 consecutive patients who were admitted with acute ischemic stroke (41.0% males, age 79.4±6.8years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Stress hyperglycemia was defined as fasting serum glucose levels at the second day after admission ≥126mg/dl in patients without type 2 diabetes mellitus (T2DM). The outcome was assessed with adverse outcome rates at discharge (modified Rankin scale between 2 and 6) and with in-hospital mortality. In the total study population, 8.6% had stress hyperglycemia. Patients with stress hyperglycemia had more severe stroke. Independent predictors of adverse outcome at discharge were age, prior ischemic stroke and NIHSS at admission whereas treatment with statins prior to stroke was associated with favorable outcome. When the NIHSS was removed from the multivariate model, independent predictors of adverse outcome were age, heart rate at admission, prior ischemic stroke, log-triglyceride (TG) levels and stress hyperglycemia, whereas treatment with statins prior to stroke was associated with favorable outcome. Independent predictors of in-hospital mortality were atrial fibrillation (AF), diastolic blood pressure (DBP), serum log-TG levels and NIHSS at admission. When the NIHSS was removed from the multivariate model, independent predictors of in-hospital mortality were age, AF, DBP, log-TG levels and stress hyperglycemia. Stress hyperglycemia does not appear to be directly associated with the outcome of acute ischemic stroke. However, given that patients with stress hyperglycemia had higher prevalence of cardiovascular risk factors than

  17. Role of plasma matrix-metalloproteases (MMPs) and their polymorphisms (SNPs) in sepsis development and outcome in ICU patients

    PubMed Central

    Martin, Guadalupe; Asensi, Víctor; Montes, A. Hugo; Collazos, Julio; Alvarez, Victoria; Carton, José A.; Taboada, Francisco; Valle-Garay, Eulalia

    2014-01-01

    Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs), modulated by different single nucleotide polymorphisms (SNPs), are critical in sepsis development. Ninety ICU severely septic and 91 ICU uninfected patients were prospectively studied. MMP-1 (−1607 1G/2G), MMP-3 (−1612 5A/6A), MMP-8 (−799 C/T), MMP-9 (−1562 C/T), and MMP-13 (−77A/G) SNPs were genotyped. Plasma MMPs (-1, -2, -3, -8, -9, -10, -13) and TIMPs (-1,-2,-4) were measured. AA homozygotes and A allele carriers of MMP-13 (−77 A/G) and 1G2G carriers of the MMP-1 (−1607 1G/2G) SNPs frequencies were different between septic and uninfected patients (p < 0.05), as well as plasma MMP-3, -8, -9 -10 and TIMP-2 levels (p < 0.04). No differences in MMPs levels among MMP-13 or MMP-1 SNPs genotypes carriers were observed. The area under the ROC curve for MMP-8 in the diagnosis of sepsis was 0.87 (95% CI 0.82–0.92), and that of CRP was 0.98 (0.94–0.998), whereas the area of MMP-9 in the detection of non-septic state was 0.73 (0.65–0.80), p < 0.0001 for all curves. Sepsis associated with increased MMP-8 and decreased MMP-9 levels in multivariate analysis (p < 0.0002). We report for the first time an association between MMP-13 and MMP-1 SNPs and sepsis. An independent association of MMP-8 and MMP-9 levels with sepsis was also observed. PMID:24833564

  18. The effect of resolution time of acute kidney injury on clinical outcomes

    PubMed Central

    Chavez-Iñiguez, J. S.; Garcia-Garcia, G.; Briseño-Ramirez, J.; Medina-Gonzalez, R.; Jimenez-Cornejo, M.

    2017-01-01

    Acute kidney injury (AKI) is a frequent and complex disease. It is not clearly defined whether its duration is related to adverse outcomes. We determined the effect of AKI resolution time on patient's clinical outcomes. A prospective cohort of hospitalized patients with AKI by AKI network (AKIN) creatinine criteria was included. Variables for prognosis and follow-up were analyzed. One hundred and thirteen patients were included in the study. Seventy-seven (68.1%) were males, mean age 55 years (range, 16–76 years), and 48 (42.5%) were diabetic. The most common cause of AKI was sepsis (31%). AKI resolution time ≤2 days and >2 days was seen in 47 (41.6%) and 66 (58.4%) of the cases, respectively. AKI resolution time >2 days was common in older patients (66.24 ± 17.6 year vs. 47.16 ± 12.32 year, P = 0.004), with the use of mechanical ventilation (27% vs. 4%, P = 0.02) and vasopressors (41% vs. 11%, P ≤ 0.01); it was associated with increased mortality (47% vs. 4%, P ≤ 0.01), and a discharge estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (52% vs. 2%, P = 0.01), than in patients with resolution time ≤2 days. Survival rate was significantly worse in patients with a resolution time >2 days. By multivariate logistic step-wise regression analysis, AKI >2days, vasopressor use, and AKIN stage 2–3 were independently associated with higher mortality. AKI >2 days and vasopressor utilization were independently associated to an eGFR <60 ml/min/1.73 m2 at the time of discharge. We conclude that AKI resolution time >2 days is linked to adverse clinical outcomes. PMID:28356659

  19. Outcomes of acute kidney injury patients with and without cancer.

    PubMed

    Juwon, Lee; Jang, Gookhwan; Kim, Sunmin; Kim, Dajung; Lee, Jinwook; Park, Hyunjoon; Lee, Junyeob; Kim, Sangbin; Kim, Yunkyung; Kim, Soo Young; Yang, Joung Wook; Gwoo, Sangeon; Kim, Ye Na; Shin, Ho Sik; Jung, Yeonsoon; Rim, Hark

    2015-11-01

    Incidence of AKI in hospitalized patients with cancer is increasing, but there have been few studies on AKI in patients with cancer. We conducted a retrospective cohort study in a South Korean tertiary care hospital. A total of 2211 consecutive patients (without cancer 61.5%; with cancer 38.5%) were included over a 140-month period. Predictors of all-cause death were examined using the Kaplan-Meier method and the Cox proportional hazards model. The main contributing factors of AKI were sepsis (31.1%) and ischemia (52.7%). AKI was multifactorial in 78% of patients with cancer and in 71% of patients without cancer. Hospital mortality rates were higher in patients with cancer (42.8%) than in patients without cancer (22.5%) (p = 0.014). In multivariate analyses, diabetes mellitus (DM) and cancer diagnosis were associated with hospital mortality. Cancer diagnosis was independently associated with mortality [odds ratio = 3.010 (95% confidence interval, 2.340-3.873), p = 0.001]. Kaplan-Meier analysis revealed that subjects with DM and cancer (n = 146) had lower survival rates than subjects with DM and without cancer (n = 687) (log rank test, p = 0.001). The presence of DM and cancer was independently associated with mortality in AKI patients both with and without cancer. Studies are warranted to determine whether proactive measures may limit AKI and improve outcomes.

  20. Biomarkers for Sepsis

    PubMed Central

    Henriquez-Camacho, Cesar; Losa, Juan

    2014-01-01

    Bloodstream infections are a major concern because of high levels of antibiotic consumption and of the increasing prevalence of antimicrobial resistance. Bacteraemia is identified in a small percentage of patients with signs and symptoms of sepsis. Biomarkers are widely used in clinical practice and they are useful for monitoring the infectious process. Procalcitonin (PCT) and C-reactive protein (CRP) have been most widely used, but even these have limited abilities to distinguish sepsis from other inflammatory conditions or to predict outcome. PCT has been used to guide empirical antibacterial therapy in patients with respiratory infections and help to determine if antibacterial therapy can be stopped. New biomarkers such as those in this review will discuss the major types of biomarkers of bloodstream infections/sepsis, including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble urokinase-type plasminogen receptor (suPAR), proadrenomedullin (ProADM), and presepsin. PMID:24800240

  1. Biomarkers for sepsis.

    PubMed

    Henriquez-Camacho, Cesar; Losa, Juan

    2014-01-01

    Bloodstream infections are a major concern because of high levels of antibiotic consumption and of the increasing prevalence of antimicrobial resistance. Bacteraemia is identified in a small percentage of patients with signs and symptoms of sepsis. Biomarkers are widely used in clinical practice and they are useful for monitoring the infectious process. Procalcitonin (PCT) and C-reactive protein (CRP) have been most widely used, but even these have limited abilities to distinguish sepsis from other inflammatory conditions or to predict outcome. PCT has been used to guide empirical antibacterial therapy in patients with respiratory infections and help to determine if antibacterial therapy can be stopped. New biomarkers such as those in this review will discuss the major types of biomarkers of bloodstream infections/sepsis, including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble urokinase-type plasminogen receptor (suPAR), proadrenomedullin (ProADM), and presepsin.

  2. Defining Neonatal Sepsis

    PubMed Central

    Wynn, James L.

    2016-01-01

    Purpose of the review Although infection rates have modestly decreased in the neonatal intensive care unit (NICU) as a result of ongoing quality improvement measures, neonatal sepsis remains a frequent and devastating problem among hospitalized preterm neonates. Despite multiple attempts to address this unmet need, there have been minimal advances in clinical management, outcomes, and accuracy of diagnostic testing options over the last three decades. One strong contributor to a lack of medical progress is a variable case definition of disease. The inability to agree on a precise definition greatly reduces the likelihood of aligning findings from epidemiologists, clinicians, and researchers, which, in turn, severely hinders progress towards improving outcomes. Recent findings Pediatric consensus definitions for sepsis are not accurate in term infants and are not appropriate for preterm infants. In contrast to the defined multi-stage criteria for other devastating diseases encountered in the NICU (e.g., bronchopulmonary dysplasia), there is significant variability in the criteria used by investigators to substantiate the diagnosis of neonatal sepsis. Summary The lack of an accepted consensus definition for neonatal sepsis impedes our efforts towards improved diagnostic and prognostic options as well as accurate outcomes information for this vulnerable population. PMID:26766602

  3. Sepsis-associated encephalopathy.

    PubMed

    Cotena, Simona; Piazza, Ornella

    2012-01-01

    Sepsis-associated encephalopathy (SAE) is defined as a diffuse or multifocal cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct brain infection. Its pathogenesis is multifactorial. SAE generally occurs early during severe sepsis and precedes multiple-organ failure. The most common clinical feature of SAE is the consciousness alteration which ranges from mildly reduced awareness to unresponsiveness and coma. Diagnosis of SAE is primarily clinical and depends on the exclusion of other possible causes of brain deterioration. Electroencephalography (EEG) is almost sensitive, but it is not specific for SAE. Computed Tomography (CT) head scan generally is negative in case of SAE, while Magnetic Resonance Imaging (MRI) can show brain abnormalities in case of SAE, but they are not specific for this condition. Somatosensitive Evoked Potentials (SEPs) are sensitive markers of developing cerebral dysfunction in sepsis. Cerebrospinal fluid (CBF) analysis is generally normal, a part an inconstant elevation of proteins concentration. S100B and NSE have been proposed like biomarkers for diagnosis of SAE, but the existing data are controversial. SAE is reversible even if survivors of severe sepsis have often long lasting or irreversible cognitive and behavioral sequel; however the presence of SAE can have a negative influence on survival. A specific therapy of SAE does not exist and the outcome depends on a prompt and appropriate treatment of sepsis as whole.

