Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed
OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: 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 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...
Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed
OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: 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 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...
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, Younsuck; 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
Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012!' Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings
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
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
Grek, Ami; Booth, Sandra; Festic, Emir; Maniaci, Michael; Shirazi, Ehsan; Thompson, Kristine; Starbuck, Angela; Mcree, Chad; Naessens, James M; Moreno Franco, Pablo
The Surviving Sepsis Campaign guidelines are designed to decrease mortality through consistent application of a 7-element bundle. This study evaluated the impact of improvement in bundle adherence using a time-series analysis of compliance with the bundle elements before and after interventions intended to improve the process, while also looking at hospital mortality. This article describes interventions used to improve bundle compliance and hospital mortality in patients admitted through the emergency department with sepsis, severe sepsis, or septic shock. Quality improvement methodology was used to develop high-impact interventions that led to dramatically improved adherence to the Surviving Sepsis Campaign guidelines bundle. Improved performance was associated with a significant decrease in the in-hospital mortality of severe sepsis patients presenting to the emergency department.
Aitken, Leanne M; Williams, Ged; Harvey, Maurene; Blot, Stijn; Kleinpell, Ruth; Labeau, Sonia; Marshall, Andrea; Ray-Barruel, Gillian; Moloney-Harmon, Patricia A; Robson, Wayne; Johnson, Alexander P; Lan, Pang Nguk; Ahrens, Tom
To provide a series of recommendations based on the best available evidence to guide clinicians providing nursing care to patients with severe sepsis. Modified Delphi method involving international experts and key individuals in subgroup work and electronic-based discussion among the entire group to achieve consensus. We used the Surviving Sepsis Campaign guidelines as a framework to inform the structure and content of these guidelines. We used the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system to rate the quality of evidence from high (A) to very low (D) and to determine the strength of recommendations, with grade 1 indicating clear benefit in the septic population and grade 2 indicating less confidence in the benefits in the septic population. In areas without complete agreement between all authors, a process of electronic discussion of all evidence was undertaken until consensus was reached. This process was conducted independently of any funding. Sixty-three recommendations relating to the nursing care of severe sepsis patients are made. Prevention recommendations relate to education, accountability, surveillance of nosocomial infections, hand hygiene, and prevention of respiratory, central line-related, surgical site, and urinary tract infections, whereas infection management recommendations related to both control of the infection source and transmission-based precautions. Recommendations related to initial resuscitation include improved recognition of the deteriorating patient, diagnosis of severe sepsis, seeking further assistance, and initiating early resuscitation measures. Important elements of hemodynamic support relate to improving both tissue oxygenation and macrocirculation. Recommendations related to supportive nursing care incorporate aspects of nutrition, mouth and eye care, and pressure ulcer prevention and management. Pediatric recommendations relate to the use of antibiotics, steroids, vasopressors and
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, Younsuck; 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
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.
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
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.
Dellinger, R Phillip
The Surviving Sepsis Campaign develops and promotes evidence-based guidelines and performance-improvement practices aimed at reducing deaths from sepsis worldwide. The most recent guidelines, published in 2013, provide detailed management strategies for acute care, fluid resuscitation, and vasopressor use. In addition, the campaign has developed simple, short protocols for what to do within 3 and 6 hours of recognition of sepsis. These protocols are associated with reduced mortality rates. Copyright © 2015 Cleveland Clinic.
Lilian Vloet; J. Schouten; N. Stevens; A. Rensen; A. Willems; F. Zeegers
Sepsis komt vaak voor in ziekenhuizen. Ernstige sepsis is verantwoordelijk voor 10 - 20% van alle Intensive Care (IC) opnames en is de belangrijkste doodsoorzaak op niet-cardiale IC?s. De gemiddelde mortaliteit van volwassenen met ernstige sepsis op de IC is 33% en van volwassenen met septische
Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui
To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B
Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui
To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de
Watkins, Richard R; Haller, Nairmeen; Wayde, Melinda; Armitage, Keith B
We aimed to assess the knowledge, attitudes, and perceptions of resident physicians regarding sepsis in general and the Surviving Sepsis Campaign Guidelines in particular. After institutional review board approval, we surveyed internal medicine (IM) and emergency medicine (EM) house staff from 3 separate institutions. House staff were notified of the survey via e-mail from their residency director or chief resident. The survey was Internet-based (using http://www.surveymonkey.com ), voluntary, and anonymous. The Surviving Sepsis Campaign Guidelines were used to develop the survey. The survey was open between December 2015 and April 2016. No incentives for participation were given. Reminder e-mails were sent approximately every 3 to 4 weeks to all eligible participants. Comparisons of responses were evaluated using the N-1 2-proportion test. A total of 133 responses were received. These included 84 from IM house staff, 27 from EM house staff, and 22 who selected "other." Eighty (101/126) percent reported managing at least 1 patient with sepsis in the preceding 30 days, 85% (97/114) rated their knowledge of the Surviving Sepsis Guidelines as "very familiar" or at least "somewhat familiar," and 84% (91/108) believed their training in the diagnosis and management of sepsis was "excellent" or at least "good." However, 43% (47/108) reported not receiving any feedback on their treatment of patients with sepsis in the last 30 days, while 24% (26/108) received feedback once. Both IM and EM house staff received comparable rates of feedback (62% vs 48%, respectively; P = .21). For the 3 questions that directly tested knowledge of the guidelines, the scores of the IM and EM house staff were similar. Notably, house staff on the Surviving Sepsis Campaign Guidelines is warranted, along with more consistent feedback regarding their diagnosis and management of sepsis.
IDSA did not endorse the 2016 Surviving Sepsis Campaign Guidelines despite being represented in the working group that drafted the guidelines document. Leadership from the IDSA, the Surviving Sepsis Campaign Guidelines, and the Society of Critical Care Medicine had numerous amicable discussions primarily regarding the bolded, rated guidelines recommendations. Our societies had different perspectives, however, regarding the interpretation of the major studies that informed the guidelines' recommendations, thus leading us to different conclusions and different perspectives on the recommendations. IDSA consequently elected not to endorse the guidelines. IDSA nonetheless hopes to be able to continue collaborating with the Surviving Sepsis Campaign and the Society of Critical Care Medicine to resolve our differences and to develop further strategies together to prevent sepsis and septic shock as well as reduce death and disability from these conditions both nationally and globally.
Full Text Available The Surviving Sepsis Campaign (SSC guidelines describe best practice for the management of severe sepsis and septic shock in developed countries, but most deaths from sepsis occur where healthcare is not sufficiently resourced to implement them. Our objective was to define the feasibility and basis for modified guidelines in a resource-restricted setting.We undertook a detailed assessment of sepsis management in a prospective cohort of patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital in lower-middle income Thailand. We compared their management with the SSC guidelines to identify care bundles based on existing capabilities or additional activities that could be undertaken at zero or low cost. We identified 72 patients with severe sepsis or septic shock associated with S. aureus bacteraemia, 38 (53% of who died within 28 days. One third of patients were treated in intensive care units (ICUs. Numerous interventions described by the SSC guidelines fell within existing capabilities, but their implementation was highly variable. Care available to patients on general wards covered the fundamental principles of sepsis management, including non-invasive patient monitoring, antimicrobial administration and intravenous fluid resuscitation. We described two additive care bundles, one for general wards and the second for ICUs, that if consistently performed would be predicted to improve outcome from severe sepsis.It is feasible to implement modified sepsis guidelines that are scaled to resource availability, and that could save lives prior to the publication of international guidelines for developing countries.
Almeida, Mónica; Ribeiro, Orquídea; Aragão, Irene; Costa-Pereira, Altamiro; Cardoso, Teresa
Higher compliance with Surviving Sepsis Campaign (SSC) recommendations has been associated with lower mortality. The authors evaluate differences in compliance with SSC 6-hour bundle according to hospital entrance time (day versus night) and its impact on hospital mortality. Prospective cohort study of all patients with community-acquired severe sepsis admitted to the intensive care unit of a large university tertiary care hospital, over 3.5 years with a follow-up until hospital discharge. Time to compliance with each recommendation of the SSC 6-hour bundle was calculated according to hospital entrance period: day (08:30 to 20:30) versus night (20:30 to 08:30). For the same periods, clinical staff composition and the number of patients attending the emergency department (ED) was also recorded. In this period 300 consecutive patients were included. Compliance rate was (night vs. day): serum lactate measurement 57% vs. 49% (P = 0.171), blood cultures drawn 59% vs. 37% (P 8 mmHg 45% vs. 29% (P = 0.021), and central venous oxygen saturation (SvcO₂) >70%, 7% vs. 2% (P = 0.082); fluids were administered in all patients with hypotension in both periods and vasopressors were administered in patients with hypotension not responsive to fluids in 100% vs. 99%. Time to get specific actions done was also different (night vs. day): serum lactate measurement (4.5 vs. 7 h, P = 0.018), blood cultures drawn (4 vs. 8 h, P night with a higher proportion of less differentiated doctors. The number of patients attending the Emergency Department was lower overnight. Hospital mortality rate was 34% in patients entering in the night period vs. 40% in those entering during the day (P = 0.281). Compliance with SSC recommendations was higher at night. A possible explanation might be the increased nurse to patient ratio in that period. Adjustment of the clinical team composition to the patients' demand is needed to increase compliance and improve prognosis.
Mung'ayi, V; Karuga, R
There are emerging therapies for managing septic critically-ill patients. There is little data from the developing world on their usage. To determine the conformity rate for resuscitation and management bundles for septic patients amongst physicians in a general intensive care unit. Cross sectional observational study. The general intensive care unit, Aga Khan University Hospital,Nairobi. Admitting physicians from all specialties in the general intensive care unit. The physicians had high conformity rates of 92% and 96% for the fluid resuscitation and use of va so pressors respectively for the initial resuscitation bundle. They had moderate conformity rates for blood cultures prior to administering antibiotics (57%) and administration of antibiotics within first hour of recognition of septic shock (54%). There was high conformity rate to the glucose control policy (81%), use of protective lung strategy in acute lung injury/Acute respiratory distress syndrome, venous thromboembolism prophylaxis (100%) and stress ulcer prophylaxis (100%) in the management bundle. Conformity was moderate for use of sedation, analgesia and muscle relaxant policy (69%), continuous renal replacement therapies (54%) and low for steroid policy (35%), administration ofdrotrecogin alfa (0%) and selective digestive decontamination (15%). There is varying conformity to the international sepsis guidelines among physicians caring for patients in our general ICU. Since increased conformity would improve survival and reduce morbidity, there is need for sustained education and guideline based performance improvement.
Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens
To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis.......To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis....
Severe sepsis is a major cause of morbidity and mortality, claiming between 36 000 and 64 000 lives annually in the UK, with a mortality rate of 35%. International guidelines for the management of severe sepsis were published in 2004 by the Surviving Sepsis Campaign and condensed into two Care Bundles. In 2010, the Campaign published results from its improvement programme showing that, although an absolute mortality reduction of 5.4% was seen over a 2 year period in line with increasing compliance with the Bundles, reliability was not achieved and Bundle compliance reached only 31%. This article explores current challenges in sepsis care and opportunities for further improvements. Basic care tasks [microbiological sampling and antibiotic delivery within 1 h, fluid resuscitation, and risk stratification using serum lactate (or alternative)] are likely to benefit patients most, yet are unreliably performed. Barriers include lack of awareness and robust process, the lack of supporting controlled trials, and complex diagnostic criteria leading to recognition delays. Reliable, timely delivery of more complex life-saving tasks (such as early goal-directed therapy) demands greater awareness, faster recognition and initiation of basic care, and more effective collaboration between clinicians and nurses on the front line, in critical care and in specialist support services, such as microbiology and infectious diseases. Organizations such as Survive Sepsis, the Surviving Sepsis Campaign and the Global Sepsis Alliance are working to raise awareness and promote further improvement initiatives. Future developments will focus on sepsis biomarkers and microarray techniques to rapidly screen for pathogens, risk stratification using genetic profiling, and the development of novel therapeutic agents targeting immunomodulation.
Background: There are emerging therapies for managing septic critically-ill patients. There is little data from the developing world on their usage. Objectives: To determine the conformity rate for resuscitation and management bundles for septic patients amongst physicians in a general intensive care unit. Design: Cross ...
Kasal, Jan; Andersen, Zorana Jovanovic; Clermont, Gilles
Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate....
Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens
OBJECTIVE: To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis. DESIGN: A prospective study of mortality in patients with sepsis whose serum levels of sL-selectin were measured on admission to an intensive care unit (ICU) and 4 days later. Follow-up data......, and 3 and 12 months after admission. Serum sL-selectin levels were significantly lower in the patients than in the controls. Sepsis nonsurvivors had significantly lower levels than survivors. Efficiency analysis and receiver operation characteristics showed that the ideal cutoff point for s......L-selectin as a test for sepsis survival was 470 ng/ml. The accumulated mortality in patients with subnormal sL-selectin levels on admission was significantly increased. No correlation was found between clinical or paraclinical markers, including SAPS II and sL-selectin, and no relationship to the microbial diagnosis...
Liao, Xue-Lian; Xie, Zhi-Chao; Kang, Yan
Sepsis is a critical clinical syndrome which keep puzzling the medical profession for many years. Recently, the results from several large-scale trials challenged the necessity of early goal directed therapy (EGDT) in surviving sepsis bundle, These trials were not opposed to EGDT but bring new concept that it is essential to utilize therapy with multiple monitoring measures in order to minimize injury while guarantee the safety . Deeper understanding in the pathogenesis of sepsis gives rise to the update of its definition based on vital organ dysfunction. The importance of dynamic monitoring in defining sepsis also need to be emphasized. Developing more effective monitoring measures could provide better treatments, thus improve the prognosis of septic patients. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).