  4. The interplay between microbiota and inflammation: lessons from peritonitis and sepsis

    PubMed Central

    Lobo, Leandro A; Benjamim, Claudia F; Oliveira, Ana Carolina

    2016-01-01

    Mammals harbor a complex gut-associated microbiota, comprising bacteria that provide immunological, metabolic and neurological benefits to the host, and contribute to their well-being. However, dysregulation of the microbiota composition, known as dysbiosis, along with the associated mucosal immune response have a key role in the pathogenesis of many inflammatory diseases, including inflammatory bowel diseases (IBDs), type 1 and type 2 diabetes, asthma, multiple sclerosis, among others. In addition, outside the gut lumen, bacteria from microbiota are the causative agent of peritoneal inflammation, abdominal sepsis and systemic sepsis. Critical care interventions during sepsis by antibiotics induce dysbiosis and present acute and long-term poor prognosis. In this review, we discuss immunomodulatory effects of the microbial molecules and products, highlighting the role of Bacteroides fragilis, a human commensal with ambiguous interactions with the host. Moreover, we also address the impact of antibiotic treatment in sepsis outcome and discuss new insights for microbiota modulation. PMID:27525063

  5. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes

    PubMed Central

    Graham, Garth

    2016-01-01

    In the USA and internationally, women experience farranging differences with respect to acute coronary syndrome (ACS) and myocardial infarction (MI). Women suffer from more comorbidities than men, such as smoking, obesity, hypertension, diabetes, and poor mental health. They some-times exhibit atypical MI presentation symptoms and are overall less likely to present with chest pain. Women are more likely than men to encounter delays between the onset of symptoms and arrival at the hospital or to guideline treatment. The use of various surgical and pharmacological treatments, including revascularization approaches, also differs. Women, on average, have worse outcomes than men following MI, with more complications, higher mortality rates, and poorer recovery. Internationally, outcomes are similar despite various differences in health care and culture in non-US countries. In this review, we detail differences regarding ACS and MI in women, describing their complex correlations and discussing their possible causes. Educational approaches that are tailored to women might help to reduce the incidence of ACS and MI, as well as outcomes following hospitalization. Although outcomes following acute MI have been improving over the years, women may require special consideration in order to see continued improvement. PMID:26884685

  6. Decreased connexin 43 in astrocytes inhibits the neuroinflammatory reaction in an acute mouse model of neonatal sepsis.

    PubMed

    Zhou, Jing-Jing; Cheng, Cheng; Qiu, Zilong; Zhou, Wen-Hao; Cheng, Guo-Qiang

    2015-12-01

    Neonatal sepsis is common in neonatal intensive care units, often complicated by injury to the immature brain. Previous studies have shown that the expression of the gap junction protein connexin 43 (Cx43) in the brain decreases when stimulated by neuro-inflammatory drugs such as lipopolysaccharide (LPS). Here we showed that partial deletion of Cx43 in astrocytes resulted in weakened inflammatory responses. The up-regulation of pro-inflammatory cytokines was significantly reduced in mice with partial deletion of Cx43 in astrocytes compared with wild-type littermates after systemic LPS injection. Moreover, microglial activation was inhibited in mice with partial deletion of Cx43. These results showed that Cx43 in astrocytes plays a critical role in neuro-inflammatory responses. This work provides a potential therapeutic target for inhibiting neuro-inflammatory responses in neonatal sepsis.

  7. Sepsis and ARDS: The Dark Side of Histones.

    PubMed

    Xu, Zhiheng; Huang, Yongbo; Mao, Pu; Zhang, Jianrong; Li, Yimin

    2015-01-01

    Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases.

  8. Sepsis and ARDS: The Dark Side of Histones

    PubMed Central

    Xu, Zhiheng; Huang, Yongbo; Mao, Pu; Zhang, Jianrong; Li, Yimin

    2015-01-01

    Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases. PMID:26609197

  9. Demographic Diversity, Value Congruence, and Workplace Outcomes in Acute Care

    PubMed Central

    Gates, Michael G.; Mark, Barbara A.

    2012-01-01

    Nursing scholars and healthcare administrators often assume that a more diverse nursing workforce will lead to better patient and nurse outcomes, but this assumption has not been subject to rigorous empirical testing. In a study of nursing units in acute care hospitals, the influence of age, gender, education, race/ethnicity, and perceived value diversity on nurse job satisfaction, nurse intent to stay, and patient satisfaction were examined. Support was found for a negative relationship between perceived value diversity and all outcomes and for a negative relationship between education diversity and intent to stay. Additionally, positive relationships were found between race/ethnicity diversity and nurse job satisfaction as well as between age diversity and intent to stay. From a practice perspective, the findings suggest that implementing retention, recruitment, and management practices that foster a strong shared value system among nurses may lead to better workplace outcomes. PMID:22377771

  10. Demographic diversity, value congruence, and workplace outcomes in acute care.

    PubMed

    Gates, Michael G; Mark, Barbara A

    2012-06-01

    Nursing scholars and healthcare administrators often assume that a more diverse nursing workforce will lead to better patient and nurse outcomes, but this assumption has not been subject to rigorous empirical testing. In a study of nursing units in acute care hospitals, the influence of age, gender, education, race/ethnicity, and perceived value diversity on nurse job satisfaction, nurse intent to stay, and patient satisfaction were examined. Support was found for a negative relationship between perceived value diversity and all outcomes and for a negative relationship between education diversity and intent to stay. Additionally, positive relationships were found between race/ethnicity diversity and nurse job satisfaction as well as between age diversity and intent to stay. From a practice perspective, the findings suggest that implementing retention, recruitment, and management practices that foster a strong shared value system among nurses may lead to better workplace outcomes. Copyright © 2012 Wiley Periodicals, Inc.

  11. The evolutionary logic of sepsis.

    PubMed

    Rózsa, Lajos; Apari, Péter; Sulyok, Mihály; Tappe, Dennis; Bodó, Imre; Hardi, Richárd; Müller, Viktor

    2017-09-09

    The recently proposed Microbiome Mutiny Hypothesis posits that members of the human microbiome obtain information about the host individuals' health status and, when host survival is compromised, switch to an intensive exploitation strategy to maximize residual transmission. In animals and humans, sepsis is an acute systemic reaction to microbes invading the normally sterile body compartments. When induced by formerly mutualistic or neutral microbes, possibly in response to declining host health, sepsis appears to fit the 'microbiome mutiny' scenario except for its apparent failure to enhance transmission of the causative organisms. We propose that the ability of certain species of the microbiome to induce sepsis is not a fortuitous side effect of within-host replication, but rather it might, in some cases, be the result of their adaptive evolution. Whenever host health declines, inducing sepsis can be adaptive for those members of the healthy human microbiome that are capable of colonizing the future cadaver and spread by cadaver-borne transmission. We hypothesize that such microbes might exhibit switches along the 'mutualist - lethal pathogen - decomposer - mutualist again' scenario, implicating a previously unsuspected, surprising level of phenotypic plasticity. This hypothesis predicts that those species of the healthy microbiome that are recurring causative agents of sepsis can participate in the decomposition of cadavers, and can be transmitted as soil-borne or water-borne infections. Furthermore, in individual sepsis cases, the same microbial clones that dominate the systemic infection that precipitates sepsis, should also be present in high concentration during decomposition following death: this prediction is testable by molecular fingerprinting in experimentally induced animal models. Sepsis is a leading cause of human death worldwide. If further research confirms that some cases of sepsis indeed involve the 'mutiny' (facultative phenotypic switching) of

  12. Poverty, process of care, and outcome in acute coronary syndromes.

    PubMed

    Rao, Sunil V; Kaul, Padma; Newby, L Kristin; Lincoff, A Michael; Hochman, Judith; Harrington, Robert A; Mark, Daniel B; Peterson, Eric D

    2003-06-04

    We sought to determine whether income-based disparities in care processes and outcome exist in patients with acute coronary syndromes. Using income proxies and limited clinical data, some observational studies have shown income disparities in outcome after acute myocardial infarction (MI). Using annual household income from the economic substudy of the PURSUIT (Platelet Glycoprotein IIB/IIIA In Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial, patients were grouped into low-, middle-, and high-income categories based on the U.S. Census Bureau definition of poverty. Logistic regression analysis was used to examine the association between income category and the use of cardiac procedures and the prescription of evidence-based medications at hospital discharge. Cox regression analysis was used to examine the hazard of 30-day and six-month death or recurrent MI across income categories, after adjusting for baseline characteristics. Low-income patients had more chronic medical conditions and were sicker at presentation. Among low-income patients, the use of some evidence-based medications and cardiac procedures was lower and the unadjusted rates of 30-day death and six-month death or MI was higher. After multivariable adjustment, there was no consistent pattern for disparity in care processes, but the trend for higher short and intermediate-term death or MI persisted for low-income patients. Income level is associated with a trend toward worse outcome among patients with acute coronary syndromes. The disparity in 30-day and six-month death or MI between low and high-income patients could not be readily explained by differences in in-hospital medical or invasive treatment, suggesting that the poor outcomes may be due to differences occurring after hospital discharge.

  13. [Recognizing prevention and treatment of burn sepsis with the concept of holistic integrative medicine].

    PubMed

    Huan, J N

    2017-04-20

    Sepsis remains a major cause of death in severe burns. The effect of sepsis management is influenced by its complicated pathophysiologic changes. In order to improve the outcome of burn sepsis, the predisposing factor of sepsis after burn analyzed by advanced technology, the early prevention, antibiotics therapy, and combined treatment in severe burns with sepsis are discussed using the concept of holistic integrative medicine.

  14. Outcome of children with acute encephalitis and refractory status epilepticus.

    PubMed

    Sasaki, Jun; Chegondi, Madhurandhar; Raszynski, Andre; Totapally, Balagangadhar R

    2014-12-01

    Acute encephalitis in children is a life-threatening neurological emergency. However, little is reported about the outcome of this devastating illness in the United States. The authors retrospectively reviewed the charts of patients admitted to a regional pediatric intensive care unit with the diagnosis of acute encephalitis between 2006 and 2011. In 41 cases that met the inclusion criteria, the most common presenting symptoms were fever (65.9%), altered mental status (61%), and seizures (58.5%). Eight patients (19.5%) who presented with refractory status epilepticus had a longer median length of stay in the pediatric intensive care unit (46 vs. 4 days; P < .0001) and a significant worsening of Pediatric Cerebral Performance Category score on discharge by 2 or more points (odds ratio 20.38; 95% confidence interval, 2.89-143.52). All children survived to hospital discharge. In conclusion, children with acute encephalitis who present with refractory status epilepticus have a worse neurological outcome and a longer stay in the pediatric intensive care unit. © The Author(s) 2014.

  15. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey.

    PubMed

    Iba, Toshiaki; Nisio, Marcello Di; Levy, Jerrold H; Kitamura, Naoya; Thachil, Jecko

    2017-09-27

    Recent clinical studies have shown that anticoagulant therapy might be effective only in specific at-risk subgroups of patients with sepsis and coagulation dysfunction. The definition of sepsis was recently modified, and as such, old scoring systems may no longer be appropriate for the diagnosis of sepsis-associated coagulopathy. The aim of this study was to evaluate prognostic factors in patients diagnosed with sepsis and coagulopathy according to the new sepsis definition and assess their accuracy in comparison with existing models. Retrospective analysis of the nationwide survey for recombinant human soluble thrombomodulin. General emergency and critical care centres in secondary and tertiary care hospitals. We evaluated the prognostic value of the newly proposed diagnostic criteria for sepsis-induced coagulopathy (SIC). A total of 1498 Japanese patients with sepsis and coagulopathy complications who were treated with recombinant thrombomodulin were analysed in this study. The platelet count, prothrombin time (PT) ratio, fibrinogen/fibrin degradation products, systemic inflammatory response syndrome score and Sequential Organ Failure Assessment (SOFA) score obtained just before the start of treatment were examined in relation to the 28-day mortality rate. The platelet count, PT ratio and total SOFA were independent predictors of a fatal outcome in a logistic regression model. A SIC score was defined using the three above-mentioned variables with a positivity threshold of 4 points or more. The SIC score predicted higher 28-day mortality rate compared with the current Japanese Association for Acute Medicine-disseminated intravascular coagulation score (38.4%vs34.7%). The SIC score is based on readily available parameters, is easy to calculate and has a high predictive value for 28-day mortality. Future studies are warranted to evaluate whether the SIC score may guide the decision to initiate anticoagulant therapy. © Article author(s) (or their employer(s) unless

  16. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children

    PubMed Central

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-01-01

    Abstract Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness. A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression. HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05). Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern. PMID:27583886

  17. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

    PubMed

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-08-01

    Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05).Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern.

  18. Mechanical Ventilation in Sepsis: A Reappraisal.

    PubMed

    Zampieri, Fernando G; Mazza, Bruno

    2017-01-01

    Sepsis is the main cause of close to 70% of all cases of acute respiratory distress syndromes (ARDS). In addition, sepsis increases susceptibility to ventilator-induced lung injury. Therefore, the development of a ventilatory strategy that can achieve adequate oxygenation without injuring the lungs is highly sought after for patients with acute infection and represents an important therapeutic window to improve patient care. Suboptimal ventilatory settings cannot only harm the lung, but may also contribute to the cascade of organ failure in sepsis due to organ crosstalk.Despite the prominent role of sepsis as a cause for lung injury, most of the studies that addressed mechanical ventilation strategies in ARDS did not specifically assess sepsis-related ARDS patients. Consequently, most of the recommendations regarding mechanical ventilation in sepsis patients are derived from ARDS trials that included multiple clinical diagnoses. While there have been important improvements in general ventilatory management that should apply to all critically ill patients, sepsis-related lung injury might still have particularities that could influence bedside management.After revisiting the interplay between sepsis and ventilation-induced lung injury, this review will reappraise the evidence for the major components of the lung protective ventilation strategy, emphasizing the particularities of sepsis-related acute lung injury.

  19. microRNA-23a-5p acts as a potential biomarker for sepsis-induced acute respiratory distress syndrome in early stage.

    PubMed

    Liu, S; Liu, C; Wang, Z; Huang, J; Zeng, Q

    2016-02-04

    Sepsis is a significant cause of morbidity and mortality worldwide. Acute respiratory distress syndrome (ARDS) is the most common and serious complication of sepsis, which presents with rapid and progressive acute onset respiratory failure. The microRNA-23a-5p, as a kind of circulating microRNA (miRNA), is considered to be a candidate biomarker for cardiovascular diseases. However, correlation between ARDS and miR-23a-5p is also elusive. This study aims to investigate the role of miR-23a-5p as the biomarkers for ARDS. In this study, ARDS was induced by intraperitoneally injected with LPS of Sprague-Dawley rats and serum and lung tissues were collected. The NR8383 macrophages were stimulated with LPS. TNF-α, IL-1β, and miR-23a-5p levels in serum, lung tissues and NR8383 were determined using SYBR-based miRNA quantitative real-time polymerase chain reactions (qRT-PCRs). The results indicated that serum miR-23a-5p was increased by 7 fold, 4 fold and 2 fold at 3 h, 6h, and 12h after injection of LPS, respectively. While the miR-23a-5p in NR8383 was elevated by 3.5 fold, 3 fold, 2.5 fold and 5 fold, at 3 h, 6h, 12h and 24h after stimulated with LPS, respectively. In conclusion, the miR-23a-5p might be employed as the potential biomarkers for ARDS in early stage.

  20. Glycosylated Hemoglobin and Functional Outcome after Acute Ischemic Stroke.

    PubMed

    Lattanzi, Simona; Bartolini, Marco; Provinciali, Leandro; Silvestrini, Mauro

    2016-07-01

    Diabetes mellitus (DM) is associated to an increased incidence of cerebral and myocardial infarction which could be reduced by long-term maintenance of optimal glycemic values. The aim of the study was to evaluate in diabetic patients with ischemic stroke the chronic glycemic status and its relationship with functional outcome. We retrospectively identified consecutive diabetic patients hospitalized for acute ischemic stroke. Clinical and biochemical characteristics at admission were assessed. The outcome measures were the attainment of the recommended glycosylated hemoglobin A1 (HbA1c) level and the 3-month functional status according to the modified Rankin Scale score. Among the 112 enrolled patients, 39 (34.8%) met the recommended goal of HbA1c less than 7%. Higher education level was predictive of good prestroke glycemic control (adjusted OR 1.32 per year [95% CI 1.15-1.51], P < .001). At the 3-month evaluation, 44 (39.3%) patients were classified as having a poor outcome. After categorization of HbA1c values into tertiles, a dose-response relationship with poor functional recovery was found (P = .001). The suboptimal prestroke glycemic status was an independent predictor of unfavorable outcome (adjusted OR 6.22 [95% CI 1.94-19.98] for HbA1c ≥7%, P = .002). The management of DM was suboptimal in nearly two thirds of diabetic subjects presenting with acute ischemic stroke. The glycemic control before stroke occurrence was an independent prognostic factor and HbA1c values above the recommended goals increased the risk of unfavorable 3-month outcome. The improvement of DM management may be an effective strategy to either decrease the burden of cerebrovascular disease or influence its clinical course. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Predictors of Clinical Outcome After Acute Achilles Tendon Ruptures.

    PubMed

    Olsson, Nicklas; Petzold, Max; Brorsson, Annelie; Karlsson, Jón; Eriksson, Bengt I; Silbernagel, Karin Grävare

    2014-06-01

    In patients with an acute Achilles tendon rupture, it has not been possible to determine the superiority of a single specific treatment modality over other treatments with respect to symptoms and function. When several pertinent treatment protocols are available for an injury, it is of interest to understand how other variables, such as age, sex, or physical activity level, affect outcome to better individualize the treatment. To investigate predictors of both symptomatic and functional outcomes after an acute Achilles tendon rupture. Cohort study (Prognosis); Level of evidence, 2. Ninety-three patients (79 men and 14 women; mean age, 40 years) were evaluated prospectively at 3, 6, and 12 months. The main outcome measures in this study were the Achilles tendon Total Rupture Score (ATRS) for symptoms and maximum heel-rise height for function. The independent variables evaluated as possible predictors of outcome included treatment, sex, age, body mass index (BMI), physical activity level, symptoms, and quality of life. Treatment, age, BMI, physical activity level, heel-rise height at 6 months, and the ATRS at 3 months were eligible for further analysis. Only male sex was included for the prediction models. The 4 different multiple linear regression models (predicting the ATRS at 6 and 12 months and heel-rise height at 6 and 12 months) were significant (P < .001-.002), and the R (2) values for the models were 0.222 to 0.409. Surgical or nonsurgical treatment is a moderate predictor of symptoms and a weak predictor of heel-rise height after an acute Achilles tendon rupture. At the 6-month follow-up, surgical treatment was associated with a larger heel-rise height, but the opposite was seen at 12 months. Surgical treatment resulted in a lower degree of symptoms. Increasing age was a strong predictor of reduced heel-rise height, and an increase in age of 10 years reduced the expected heel-rise height by approximately 8%. A higher BMI was also a strong predictor of a

  2. Combined Therapy With Adipose-Derived Mesenchymal Stem Cells and Ciprofloxacin Against Acute Urogenital Organ Damage in Rat Sepsis Syndrome Induced by Intrapelvic Injection of Cecal Bacteria

    PubMed Central

    Sung, Pei-Hsun; Chiang, Hsin-Ju; Chen, Chih-Hung; Chen, Yi-Ling; Huang, Tien-Hung; Zhen, Yen-Yi; Chang, Meng-Wei; Liu, Chu-Feng; Chung, Sheng-Ying; Chen, Yung-Lung; Chai, Han-Tan; Sun, Cheuk-Kwan

    2016-01-01

    We hypothesized that combined treatment with autologous adipose-derived mesenchymal stem cell (ADMSC) and ciprofloxacin is superior to ciprofloxacin only in reducing sepsis-induced urogenital organ damage and mortality in rat sepsis syndrome (SS) caused by intrapelvic injection of cecal bacteria (1.0 × 104 cells per milliliter; total, 5.0 ml). Male Sprague-Dawley rats (n = 60) equally divided into group 1 (sham-control), group 2 (SS), group 3 (SS-ADMSC [5.0 × 105 intravenously at 0.5, 6, and 18 hours after sepsis induction]), group 4 (SS-ciprofloxacin [3.0 mg/kg, b.i.d.] for 5 days), and group 5 (SS-ADMSC-ciprofloxacin) were sacrificed by day 5. Mortality rate and creatinine level were highest in group 2 and lowest in group 1 and significantly higher in groups 3 and 4 than those in group 5, but there was no difference between groups 3 and 4 (all p < .005). The kidney injury score, inflammatory biomarker expressions at protein (tumor necrosis factor-1α, nuclear factor-κB, matrix metallopeptidase-9, regulated on activation, normal T-cell expressed and secreted, interleukin-1β) and cellular (CD14+, migratory inhibitor factor positive, CD68+) levels in kidneys and urinary bladder were lowest in group 1 and highest in group 2, higher in group 4 than in groups 3 and 5, and higher in group 3 than in group 5 (all p < .001). Protein expressions of apoptosis (Bax, cleaved caspase 3 and poly[ADP-ribose] polymerase 1, p21 protein [Cdc42/Rac]-activated kinase 2) and oxidative stress (oxidized protein, NADPH oxidase (NOX)-1, NOX-2) in these organs showed an identical pattern compared with that of inflammation in all groups (all p < .001). In conclusion, ADMSC-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rat. Significance Autologous adipose-derived mesenchymal stem cell-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rats. PMID:27075767

  3. Combined Therapy With Adipose-Derived Mesenchymal Stem Cells and Ciprofloxacin Against Acute Urogenital Organ Damage in Rat Sepsis Syndrome Induced by Intrapelvic Injection of Cecal Bacteria.