Joseph, Bellal; Khalil, Mazhar; Hashmi, Ammar; Hecker, Louise; Kulvatunyou, Narong; Tang, Andrew; Friese, Randall S; Rhee, Peter
Sepsis remains the leading cause of death in the surgical intensive care unit. Prior studies have demonstrated a survival benefit of remote ischemic conditioning (RIC) in many disease states. The aim of this study was to determine the effects of RIC on survival in sepsis in an animal model and to assess alterations in inflammatory biochemical profiles. We hypothesized that RIC alters inflammatory biochemical profiles resulting in decreased mortality in a septic mouse model. Eight to 12 week C57BL/6 mice received intra-peritoneal injection of 12.5-mg/kg lipopolysaccharide (LPS). Septic animals in the experimental group underwent RIC at 0, 2, and 6 h after LPS by surgical exploration and alternate clamping of the femoral artery. Six 4-min cycles of ischemia-reperfusion were performed. Primary outcome was survival at 5-d after LPS injection. Secondary outcome was to assess the following serum cytokine levels: interferon-γ (IFN-γ), interleukin (IL)-10, IL-1β, and tumor necrosis factoralpha (TNFα) at the baseline before LPS injection, 0 hour after LPS injection, and at 2, 4, 24 hours after induction of sepsis (RIC was performed at 2 h after LPS injection). Kaplan-Meier survival analysis and log-rank test were used. ANOVA test was used to compare cytokine measurements. We performed experiments on 44 mice: 14 sham and 30 RIC mice (10 at each time point). Overall survival was higher in the experimental group compared to the sham group (57% versus 21%; P = 0.02), with the highest survival rate observed in the 2-hour post-RIC group (70%). On Kaplan-Meier analysis, 2-h post-RIC group had increased survival at 5 days after LPS (P = 0.04) with hazard ratio of 0.3 (95% confidence interval = 0.09-0.98). In the RIC group, serum concentrations of IFN-γ, IL-10, IL-1β, and TNFα peaked at 2 h after LPS and then decreased significantly over 24 hours (P sepsis and has the potential for implementation in the clinical practice. Early implementation of RIC may play an
Aquina, Christopher T; Blumberg, Neil; Becerra, Adan Z; Boscoe, Francis P; Schymura, Maria J; Noyes, Katia; Monson, John R T; Fleming, Fergal J
To investigate the potential additive effects of blood transfusion and sepsis on colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival after colon cancer surgery. Perioperative blood transfusions are associated with infectious complications and increased risk of cancer recurrence through systemic inflammatory effects. Furthermore, recent studies have suggested an association among sepsis, subsequent systemic inflammation, and adverse cardiovascular outcomes. However, no study has investigated the association among transfusion, sepsis, and disease-specific survival in postoperative patients. The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I to III colon cancer resections from 2004 to 2011. Propensity-adjusted survival analyses assessed the association of perioperative allogeneic blood transfusion, sepsis, and 5-year colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival. Among 24,230 patients, 29% received a transfusion and 4% developed sepsis. After risk adjustment, transfusion and sepsis were associated with worse colon cancer disease-specific survival [(+)transfusion: hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.09-1.30; (+)sepsis: HR 1.84, 95% CI 1.44-2.35; (+)transfusion/(+)sepsis: HR 2.27, 95% CI 1.87-2.76], cardiovascular disease-specific survival [(+)transfusion: HR 1.18, 95% CI 1.04-1.33; (+)sepsis: HR 1.63, 95% CI 1.14-2.31; (+)transfusion/(+)sepsis: HR 2.04, 95% CI 1.58-2.63], and overall survival [(+)transfusion: HR 1.21, 95% CI 1.14-1.29; (+)sepsis: HR 1.76, 95% CI 1.48-2.09; (+)transfusion/(+)sepsis: HR 2.36, 95% CI 2.07-2.68] relative to (-)transfusion/(-)sepsis. Additional analyses suggested an additive effect with those who both received a blood transfusion and developed sepsis having even worse survival. Perioperative blood transfusions are associated with shorter survival
Farah C. Thabet
Full Text Available Objectives: To assess the compliance with the 2006 American College of Critical Care-Pediatric Advanced Life Support (ACCM-PALS guidelines for sepsis management, and the 2012 surviving sepsis campaign (SSC, for the management of pediatric patients with sepsis and to identify the main barriers to adherence to these guidelines. Methods: In November 2015, a prospective cohort study in which a web based electronic survey using a case scenario to explore the usual management of a child with severe sepsis was designed and sent to all consultant pediatric intensivists practicing in Kingdom of Saudi Arabia (KSA. Adherences to 2012 SSC guidelines and to 4 algorithmic time-specific goals outlined in the ACCM-PALS guidelines were measured. Results: Sixty-one (76% of 80 consultant pediatric intensivists working in KSA responded to the survey. Of the 61 respondents, 94% reported administering antibiotics within one hour of the child presentation, 98% reported starting resuscitation by giving fluid boluses, 93% reported starting vasopressor if the patient remained hypotensive despite fluid resuscitation, and 86% reported they would start hydrocortisone in case of catecholamine refractory shock. In total, 80% of the intensivists reported full adherence to all of the 4 components in the ACCM-PALS bundle; 50% reported that the absence of a locally written protocol was the main barrier to adherence to the SSC guidelines. Conclusion: Pediatric intensivists reported good adherence to the 2006 ACCM-PALS guidelines and 2012 SSC guidelines with some variability in interpretation of the recommendations. The absence of a written protocol was the main reported barrier to adherence to these guidelines.
... mild sepsis, but the mortality rate for septic shock is nearly 50 percent. Also, an episode of severe sepsis may ... of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...
Bakalov, Veli; Amathieu, Roland; Triba, Mohamed N.; Clément, Marie-Jeanne; Reyes Uribe, Laura; Le Moyec, Laurence; Kaynar, Ata Murat
Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate. PMID:28009836
Perner, Anders; Gordon, Anthony C; De Backer, Daniel
Sepsis is a major growing global burden and a major challenge to intensive care clinicians, researchers, guideline committee members and policy makers, because of its high and increasing incidence and great pathophysiological, molecular, genetic and clinical complexity. In spite of recent progress......, short-term mortality remains high and there is growing evidence of long-term morbidity and increased long-term mortality in survivors of sepsis both in developed and developing countries. Further improvement in the care of patients with sepsis will impact upon global health. In this narrative review...... and subsequent outcomes are to be improved in patients with sepsis....
Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi
Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Cairo, M.S.; Rucker, R.; Bennetts, G.A.; Hicks, D.; Worcester, C.; Amlie, R.; Johnson, S.; Katz, J.
To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions
Hou, JinChao; Chen, QiXing; Wu, XiaoLiang; Zhao, DongYan; Reuveni, Hadas; Licht, Tamar; Xu, MengLong; Hu, Hu; Hoeft, Andreas; Ben-Sasson, Shmuel A; Shu, Qiang; Fang, XiangMing
Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown. To investigate the role of S1PR3 in antibacterial immunity during sepsis. Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers. S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3 -/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3 -/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3 -/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes. S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.
Perner, Anders; Rhodes, Andrew; Venkatesh, Bala
Because of its high incidence and clinical complexity, sepsis is a major challenge to clinicians and researchers and a global burden to healthcare systems and society. Despite recent progress, short- and long-term morbidity, mortality and costs remain high in both developed and developing countri...
Full Text Available Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g were submitted to cecal ligation and puncture (CLP, and 44 were submitted to sham operation. Forty-four rats (40% survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory, 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05. In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05, suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.
Perl, T M; Dvorak, L; Hwang, T; Wenzel, R P
To determine the long-term (> 3 months) survival of septic patients, to develop mathematical models that predict patients likely to survive long-term, and to measure the health and functional status of surviving patients. A large tertiary care university hospital and an associated Veterans Affairs Medical Center. From December 1986 to December 1990, a total of 103 patients with suspected gram-negative sepsis entered a double-blind, placebo-controlled efficacy trial of monoclonal antiendotoxin antibody. Of these, we followed up 100 patients for 7667 patient-months. Beginning in May 1992, we reviewed hospital records and contacted all known survivors. We measured the health status of all surviving patients. The determinants of long-term survival (up to 6 years) were identified through two Cox proportional hazard regression models: one that included patient characteristics identified at the time of sepsis (bedside model) and another that included bedside, infection-related, and treatment characteristics (overall model). Of the 60 patients in the cohort who died at a median interval of 30.5 days after sepsis, 32 died within the first month of the septic episode, seven died within 3 months, and four more died within 6 months. In the bedside multivariate model constructed to predict long-term survival, large hazard ratios (HRs) were associated with severity of underlying illness as classified by McCabe and Jackson criteria (for rapidly fatal disease, HR = 30.4, P respiratory distress syndrome (HR = 2.3; P = .02) predicted patients most likely to die. The Acute Physiology and Chronic Health Evaluation II score was not a significant predictor of outcome when either model included the simpler McCabe and Jackson classification of underlying disease severity. We compared the health status scores with norms for the general population and found that patients with resolved sepsis reported more physical dysfunction (P bedridden), suggesting that the patients' physical function
Choudhury, Soumen; Kannan, Kandasamy; Pule Addison, M; Darzi, Sazad A; Singh, Vishakha; Singh, Thakur Uttam; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Parida, Subhashree; Debroy, Biplab; Paul, Avishek; Mishra, Santosh Kumar
We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Copyright © 2015 Elsevier Inc. All rights reserved.
Beffa, David C; Fischman, Alan J.; Fagan, Shawn P.; Hamrahi, Victoria F.; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Carter, Edward A.
Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model. PMID:21145172
Stromberg, Paul E; Woolsey, Cheryl A; Clark, Andrew T; Clark, Jessica A; Turnbull, Isaiah R; McConnell, Kevin W; Chang, Katherine C; Chung, Chun-Shiang; Ayala, Alfred; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M
Lymphocytes help determine whether gut epithelial cells proliferate or differentiate but are not known to affect whether they live or die. Here, we report that lymphocytes play a controlling role in mediating gut epithelial apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is similar in unmanipulated Rag-1(-/-) and wild-type (WT) mice. However, Rag-1(-/-) animals have a 5-fold augmentation in gut epithelial apoptosis following cecal ligation and puncture (CLP) compared to septic WT mice. Reconstitution of lymphocytes in Rag-1(-/-) mice via adoptive transfer decreases intestinal apoptosis to levels seen in WT animals. Subset analysis indicates that CD4(+) but not CD8(+), gammadelta, or B cells are responsible for the antiapoptotic effect of lymphocytes on the gut epithelium. Gut-specific overexpression of Bcl-2 in transgenic mice decreases mortality following CLP. This survival benefit is lymphocyte dependent since gut-specific overexpression of Bcl-2 fails to alter survival when the transgene is overexpressed in Rag-1(-/-) mice. Further, adoptively transferring lymphocytes to Rag-1(-/-) mice that simultaneously overexpress gut-specific Bcl-2 results in improved mortality following sepsis. Thus, sepsis unmasks CD4(+) lymphocyte control of gut apoptosis that is not present under homeostatic conditions, which acts as a key determinant of both cellular survival and host mortality.
Full Text Available Abstract Background Hospital associated infections are major problems, which are increasing in incidence and very costly. However, most research has focused only on measuring consequences associated with the initial hospitalization. We explored the long-term consequences of infections in elderly Medicare patients admitted to an intensive care unit (ICU and discharged alive, focusing on: sepsis, pneumonia, central-line-associated bloodstream infections (CLABSI, and ventilator-associated pneumonia (VAP; the relationships between the infections and long-term survival and resource utilization; and how resource utilization was related to impending death during the follow up period. Methods Clinical data and one year pre- and five years post-index hospitalization Medicare records were examined. Hazard ratios (HR and healthcare utilization incidence ratios (IR were estimated from state of the art econometric models. Patient demographics (i.e., age, gender, race and health status and Medicaid status (i.e., dual eligibility were controlled for in these models. Results In 17,537 patients, there were 1,062 sepsis, 1,802 pneumonia, 42 CLABSI and 52 VAP cases. These subjects accounted for 62,554 person-years post discharge. The sepsis and CLABSI cohorts were similar as were the pneumonia and VAP cohorts. Infection was associated with increased mortality (sepsis HR = 1.39, P Conclusions The infections had significant and lasting adverse consequences among the elderly. Yet, many of these infections may be preventable. Investments in infection prevention interventions are needed in both community and hospitals settings.
Bonet, Mercedes; Souza, Joao Paulo; Abalos, Edgardo; Fawole, Bukola; Knight, Marian; Kouanda, Seni; Lumbiganon, Pisake; Nabhan, Ashraf; Nadisauskiene, Ruta; Brizuela, Vanessa; Metin Gülmezoglu, A
Maternal sepsis is the underlying cause of 11% of all maternal deaths and a significant contributor to many deaths attributed to other underlying conditions. The effective prevention, early identification and adequate management of maternal and neonatal infections and sepsis can contribute to reducing the burden of infection as an underlying and contributing cause of morbidity and mortality. The objectives of the Global Maternal Sepsis Study (GLOSS) include: the development and validation of identification criteria for possible severe maternal infection and maternal sepsis; assessment of the frequency of use of a core set of practices recommended for prevention, early identification and management of maternal sepsis; further understanding of mother-to-child transmission of bacterial infection; assessment of the level of awareness about maternal and neonatal sepsis among health care providers; and establishment of a network of health care facilities to implement quality improvement strategies for better identification and management of maternal and early neonatal sepsis. This is a facility-based, prospective, one-week inception cohort study. This study will be implemented in health care facilities located in pre-specified geographical areas of participating countries across the WHO regions of Africa, Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific. During a seven-day period, all women admitted to or already hospitalised in participating facilities with suspected or confirmed infection during any stage of pregnancy through the 42nd day after abortion or childbirth will be included in the study. Included women will be followed during their stay in the facilities until hospital discharge, death or transfer to another health facility. The maximum intra-hospital follow-up period will be 42 days. GLOSS will provide a set of actionable criteria for identification of women with possible severe maternal infection and maternal sepsis. This study
Ahmed, Asma; Dolasia, Komal; Mukhopadhyay, Sangita
Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli- induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-α, IL-1β, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of E. coli Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture-induced sepsis, rPPE18 reduced TNF-α, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis. Copyright © 2018 by The American Association of Immunologists, Inc.