    PubMed

    Sung, Pei-Hsun; Chiang, Hsin-Ju; Chen, Chih-Hung; Chen, Yi-Ling; Huang, Tien-Hung; Zhen, Yen-Yi; Chang, Meng-Wei; Liu, Chu-Feng; Chung, Sheng-Ying; Chen, Yung-Lung; Chai, Han-Tan; Sun, Cheuk-Kwan; Yip, Hon-Kan

    2016-06-01

    We hypothesized that combined treatment with autologous adipose-derived mesenchymal stem cell (ADMSC) and ciprofloxacin is superior to ciprofloxacin only in reducing sepsis-induced urogenital organ damage and mortality in rat sepsis syndrome (SS) caused by intrapelvic injection of cecal bacteria (1.0 × 10(4) cells per milliliter; total, 5.0 ml). Male Sprague-Dawley rats (n = 60) equally divided into group 1 (sham-control), group 2 (SS), group 3 (SS-ADMSC [5.0 × 10(5) intravenously at 0.5, 6, and 18 hours after sepsis induction]), group 4 (SS-ciprofloxacin [3.0 mg/kg, b.i.d.] for 5 days), and group 5 (SS-ADMSC-ciprofloxacin) were sacrificed by day 5. Mortality rate and creatinine level were highest in group 2 and lowest in group 1 and significantly higher in groups 3 and 4 than those in group 5, but there was no difference between groups 3 and 4 (all p < .005). The kidney injury score, inflammatory biomarker expressions at protein (tumor necrosis factor-1α, nuclear factor-κB, matrix metallopeptidase-9, regulated on activation, normal T-cell expressed and secreted, interleukin-1β) and cellular (CD14+, migratory inhibitor factor positive, CD68+) levels in kidneys and urinary bladder were lowest in group 1 and highest in group 2, higher in group 4 than in groups 3 and 5, and higher in group 3 than in group 5 (all p < .001). Protein expressions of apoptosis (Bax, cleaved caspase 3 and poly[ADP-ribose] polymerase 1, p21 protein [Cdc42/Rac]-activated kinase 2) and oxidative stress (oxidized protein, NADPH oxidase (NOX)-1, NOX-2) in these organs showed an identical pattern compared with that of inflammation in all groups (all p < .001). In conclusion, ADMSC-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rat. Autologous adipose-derived mesenchymal stem cell-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rats. ©AlphaMed Press.

  4. Impact of the implementation of a Sepsis Code hospital protocol in antibiotic prescription and clinical outcomes in an intensive care unit.

    PubMed

    García-López, L; Grau-Cerrato, S; de Frutos-Soto, A; Bobillo-De Lamo, F; Cítores-Gónzalez, R; Diez-Gutierrez, F; Muñoz-Moreno, M F; Sánchez-Sánchez, T; Gandía-Martínez, F; Andaluz-Ojeda, D

    A study was performed to analyze the impact of an in-hospital Sepsis Code (SC) program on use of antibiotic and clinical outcomes. Quasi-experimental observational retrospective study. Polyvalent 11 beds ICU belonging to a tertiary Universitary hospital. Patients admitted consecutively to the ICU with diagnosis of severe sepsis or septic shock. A post intervention group (POST-SC) (September 2012-August 2013) was compared with a historical group (PRE-SC) used as control (January-December 2010). Antibiotic treatment, therapeutic antibiotic strategy, mortality and length of stay. Antibiotic consumption was expressed as defined daily doses (DDD)/ 100 stays. 42 patients with SS/SS in POST-SC group and 50 patients in PRE-SC group were consecutively recluted and further analyzed. Total antibiotic consumption (DDD) was similar in both groups. Rate of de-escalation therapy was significantly higher in POST-SC group (75% vs 30,8%, p<0,005) while prescription of restricted antibiotics was significantly lower (74% vs 52%, p=0,031). Finally POST-SC patients showed a significantly decrease in hospital and 28 days mortality rates [23% vs 44%, (p=0,035) and 31% vs 56% (p=0,014) respectively] as well as a reduction in ICU length of stay compared to PRE-SC cohort (5 days vs 10,5 days, p=0,05). The implementation of a Sepsis Code-hospital protocol is associated to an improvement in the management of antibiotic therapy with a significant increase in de-escalation therapy and lesser utilization of restricted use antibiotics, as well as a significant reduction in mortality, and a tendency towards shorter ICU length stay. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  5. Patient Characteristics, Management, and Predictors of Outcome from Severe Community-Onset Staphylococcal Sepsis in Northeast Thailand: A Prospective Multicenter Study.

    PubMed

    West, T Eoin; Wikraiphat, Chanthiwa; Tandhavanant, Sarunporn; Ariyaprasert, Pitchayanant; Suntornsut, Pornpan; Okamoto, Shawna; Mahavanakul, Weera; Srisamang, Pramot; Phiphitaporn, Sunchai; Anukunananchai, Jirasak; Chetchotisakd, Ploenchan; Peacock, Sharon J; Chantratita, Narisara

    2017-05-01

    AbstractStaphylococcus aureus infection is a persistent threat in resource-restricted settings in southeast Asia but informative data about this disease remain limited. We analyzed characteristics, management, and predictors of outcome in severely septic patients with community-onset S. aureus infection in northeast Thailand. We performed a prospective, multicenter observational cohort study of community-onset S. aureus sepsis in four referral hospitals recruiting patients at least 14 years of age admitted between March 2010 and December 2013. One hundred and nineteen patients with severe staphylococcal sepsis were enrolled. Diabetes was the most common underlying condition. Methicillin-resistant infection was rare. Twenty-eight-day mortality was 20%. Ninety-two percent of patients received appropriate antibiotic therapy and 82% were administered intravenous fluids on the first hospital day, although only 14% were managed in an intensive care unit (ICU). On univariable analysis, clinical variables at enrollment significantly associated with death at 28 days were coagulopathy or respiratory failure. Plasma interleukin (IL)-8 concentration alone accurately predicted mortality (area under the receiver operating curve = 0.82, 95% confidence interval = 0.73-0.90). In multivariable analysis, addition of IL-8 concentration to a mortality prediction model containing clinical variables further improved the predictive ability of the model. We conclude that severe staphylococcal sepsis in northeast Thailand causes significant mortality. Diabetes is a common preexisting condition and most patients are managed outside the ICU even if they receive vasoactive/inotropic agents or mechanical ventilation. While clinical factors apparent on presentation including coagulopathy and respiratory failure predict death, plasma IL-8 improves this prediction.

  6. Patient Characteristics, Management, and Predictors of Outcome from Severe Community-Onset Staphylococcal Sepsis in Northeast Thailand: A Prospective Multicenter Study

    PubMed Central

    West, T. Eoin; Wikraiphat, Chanthiwa; Tandhavanant, Sarunporn; Ariyaprasert, Pitchayanant; Suntornsut, Pornpan; Okamoto, Shawna; Mahavanakul, Weera; Srisamang, Pramot; Phiphitaporn, Sunchai; Anukunananchai, Jirasak; Chetchotisakd, Ploenchan; Peacock, Sharon J.; Chantratita, Narisara

    2017-01-01

    Staphylococcus aureus infection is a persistent threat in resource-restricted settings in southeast Asia but informative data about this disease remain limited. We analyzed characteristics, management, and predictors of outcome in severely septic patients with community-onset S. aureus infection in northeast Thailand. We performed a prospective, multicenter observational cohort study of community-onset S. aureus sepsis in four referral hospitals recruiting patients at least 14 years of age admitted between March 2010 and December 2013. One hundred and nineteen patients with severe staphylococcal sepsis were enrolled. Diabetes was the most common underlying condition. Methicillin-resistant infection was rare. Twenty-eight-day mortality was 20%. Ninety-two percent of patients received appropriate antibiotic therapy and 82% were administered intravenous fluids on the first hospital day, although only 14% were managed in an intensive care unit (ICU). On univariable analysis, clinical variables at enrollment significantly associated with death at 28 days were coagulopathy or respiratory failure. Plasma interleukin (IL)-8 concentration alone accurately predicted mortality (area under the receiver operating curve = 0.82, 95% confidence interval = 0.73–0.90). In multivariable analysis, addition of IL-8 concentration to a mortality prediction model containing clinical variables further improved the predictive ability of the model. We conclude that severe staphylococcal sepsis in northeast Thailand causes significant mortality. Diabetes is a common preexisting condition and most patients are managed outside the ICU even if they receive vasoactive/inotropic agents or mechanical ventilation. While clinical factors apparent on presentation including coagulopathy and respiratory failure predict death, plasma IL-8 improves this prediction. PMID:28167592

  7. [Glycemic control in sepsis and septic shock: friend or foe?].

    PubMed

    Ellger, B; Westphal, M; Stubbe, H D; Van den Heuvel, I; Van Aken, H; Van den Berghe, G

    2008-01-01

    Intensive care patients commonly suffer from hyperglycemia. Evidence is growing that strictly maintaining normoglycemia by intensive insulin therapy (IIT) ameliorates outcome in these patients. Whether or not this also holds true for patients with sepsis and septic shock is the issue of this post-hoc analysis of the database (2,748 patients) of 2 recent prospective clinical trials. A total of 950 patients suffering from sepsis were identified and of these 462 fulfilled the diagnostic criteria of septic shock upon admission to the intensive care unit (ICU). Patients were treated by either IIT [mean glycemia 5.88 mmol/l (106 mg/dl)] or conventional glucose management [mean glycemia 8.44 mmol/l (152 mg/dl)]. Under IIT the mortality of patients treated for more than 3 days in the ICU was lowered by 7.6% (p=0.03) in septic patients and by 8.7% (p=0.08) in septic shock patients. Polyneuropathy occurred less frequently under IIT compared to conventional glucose management (sepsis -9.8%, septic shock -14%; p<0.001). The incidence of acute renal failure was not affected by either treatment regimen (sepsis -3.3%, septic shock -3.1%; p<0.25). Intensive insulin therapy was associated with an increased risk of hypoglycemia (sepsis +16.7%, septic shock +18.8; p<0.0001) which did not, however, directly affect morbidity nor mortality. These data suggest that IIT improves outcome of patients with sepsis or septic shock. Hypoglycemia is a frequent complication, but its clinical relevance remains to be defined.

  8. [Adverse outcomes in the surgical treatment of acute appendicitis].

    PubMed

    Aguiló, Javier; Peiró, Salvador; Muñoz, Carmen; García del Caño, Julián; Garay, Miguel; Viciano, Vicente; Ferri, Ramón; García-Botella, Miguel; Medrano, José; Torró, José

    2005-11-01

    To describe adverse outcomes after appendectomy for acute appendicitis and to analyze the association between these outcomes and specific characteristics of the patient and hospital admission. We studied a cohort of 792 patients who underwent appendectomy for acute appendicitis. Postoperative complications, reoperations and deaths were prospectively studied and all readmissions were retrospectively identified. Logistic regression was used to evaluate the relationship between complications and patient characteristics, as well as hospital admission. Postsurgical complications developed in 9.8% of the patients. These complications mainly consisted of surgical wound infection (4.2%) and intra-abdominal complications (2.1%). A total of 0.7% of patients underwent reoperation during admission, 0.5% were admitted to the intensive care unit and five patients (0.6%) died in hospital. The rate of operation-related readmissions in the following year was 3.2%. Length of hospital stay was longer in patients with complications than in those without complications (9.6 and 3.5 days, respectively). Postoperative complications were associated with older age (45-65 years, OR 3.62, p < 0.001; more than 65 years OR 8.68, p < 0.001) and acute appendicitis complicated with peritonitis or perforation (OR 3.69, p < 0.005). Readmissions related to previous surgery were associated only with complications during the first admission (OR 18.79, p < 0.001). In appendectomy, the most frequent adverse outcomes are surgical wound infection and intra-abdominal complications, which are associated with older patients and perforations. This subgroup of patients at high risk requires closer surveillance.