Alcayaga-Miranda, Francisca; Cuenca, Jimena; Martin, Aldo; Contreras, Luis; Figueroa, Fernando E; Khoury, Maroun
Sepsis is a clinical syndrome associated with a severe systemic inflammation induced by infection. Although different anti-microbial drugs have been used as treatments, morbidity and mortality rates remain high. Mesenchymal stem cells (MSCs) derived from the bone marrow have demonstrated a partial protective effect in sepsis. Menstrual derived MSCs (MenSCs) emerge as an attractive candidate because they present important advantages over other sources, including improved proliferation rates and paracrine response under specific stress conditions. Here, we evaluate their therapeutic effect in a polymicrobial severe sepsis model. The antimicrobial activity of MenSCs was determined in vitro through direct and indirect bacterial growth assays and the measurement of the expression levels of different antimicrobial peptides (AMPs) by quantitative reverse transcription-polymerase chain reaction. The therapeutic effect of MenSCs was determined in the cecal ligation and puncture (CLP) mouse model. Mice were then treated with antibiotics (AB) or MenSCs alone or in combination. The survival rates and histological and biochemical parameters were evaluated, and the systemic levels of pro- and anti-inflammatory cytokines as well as the response of specific lymphocyte subsets were determined by flow cytometry. MenSCs exerted an important antimicrobial effect in vitro, mediated by a higher expression of the AMP-hepcidin. In the CLP mouse model, MenSCs in synergy with AB (a) improved the survival rate (95 %) in comparison with saline (6 %), AB (73 %), and MenSCs alone (48 %) groups; (b) enhanced bacterial clearance in the peritoneal fluids and blood; (c) reduced organ injuries evaluated by lower concentrations of the liver enzymes alanine aminotransferase and aspartate aminotransferase; and (d) modulated the inflammatory response through reduction of pro- and anti-inflammatory cytokines without significant loss of T and B lymphocytes. We conclude that MenSCs in combination with AB
Klingensmith, Nathan J; Yoseph, Benyam P; Liang, Zhe; Lyons, John D; Burd, Eileen M; Margoles, Lindsay M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M
Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. Six-week-old FVB/N mice were randomized to receive 20% alcohol or water for 12 weeks. All mice then underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive either intraperitoneal injection of EGF (150 μg/kg/day) or normal saline. Water-fed mice given EGF had decreased 7-day mortality compared with water-fed mice (18% vs. 55%). Alcohol-fed mice given EGF also had decreased 7-day mortality compared with alcohol-fed mice (48% vs. 79%). Notably, while systemic EGF improved absolute survival to a similar degree in both water-fed and alcohol-fed mice, mortality was significantly higher in alcohol+EGF mice compared with water+EGF mice. Compared with water-fed septic mice, alcohol-fed septic mice had worsened intestinal integrity with intestinal hyperpermeability, increased intestinal epithelial apoptosis, decreased proliferation and shorter villus length. Systemic administration of EGF to septic alcohol-fed mice decreased intestinal permeability compared with septic alcohol-fed mice given vehicle, with increased levels of the tight junction mediators claudin-5 and JAM-A. Systemic administration of EGF to septic alcohol-fed mice also decreased intestinal apoptosis with an improvement in the Bax/Bcl-2 ratio. EGF also improved both crypt proliferation and villus length in septic alcohol-fed mice. EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore
Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M
Targeted IL-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic Inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild-type (WT) littermates (n = 127) were subjected to cecal ligation and puncture with a 27-gauge needle. The 7-day survival rate was 45% in transgenic animals and 30% in WT animals (P < or = 0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals regardless of whether they expressed the transgene. Local parameter of injury, including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines, and stimulated cytokines from intraepithelial lymphocytes, were similar between transgenic and WT mice. However, in stimulated splenocytes, proinflammatory cytokines monocyte chemoattractant protein 1 (189 +/- 43 vs. 40 +/- 8 pg/mL) and IL-6 (116 +/- 28 vs. 34 +/- 9 pg/mL) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (P < 0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the 2 groups, as were circulating LPS levels. Transgenic mice also had lower white blood cell counts associated with lower absolute neutrophil counts (0.5 +/- 0.1 vs. 1.0 +/- 0.2 10(3)/mm3; P < 0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage.
Villa, P; Demitri, M T; Meazza, C; Sironi, M; Gnocchi, P; Ghezzi, P
The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.
Renko, Marjo; Valkonen, Päivi; Tapiainen, Terhi; Kontiokari, Tero; Mattila, Pauli; Knuuttila, Matti; Svanberg, Martti; Leinonen, Maija; Karttunen, Riitta; Uhari, Matti
Background Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. Results We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis. PMID:18334022
Klingensmith, Nathan J; Chen, Ching-Wen; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Arbiser, Jack L; Ford, Mandy L; Coopersmith, Craig M
Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and anti-bacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce polymicrobial intraabdominal sepsis. Mice were then randomized to receive an injection of either Honokiol (120 mg/kg/day) or vehicle and were sacrificed after 24 hours for functional studies or followed 7 days for survival. Honokiol treatment after sepsis increased the frequency of CD4 T cells and increased activation of CD4 T cells as measured by the activation marker CD69. Honokiol also increased splenic dendritic cells. Honokiol simultaneously decreased frequency and number of CD8 T cells. Honokiol decreased systemic TNF without impacting other systemic cytokines. Honokiol did not have a detectable effect on kidney function, lung physiology, liver function or intestinal integrity. In contrast to prior studies of Honokiol in a lethal model of sepsis, Honokiol did not alter survival at seven days (70% mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective in modulating the host immune response and inflammation following a clinically relevant model of sepsis but is not sufficient to alter survival.
Grégoire, Murielle; Tadié, Jean-Marc; Uhel, Fabrice; Gacouin, Arnaud; Piau, Caroline; Bone, Nathaniel; Le Tulzo, Yves; Abraham, Edward; Tarte, Karin; Zmijewski, Jaroslaw W
Sepsis is accompanied by the initial activation of proinflammatory pathways and long-lasting immunosuppression that appears to contribute to late-occurring mortality. Although high-mobility group box 1 (HMGB1) is involved in many aspects of inflammation, its role in sepsis-induced immune suppression remains unclear. In this study, we examined HMGB1's contribution to neutrophil NADPH oxidase activity dysfunction and associated neutrophil-dependent bacterial clearance in mice subjected to sepsis and in patients who survive septic shock. Using a murine model of polymicrobial septic peritonitis, we demonstrated that treatment with anti-HMGB1 Ab significantly diminished sepsis-induced dysfunction of neutrophil NADPH oxidase activity. In a subsequent set of experiments, we found that blocking HMGB1 preserved the ability of neutrophils from patients recovering from septic shock to activate NADPH oxidase. Taken together, our data suggest that HMGB1 accumulation in the late phase of sepsis plays a specific role in the development of postsepsis immunosuppression and specifically affects neutrophil-dependent antibacterial defense mechanisms. Thus, blocking HMGB1 may be a promising therapeutic intervention to diminish the adverse effects of sepsis-induced immunosuppression. © Society for Leukocyte Biology.
Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M
Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK -/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.
Keeley, Alexander; Hine, Paul; Nsutebu, Emmanuel
Sepsis is common, often fatal and requires rapid interventions to improve outcomes. While the optimal management of sepsis in the intensive care setting is the focus of extensive research interest, the mainstay of the recognition and initial management of sepsis will occur outside the intensive care setting. Therefore, it is key that institutions and clinicians remain well informed of the current updates in sepsis management and continue to use them to deliver appropriate and timely interventions to enhance patient survival. This review discusses the latest updates in sepsis care including the new consensus definition of sepsis, the outcome of the proCESS, ProMISe and ARISE trials of early goal directed therapy (EGDT), and the most recent guidelines from the Surviving Sepsis Campaign. © 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.
He, Guodong; Zhang, Xu; Chen, Yanhua; Chen, Jing; Li, Li; Xie, Yubo
Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of mortality worldwide. It involves uncontrolled inflammatory response resulting in multi-organ failure and even death. Isoalantolactone (IAL), a sesquiterpene lactone, is known for its anti-cancer effects. Nevertheless, little is known about the anti-inflammatory effects of IAL, and the role of IAL in sepsis is unclear. In this study, we demonstrated that IAL decreased lipopolysaccharide (LPS)-mediated production of nitric oxide, PEG 2 and cytokines (IL-6, TNF-α) in peritoneal macrophages and RAW 264.7 macrophages. Moreover, molecular mechanism studies indicated that IAL plays an anti-inflammatory role by inhibiting LPS-induced activation of NF-κB pathway in peritoneal macrophages. In vivo, IAL reduced the secretion of IL-6 and TNF-α in serum, and increased the survival rate of mice with LPS-induced sepsis. In addition, IAL attenuated the activation of NF-κB pathway in liver. Taken together, our data suggest that IAL may represent a potentially new drug candidate for the treatment of sepsis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Full Text Available BACKGROUND: An imbalance between overwhelming inflammation and lymphocyte apoptosis is the main cause of high mortality in patients with sepsis. Baicalin, the main active ingredient of the Scutellaria root, exerts anti-inflammatory, anti-apoptotic, and even antibacterial properties in inflammatory and infectious diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP in C57BL/6 mice. Mice were infused with baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal cavity were calculated to assess the bacterial clearance. Neutrophil count in peritoneal lavage fluid was also calculated. Injuries to the lung and liver were detected by hematoxylin and eosin staining. Levels of cytokines, including tumor necrosis factor (TNF-alpha, interleukin (IL-6, IL-10 and IL-17, in blood and peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune function was assessed by apoptosis of lymphocytes in the thymus and counts of different cell types in the spleen. Baicalin significantly enhanced bacterial clearance and improved survival of septic mice. The number of neutrophils in peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of the lung and liver in baicalin-treated mice was associated with attenuated injuries to these organs. Baicalin significantly reduced the levels of proinflammatory cytokines but increased the level of anti-inflammatory cytokine in blood and peritoneum. Apoptosis of CD3(+ T cell was inhibited in the thymus. The numbers of CD4(+, CD8(+ T lymphocytes and dendritic cells (DCs were higher, while the number of CD4(+CD25(+ regulatory T cells was lower in the baicalin group compared with the CLP group. CONCLUSIONS/SIGNIFICANCE: Baicalin improves survival of mice
Contrael, Katlynd M; Killian, Alley J; Gregg, Sara R; Buchman, Timothy G; Coopersmith, Craig M
The Surviving Sepsis Campaign suggests giving hydrocortisone to septic patients only if their "blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy." Because the definition of "poorly responsive" is not provided, the purpose of this study was to identify prescribing triggers for hydrocortisone in septic shock. Retrospective chart review of patients with septic shock over 17 months, who received hydrocortisone, followed by a survey of all intensivists who attended in the study ICUs to determine whether provider attitudes matched clinical practice. Eight ICUs in an academic hospital and a hybrid academic/community hospital. A total of 155 patients with septic shock in whom vasopressors were initiated and hydrocortisone was prescribed. Ninety-nine patients (64%) were already receiving two vasopressors before hydrocortisone was prescribed. An additional 22 patients were on a single high-dose vasopressor prior to corticosteroid initiation. Of patients who survived to have their hydrocortisone dose changed, 57% had their corticosteroids tapered, whereas 43% were abruptly discontinued. Seventy-six percent of patients were no longer on vasopressors when the first dosing change was made. Twenty-seven out of 36 intensivists (75%) completed the survey. The majority (72%) defined "poorly responsive to vasopressors" as the presence of two vasopressors, and 70% stated that they required patients to be off vasopressors prior to altering the corticosteroid dose. Significant variability exists when corticosteroids are prescribed for septic shock, with the most common interpretation in our institution of "poorly responsive to fluid resuscitation and vasopressor therapy" being the presence of two vasopressors. The method and timing of corticosteroid discontinuation also differed among providers. Self-described prescribing patterns from intensivists closely matched their actual behavior, suggesting variability is due to differing interpretations of the
Ramonell, Kimberly M; Zhang, Wenxiao; Hadley, Annette; Chen, Ching-Wen; Fay, Katherine T; Lyons, John D; Klingensmith, Nathan J; McConnell, Kevin W; Coopersmith, Craig M; Ford, Mandy L
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.
Kimberly M Ramonell
Full Text Available Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.
Evans, Kambria H; Daines, William; Tsui, Jamie; Strehlow, Matthew; Maggio, Paul; Shieh, Lisa
Annually affecting over 18 million people worldwide, sepsis is common, deadly, and costly. Despite significant effort by the Surviving Sepsis Campaign and other initiatives, sepsis remains underrecognized and undertreated. Research indicates that educating providers may improve sepsis diagnosis and treatment; thus, the Stanford School of Medicine has developed a mobile-accessible, case-based, online game entitled Septris (http://med.stanford.edu/septris/). Septris, launched online worldwide in December 2011, takes an innovative approach to teaching early sepsis identification and evidence-based management. The free gaming platform leverages the massive expansion over the past decade of smartphones and the popularity of noneducational gaming.The authors sought to assess the game's dissemination and its impact on learners' sepsis-related knowledge, skills, and attitudes. In 2012, the authors trained Stanford pregraduate (clerkship) and postgraduate (resident) medical learners (n = 156) in sepsis diagnosis and evidence-based practices via 20 minutes of self-directed game play with Septris. The authors administered pre- and posttests. By October 2014, Septris garnered over 61,000 visits worldwide. After playing Septris, both pre- and postgraduate groups improved their knowledge on written testing in recognizing and managing sepsis (P game scores with sepsis knowledge.
Lam, S M; Lau, A Cw; Lam, R Pk; Yan, W W
Sepsis is a common cause of hospital admission worldwide and contributes significantly to morbidity and mortality. The definition of sepsis has evolved from the 1991 American College of Chest Physicians/Society of Critical Care Medicine definition based on the criteria of systemic inflammatory response syndrome, to the 2016 Sepsis-3 definition that incorporates the Sequential Organ Failure Assessment score. The landmark trial on protocolised early goal-directed therapy was published in 2001, but three subsequent multicentre randomised controlled trials (ProCESS, ARISE, and ProMISe) in 2014-2015 did not confirm a survival benefit with protocolised care. Over the years, there has been considerable improvement in sepsis outcome and management that hinges on early detection; timely source control; prompt, appropriate, and correctly dosed antibiotics; aggressive fluid resuscitation; and shock reversal. These are all directed by repeated bedside assessment. This article summarises recent developments and landmark trials that should guide current sepsis management.
Armstrong, Bracken A; Betzold, Richard D; May, Addison K
Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.
Klingensmith, Nathan J; Fay, Katherine T; Lyons, John D; Chen, Ching-Wen; Otani, Shunsuke; Liang, Zhe; Chihade, Deena B; Burd, Eileen M; Ford, Mandy L; Coopersmith, Craig M
Mortality is higher in septic patients with a history of alcohol use disorder than in septic patients without a history of chronic alcohol usage. We have previously described a model of chronic alcohol ingestion followed by sepsis from cecal ligation and puncture in which alcohol-fed septic mice have higher mortality than water-fed septic mice, associated with altered gut integrity and increased production of TNF and IFNγ by splenic CD4 T cells without alterations in CD8 T cell function. The purpose of this study was to determine whether this represents a common host response to the combination of alcohol and sepsis by creating a new model in which mice with chronic alcohol ingestion were subjected to a different model of sepsis. C57Bl/6 mice were randomized to receive either alcohol or water for 12 weeks and then subjected to Pseudomonas aeruginosa pneumonia. Mice were sacrificed either 24 hours after the onset of sepsis or followed for survival. Alcohol-fed septic mice had significantly higher 7-day mortality than water-fed septic mice (96% vs 58%). This was associated with a 5-fold increase in intestinal apoptosis in alcohol-fed septic animals, accompanied by an increase in the pro-apoptotic protein Bax. Serum IL-6 levels were higher and IL-2 levels were lower in alcohol-fed septic mice. In contrast, CD8 T cell frequency was lower in alcohol-fed mice than water-fed septic mice, associated with increased production of IFNγ and TNF in stimulated splenocytes. No significant differences were noted in CD4 T cells, lung injury or bacteremia. Mice with chronic alcohol ingestion thus have increased mortality regardless of their septic insult, associated with changes in both the gut and the immune system.
Baelani, Inipavudu; Jochberger, Stefan; Laimer, Thomas; Otieno, Dave; Kabutu, Jane; Wilson, Iain; Baker, Tim; Dünser, Martin W
It is unknown whether resources necessary to implement the Surviving Sepsis Campaign guidelines and sepsis bundles are available in Africa. This self-reported, continent-wide survey compared the availability of these resources between African and high-income countries, and between two African regions (Sub-Sahara Africa vs. South Africa, Mauritius and the Northern African countries). The study was conducted as an anonymous questionnaire-based, cross-sectional survey among anaesthesia providers attending a transcontinental congress. Based on the respondents' country of practice, returned questionnaires were grouped into African and high-income countries. The questionnaire contained 74 items and evaluated all material resources required to implement the most recent Surviving Sepsis Campaign guidelines. Group comparisons were performed with the Chi2, Fisher's Exact or Mann Whitney U test, as appropriate. The overall response rate was 74.3% (318/428). Three-hundred-seven questionnaires were analysed (African countries, n = 263; high-income countries, n = 44). Respondents from African hospitals were less likely to have an emergency room (85.5 vs. 97.7%, P = 0.03) or intensive care unit (73.8 vs. 100%, P resources available to implement the Surviving Sepsis Campaign guidelines in entirety. The percentage of implementable recommendations was lower in African than in high-income countries (72.6 (57.7 to 87.7)% vs. 100 (100 to 100)%, P resources to implement the majority of strong Surviving Sepsis Campaign recommendations and the sepsis bundles may allow modification of current sepsis guidelines based on available resources and implementation of a substantial number of life-saving interventions into sepsis care in Africa.
Bernal-Morell, Enrique; García-Villalba, Eva; Vera, Maria Del Carmen; Medina, Blanca; Martinez, Monica; Callejo, Victoria; Valero, Salvador; Cinesi, Cesar; Piñera, Pascual; Alcaraz, Antonia; Marin, Irene; Muñoz, Angeles; Cano, Alfredo
Midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP) and sepsis. In this paper, we examined the ability of MR-proADM to predict organ damage and long-term mortality in sepsis patients, compared to that of procalcitonin, C-reactive protein and lactate. This was a prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to internal service department. The association between biomarkers and 90-day mortality was assessed by Cox regression analysis and Kaplan-Meier curves. The accuracy of biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis. A total of 148 patients with severe sepsis, according to the criteria of the campaign to survive sepsis, were enrolled. Eighty-five (57.4%) had sepsis according to the new criteria of Sepsis-3. MR-proADM showed the best AUROC to predict sepsis as defined by the Sepsis-3 criteria (AUROC of 0.771, 95% CI 0.692-0.850, p scale, especially when scores are low. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Hotchkiss, Richard S.; Moldawer, Lyle L.; Opal, Steven M.; Reinhart, Konrad; Turnbull, Isaiah R.; Vincent, Jean-Louis
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
Steckert, Amanda V; Dominguini, Diogo; Michels, Monique; Abelaira, Helena M; Tomaz, Débora B; Sonai, Beatriz; de Moura, Airam B; Matos, Danyela; da Silva, Júlia B I; Réus, Gislaine Z; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe
The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.
The attacks of the Red Army cracked the illusion of invincibility, and demonstrated to the people there was an alternative. Such a breakthrough...647The surviving members all received a new linen tunic, a notebook, a fountain pen, an enamel bowl, an enamel pan, and a pair of chopsticks
Full Text Available Background: Recommendations have been made, following the multicenter Surviving Sepsis Campaign study, to standardize the definition of severe sepsis with reference to several parameters such as haemodynamic stability, acid-base balance, bilirubin, creatinine, International Normalized Ratio (INR, urine output and pulmonary functional value of the ratio between arterial oxigen partial pressure and inspiratory oxigen concentration. Procalcitonin (PCT is considered to be a gold standard biomarker for the inflammatory response, and recent studies have shown that it may help to discover whether a seriously ill person is developing sepsis. C-reactive protein (CRP is also used as a marker of inflammation in the body, as its blood levels increase if there is any inflammation in the body. The aim of this study was to evaluate serum procalcitonin and C-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis.
Paul, Jasmeet S; Ridolfi, Timothy J
Intra-abdominal infections are a common problem for the general surgeon and major sources of morbidity and mortality in the intensive care unit. Some of these patients present with peritonitis that can rapidly progress to septic shock. The basic principles of care include prompt resuscitation, antibiotics, and source control. This article will use a detailed case study to outline the management of a patient with severe intra-abdominal infection from diverticulitis from initial resuscitation to reconstruction. Components of the Surviving Sepsis Campaign as they pertain to surgical patients are discussed and updated, and the concept of damage control general surgery is applied. Copyright © 2012. Published by Elsevier Inc.
Full Text Available Introduction: Sepsis is one of the most deadly and costly conditions at hospitals. Our study aimed to study levels of knowledge and attitudes in management of sepsis among nurses and physicians employed at Fatebenefratelli hospital, Milano, North-Italy, with particular regard to the analysis of the effects of educational training. Methods: A cross-sectional, quasi-experimental study was conducted between June 1 and October 30, 2017. Physicians and nurses from Intensive Care Unit (ICU and non-ICU hospital wards were recruited. The study participants were invited to attend some educational workshops and, after 6 months, to fill out a questionnaire based on the 2016 Surviving Sepsis Campaign guidelines. Descriptive statistics were expressed with frequency and percentage (%. Chi-square and Student’s t-test were performed to compare the differences in awareness and knowledge between groups. P-values 75% of knowledge of procedures that increase risk of sepsis, ‘fairly‘ (50-75% levels of knowledge, attitudes and behaviour towards blood culture techniques, and ‘poor’ ( 1 years or never trained (34.8 ± 7.4% nurses (n = 99 and physicians (n = 30 (t(10 = 11.72, P = < 0.001. Discussion and Conclusion: Our findings showed that levels of knowledge concerning methods and scores for early identification of sepsis can be significantly improved by educational training. A good knowledge of sepsis guidelines is essential to correct management of this condition.
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Hasan, Gamal M; Al-Eyadhy, Ayman A; Temsah, Mohamed-Hani A; Al-Haboob, Ali A; Alkhateeb, Mohammad A; Al-Sohime, Fahad
Evaluation of feasibility and effectiveness of Surviving Sepsis Campaign (SSC) Guidelines implementation at a Pediatric Intensive Care Unit (PICU) in Saudi Arabia to reduce severe sepsis associated mortality. Retrospective data analysis for a prospective quality improvement (QI) initiative. PICU at King Saud University Medical City, Saudi Arabia. Children ≤14 years of age admitted to the PICU from July 2010 to March 2011 with suspected or proven sepsis. Comparisons were made to a previously admitted group of patients with sepsis from October 2009 to June 2010. Adaptation and implementation of the Surviving Sepsis Campaign-Clinical Practice Guidelines (SSC-CPGs) through AGREE instrument and ADAPTE process. We reported pre- and post-implementation outcome of interest for this QI initiative, annual sepsis-related mortality rate. Furthermore, we reported follow-up of annual mortality rate until December 2016. Sixty-five patients was included in the study (42 in post-guidelines implementation group and 23 in pre-guidelines implementation group). Mortality was insignificantly lower in the post-implementation group (26.2% vs. 47.8%; P = 0.079). However, when adjusted for severity, identified by number of failing organs in the multivariate regression analysis, the mortality difference was favorable for the post-implementation group (P = 0.006). The lower sepsis-related mortality rate was also sustained, with an average mortality rate of 15.11% for the subsequent years (2012-16). Adaptation and implementation of SSC Guidelines in our setting support its feasibility and potential benefits. However, a larger study is recommended to explore detailed compliance rates.
Conclusions: Our study demonstrates for the first time that pomegranate extract could increase mortality rate via increasing peritoneal cavity bacterial load, in CLP sepsis model. More studies to assess mechanisms of this effect are warranted.
Fakhri, Dicky; Djauzi, Samsuridjal; Murni, Tri Wahyu; Rachmat, Jusuf; Harahap, Alida Roswita; Rahayuningsih, Sri Endah; Mansyur, Muchtaruddin; Santoso, Anwar
Sepsis is one of the complications following open heart surgery. Toll-like receptor 2 and toll-interacting protein polymorphism influence the immune response after open heart surgery. This study aimed to assess the genetic distribution of toll-like receptor 2 N199N and toll-interacting protein rs5743867 polymorphism in the development of postoperative sepsis. A prospective cohort study was conducted in 108 children open heart surgery with a Basic Aristotle score ≥6. Patients with an accompanying congenital anomaly, human immunodeficiency virus infection, or history of previous open heart surgery were excluded. The patients' nutritional status and genetic polymorphism were assessed prior to surgery. The results of genetic polymorphism were obtained through genotyping. Patients' ages on the day of surgery and cardiopulmonary bypass times were recorded. The diagnosis of sepsis was established according to Surviving Sepsis Campaign criteria. Postoperative sepsis was observed in 21% of patients. There were 92.6% patients with toll-like receptor 2 N199N polymorphism and 52.8% with toll-interacting protein rs5743867 polymorphism. Toll-like receptor 2 N199N polymorphism tends to increase the risk of sepsis (odds ratio = 1.974; 95% confidence interval: 0.23-16.92; p = 0.504), while toll-interacting protein rs5743867 polymorphism tends to decrease the risk of sepsis (odds ratio = 0.496; 95% confidence interval: 0.19-1.27; p = 0.139) in infants open heart surgery. © The Author(s) 2016.
Teparrukkul, Prapit; Hantrakun, Viriya; Day, Nicholas P J; West, T Eoin; Limmathurotsakul, Direk
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.