  9. The outcomes of the elderly in acute care general surgery.

    PubMed

    St-Louis, E; Sudarshan, M; Al-Habboubi, M; El-Husseini Hassan, M; Deckelbaum, D L; Razek, T S; Feldman, L S; Khwaja, K

    2016-02-01

    Elderly patients form a growing subset of the acute care surgery (ACS) population. Older age may be associated with poorer outcomes for some elective procedures, but there are few studies focusing on outcomes for the elderly ACS population. Our objective is to characterize differences in mortality and morbidity for acute care surgery patients >80 years old. A retrospective review of all ACS admissions at a large teaching hospital over 1 year was conducted. Patients were classified into non-elderly (<80 years old) and elderly (≥80 years old). In addition to demographic differences, outcomes including care efficiency, mortality, postoperative complications, and length of stay were studied. Data analysis was completed with the Student's t test for continuous variables and Fisher's exact test for categorical variables using STATA 12 (College Station, TX, USA). We identified 467 non-elderly and 60 elderly patients with a mean age-adjusted Charlson score of 3.2 and 7.2, respectively (p < 0.001) and a mortality risk of 1.9 and 11.7 %, respectively (p < 0.001). The elderly were at risk of longer duration (>4 days) hospital stay (p = 0.05), increased postoperative complications (p = 0.002), admission to the ICU (p = 0.002), and were more likely to receive a non-operative procedure (p = 0.003). No difference was found (p = NS) for patient flow factors such as time to consult general surgery, time to see consult by general surgery, and time to operative management and disposition. Compared to younger patients admitted to an acute care surgery service, patients over 80 years old have a higher risk of complications, are more likely to require ICU admission, and stay longer in the hospital.

  10. Impact of Ulinastatin on Outcomes in Acute Burns Patients.

    PubMed

    Abhyankar, S V; Vartak, A M

    2017-04-03

    Burns is a global health problem with significant morbidity and mortality. Ulinastatin, a serine protease inhibitor, has the potential to improve outcomes in burns. A retrospective comparative case note review analysis was performed to assess the impact of ulinastatin on the outcomes in acute burns patients. Acute burns patients, admitted to Masina hospital, Mumbai, from October 2012 to April 2015, who received ulinastatin, were identified from the hospital records. A similarly sized cohort of patients, admitted before the introduction of ulinastatin, was also identified. Relevant data were obtained from archived patient files. The outcomes, mortality and length of hospital stay, were compared across different groups and subgroups. Data of 97 patients, 48 of whom received ulinastatin (ulinastatin group) and 49 of whom did not (control group), were captured. Patients in ulinastatin group had received ulinastatin 100,000 IU, 8 to 12 hourly, during a mean period of 8.8 days, based on clinical judgment, in addition to standard hospital care. The in-hospital mortality was lower (60.4%) in ulinastatin group compared with control group (75.5%). The difference in mortality was statistically significant (50% vs 77.27%; P = .04) in those with 41 to 80% burnt BSA. Mean length of hospital stay, where shorter duration of hospitalization is usually associated with death, was higher in ulinastatin group compared with the control group. Ulinastatin appears to reduce mortality in acute burns patients, especially in those with intermediate extent (40 to 80%) of burnt BSA. It also appears to delay death in those who ultimately succumbed to their burn injuries.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the

  11. Threonine utilization for synthesis of acute phase proteins, intestinal proteins, and mucins is increased during sepsis in rats.

    PubMed

    Faure, Magali; Choné, Frédérique; Mettraux, Christine; Godin, Jean-Philippe; Béchereau, Fabienne; Vuichoud, Jacques; Papet, Isabelle; Breuillé, Denis; Obled, Christiane

    2007-07-01

    We hypothesized that the dietary threonine demand for the anabolic response may be increased more than that of other essential amino acids during sepsis. Using a flooding dose of either L-[1 -13C]valine or L-[U -13C]threonine, we measured valine and threonine utilization for syntheses of plasma proteins (minus albumin), and wall, mucosal, and mucin proteins of the small intestine in infected (INF; d 2 and d 6 of postinfection) and control pair-fed (PF) rats. At d 2, the protein absolute synthesis rate (ASR) of INF rats was 21% (mucins) to 41% (intestinal wall) greater than that of PF when measured using valine as tracer, and 45% (mucosa) to 113% (mucins) greater than that of PF when measured with threonine as tracer. Plasma protein ASR was higher in INF than in PF rats, reaching 5- to 6-fold the value of PF. The utilization of both amino acid tracers for the protein synthesis was significantly increased by the infection in all compartments studied. The daily increased absolute threonine utilization for protein synthesis in gut wall plus plasma proteins was 446 micromol/d compared with 365 micromol/d for valine, and it represented 2.6 times the dietary threonine intake of rats at d 2. Most changes in protein ASR and threonine utilization observed at d 6 of postinfection were limited. In conclusion, sepsis increased the utilization of threonine for the anabolic splanchnic response. Because this threonine requirement is likely covered by muscle protein mobilization, increasing the threonine dietary supply would be an effective early nutritional management for patients with sepsis.

  12. Changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization at admission to ICU and the relation to outcome.

    PubMed

    Conti-Patara, Andreza; de Araújo Caldeira, Juliana; de Mattos-Junior, Ewaldo; de Carvalho, Haley da Silva; Reinoldes, Adriane; Pedron, Bruno Gregnanin; Patara, Marcelo; Francisco Talib, Mariana Semião; Faustino, Marcelo; de Oliveira, Clair Motos; Cortopassi, Silvia Renata Gaido

    2012-08-01

    To evaluate the changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization in the ICU and their relation to outcome. Prospective observational study. ICU of a veterinary university medical center. Thirty dogs with severe sepsis or septic shock caused by pyometra who underwent surgery and were admitted to the ICU. Severe sepsis was defined as the presence of sepsis and sepsis-induced dysfunction of one or more organs. Septic shock was defined as the presence of severe sepsis plus hypotension not reversed with fluid resuscitation. After the presumptive diagnosis of sepsis secondary to pyometra, blood samples were collected and clinical findings were recorded. Volume resuscitation with 0.9% saline solution and antimicrobial therapy were initiated. Following abdominal ultrasonography and confirmation of increased uterine volume, dogs underwent corrective surgery. After surgery, the animals were admitted to the ICU, where resuscitation was guided by the clinical parameters, central venous oxygen saturation (ScvO(2)), lactate, and base deficit. Between survivors and nonsurvivors it was observed that the ScvO(2), lactate, and base deficit on ICU admission were each related independently to death (P = 0.001, P = 0.030, and P < 0.001, respectively). ScvO(2) and base deficit were found to be the best discriminators between survivors and nonsurvivors as assessed via receiver operator characteristic curve analysis. Our study suggests that ScvO(2) and base deficit are useful in predicting the prognosis of dogs with severe sepsis and septic shock; animals with a higher ScvO(2) and lower base deficit at admission to the ICU have a lower probability of death. © Veterinary Emergency and Critical Care Society 2012.

  13. A simple bioscore improves diagnostic accuracy of sepsis after surgery.

    PubMed

    Liu, Zimeng; Chen, Juan; Liu, Yongjun; Si, Xiang; Jiang, Zhiyi; Zhang, Xuyu; Guan, Xiangdong

    2016-01-01

    Rapid and accurate prediction for sepsis remains a challenge in surgical intensive care units. Detection of individual biomarkers is often of marginal usefulness, and several biomarkers are difficult to measure in the clinical setting. The aim of this study was to evaluate the diagnostic and prognostic performance of three routine biomarkers, procalcitonin (PCT), B-type natriuretic peptide (BNP), and lymphocyte percentage, as individual or in combination for sepsis in surgical critically ill patients. Circulating PCT, BNP, and lymphocyte percentage were measured in surgical patients on admission to the intensive care unit. A bioscore system combining these biomarkers was constructed. All studied variables were analyzed according to the diagnosis and clinical outcomes of sepsis. A total of 320 consecutive patients were included in the analysis. One hundred fifty-six patients presented with sepsis. In the patients with sepsis, levels of PCT and BNP increased and lymphocyte percentage decreased. For individual biomarkers, PCT achieved the best area under the curve for the diagnosis of sepsis, whereas the diagnostic performance of the bioscore was better than that of each individual biomarker (area under the curve, 0.914 [95% confidence interval, 0.862-0.951]). Levels of BNP and bioscore increased in nonsurvivors in the entire cohort, but the accuracy of these two variables for mortality prediction was lower than that shown by Acute Physiology and Chronic Health Evaluation II score. Furthermore, bioscore failed to predict outcomes in septic patients. A simple bioscore combining PCT together with BNP and lymphocyte percentage improves the diagnostic accuracy for sepsis in surgical critically ill patients but fails to predict outcomes in surgical patients with sepsis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates1

    PubMed Central

    Kwok, Man Leung; Yuen, Hon; Lai, Sik To

    2003-01-01

    Severe acute respiratory syndrome (SARS) poses a major threat to the health of people worldwide. We performed a retrospective case series analysis to assess clinical outcome and identify pretreatment prognostic correlates of SARS, managed under a standardized treatment protocol. We studied 127 male and 196 female patients with a mean age of 41±14 (range 18–83). All patients, except two, received ribavirin and steroid combination therapy. In 115 (36%) patients, the course of disease was limited. Pneumonitis progressed rapidly in the remaining patients. Sixty-seven (21%) patients required intensive care, and 42 (13%) required ventilator support. Advanced age, high admission neutrophil count, and high initial lactate dehydrogenase level were independent correlates of an adverse clinical outcome. SARS-associated coronavirus caused severe illnesses in most patients, despite early treatment with ribavirin and steroid. This study has identified three independent pretreatment prognostic correlates. PMID:14519241

  15. Familial acute necrotizing encephalopathy without RANBP2 mutation: Poor outcome.

    PubMed

    Nishimura, Naoko; Higuchi, Yoshihisa; Kimura, Nobusuke; Nozaki, Fumihito; Kumada, Tomohiro; Hoshino, Ai; Saitoh, Makiko; Mizuguchi, Masashi

    2016-11-01

    Most childhood cases of acute necrotizing encephalopathy (ANE) involve neither family history nor recurrence. ANE occasionally occurs, however, as a familial disorder or recurs in Caucasian patients. A mutation of RAN-binding protein 2 (RANBP2) has been discovered in more than one half of familial or recurrent ANE patients. In contrast, there has been no report of this mutation in East Asia. Here, we report the first sibling cases of typical ANE in Japan, with poor outcome. DNA analysis of genes associated with ANE or other encephalopathies, including RANBP2 and carnitine palmitoyl transferase II (CPT2), indicated neither mutations nor disease-related polymorphisms. On literature review, recurrent or familial ANE without the RANBP2 mutation has a more severe outcome and greater predilection for male sex than that with the RANBP2 mutation. This suggests that there are unknown gene mutations linked to ANE. © 2016 Japan Pediatric Society.

  16. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study.

    PubMed

    Machado, Flavia R; Cavalcanti, Alexandre Biasi; Bozza, Fernando Augusto; Ferreira, Elaine M; Angotti Carrara, Fernanda Sousa; Sousa, Juliana Lubarino; Caixeta, Noemi; Salomao, Reinaldo; Angus, Derek C; Pontes Azevedo, Luciano Cesar

    2017-08-17

    The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome. We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models. On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4-31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8-44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2-59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02-2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37-0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9-351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital. The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the

  17. Concurrent administration of heparin and activated protein C in a patient with pulmonary embolism and severe sepsis with positive outcome.