Bentley, James; Henderson, Susan; Thakore, Shobhan; Donald, Michael; Wang, Weijie
The Sepsis 6 is an internationally accepted management bundle that, when initiated within one hour of identifying sepsis, can reduce morbidity and mortality. This management bundle was advocated by the Scottish Patient Safety Programme as part of its Acute Adult campaign launched in 2008 and adopted by NHS Tayside in 2012. Despite this, the Emergency Department (ED) of Ninewells Hospital, a tertiary referral centre and major teaching hospital in Scotland, was displaying poor success in the Sepsis 6. We therefore set out to improve compliance by evaluating the application of all aspects of the NHS Tayside Sepsis 6 bundle within one hour of ED triage time, to identify what human factors may influence achieving the one hour The Sepsis 6 bundle. This allowed us to tailor a number of specific interventions including educational sessions, regular audit and personal feedback and check list Sepsis 6 sticker. These interventions promoted a steady increase in compliance from an initial rate of 51.0% to 74.3%. The project highlighted that undifferentiated patients create a challenge in initiating the Sepsis 6. Pyrexia is a key human factor-trigger for recognising sepsis with initial nursing assessment being vital in recognition and identifying the best area (resus) of the department to manage severely septic patients. EDs need to recognise these challenges and develop educational and feedback plans for staff and utilise available resources to maximise the Sepsis 6 compliance.
Full Text Available Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS, and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs, hepatocytes and liver sinusoidal endothelial cells (LSECs. In addition, activated neutrophils, which are also recruited to the liver and produce potentially destructive enzymes and oxygen-free radicals, may further enhance acute liver injury. The clinical manifestations of sepsis-associated liver dysfunction can roughly be divided into two categories: Hypoxic hepatitis and jaundice. The latter is much more frequent in the context of sepsis. Hepatic failure is traditionally considered as a late manifestation of sepsis-induced multiple organ dysfunction syndrome. To date, no specific therapeutics for sepsis-associated liver dysfunction are available. Treatment measure is mainly focused on eradication of the underlying infection and management for severe sepsis. A better understanding of the pathophysiology of liver response in sepsis may lead to further increase in survival rates.
Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won
Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.
De Groot, Bas; Struyk, Bastiaan; Najafi, Rashed; Halma, Nieke; Pelser, Loekie; Vorst, Denise; Mertens, Bart; Ansems, Annemieke; Rijpsma, Douwe
Sepsis quality improvement programmes typically focus on severe sepsis (ie, with acute organ failure). However, quality of ED care might be improved if these programmes included patients whose progression to severe sepsis could still be prevented (ie, infection without acute organ failure). We compared the impact on mortality of implementing a quality improvement programme among ED patients with a suspected infection with or without acute organ failure. This prospective observational study among ED patients hospitalised with suspected infection was conducted in two hospitals in the Netherlands. After stratification by sepsis category (with or without organ failure), in-hospital mortality was compared between a full compliance ( all quality performance measures achieved) and an incomplete compliance group. Multivariable logistic regression analysis was used to quantify the impact of full compliance on in-hospital mortality, adjusting for disease severity, disposition and hospital. There were 1732 ED patients and 130 deaths. Full compliance was independently associated with approximately two-thirds reduction in the odds of hospital mortality ( adjusted OR of 0.30 (95% CI 0.19 to 0.47), which was similar in patients with and without organ failure. Among the 1379 patients with suspected infection without acute organ failure, there were 64 deaths, 15 (1.1%) in the full compliance group and 49 (3.6%) in the incomplete compliance group (mortality difference 2.5% (95% CI 1.6% to 3.3%)). Among 353 patients with organ failure, there were 66 deaths, 12 (3.4%) in the full compliance compared with 54 (15.3%) in the incomplete compliance group (mortality difference 11.9% (95% CI 8.5% to 15.3%)). Thus, there was a difference of 76 deaths between full and incomplete compliance groups, and 34 (45%) who benefited were those without acute organ failure. Sepsis quality improvement programmes should incorporate ED patients in earlier stages of sepsis given the potential to reduce in
Full Text Available In this paper on neonatal sepsis, after a short presentation of etiopathogenesis and physiopathology, we will briefly present the clinical picture, the diagnosis and the therapy. Concerning diagnosis, we will focus our attention on procalcitonin (PCT, serum amyloid A (SAA, presepsin (sCD14 and metabolomics. Three practical tables complete the review. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken
Tr?sy, Domonkos; Moln?r, Zsolt
Sepsis is one of the biggest challenges in critical care nowadays. Defining sepsis is a difficult task on its own and its diagnosis and treatment requires well trained, devoted personnel with interdisciplinary collaboration in order to provide the patients the best chance for survival. Immediate resuscitation, early adequate antimicrobial therapy, source control and highly sophisticated organ support on the intensive care units are all inevitable necessities for successful recovery. To help f...
Colleen D Acosta
rapid progression to severe sepsis highlights the importance of following the international Surviving Sepsis Campaign guideline of early administration of high-dose intravenous antibiotics within 1 h of admission to hospital for anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency. Please see later in the article for the Editors' Summary.
Rouco, Carlos; Moreno, Sacramento; Santoro, Simone
Vaccination campaigns against myxomatosis and rabbit haemorrhagic disease (RHD) are commonly used in translocation programs conducted for the purpose of recovering wild European rabbit populations in Iberian Mediterranean ecosystems. In most cases rabbits are vaccinated 'blind' (i.e. without assessing their prior immunological status) for economic and logistic reasons. However, there is conflicting evidence on the effectiveness of such an approach. We tested whether blind vaccination against myxomatosis and rabbit haemorrhagic disease improved rabbit survival in a rabbit translocation program where wild rabbits were kept in semi-natural conditions in three enclosures. We conducted nine capture sessions over two years (2008-2010) and used the information collected to compare the survival of vaccinated (n=511) versus unvaccinated (n=161) adult wild rabbits using capture-mark-recapture analysis. Average monthly survival was no different for vaccinated versus unvaccinated individuals, both in the period between release and first capture (short-term) and after the first capture onward (long-term). Rabbit survival was lower in the short term than in the long term regardless of whether rabbits were vaccinated or not. Lower survival in the short-term could be due to the stress induced by the translocation process itself (e.g. handling stress). However, we did not find any overall effect of vaccination on survival which could be explained by two non-exclusive reasons. First, interference of the vaccine with the natural antibodies in the donor population. Due to donor populations have high density of rabbits with, likely, high prevalence of antibodies as a result of previous natural exposure to these diseases. Second, the lack of severe outbreaks during the study period. Based on our findings we argue that blind vaccination of adult rabbits in translocation programs may be often mostly ineffective and unnecessarily costly. In particular, since outbreaks are hard to predict
Gray, Alasdair; Ward, Kirsty; Lees, Fiona; Dewar, Colin; Dickie, Sarah; McGuffie, Crawford
The Surviving Sepsis Campaign (SSC) promotes a bundle approach to the care of septic patients to improve outcome. Some have questioned the capability of delivering the bundle in emergency departments (EDs). The authors report the epidemiology and 6 h bundle compliance of patients with severe sepsis/septic shock presenting to Scottish EDs. Analysis of the previously reported Scottish Trauma Audit Group sepsis database was performed including 20 mainland Scottish EDs. A total of 308,910 attendances were screened (between 2 March and 31 May 2009), and 5285 of 27,046 patients were identified after case note review and included on the database. This analysis includes patients who had severe sepsis/septic shock before leaving the ED. Epidemiological, severity of illness criteria, and ED management data were analysed. 626 patients (median age 73; M/F ratio 1:1; 637 presentations) met entrance criteria. The median number of cases per site was 16 (range 3-103). 561 (88.1%) patients arrived by ambulance. The most common source of infection was the respiratory tract (n=411, 64.5%) The most common physiological derangements were heart rate (n=523, 82.1%), respiratory rate (n=452, 71%) and white cell count (n=432, 67.8%). The median hospital stay was 9 days (IQR 4-17 days). 201 (31.6%) patients were admitted to critical care within 2 days, 130 (20.4%) directly from the ED. 180 patients (28.3%) died. There was poor compliance with all aspect of the SSC resuscitation bundle. Sepsis presentations are of variable frequency but have typical epidemiology and clinical outcomes. SSC bundle resuscitation uptake is poor in Scottish EDs.
Full Text Available Introduction: Although significant development in the field of medicine is achieved, sepsis is still a major issue threatening humans’ lives. This study was aimed to audit the management of severe sepsis and septic shock patients in emergency department (ED according to the present standard guidelines.Method: This is a prospective audit on approaching adult septic patients who were admitted to ED. The audit checklist was created based on the protocols of Surviving Sepsis Campaign and British Royal College recommendations. The mean knowledge score and the compliance rate of studied measures regarding standard protocols were calculated using SPSS version 21.Results: 30 emergency medicine residents were audited (63.3% male. The mean knowledge score of studied residents regarding standard guidelines were 5.07 ± 1.78 (IQR = 2 in pre education and 8.17 ± 1.31 (IQR = 85 in post education phase (p < 0.001. There was excellent compliance with standard in 4 (22% studied measures, good in 2 (11%, fair in 1 (6%, weak in 2 (11%, and poor in 9 (50%. 64% of poor compliance measures correlated to therapeutic factors. After training, score of 5 measures including checking vital signs in < 20 minute, central vein pressure measurement in < 1 hour, blood culture request, administration of vasopressor agents, and high flow O2 therapy were improved clinically, but not statistically.Conclusion: The protocol adherence in management of severe sepsis and septic shock for urine output measurement, central venous pressure monitoring, administration of inotrope agents, blood transfusion, intravenous antibiotic and hydration therapy, and high flow O2 delivery were disappointingly low. It seems training workshops and implementation of Clinical audit can improve residents’ adherence to current standard guidelines regarding severe sepsis and septic shock.
Full Text Available Ali Cetinkaya,1 Abdulsamet Erden,1 Deniz Avci,1 Hatice Karagoz,1 Samet Karahan,1 Mustafa Basak,1 Kadir Bulut,1 Vedat Gencer,1 Hasan Mutlu2 1Internal Medicine Department, Kayseri Training and Research Hospital, Kayseri, Turkey; 2Medical Oncology Department, Acibadem Kayseri Hospital, Kayseri, Turkey Introduction: Sepsis and septic shock are important causes of mortality in intensive care unit patients, hence early diagnosis and therapy are important in management of their treatment. The available information on sepsis patients is not enough to recommend or to discard the routine evaluation of triglyceride (TG levels at the onset of sepsis. The aim of this study was to investigate the association of hypertriglyceridemia and clinical outcome (or mortality in patients with severe sepsis. Materials and methods: Between January 1 and December 31, 2011, a total of 84 patients with sepsis from the intensive internal care unit at the Kayseri Training and Research Hospital, Kayseri, Turkey, were investigated retrospectively. Sepsis was defined according to the American College of Chest Physicians/Society of Critical Care Medicine/European Society of Intensive Care Medicine consensus conference definitions. For each patient, survival was recorded at the end of the last day of hospitalization as dead or alive. The TG values were taken retrospectively from the records, which were performed routinely for each patient with sepsis at the time of diagnosis. TG >150 mg/dL was considered as hypertriglyceridemia. Results: The percentages of male and female patients were 44% and 56%, respectively. The mean age of patients was 71.49±11.071 years. The percentage of patients with TG values more than 150 mg/dL was 81% (25/31 in the non-survivor group and 19% (6/31 in the survivor group. There was a significant difference regarding TG values between groups (P=0.039. Discussion: It was observed in this study that patients in the intensive care unit with sepsis had high
Volbeda, M; Wetterslev, J; Gluud, C
INTRODUCTION: Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light...... for sepsis patients (systemic inflammatory response syndrome, sepsis, severe sepsis or septic shock) aged >18 years. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/Medline, Embase, Web of Science and Cinahl were searched until 18 February 2015. No language restrictions were applied. Primary......-adjusted CI 0.7-1.48). The effects did not vary according to the degree of sepsis. TSA showed that many more randomised patients are needed before definitive conclusions may be drawn. CONCLUSION: Evidence to support or negate the use of steroids in any dose in sepsis patients is lacking. The results...
Full Text Available Ignacio Martin-Loeches,1 Mitchell M Levy,2 Antonio Artigas31Multidisciplinary Intensive Care Research Organization (MICRO, St James’s University Hospital, Trinity Centre for Health Sciences, Dublin, Ireland; 2Brown University, Providence, RI, USA; 3Critical Care Center, CIBER Enfermedades Respiratorias, Sabadell Hospital, Corporació Sanitaria Universitaria Parc Tauli, Autonomous University of Barcelona, Barcelona, SpainAbstract: The complexity of treating severe sepsis and septic shock has been elucidated in myriad studies, particularly in the past 10 years. The development of clinical guidelines, insight into the effect of bundle elements, and results of clinical trials have brought to light further opportunities and questions in the approach to pharmaceutical interventions for the global challenge to save lives and reduce healthcare costs. Therapeutic interventions including fluid resuscitation, hemodynamic monitoring, glycemic control, corticosteroids, and antimicrobial therapy and stewardship inform outcomes. Research on biomarkers, use of mesenchymal stem cells, blood purification, immunoglobulins, and antioxidative treatments apropos the immune response may soon yield viable therapies.Keywords: sepsis, septic shock, guidelines, critical care, biomarkers, surviving sepsis campaign
Ortiz Leyba, C; López Martínez, J; Blesa Malpica, A L
Although it is considered that metabolic and nutritional support must be part of the management of septic patients, it has not been conclusively shown that nutritional support will improve survival or complications from sepsis. Specific data on this issue are scarce since there are few studies that have investigated specialized nutritional support in septic patients. Thus, most of the recommendations are based on outcomes obtained in severely ill patients with different pathologies. It is assumed that nutritional support should be carried out through the enteral route whenever possible, as in other critically ill patients. The energetic waste in these patients is highly variable, although in general terms the hypermetabolic situation may be classified as moderate. An adjustment factor of 1.25-1.30 is recommended for the Harris-Benedict's equation to calculate the caloric intake. Septic patients should receive a hyperproteic intake. The amount of glucose administered should not exceed 70% of non-protein calories, and lipids intake should not exceed 40%. With regards to micronutrients, it is recommended to increase the supply of those with antioxidant properties (vitamin E, carotenes, vitamin C, selenium). There are data to consider that the use of diets enriched with pharmaco-nutrients (both with parenteral and enteral routes) may be beneficial in septic patients, although there is some controversy when interpreting the outcomes.