    PubMed

    Juneja, Deven; Mohan, S; Veturi, Vivek V; Gopal, Palepu B

    2009-01-01

    Results of the PROWESS trial suggested that heparin may reduce the efficacy of recombinant human activated protein C (rhAPC) and the XPRESS study also showed increased bleeding complications in patients receiving heparin with rhAPC. Although it has been shown that heparin prophylaxis may be used along with rhAPC, no study has shown the interaction between continuous heparin infusion and rhAPC. Here, we report a case of severe sepsis with pulmonary embolism who was concurrently administered heparin and rhAPC infusions, with positive results and no bleeding complications.

  18. Chronic filarial infection provides protection against bacterial sepsis by functionally reprogramming macrophages.

    PubMed

    Gondorf, Fabian; Berbudi, Afiat; Buerfent, Benedikt C; Ajendra, Jesuthas; Bloemker, Dominique; Specht, Sabine; Schmidt, David; Neumann, Anna-Lena; Layland, Laura E; Hoerauf, Achim; Hübner, Marc P

    2015-01-01

    Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s.) and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases, but may also

  19. Renal blood flow in sepsis

    PubMed Central

    Langenberg, Christoph; Bellomo, Rinaldo; May, Clive; Wan, Li; Egi, Moritoki; Morgera, Stanislao

    2005-01-01

    Introduction To assess changes in renal blood flow (RBF) in human and experimental sepsis, and to identify determinants of RBF. Method Using specific search terms we systematically interrogated two electronic reference libraries to identify experimental and human studies of sepsis and septic acute renal failure in which RBF was measured. In the retrieved studies, we assessed the influence of various factors on RBF during sepsis using statistical methods. Results We found no human studies in which RBF was measured with suitably accurate direct methods. Where it was measured in humans with sepsis, however, RBF was increased compared with normal. Of the 159 animal studies identified, 99 reported decreased RBF and 60 reported unchanged or increased RBF. The size of animal, technique of measurement, duration of measurement, method of induction of sepsis, and fluid administration had no effect on RBF. In contrast, on univariate analysis, state of consciousness of animals (P = 0.005), recovery after surgery (P < 0.001), haemodynamic pattern (hypodynamic or hyperdynamic state; P < 0.001) and cardiac output (P < 0.001) influenced RBF. However, multivariate analysis showed that only cardiac output remained an independent determinant of RBF (P < 0.001). Conclusion The impact of sepsis on RBF in humans is unknown. In experimental sepsis, RBF was reported to be decreased in two-thirds of studies (62 %) and unchanged or increased in one-third (38%). On univariate analysis, several factors not directly related to sepsis appear to influence RBF. However, multivariate analysis suggests that cardiac output has a dominant effect on RBF during sepsis, such that, in the presence of a decreased cardiac output, RBF is typically decreased, whereas in the presence of a preserved or increased cardiac output RBF is typically maintained or increased. PMID:16137349

  20. Mean platelet volume and cardiovascular outcomes in acute myocardial infarction

    PubMed Central

    Ranjith, Mangalachulli Pottammal; DivyaRaj, Rajendran; Mathew, Dolly; George, Biju; Krishnan, Mangalath Narayanan

    2016-01-01

    Objective High levels of mean platelet volume (MPV) may be associated with adverse outcomes in patients with myocardial infarction (MI). We examined the association between MPV and the risk of death and adverse cardiovascular outcomes in patients with MI. Methods We studied consecutive patients with MI admitted to a tertiary-care hospital during a period of 1 year. MPV was measured at admission and at third month. Patients were followed up for 1-year primary composite outcome of cardiovascular death, stroke, fatal or non-fatal MI and cardiac failure. Patients were classified according to tertile of baseline MPV. Results A total of 1206 patients with MI, including 934 men (77.4%) and 272 women (22.6%) were studied. The mean age of the study population was 56 years. At 1-year follow-up, 292 (28.57%) primary outcome occurred: cardiovascular mortality 78 (7.6%), fatal or non-fatal MI 153 (15.0%), stroke 30 (2.9%) and cardiac failure 128 (12.52%). Patients with the highest tertile MPV had higher primary outcome as compared with those with MPV in the lowest tertile (adjusted OR=2.31; 95% CI 1.60 to 3.35; p<0.001). Total mortality was also more in high-MPV group (adjusted OR 2.62; 95% CI 1.47 to 4.70; p<0.001). There were no significant changes in mean MPV values at admission from those at third month interval (9.15, (SD 0.99) vs 9.19 (SD 0.94); p=0.2). Conclusions Elevated MPV was associated with worse outcome in patients with acute MI. Elevated MPV in these patients may be due to inherently large platelets. Trial registration number http://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=5485&EncHid=98036.61144&modid=1&compid=19; CTRI/2012/12/003222. PMID:27326224

  1. Mean platelet volume and cardiovascular outcomes in acute myocardial infarction.

    PubMed

    Ranjith, Mangalachulli Pottammal; DivyaRaj, Rajendran; Mathew, Dolly; George, Biju; Krishnan, Mangalath Narayanan

    2016-01-01

    High levels of mean platelet volume (MPV) may be associated with adverse outcomes in patients with myocardial infarction (MI). We examined the association between MPV and the risk of death and adverse cardiovascular outcomes in patients with MI. We studied consecutive patients with MI admitted to a tertiary-care hospital during a period of 1 year. MPV was measured at admission and at third month. Patients were followed up for 1-year primary composite outcome of cardiovascular death, stroke, fatal or non-fatal MI and cardiac failure. Patients were classified according to tertile of baseline MPV. A total of 1206 patients with MI, including 934 men (77.4%) and 272 women (22.6%) were studied. The mean age of the study population was 56 years. At 1-year follow-up, 292 (28.57%) primary outcome occurred: cardiovascular mortality 78 (7.6%), fatal or non-fatal MI 153 (15.0%), stroke 30 (2.9%) and cardiac failure 128 (12.52%). Patients with the highest tertile MPV had higher primary outcome as compared with those with MPV in the lowest tertile (adjusted OR=2.31; 95% CI 1.60 to 3.35; p<0.001). Total mortality was also more in high-MPV group (adjusted OR 2.62; 95% CI 1.47 to 4.70; p<0.001). There were no significant changes in mean MPV values at admission from those at third month interval (9.15, (SD 0.99) vs 9.19 (SD 0.94); p=0.2). Elevated MPV was associated with worse outcome in patients with acute MI. Elevated MPV in these patients may be due to inherently large platelets. http://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=5485&EncHid=98036.61144&modid=1&compid=19; CTRI/2012/12/003222.

  2. Acute care surgery program: mentoring fellows and patient outcomes.

    PubMed

    Diaz, Jose J; Norris, Patrick R; Miller, Richard S; Rodriguez, Philip Andres; Riordan, William P; Collier, Bryan R; May, Addison K; Morris, John A

    2010-05-15

    Acute care surgery programs have demonstrated that trauma patient outcomes have not changed with the addition of emergency general surgery (EGS) responsibilities. EGS patient outcomes and the mentoring of fellows on EGS service have not been previously studied. We hypothesize that EGS patient outcomes would not differ by provider on a service driven by evidence-based medicine (EBM) protocols. Retrospective study of prospectively collected EGS repository. academic level I trauma center, and regional EGS referral center from 2003 to 2007. There were 14 faculty and seven fellows during the study period. EGS coverage is a full week, with weeknight coverage by the in-house trauma/EGS faculty. Fellows are mentored by designated faculty while on service, who discuss patients, assist in the OR, or assume care if necessary. Data collected included age, gender, LOS, ICU LOS, ventilator days, disposition (home/rehab), and infectious complications(IC) (VAP, BSI, UTI, SSI). Primary outcome was mortality. 1769 patients met study criteria. The mean age was 47.1 (+/-18), 47% were males. The average ICU LOS was 2.9 d (+/-7.9), ventilator d 2.6 (+/-7.6); 82.1% were discharged home and 13.7% were referred to rehab. There was no statistical difference in mortality, LOS, ICU LOS, disposition, ventilator d, and IC between faculty and fellow providers. An EGS service with EBM protocols assures consistency in patient outcomes independent of provider level: faculty or fellows. Our model for mentoring fellows did not decrease EGS patient outcomes. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  3. A prehospital screening tool utilizing end-tidal carbon dioxide predicts sepsis and severe sepsis.

    PubMed

    Hunter, Christopher L; Silvestri, Salvatore; Ralls, George; Stone, Amanda; Walker, Ayanna; Papa, Linda

    2016-05-01

    To determine the utility of a prehospital sepsis screening protocol utilizing systemic inflammatory response syndrome (SIRS) criteria and end-tidal carbon dioxide (ETCO2). We conducted a prospective cohort study among sepsis alerts activated by emergency medical services during a 12 month period after the initiation of a new sepsis screening protocol utilizing ≥2 SIRS criteria and ETCO2 levels of ≤25 mmHg in patients with suspected infection. The outcomes of those that met all criteria of the protocol were compared to those that did not. The main outcome was the diagnosis of sepsis and severe sepsis. Secondary outcomes included mortality and in-hospital lactate levels. Of 330 sepsis alerts activated, 183 met all protocol criteria and 147 did not. Sepsis alerts that followed the protocol were more frequently diagnosed with sepsis (78% vs 43%, P < .001) and severe sepsis (47% vs 7%, P < .001), and had a higher mortality (11% vs 5%, P = .036). Low ETCO2 levels were the strongest predictor of sepsis (area under the ROC curve (AUC) of 0.99, 95% CI 0.99-1.00; P < .001), severe sepsis (AUC 0.80, 95% CI 0.73-0.86; P < .001), and mortality (AUC 0.70, 95% CI 0.57-0.83; P = .005) among all prehospital variables. Sepsis alerts that followed the protocol had a sensitivity of 90% (95% CI 81-95%), a specificity of 58% (95% CI 52-65%), and a negative predictive value of 93% (95% CI 87-97%) for severe sepsis. There were significant associations between prehospital ETCO2 and serum bicarbonate levels (r = 0.415, P < .001), anion gap (r = -0.322, P < .001), and lactate (r = -0.394, P < .001). A prehospital screening protocol utilizing SIRS criteria and ETCO2 predicts sepsis and severe sepsis, which could potentially decrease time to therapeutic intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. [Analysis of the risk factors of acute respiratory distress syndrome of Berlin new definition in patients with sepsis in emergency department].