Larsen, Frederik Fruergaard; Petersen, J Asger
BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...
Political campaigns are orchestrated attempts by political organizations to garner public support through persuasive communication in order to influence public policy in their favor. This broad definition encapsulates all forms of campaigns from those of neighborhood organizations seeking to influence local politicians to the campaigns of political parties and candidates who seek election to office in order to shape policy themselves. In pluralist democracies, campaigns are crucial for repres...
Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440
Full Text Available There is a higher sepsis rate in the intensive care unit (ICU patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s triggering receptor expressed on myeloid cells-1 (sTREM-1 suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT and C-reactive protein (CRP in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR -146a , miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.
Schachtner, Thomas; Stein, Maik; Reinke, Petra
As immunosuppressive therapy and allograft survival have improved, the increased incidence of sepsis has become a major hurdle of disease-free survival after renal transplantation. We identified 112 of 957 kidney transplant recipients (KTRs) with sepsis. In all, 31 KTRs developed severe sepsis or septic shock, and 30 KTRs died from sepsis. KTRs without sepsis were used for comparison. CMV-specific and alloreactive T cells were measured using an interferon-γ Elispot assay. The extent of immunosuppression was quantified by lymphocyte subpopulations. Five-year patient survival was 70.3% with sepsis compared to 88.2% without (Psepsis (Psepsis (Psepsis was associated with decreased CD3+ and CD4+ T cells pre-transplantation (Psepsis (Psepsis (Psepsis show inferior patient survival and allograft function. Identified risk factors and differences in lymphocyte counts, CMV-specific immunity, and alloreactivity may prove useful to identify KTRs at increased risk. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Beck, Mette Kristina; Jensen, Anders Boeck; Nielsen, Annelaura Bach
Sepsis affects millions of people every year, many of whom will die. In contrast to current survival prediction models for sepsis patients that primarily are based on data from within-admission clinical measurements (e.g. vital parameters and blood values), we aim for using the full disease histo...... of disease history to scoring based on within-admission clinical measurements emphasizing the value of long term data in novel patient scores that combine the two types of data.......Sepsis affects millions of people every year, many of whom will die. In contrast to current survival prediction models for sepsis patients that primarily are based on data from within-admission clinical measurements (e.g. vital parameters and blood values), we aim for using the full disease history...... recurrent trajectories of time-ordered co-morbidities had significantly increased sepsis mortality compared to those who did not follow a trajectory. We identified trajectories which significantly altered sepsis mortality, and found three major starting points in a combined temporal sepsis network: Alcohol...
Nemati, Shamim; Holder, Andre; Razmi, Fereshteh; Stanley, Matthew D; Clifford, Gari D; Buchman, Timothy G
Sepsis is among the leading causes of morbidity, mortality, and cost overruns in critically ill patients. Early intervention with antibiotics improves survival in septic patients. However, no clinically validated system exists for real-time prediction of sepsis onset. We aimed to develop and validate an Artificial Intelligence Sepsis Expert algorithm for early prediction of sepsis. Observational cohort study. Academic medical center from January 2013 to December 2015. Over 31,000 admissions to the ICUs at two Emory University hospitals (development cohort), in addition to over 52,000 ICU patients from the publicly available Medical Information Mart for Intensive Care-III ICU database (validation cohort). Patients who met the Third International Consensus Definitions for Sepsis (Sepsis-3) prior to or within 4 hours of their ICU admission were excluded, resulting in roughly 27,000 and 42,000 patients within our development and validation cohorts, respectively. None. High-resolution vital signs time series and electronic medical record data were extracted. A set of 65 features (variables) were calculated on hourly basis and passed to the Artificial Intelligence Sepsis Expert algorithm to predict onset of sepsis in the proceeding T hours (where T = 12, 8, 6, or 4). Artificial Intelligence Sepsis Expert was used to predict onset of sepsis in the proceeding T hours and to produce a list of the most significant contributing factors. For the 12-, 8-, 6-, and 4-hour ahead prediction of sepsis, Artificial Intelligence Sepsis Expert achieved area under the receiver operating characteristic in the range of 0.83-0.85. Performance of the Artificial Intelligence Sepsis Expert on the development and validation cohorts was indistinguishable. Using data available in the ICU in real-time, Artificial Intelligence Sepsis Expert can accurately predict the onset of sepsis in an ICU patient 4-12 hours prior to clinical recognition. A prospective study is necessary to determine the
Sepsis is the life-threatening condition with organ dysfunction caused by dysregulated host response to the infection. Septic shock is part of sepsis where circulatory abnormalities and cellular metabolism occur. Sepsis and septic shock are still a problem in the world, where one in four people with sepsis will die. As well as any trauma case, acute myocardial infarction, or stroke, early identification and appropriate treatment of sepsis immediately after sepsis will improve the prognosis of the patient. Comprehensive management of septic patients is required, ranging from infection controls that include antibiotic administration and infection source control as well as hemodynamic stabilization that included fluid resuscitation and vasoactive drug delivery.
... the body like a battleground,” says Dr. Derek Angus, a critical care physician at the University of ... lead to a dangerous drop in blood pressure,” Angus says. As blood pressure falls, tissues become starved ...
Hansen, Kasper Møller; Pedersen, Rasmus Tue
and the external efficacy increase over the course of the campaign, with gains found across different demographic groups, particularly narrowing the gaps in internal efficacy. The news media play a crucial role, as increased knowledge and efficacy are partly driven by media use, although tabloids actually decrease...... external efficacy. The findings suggest that positive campaign effects are universal across various media and party systems.......Election campaigns are more than simple competitions for votes; they also represent an opportunity for voters to become politically knowledgeable and engaged. Using a large-scale web panel (n≈5,000), we track the development of political knowledge, internal efficacy and external efficacy among...
Lerman, Yelena V; Kim, Minsoo
Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host.
Trásy, Domonkos; Molnár, Zsolt
Sepsis is one of the biggest challenges in critical care nowadays. Defining sepsis is a difficult task on its own and its diagnosis and treatment requires well trained, devoted personnel with interdisciplinary collaboration in order to provide the patients the best chance for survival. Immediate resuscitation, early adequate antimicrobial therapy, source control and highly sophisticated organ support on the intensive care units are all inevitable necessities for successful recovery. To help fast and accurate diagnosis biomarkers have been measured for decades. Procalcitonin (PCT) is one of the most studied, but the results are conflicting. Sepsis means a very loose cohort of a large heterogeneous patient population, hence defining certain cut off values for PCT to differentiate between different severities of the disease is almost impossible. Clinicians first have to understand the pathophysiological background of sepsis to be able to interpret correctly the PCT results. Nevertheless, PCT has been shown to have the best sensitivity and specificity to indicate infection, antibiotic appropriateness and stopping therapy. In this article we will focus on some important aspects of pathophysiology and advice on how to implement that in the everyday clinical practice. We believe that this multimodal evaluation of the clinical picture together with PCT results can be a useful tool to make the most out of the PCT results, and do the best for patients on the ICU.
Song, Zhixin; Zhang, Xuemei; Zhang, Liping; Xu, Fang; Tao, Xintong; Zhang, Hua; Lin, Xue; Kang, Lihua; Xiang, Yu; Lai, Xaiofei; Zhang, Qun; Huang, Kun; Dai, Yubing; Yin, Yibing; Cao, Ju
Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. To assess the role of progranulin in the host response to sepsis. Effects of progranulin on host response to sepsis were determined. Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.
Pandey, Nishant Raj; Bian, Yu-Yao; Shou, Song-Tao
This study was undertaken to observe the characteristics of blood pressure variability (BPV) and sepsis and to investigate changes in blood pressure and its value on the severity of illness in patients with sepsis. Blood parameters, APACHE II score, and 24-hour ambulatory BP were analyzed in 89 patients with sepsis. In patients with APACHE II score>19, the values of systolic blood pressure (SBPV), diasystolic blood pressure (DBPV), non-dipper percentage, cortisol (COR), lactate (LAC), platelet count (PLT) and glucose (GLU) were significantly higher than in those with APACHE II score ≤19 (Pblood cell (WBC), creatinine (Cr), PaO2, C-reactive protein (CRP), adrenocorticotropic hormone (ACTH) and tumor necrosis factor α (TNF-α) were not statistically significant (P>0.05). Correlation analysis showed that APACHE II scores correlated significantly with SBPV and DBPV (P0.05). Logistic regression analysis of SBPV, DBPV, APACHE II score, and LAC was used to predict prognosis in terms of survival and non-survival rates. Receiver operating characteristics curve (ROC) showed that DBPV was a better predictor of survival rate with an AUC value of 0.890. However, AUC of SBPV, APACHE II score, and LAC was 0.746, 0.831 and 0.915, respectively. The values of SBPV, DBPV and non-dipper percentage are higher in patients with sepsis. DBPV and SBPV can be used to predict the survival rate of patients with sepsis.
Full Text Available Micronutrients are nutrients which are needed by the body to perform the function of body. The amounts is less than 100% μg per day and consist of vitamins and minerals. It cannot be synthesized in the body. Research in the US mentioned that the rate prevalence of sepsis is tended to be increased 8.7 % annually. In sepsis, nutrition is one of the important component which could drive the success treatment. Micronutrient, especially a vitamin which is soluble in fats, it would be toxic if the number exceed the capability of body to receive it. Although there are guidance and mutual agreement about sepsis using, it still need to concern on micronutrient which potentially giving bad effect. In sepsis case, micronutrients also determine the success of treatment due to redistribution of vitamin and trace element from circulation to the tissue which involved in the proteins formation and immune system. The conclusions of the latest 7 experiments and 4 random controlled studies of multi-centre support the micronutrients supplementation because it can decrease mortality rate. However, it still need to be aware to the toxicity of fat soluble micronutrient if the doses are excessive.
The treatment includes supportive care along with administration of appropriate antibiotics. Adjuvant treatment includes IVIG, GCSF, exchange transfusion and pentoxifylline administration. This paper aims to present an algorithmic approach to neonatal sepsis to expedite the diagnosis along with providing appropriate and adequate treatment.
El-Haj, Lama; Bestle, Morten Heiberg
The main purpose of this study is to review the function of nitric oxide during sepsis and septic shock. Futhermore, the study reviews the various physiological functions of nitric oxide in the human body, and how these functions can and have been used clinically. Nitric oxide plays an important ...
Full Text Available Sepsis associated encephalopathy (SAE is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis.
Sophie Sarrassat, PhD
Full Text Available Summary: Background: Media campaigns can potentially reach a large audience at relatively low cost but, to our knowledge, no randomised controlled trials have assessed their effect on a health outcome in a low-income country. We aimed to assess the effect of a radio campaign addressing family behaviours on all-cause post-neonatal under-5 child mortality in rural Burkina Faso. Methods: In this repeated cross-sectional, cluster randomised trial, clusters (distinct geographical areas in rural Burkina Faso with at least 40 000 inhabitants were selected by Development Media International based on their high radio listenership (>60% of women listening to the radio in the past week and minimum distances between radio stations to exclude population-level contamination. Clusters were randomly allocated to receive the intervention (a comprehensive radio campaign or control group (no radio media campaign. Household surveys were performed at baseline (from December, 2011, to February, 2012, midline (in November, 2013, and after 20 months of campaigning, and endline (from November, 2014, to March, 2015, after 32 months of campaigning. Primary analyses were done on an intention-to-treat basis, based on cluster-level summaries and adjusted for imbalances between groups at baseline. The primary outcome was all-cause post-neonatal under-5 child mortality. The trial was designed to detect a 20% reduction in the primary outcome with a power of 80%. Routine data from health facilities were also analysed for evidence of changes in use and these data had high statistical power. The indicators measured were new antenatal care attendances, facility deliveries, and under-5 consultations. This trial is registered with ClinicalTrial.gov, number NCT01517230. Findings: The intervention ran from March, 2012, to January, 2015. 14 clusters were selected and randomly assigned to the intervention group (n=7 or the control group (n=7. The average number of villages included per
Stec, Piotr; Connell, Rowan
Tension-free vaginal tape (TVT), is a commonly performed, low risk procedure for treatment of stress urinary incontinence (SUI). Severe complications are rare, but can be potentially life threatening. We present a case of 66 year old patient who sustained bladder perforation at the time of TVT procedure and subsequently developed sepsis rapidly leading to multi-organ failure and triggering sequence of serious complications. During her inpatient stay she required ITU admission, emergency laparotomy, TVT mesh removal, bowel resection due to ischemic colitis and anticoagulation for pulmonary embolism. Despite of clinical picture of sepsis her microbiology tests were almost consistently negative. This case emphasise importance of awareness and quick recognition of TVT related complications. Patient ultimately survived and recovered thanks to timely and coordinated management by the multidisciplinary team of doctors.
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
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.
Virginia Hospital Center embarked on a branding effort in hopes of raising customer awareness of the hospital's state-of-the-art technologies in advanced medical care. The campaign launched a new phase of TV spots that highlight the facility's advanced services, such as the computed tomography angiogram, the argon plasma coagulator, and heart valve replacement surgery.