    PubMed

    Qiao, Liang; Liu, Zhi

    2015-07-01

    To discuss the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis in emergency department. 312 patients with sepsis admitted to Department of Emergency of China Medical University Affiliated First Hospital were retrospectively analyzed, and they were divided into two groups according to development of ARDS, which was defined according to the Berlin new definition. The age, gender, vital signs, laboratory results, underlying disease, the mortality in emergency department sepsis (MEDS) score and lung injury prediction score (LIPS) were collected. Univariate analysis was done for each parameter. Statistical significance results were evaluated by multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of the parameter for ARDS. The incidence of sepsis-related ARDS was 11.2% (35/312). Within 35 cases of ARDS, there were 10 cases of mild ARDS, 18 cases of moderate ARDS, and 7 cases of severe ARDS. Univariate analysis showed that age (t=-2.134, P=0.035), oxygenation index (t=-4.245, P=0.001), arterial lactate (Lac, t=6.245, P<0.001), drugs for vascular diseases (χ2=4.261, P=0.026), shock (χ2=4.386, P=0.021), MEDS (t=4.021, P=0.045), LIPS (t=5.569, P<0.001), lung infections (χ2=4.289, P=0.025), and mechanical ventilation (χ2=6.245, P=0.001) were related to ARDS. The incidence of ARDS was different in different levels of Lac, which was 5.00% (3/16) at low level of Lac (<2.0 mmol/L), 9.46% (14/148) at middle level of Lac (2.0-3.9 mmol/L) and 17.31% (18/104) at high level of Lac (≥4.0 mmol/L). It was shown by multivariate logistic regression analysis that LIPS [ odds ratio (OR)=5.124, 95% confidence interval (95%CI)=3.642-10.153, P=0.002], Lac (OR=18.180, 95%CI=7.677-32.989, P<0.001) were independent risk factors for ARDS. It was shown by area under ROC (AUC) that the predictive value of LIPS and Lac in ARDS occurrence was significant. AUC of LIPS was 0.725, the

  5. Etiology and Outcome of Diffuse Acute Infectious Bronchiolitis in Adults.

    PubMed

    Ryu, Kai; Takayanagi, Noboru; Ishiguro, Takashi; Kanauchi, Tetsu; Kawate, Eriko; Kagiyama, Naho; Sugita, Yutaka

    2015-12-01

    The etiology and outcome of diffuse acute infectious bronchiolitis (DAIB) in adults is not well known. To retrospectively review adult patients with DAIB without pneumonia, document the etiologies and outcomes, and assess the relation between DAIB and postinfectious bronchiolitis obliterans. We retrospectively analyzed medical records of 1,664 patients with lower respiratory tract infections admitted to our institution in Saitama, Japan. DAIB was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated mainly multiple centrilobular nodules in four or more lobes. Pneumonia was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated consolidation and/or ground-glass opacities with or without centrilobular nodules. Of the 1,664 patients, 20 (1.2%) and 1,644 (98.8%) patients were diagnosed as having DAIB and pneumonia, respectively. Of the 20 patients with DAIB, the etiology was determined in 16 (80%): 13 (65.0%) had a single pathogen and 3 (15.0%) had two pathogens. Detected organisms included Mycoplasma pneumoniae in eight (40.0%) patients, influenza virus in two (10.0%), influenza virus and Streptococcus pneumoniae in two (10.0%), Haemophilus influenzae in three (15.0%), and respiratory syncytial virus and rhinovirus in one (5.0%) patient. All patients improved and none developed postinfectious bronchiolitis obliterans. The three most common etiologies of DAIB in the studied adults were M. pneumoniae, influenza virus, and H. influenzae. None of the patients with DAIB developed postinfectious bronchiolitis obliterans.

  6. High-volume haemofiltration for sepsis.

    PubMed

    Borthwick, Emma M J; Hill, Christopher J; Rabindranath, Kannaiyan S; Maxwell, Alexander P; McAuley, Danny F; Blackwood, Bronagh

    2013-01-31

    Severe sepsis and septic shock are leading causes of death in the intensive care unit (ICU). This is despite advances in the management of patients with severe sepsis and septic shock including early recognition, source control, timely and appropriate administration of antimicrobial agents, and goal directed haemodynamic, ventilatory and metabolic therapies. High-volume haemofiltration (HVHF) is a blood purification technique which may improve outcomes in critically ill patients with severe sepsis or septic shock. The technique of HVHF has evolved from renal replacement therapies used to treat acute kidney injury (AKI) in critically ill patients in the ICU. This review assessed whether HVHF improves clinical outcome in adult critically ill patients with sepsis in an ICU setting. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011, Issue 7); MEDLINE (1990 to August 2011), EMBASE (1990 to August 2011); LILACS (1982 to August 2011), Web of Science (1990 to August 2011), CINAHL (1982 to August 2011) and specific websites. We included randomized controlled trials (RCTs) and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration to standard or usual dialysis therapy; and RCTs and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration to no similar dialysis therapy. The studies involved adults in critical care units. Three review authors independently extracted data and assessed trial quality. We sought additional information as required from trialists. We included three randomized trials involving 64 participants. Due to the small number of studies and participants, it was not possible to combine data or perform sub-group analyses. One trial reported ICU and 28-day mortality, one trial reported hospital mortality and in the third, the number of deaths stated did not match the quoted mortality rates. No trials reported length of stay in ICU or hospital and one reported organ dysfunction

  7. The role of Nox2-derived ROS in the development of cognitive impairment after sepsis

    PubMed Central

    2014-01-01

    Background Sepsis- associated encephalopathy (SAE) is an early and common feature of severe infections. Oxidative stress is one of the mechanisms associated with the pathophysiology of SAE. The goal of this study was to investigate the involvement of NADPH oxidase in neuroinflammation and in the long-term cognitive impairment of sepsis survivors. Methods Sepsis was induced in WT and gp91phox knockout mice (gp91phox-/-) by cecal ligation and puncture (CLP) to induce fecal peritonitis. We measured oxidative stress, Nox2 and Nox4 gene expression and neuroinflammation in the hippocampus at six hours, twenty-four hours and five days post-sepsis. Mice were also treated with apocynin, a NADPH oxidase inhibitor. Behavioral outcomes were evaluated 15 days after sepsis with the inhibitory avoidance test and the Morris water maze in control and apocynin-treated WT mice. Results Acute oxidative damage to the hippocampus was identified by increased 4-HNE expression in parallel with an increase in Nox2 gene expression after sepsis. Pharmacological inhibition of Nox2 with apocynin completely inhibited hippocampal oxidative stress in septic animals. Pharmacologic inhibition or the absence of Nox2 in gp91phox-/- mice prevented glial cell activation, one of the central mechanisms associated with SAE. Finally, treatment with apocynin and inhibition of hippocampal oxidative stress in the acute phase of sepsis prevented the development of long-term cognitive impairment. Conclusions Our results demonstrate that Nox2 is the main source of reactive oxygen species (ROS) involved in the oxidative damage to the hippocampus in SAE and that Nox2-derived ROS are determining factors for cognitive impairments after sepsis. These findings highlight the importance of Nox2-derived ROS as a central mechanism in the development of neuroinflammation associated with SAE. PMID:24571599

  8. The role of the liver in sepsis

    PubMed Central

    Yan, Jun; Li, Song; Li, Shulin

    2014-01-01

    Despite the progress made in the clinical management of sepsis, sepsis morbidity and mortality rates remain high. The inflammatory pathogenesis and organ injury leading to death from sepsis are not fully understood for vital organs, especially the liver. Only recently has the role of the liver in sepsis begun to be revealed. Pre-existing liver dysfunction is a risk factor for the progression of infection to sepsis. Liver dysfunction after sepsis is an independent risk factor for multiple organ dysfunction and sepsis-induced death. The liver works as a lymphoid organ in response to sepsis. Acting as a double-edged sword in sepsis, the liver-mediated immune response is responsible for clearing bacteria and toxins but also causes inflammation, immunosuppression, and organ damage. Attenuating liver injury and restoring liver function lowers morbidity and mortality rates in patients with sepsis. This review summarizes the central role of liver in the host immune response to sepsis and in clinical outcomes. PMID:24611785

  9. Leukoaraiosis, intracerebral hemorrhage, and functional outcome after acute stroke thrombolysis

    PubMed Central

    Kongbunkiat, Kannikar; Wilson, Duncan; Kasemsap, Narongrit; Tiamkao, Somsak; Jichi, Fatima; Palumbo, Vanessa; Hill, Michael D.; Buchan, Alastair M.; Jung, Simon; Mattle, Heinrich P.; Henninger, Nils

    2017-01-01

    Objective: To perform a systematic review and pooled meta-analysis of published studies to assess whether the presence of leukoaraiosis on neuroimaging before treatment with thrombolysis (IV or intra-arterial) is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome. Methods: We included studies of patients with acute ischemic stroke, treated with IV or intra-arterial thrombolysis, which assessed functional outcome (3-month modified Rankin Scale [mRS]) or sICH in relation to leukoaraiosis on pretreatment neuroimaging (CT or MRI). We used random-effects models to calculate pooled relative risks (RR) of sICH and poor functional outcome (mRS ≥ 2) for any vs no leukoaraiosis (using any rating scale) and for no to mild vs moderate to severe leukoaraiosis (using the Van Swieten or Fazekas Schmidt scale). Results: We identified 15 studies (total n = 6,967). For sICH outcome, the RR was 1.65 (n = 5,551; 95% confidence interval [CI] 1.26–2.16, p = 0.001) with an absolute risk (AR) increase of 2.5% for any leukoaraiosis vs none. The RR was 2.4 (n = 4,192; 95% CI 1.83–3.14, p = 0.001) with an AR increase of 6.2% for moderate to severe vs no to mild leukoaraiosis. For poor functional outcome; the RR was 1.30 (n = 3,401; 95% CI 1.19–1.42, p = 0.001) with an AR increase of 15.4% for any leukoaraiosis vs none. The RR was 1.31 (n = 3,659; 95% CI 1.22–1.42, p = 0.001) with an AR increase of 17.5% for moderate to severe vs no to mild leukoaraiosis. No statistical heterogeneity was noted for any of the analyses. Conclusions: Leukoaraiosis presence and severity are consistently associated with an increased risk of sICH and poor functional outcome after IV or intra-arterial thrombolysis for acute ischemic stroke. PMID:28130468

  10. Low Plasma Levels of Adiponectin Do Not Explain Acute Respiratory Distress Syndrome Risk: a Prospective Cohort Study of Patients with Severe Sepsis.

    PubMed

    Palakshappa, Jessica A; Anderson, Brian J; Reilly, John P; Shashaty, Michael G S; Ueno, Ryo; Wu, Qufei; Ittner, Caroline A G; Tommasini, Anna; Dunn, Thomas G; Charles, Dudley; Kazi, Altaf; Christie, Jason D; Meyer, Nuala J

    2016-03-16

    Obesity is associated with the development of acute respiratory distress syndrome (ARDS) in at-risk patients. Low plasma levels of adiponectin, a circulating hormone-like molecule, have been implicated as a possible mechanism for this association. The objective of this study was to determine the association of plasma adiponectin level at ICU admission with ARDS and 30-day mortality in patients with severe sepsis and septic shock. This is a prospective cohort study of patients admitted to the medical ICU at the Hospital of the University of Pennsylvania. Plasma adiponectin was measured at the time of ICU admission. ARDS was defined by Berlin criteria. Multivariable logistic regression was used to determine the association of plasma adiponectin with the development of ARDS and mortality at 30 days. The study included 164 patients. The incidence of ARDS within 5 days of admission was 45%. The median initial plasma adiponectin level was 7.62 mcg/ml (IQR: 3.87, 14.90) in those without ARDS compared to 8.93 mcg/ml (IQR: 4.60, 18.85) in those developing ARDS. The adjusted odds ratio for ARDS associated with each 5 mcg increase in adiponectin was 1.12 (95% CI 1.01, 1.25), p-value 0.025). A total of 82 patients (51%) of the cohort died within 30 days of ICU admission. There was a statistically significant association between adiponectin and mortality in the unadjusted model (OR 1.11, 95% CI 1.00, 1.23, p-value 0.04) that was no longer significant after adjusting for potential confounders. In this study, low levels of adiponectin were not associated with an increased risk of ARDS in patients with severe sepsis and septic shock. This argues against low levels of adiponectin as a mechanism explaining the association of obesity with ARDS. At present, it is unclear whether circulating adiponectin is involved in the pathogenesis of ARDS or simply represents an epiphenomenon of other unknown functions of adipose tissue or metabolic alterations in sepsis.