Peter A. Ward
Full Text Available Complement activation products are known to be generated in the setting of both experimental and human sepsis. C5 activation products (C5a anaphylatoxin and the membrane attack complex [MAC] C5b-9 are generated during sepsis following infusion of endotoxin, or after cecal ligation and puncture (CLP, which produces polymicrobial sepsis. C5a reacts with its receptors C5aR and C5L2 in a manner that creates the “cytokine storm”, and is associated with development of multiorgan failure (MOF. A number of other complications arising from the interaction of C5a with its receptors include apoptosis of lymphoid cells, loss of innate immune functions of neutrophils (PMNs, polymorphonuclear leukocytes, cardiomyopathy, disseminated intravascular coagulation, and complications associated with MOF. Neutralization of C5a in vivo or absence/blockade of C5a receptors greatly reduces the adverse events in the setting of sepsis, markedly attenuates MOF, and greatly improves survival. Regarding the possible role of C5b-9 in sepsis, the literature is conflicting. Some studies suggest that C5b-9 is protective, while other studies suggest the contrary. Clearly, in human sepsis, C5a and its receptors may be logical targets for interception.
de Prost, Nicolas; Razazi, Keyvan; Brun-Buisson, Christian
Sepsis involves a wide array of sources and microorganisms, only a fraction of which are microbiologically documented. Culture-negative sepsis poses special diagnostic challenges to both clinicians and microbiologists and further questions the validity of sepsis definitions.
Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.
Renata H. Dalaqua
Full Text Available This article analyses the security practices of the anti-nuclear movement in the post-Cold War period through the prism of securitisation theory. By exploring Buzan and Wæver's conceptual developments on macrosecuritisations, the practices involved in the struggle against the Bomb are interpreted as securitising moves, in which the anti-nuclear movement is the leading securitiser. In the capacity of securitising actors, nuclear abolition activists argue that nuclear disarmament, under a Nuclear Weapons Convention (NWC, would be the only way to protect humankind from the threat posed by the existence of nuclear weapons. The empirical analysis of these non-state actors and their campaign for a NWC shows that, despite uttering security, the anti-nuclear movement has so far failed to achieve the proposed security measure, that is, nuclear disarmament. Nonetheless, securitisation has been instrumental for these non-state actors as a way of raising an issue on the agenda of decision-makers and urging them to take action.
Okeke, Emeka B; Uzonna, Jude E
In spite of over half a century of research, sepsis still constitutes a major problem in health care delivery. Although advances in research have significantly increased our knowledge of the pathogenesis of sepsis and resulted in better prognosis and improved survival outcome, sepsis still remains a major challenge in modern medicine with an increase in occurrence predicted and a huge socioeconomic burden. It is generally accepted that sepsis is due to an initial hyperinflammatory response. However, numerous efforts aimed at targeting the proinflammatory cytokine network have been largely unsuccessful and the search for novel potential therapeutic targets continues. Recent studies provide compelling evidence that dysregulated anti-inflammatory responses may also contribute to sepsis mortality. Our previous studies on the role of regulatory T cells and phosphoinositide 3-kinases in sepsis highlight immunological approaches that could be explored for sepsis therapy. In this article, we review the current and emerging concepts in sepsis, highlight novel potential therapeutic targets and immunological approaches for sepsis treatment and propose a biphasic treatment approach for management of the condition. © 2016 S. Karger AG, Basel.
The report by the National Radiological Protection Board in the Medical Research Council's study of some of the UKAEA workers is criticized. It is argued that the cancer risk estimates of the International Commission on Radiological Protection are seriously wrong, and that as they are used as a basis for radiation protection standards in the UK, these standards now need revising. The subject is discussed under the headings: broad-based campaign; all radiation is a hazard; building networks (of scientific and medical expertise). (U.K.)
Pollach, Gregor; Namboya, Felix
The Global Sepsis Initiative recommends prevention of sepsis through immunizations, vitamins, breast feeding, and other important interventions. In our study, we consider a second set of proposals for preventing intensive care admissions for sepsis in tropical Africa, which have been specifically designed to further prevent ICU admissions for sepsis in the group A nation hospital setting. To reduce admissions with severe sepsis in an ICU of a group A nation through the identification of challenges leading to preventable, foreseeable, or nosocomial sepsis specific to our setting. Malawi is one of the poorest countries in the world. Lacking the ability to comply with standard sepsis treatment, we conducted over 4 years several studies, audits, and surveys to identify challenges leading to preventable pediatric sepsis in our setting. We developed a method to identify malnourished children through a "gatekeeper" in the theaters without any equipment, tried to implement the World Health Organization's Safe Surgery Campaign checklist, evaluated our educational courses for the districts to improve the quality of referrals, looked into the extreme fasting times discovered in our hospital, trained different cadres in the districts to deal with peripartal and posttraumatic sepsis, and identified the needs in human resources to deal with pediatric sepsis in our setting. Six foci were identified as promising to work on in future. Focus 1: Preventing elective operations and procedures in malnourished children in the hospital and in the district: 134 of 145 nurses (92.4%) and even 25 of 31 African laymen (80.6%) were able to identify malnourished children with their own fingers. Focus 2: Preventing sepsis-related problems in emergencies through the implementation of the Safe Surgery Campaign checklist: only 100 of 689 forms (14.5%) were filled in due to challenges in ownership, communication responsibility, and time constraints. Focus 3: Preventing sepsis through the reduction
A. F. Potapov
Full Text Available Objective. To comparatively analyze the efficiency of methods for extracorporeal detoxification (ED of the body in abdominal sepsis (AS and to choose the optimum detoxifying methods in relation to the level of endotoxicosis.Material and methods. 56 patients (41 males and 15 females; mean age 39.4±12.2 years with surgical abdominal infection of various genesis, complicated by the development of sepsis whose treatment included ED methods, were examined. The level of intoxication and the efficiency of detoxification were evaluated by general clinical and biochemical blood parameters, the leukocytic intoxication index, the levels of low and medium molecular-weight substances in the body’s media. Hemosorption, plasmapheresis, hemodialysis, hemodiafiltration, and hemofiltration were used for detoxification.Results. Surgical abdominal infection is accompanied by endotoxemia that has no clear nosological specificity, but it depends on the pattern of a clinical course of the disease and is most pronounced in the septic syndrome. In AS, 80.4% of the patients are observed to have an irreversible decompensation phase and a terminal degree of endotoxicosis, which require detoxification. The use of different ED methods according to the level of intoxication may reduce the level of endotoxicosis and yield a persistent beneficial effect in 85.2% of cases of its application. Conclusion. Filtration and dialysis techniques (hemodialysis, hemofiltration, and hemodiafiltration are the methods of choice in AS. Hemosorption and plasmapheresis may be recommended for use at the early stages of endotoxicosis development and in preserved renal excretory function.
Remick, Daniel G; Ayala, Alfred; Chaudry, Irshad; Coopersmith, Craig M; Deutschman, Clifford; Hellman, Judith; Moldawer, Lyle; Osuchowski, Marcin
Sepsis morbidity and mortality exacts a toll on patients and contributes significantly to healthcare costs. Preclinical models of sepsis have been used to study disease pathogenesis and test new therapies, but divergent outcomes have been observed with the same treatment even when using the same sepsis model. Other disorders such as diabetes, cancer, malaria, obesity and cardiovascular diseases have used standardized, preclinical models that allow laboratories to compare results. Standardized models accelerate the pace of research and such models have been used to test new therapies or changes in treatment guidelines. The National Institutes of Health (NIH) mandated that investigators increase data reproducibility and the rigor of scientific experiments and has also issued research funding announcements about the development and refinement of standardized models. Our premise is that refinement and standardization of preclinical sepsis models may accelerate the development and testing of potential therapeutics for human sepsis, as has been the case with preclinical models for other disorders. As a first step towards creating standardized models, we suggest 1) standardizing the technical standards of the widely used cecal ligation and puncture model and 2) creating a list of appropriate organ injury and immune dysfunction parameters. Standardized sepsis models could enhance reproducibility and allow comparison of results between laboratories and may accelerate our understanding of the pathogenesis of sepsis.
This conference paper will explore the difference between communicating changes and changing communication. Based on a case study in which a manager applies two quite different approaches to organizational communication in order to change the organization he is leading. The first and failing...... approach will in be named: organizational campaigning and means (e.g. Kotter, 2012, p. 9 and Clegg, Kornberger & Pitsis, 2009) that the manager takes control with communication and communication cannels in order to ensure successful organizational changes. Since the changes were not succeeding the approach...... is replaced with a new approach which will be named organizing communication. During the case analysis we will see that this change in approach not only change the managers perception of communication but also his perception of the organization he is leading....
Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine
Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564
César Cabrera C
Full Text Available Se presenta un caso raro de sepsis por Shigella flexneri en una paciente de 45 años de edad quien estando hospitalizada para el estudio de un tumor cerebral, requirió el uso de manitol y dosis altas de corticoides; luego de ello presenta deposiciones líquidas con moco y sangre, desarrolla síndrome de respuesta inflamatoria sistémica, luego se aísla Shigella flexneri en el hemocultivo; recibió tratamiento antibiótico con ciprofloxacina. Se describen las características del caso y se comenta de acuerdo con la revisión de literatura.
Full Text Available Moraxella catarrhalis is a Gram-negative aerobic diplococcus, commensal of the oro-pharingeal cavity, actually playing an emerging role in the upper respiratory tract infections together with Streptococcus pneumoniae and Haemophilus influenzae. This study reports the case of a twoyearold child who was admitted into hospital with fever, headache and vomit. The chest radiograph showed signs of basal lung involvementmaking the clinical suspicion of bacterial infectionlikely. From blood culture a Moraxella catarrhalis strain was isolated. In young children M. catarrhalis is known to cause otitis media and sinusitis, but only rarely bacteremia. In this case the child showed a clinical picture of lung infection and consequent sepsis due to M. catarrhalis.
Claushuis, T. A. M.; de Stoppelaar, S. F.; Stroo, I.; Roelofs, J. J. T. H.; Ottenhoff, R.; van der Poll, T.; van't Veer, C.
Essentials Immunity and coagulation are linked during sepsis but the role of thrombin is not fully elucidated. We investigated the effect of thrombin inhibition on murine Klebsiella pneumosepsis outcome. Thrombin is crucial for survival and limiting bacterial growth in pneumonia derived sepsis.
Franciele do Nascimento Santos
Full Text Available Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control; SHAM+Statin (0.5 mg/kg simvastatin, orally; Sepsis (cecal puncture ligation – CPL; Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.
Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won; Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong
To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment
Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong [Sansung Medical Center, Seoul (Korea, Republic of)
To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment.
Menéndez, R; Torres, A; Reyes, S; Zalacain, R; Capelastegui, A; Aspa, J; Borderías, L; Martín-Villasclaras, J J; Bello, S; Alfageme, I; de Castro, F R; Rello, J; Molinos, L; Ruiz-Manzano, J
Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.
Full Text Available IMPORTANCE: The association between hospital volume and inpatient mortality for severe sepsis is unclear. OBJECTIVE: To assess the effect of severe sepsis case volume and inpatient mortality. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011. EXPOSURES: The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles. MAIN OUTCOMES AND MEASURES: Inpatient mortality. RESULTS: Compared with the highest tertile of severe sepsis volume (>60 cases per year, the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (≤10 severe sepsis cases per year was 1.188 (95% CI: 1.074-1.315, while the odds ratio was 1.090 (95% CI: 1.031-1.152 for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64-38.03 for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51-32.64 for hospitals with the highest volume. CONCLUSIONS AND RELEVANCE: We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients.
Maurya, Harikesh; Mangal, Vaishali; Gandhi, Sanjay; Prabhu, Kathiresan; Ponnudurai, Kathiresan
Present study is to investigate the effect of Gallic acid pretreatment on survival of septic animals and oxidative stress in different organs like lungs, liver, kidney, spleen, and vascular dysfunction of mice. Sepsis was induced by cecal ligation and puncture (CLP) in healthy adult male albino mice (25–30 g) and was divided into 3 groups each consisting of 6 animals, that is, sham-operated (SO group (Group I), SO + sepsis (Group II), and Gallic acid + sepsis (Group III)). Group III animals w...
Moser, Claus; Hartvig, Tom; Schierbeck, Jens
Early, relevant antibiotic treatment is of pivotal significance for survival for patients with sepsis. Recent reports reveal, that critically ill patients may need substantially higher dosing of antibiotics than the usual standards. The background is the newly described augmented renal clearance...... (ARC), which can be observed in critically ill patients with sepsis. ARC results in significantly reduced antibiotic concentrations in patients with sepsis and can potentially have fatal consequences. The purpose of this paper is to make medical doctors aware of the phenomenon and to compensate...
Full Text Available Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused by methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally "unintended" interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches.
Jabaley, Craig S; Blum, James M; Groff, Robert F; O'Reilly-Shah, Vikas N
Sepsis is an established global health priority with high mortality that can be curtailed through early recognition and intervention; as such, efforts to raise awareness are potentially impactful and increasingly common. We sought to characterize trends in the awareness of sepsis by examining temporal, geographic, and other changes in search engine utilization for sepsis information-seeking online. Using time series analyses and mixed descriptive methods, we retrospectively analyzed publicly available global usage data reported by Google Trends (Google, Palo Alto, CA, USA) concerning web searches for the topic of sepsis between 24 June 2012 and 24 June 2017. Google Trends reports aggregated and de-identified usage data for its search products, including interest over time, interest by region, and details concerning the popularity of related queries where applicable. Outlying epochs of search activity were identified using autoregressive integrated moving average modeling with transfer functions. We then identified awareness campaigns and news media coverage that correlated with epochs of significantly heightened search activity. A second-order autoregressive model with transfer functions was specified following preliminary outlier analysis. Nineteen significant outlying epochs above the modeled baseline were identified in the final analysis that correlated with 14 awareness and news media events. Our model demonstrated that the baseline level of search activity increased in a nonlinear fashion. A recurrent cyclic increase in search volume beginning in 2012 was observed that correlates with World Sepsis Day. Numerous other awareness and media events were correlated with outlying epochs. The average worldwide search volume for sepsis was less than that of influenza, myocardial infarction, and stroke. Analyzing aggregate search engine utilization data has promise as a mechanism to measure the impact of awareness efforts. Heightened information-seeking about sepsis
Full Text Available Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs. The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl is widely used to treat rheumatoid arthritis (RA. However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3 puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM. 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities.