  11. Senegenin Ameliorate Acute Lung Injury Through Reduction of Oxidative Stress and Inhibition of Inflammation in Cecal Ligation and Puncture-Induced Sepsis Rats.

    PubMed

    Liu, Chun-Hong; Zhang, Wei-Dong; Wang, Jian-Jie; Feng, Shan-Dan

    2016-04-01

    The purpose of this study was to assess the protective effect of senegenin on acute lung injury (ALI) in rats induced by sepsis. Rat ALI model was reproduced by cecal ligation and puncture (CLP). All rats were randomly divided into five groups: group 1 (control), group 2 (CLP), group 3 (CLP + senegenin 15 mg/kg), group 4 (CLP + senegenin 30 mg/kg), and group 5 (CLP + senegenin 60 mg/kg). CLP + senegenin groups received senegenin by gavage daily for consecutive 5 days, respectively, while the mice in control and CLP groups were given an equivalent volume of saline. We detected the lung wet/dry weight ratios and the histopathology of the lung. The levels of lung tissue myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were determined. Meanwhile, the nuclear factor-kappa B (NF-κB) activation, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) levels were studied. The results demonstrated that senegenin treatment significantly attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, protein leak, infiltration of leukocytes, and MPO activity. In addition, senegenin markedly decreased MDA content and increased SOD activity and GSH level. Serum levels of TNF-α and IL-1β were also decreased by senegenin administration. Furthermore, senegenin administration inhibited the nuclear translocation of NF-κB in the lungs. These findings indicate that senegenin exerts protective effects on CLP-induced septic rats. Senegenin may be a potential therapeutic agent against sepsis.

  12. Clinical profile and outcome of acute kidney injury related to pregnancy in developing countries: a single-center study from India.

    PubMed

    Godara, Suraj M; Kute, Vivek B; Trivedi, Hargovind L; Vanikar, Aruna V; Shah, Pankaj R; Gumber, Manoj R; Patel, Himanshu V; Gumber, Vandana M

    2014-07-01

    Acute kidney injury (AKI) is one of the most challenging and serious complications of pregnancy. We present our experience on the clinical profile and outcome of 57 patients with pregnancy-related AKI, of a total of 580 patients with AKI seen during the study period. This is a prospective single-center study in a civil hospital conducted from January to December 2010. The most common age group of the study patients was 20-25 years; 43.8% of the patients had received antenatal care. AKI was observed in the puerperium (n = 34), early pregnancy (n = 10) and late pregnancy (n = 13). The cause of AKI included puerperal sepsis (63.1%), pregnancy-induced hypertension (PIH) (33.33%), post-abortion (22.80%), ante-partum hemorrhage (APH) (14%) and post-partum hemorrhage (PPH) (8%). Complete, partial and no renal recovery was observed in 52.64%, 21.05% and 26.31% of the patients, respectively. Low platelet count and plasma fibrinogen and high bilirubin, D-dimer and activated partial thromboplast in time were observed more commonly in patients with partial recovery. Of the 57 patients, 50 received hemodialysis, three received peritoneal dialysis and seven patients were managed conservatively. A total of 13 patients developed cortical necrosis that was associated with sepsis in six, PPH and pre-eclampsia/eclampsia in three patients each and APH in one. Nine patients died, and the cause of death was septicemia in four, pre-eclampsia in three and APH and PPH in one patient each. In our study, puerperal sepsis was the most common etiological factor for pregnancy-related AKI. Prolonged oliguria or anuria were bad prognostic factors for renal recovery. Sepsis, thrombocytopenia, disseminated intra-vascular coagulation and liver involvement were associated with increased mortality.

  13. Compliance with severe sepsis bundles and its effect on patient outcomes of severe community-acquired pneumonia in a limited resources country

    PubMed Central

    Li, Hai-Yan; Li, Yi-Min; Nong, Ling-Bo; Xu, Yuan-Da; He, Guo-Qing; Liu, Xiao-Qing; Jiang, Mei; Xiao, Zheng-Iun; Zhong, Nan-Shan

    2014-01-01

    Introduction Validation of compliance with severe sepsis bundles is still needed. The purpose of this study was to determine compliance and its outcomes in severe community-acquired pneumonia (CAP) patients in a limited resources country. Material and methods A prospective cohort study of 212 severe CAP patients was carried out. The implementation programme was organized into two continuous phases. The primary outcomes were compliance and hospital mortality. Results Compliance with administration of antibiotics and vasopressors as well as plateau pressure on average < 30 cm H2O was high in both groups. In the bundles group, patients received more serum lactate monitoring (62.3% vs. 11.3%), more blood cultures (47.1% vs. 24.5%), more fluid resuscitation (63.2% vs. 26.4%) and volumes infused (1319.8 ±1107.4 ml vs. 461.9 ±799.3 ml), more inotropic dobutamine and/or packed red blood cells (21.7% vs. 10.0%), more low-dose steroids (56.5% vs. 15.0%), and more glucose control (51.9% vs. 6.6%) compared with such patients in the control group. The rates of total compliance with 6-hour, 24-hour, and 6/24-hour bundles in the prospective period were 47.1%, 51.9%, and 42.5%, respectively. Hospital mortality was reduced from 44.3% to 29.2% (p = 0.023) in the bundles group, and the compliant subgroup had a more than twofold decrease in mortality (17.8% vs. 37.7%, p = 0.003). Serum lactate measured, blood cultures, and fluid resuscitation showed independent relationships with decreased mortality. Conclusions Total compliance was relatively low, but the implementation of severe sepsis bundles could clearly reduce mortality from severe CAP. PMID:25395949

  14. Sex and age differences and outcomes in acute coronary syndromes.

    PubMed

    Vasiljevic-Pokrajcic, Zorana; Mickovski, Natasa; Davidovic, Goran; Asanin, Milika; Stefanovic, Branislav; Krljanac, Gordana; Radosavljevic-Radovanovic, Mina; Radovanovic, Nebojsa; Lasica, Ratko; Milanović, Sladjan; Bjekić, Jovana; Majstorovic-Stakic, Marta; Trifunovic, Danijela; Karadzic, Ana; Rajic, Dubravka; Milosevic, Aleksandra; Zdravkovic, Marija; Saric, Jelena; Bugiardini, Raffaele

    2016-08-01

    There is conflicting information about sex differences in presentation, treatment, and outcome after acute coronary syndromes (ACS) in the era of reperfusion therapy and percutaneous coronary intervention. The aim of this study was to examine presentation, acute therapy, and outcomes of men and women with ACS with special emphasis on their relationship with younger age (≤65years). From January 2010 to June 2015, we enrolled 5140 patients from 3 primary PCI capable hospitals. Patients were registered according to the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) registry protocol (ClinicalTrials.gov: NCT01218776). The primary outcome was the incidence of in-hospital mortality. The study population was constituted by 2876 patients younger than 65years and 2294 patients older. Women were older than men in both the young (56.2±6.6 vs. 54.1±7.4) and old (74.9±6.4 vs. 73.6±6.0) age groups. There were 3421 (66.2%) patients with ST elevation ACS (STE-ACS) and 1719 (33.8%) patients without ST elevation ACS (NSTE-ACS). In STE-ACS, the percentage of patients who failed to receive reperfusion was higher in women than in men either in the young (21.7% vs. 15.8%) than in the elderly (35.2% vs. 29.6%). There was a significant higher mortality in women in the younger age group (age-adjusted OR 1.52, 95% CI: 1.01-2.29), but there was no sex difference in the older group (age-adjusted OR 1.10, 95% CI: 0.87-1.41). Significantly sex differences in mortality were not seen in NSTE-ACS patients. In-hospital mortality from ACS is not different between older men and women. A higher short-term mortality can be seen only in women with STEMI and age of 65 or less. Copyright © 2016. Published by Elsevier Ireland Ltd.

  15. Severe sepsis in older adults.

    PubMed

    Umberger, Reba; Callen, Bonnie; Brown, Mary Lynn

    2015-01-01

    Severe sepsis may be underrecognized in older adults. Therefore, the purpose of this article is to review special considerations related to early detection of severe sepsis in older adults. Normal organ changes attributed to aging may delay early detection of sepsis at the time when interventions have the greatest potential to improve patient outcomes. Systems are reviewed for changes. For example, the cardiovascular system may have a limited or absent compensatory response to inflammation after an infectious insult, and the febrile response and recruitment of white blood cells may be blunted because of immunosenescence in aging. Three of the 4 hallmark responses (temperature, heart rate, and white blood cell count) to systemic inflammation may be diminished in older adults as compared with younger adults. It is important to consider that older adults may not always manifest the typical systemic inflammatory response syndrome. Atypical signs such as confusion, decreased appetite, and unsteady gait may occur before sepsis related organ failure. Systemic inflammatory response syndrome criteria and a comparison of organ failure criteria were reviewed. Mortality rates in sepsis and severe sepsis remain high and are often complicated by multiple organ failures. As the numbers of older adults increase, early identification and prompt treatment is crucial in improving patient outcomes.

  16. Trends and disparities in sepsis hospitalisations in Victoria, Australia.

    PubMed

    Ore, Timothy

    2015-12-14

    Objective The aim of the present study was to determine the clinical and epidemiological characteristics of patients with sepsis admitted to hospitals in Victoria, Australia, during the period 2004-14. The data include incidence, severity and mortality.Methods In all, 44 222 sepsis hospitalisations were identified between 2004-05 and 2013-14 from the Victorian Admitted Episodes Dataset. The dataset contains clinical and demographic information on all admissions to acute public and private hospitals. Using the International Classification of Diseases (10th Revision) Australian Modification codes, incidence rates, severity of disease and mortality were calculated.Results Sepsis hospitalisation rates per 10 000 population increased significantly (P < 0.01) over the period, from 6.9 (95% confidence interval (CI) 5.6-7.8) to 10.0 (95% CI 9.1-11.1), an annual growth rate of 3.8%. The age-standardised in-hospital death rates per 100 000 population grew significantly (P < 0.01) from 9.2 (95% CI 7.8-10.4) in 2004-05 to 13.0 (95% CI 11.7-14.6) in 2013-14, an annual growth rate of 3.1%. Among people under 45 years of age, the 0-4 years age group had the highest hospitalisation rate (3.0 per 10 000 population; 95% CI 2.7-3.4). Nearly half (46.2%) of all sepsis hospitalisations were among patients born overseas, with a rate of 14.5 per 10 000 population (95% CI 12.4-16.2) in that group compared with a rate of 5.9 per 10 000 population (95% CI 5.3-6.7) for patients born in Australia. The age-standardised sepsis hospitalisation rate was 2.6-fold greater in the lowest compared with highest socioeconomic areas (12.7 per 10 000 population (95% CI 11.2-13.8) vs 4.8 per 10 000 population (95% CI 4.1-5.7), respectively).Conclusion This paper shows a significant upward trend in both sepsis separation rates and in-hospital death rates over the period; unlike sepsis, in-hospital death rates from all diagnoses fell over the same period. The results can be used to stimulate review of

  17. Anaemia to predict outcome in patients with acute coronary syndromes.

    PubMed

    Ennezat, Pierre Vladimir; Maréchaux, Sylvestre; Pinçon, Claire; Finzi, Jonathan; Barrailler, Stéphanie; Bouab