Pizzolato, Elisa; Ulla, Marco; Galluzzo, Claudia; Lucchiari, Manuela; Manetta, Tilde; Lupia, Enrico; Mengozzi, Giulio; Battista, Stefania
Sepsis, severe sepsis and septic shock are among the most common conditions handled in the emergency department (ED). According to new Sepsis Guidelines, early diagnosis and treatment are the keys to improve survival. Plasma C-reactive protein (CRP) and procalcitonin (PCT) levels, when associated with documented or suspected infection, are now part of the definitions of sepsis. Blood culture is the gold standard method for detecting microorganisms but it requires too much time for results to be known. Sensitive biomarkers are required for early diagnosis and as indexes of prognosis sepsis. CRP is one of the acute phase proteins synthesized by the liver: it has a great sensitivity but a very poor specificity for bacterial infections. Moreover, the evolution of sepsis does not correlate with CRP plasma changes. In recent years PCT has been widely used for sepsis differential diagnosis, because of its close correlation with infections, but it still retains some limitations and false positivity (such as in multiple trauma and burns). Soluble CD14 subtype (sCD14-ST), also known as presepsin, is a novel and promising biomarker that has been shown to increase significantly in patients with sepsis, in comparison to the healthy population. Studies pointed out the capability of this biomarker for diagnosing sepsis, assessing the severity of the disease and providing a prognostic evaluation of patient outcome. In this mini review we mainly focused on presepsin: we evaluate its diagnostic and prognostic roles in patients presenting to the ED with systemic inflammatory response syndrome (SIRS), suspected sepsis or septic shock.
Davydow, Dimitry S; Hough, Catherine L; Langa, Kenneth M; Iwashyna, Theodore J
To examine if incident severe sepsis is associated with increased risk of subsequent depressive symptoms and to assess which patient characteristics are associated with increased risk of depressive symptoms. Prospective longitudinal cohort study. Population-based cohort of older U.S. adults interviewed as part of the Health and Retirement Study (1998-2006). A total of 439 patients who survived 471 hospitalizations for severe sepsis and completed at least one follow-up interview. Depressive symptoms were assessed with a modified version of the Center for Epidemiologic Studies Depression Scale. Severe sepsis was identified using a validated algorithm in Medicare claims. The point prevalence of substantial depressive symptoms was 28% at a median of 1.2 years before sepsis, and remained 28% at a median of 0.9 years after sepsis. Neither incident severe sepsis (relative risk [RR]: 1.00; 95% confidence interval [CI]: 0.73, 1.34) nor severe sepsis-related clinical characteristics were significantly associated with subsequent depressive symptoms. These results were robust to potential threats from missing data or alternative outcome definitions. After adjustment, presepsis substantial depressive symptoms (RR: 2.20; 95% CI: 1.66, 2.90) and worse postsepsis functional impairment (RR: 1.08 per new limitation; 95% CI: 1.03, 1.13) were independently associated with substantial depressive symptoms after sepsis. The prevalence of substantial depressive symptoms in severe sepsis survivors is high but is not increased relative to their presepsis levels. Identifying this large subset of severe sepsis survivors at increased risk for major depression, and beginning interventions before hospital discharge, may improve outcomes. Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Voyles, J. W. [DOE ARM Climate Research Facility, Washington, DC (United States); Chapman, L. A. [DOE ARM Climate Research Facility, Washington, DC (United States)
This document establishes a common set of guidelines for the Atmospheric Radiation Measurement (ARM) Climate Research Facility for planning, executing, and closing out field campaigns. The steps that guide individual field campaigns are described in the Field Campaign Tracking System and are specifically tailored to meet the scope of each field campaign.
Farrell, Deborah; Nadel, Simon
Severe sepsis and septic shock remains a leading cause of mortality and morbidity in children. There is ongoing uncertainty regarding the optimal treatment pathways however the initial management of sepsis is crucial. This article is designed to be an informal and personal review of recent developments in paediatric sepsis over the past 3?years.
Kingsley, S Manoj Kumar; Bhat, B Vishnu
MicroRNAs have been found to be of high significance in the regulation of various genes and processes in the body. Sepsis is a serious clinical problem which arises due to the excessive host inflammatory response to infection. The non-specific clinical features and delayed diagnosis of sepsis has been a matter of concern for long time. MicroRNAs could enable better diagnosis of sepsis and help in the identification of the various stages of sepsis. Improved diagnosis may enable quicker and more effective treatment measures. The initial acute and transient phase of sepsis involves excessive secretion of pro-inflammatory cytokines which causes severe damage. MicroRNAs negatively regulate the toll-like receptor signaling pathway and regulate the production of inflammatory cytokines during sepsis. Likewise, microRNAs have shown to regulate the vascular barrier and endothelial function in sepsis. They are also involved in the regulation of the apoptosis, immunosuppression, and organ dysfunction in later stages of sepsis. Their importance at various levels of the pathophysiology of sepsis has been discussed along with the challenges and future perspectives. MicroRNAs could be key players in the diagnosis and staging of sepsis. Their regulation at various stages of sepsis suggests that they may have an important role in altering the outcome associated with sepsis.
McColl, Tamara; Gatien, Mathieu; Calder, Lisa; Yadav, Krishan; Tam, Ryan; Ong, Melody; Taljaard, Monica; Stiell, Ian
In 2008-2009, the Canadian Institute for Health Information reported over 30,000 cases of sepsis hospitalizations in Canada, an increase of almost 4,000 from 2005. Mortality rates from severe sepsis and septic shock continue to remain greater than 30% in Canada and are significantly higher than other critical conditions treated in the emergency department (ED). Our group formed a multidisciplinary sepsis committee, conducted an ED process of care analysis, and developed a quality improvement protocol. The objective of this study was to evaluate the effects of this sepsis management bundle on patient mortality. This before and after study was conducted in two large Canadian tertiary care EDs and included adult patients with suspected severe infection that met at least two systemic inflammatory response syndrome (SIRS) criteria. We studied the implementation of a sepsis bundle including triage flagging, RN medical directive, education campaign, and a modified sepsis protocol. The primary outcomes were 30-day all-cause mortality and sepsis protocol use. We included a total of 167 and 185 patients in the pre- and post-intervention analysis, respectively. Compared to the pre-intervention group, mortality was significantly lower in the post-intervention group (30.7% versus 17.3%; absolute difference, 13.4%; 95% CI 9.8-17.0; p=0.006). There was also a higher rate of sepsis protocol use in the post-intervention group (20.3% versus 80.5%, absolute difference 60.2%; 95% CI 55.1-65.3; pimproved early identification and protocolized medical care, was associated with improved time to achieve key therapeutic interventions and a reduction in 30-day mortality. Similar low-cost initiatives could be implemented in other EDs to potentially improve outcomes for this high-risk group of patients.
Lee, YoonJe; Park, Hyun Kyung; Kim, Won Young; Kim, Myung Chun; Jung, Woong; Ko, Byuk Sung
Muscle mass depletion has been suggested to predict morbidity and mortality in various diseases. However, it is not well known whether muscle mass depletion is associated with poor outcome in sepsis. We hypothesized that muscle mass depletion is associated with poor outcome in sepsis. Retrospective observational study was conducted in an emergency department during a 9-year period. Medical records of 627 patients with sepsis were reviewed. We divided the patients into 2 groups according to 28-day mortality and compared the presence of muscle mass depletion assessed by the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on abdomen CT scans. Univariate and multivariate logistic regression analyses were conducted to examine the association of scarcopenia on the outcome of sepsis. A total of 274 patients with sepsis were finally included in the study: 45 (16.4%) did not survive on 28 days and 77 patients (28.1%) were identified as having muscle mass depletion. The presence of muscle mass depletion was independently associated with 28-day mortality on multivariate logistic analysis (OR 2.79; 95% CI 1.35-5.74, p = 0.01). Muscle mass depletion evaluated by CT scan was associated with poor outcome of sepsis patients. Further studies on the appropriateness of specific treatment for muscle mass depletion with sepsis are needed. © 2018 S. Karger AG, Basel.
Song, Xiaofei; Song, Yucheng; Zhang, Xuedong; Xue, Huanzhou
The aim of the study was to investigate the concentration and diagnostic significance of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in acute abdominal conditions. Plasma specimens were obtained from 68 patients with abdominal sepsis, 60 patients with systemic inflammatory response syndrome (SIRS), and 60 healthy individuals. The sepsis group was divided into the survival and death groups according to the 28-d outcome. Plasma sTREM-1, procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count were measured. A receiver operating characteristic curve (ROC) was used to compare the diagnostic values of sTREM-1, PCT, CRP, and WBC count. In addition, the correlation between plasma sTREM-1 and the Acute Physiology and Chronic Health Evaluation (APACHE) II score in the sepsis group was assessed by Spearman correlation analysis. The plasma concentration of sTREM-1 in the sepsis group was significantly higher than that in the SIRS and healthy groups (both p sepsis vs. SIRS showed that the area under the curve of sTREM-1 (0.82) was greater than that of PCT (0.77), CRP (0.72), and WBC count (0.70). Additionally, in the sepsis group, the plasma sTREM-1 concentration correlated positively with the APACHE II score (r = 0.41; p sepsis.
Walchok, Jason G; Pirrallo, Ronald G; Furmanek, Douglas; Lutz, Martin; Shope, Colt; Giles, Brandi; Gue, Greta; Dix, Aaron
To improve patient outcomes, the Center for Medicare and Medicaid Services (CMS) implemented core measures that outline the initial treatment of the septic patient. These measures include initial blood culture collection prior to antibiotics, adequate intravenous fluid resuscitation, and early administration of broad spectrum antibiotics. We sought to determine if Paramedics can initiate the CMS sepsis core measure bundle in the prehospital field reliably. This is a retrospective, case series from a 3rd service EMS system model in Greenville, South Carolina between November 17, 2014 and February 20, 2016. An adult Prehospital Sepsis Assessment Tool was created using the 2012 Surviving Sepsis guidelines: 2 of 3 signs of systemic inflammatory response (heart rate, respiratory rate, oral temperature) and a known or suspected source of infection. A "Sepsis Alert" was called by paramedics and upon IV access a set of blood cultures and blood for lactate analysis was collected prior to field antibiotic administration. The Sepsis Alert was compared to serum lactate levels and ICD 9 or 10 admitting diagnosis of Sepsis, Severe Sepsis, or Septic Shock. Blood culture contamination, serum lactate, and antibiotic match were determined by in-hospital laboratory analysis. A total of 120 trained paramedics called 1,185 "Sepsis Alerts" on 56,643 patients (50.3% Male, mean age 70). Patients with missing discharge diagnosis were eliminated (n = 31). The admitting diagnosis of sepsis overall was 73.5% (848/1154): Sepsis 50% (578/1154), Severe Sepsis 14.6% (169/1154), Septic Shock 8.9% (101/1154). A total of 946 blood cultures were collected in the prehospital setting, with a 95.04% (899/946) no contamination rate. Contamination was found in 4.96% (47/946). A total of 179 (18.9%) of the uncontaminated blood cultures were found to have positive growth with 720 (76.1%) having no growth. EMS administered antibiotics matched blood culture positive growth in 72% of patients. The lactate
Full Text Available We tested the hypothesis that 5-Hydroxydecanoic acid (5HD, a putative mitoK(ATP channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival.Male Sprague-Dawley rats (350-400 g were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1, Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles in the presence/absence of 5HD (100 µmoles. A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (-40% and at 6 hr post-sepsis (-20%. Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group. The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C.The data suggest that Bax activation is an upstream event that may precede the opening of the mitoK(ATP channels in sepsis. We concluded that mitoK(ATP channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial contractile dysfunction.
Chopra, Mani; Golden, Honey B; Mullapudi, Srinivas; Dowhan, William; Dostal, David E; Sharma, Avadhesh C
We tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoK(ATP) channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival. Male Sprague-Dawley rats (350-400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD (100 µmoles). A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (-40%) and at 6 hr post-sepsis (-20%). Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group) and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group). The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C. The data suggest that Bax activation is an upstream event that may precede the opening of the mitoK(ATP) channels in sepsis. We concluded that mitoK(ATP) channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial contractile dysfunction.
Full Text Available Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.
The Collision Repair Campaign targets meaningful risk reduction in the Collision Repair source category to reduce air toxic emissions in their communities. The Campaign also helps shops to work towards early compliance with the Auto Body Rule.
Francisca Hanna , Febrianti
Advertising campaign merupakan serangkaian bentuk iklan melalui berbagai media dan berpusat pada satu tema dalam satu waktu. Tujuan utama advertising campaign adalah menyampaikan pesan dalam suatu tema yang diluncurkan kepada masyarakat sehingga tema tersebut menjadi ciri khas produk. Peluncuran tema campaign oleh Coca Cola dan Pepsi yang merupakan rival dalam kategori beverage merupakan obyek dari penelitian ini. Kesuksesan sebuah tema advertising campaign dilihat dengan menggunakan paramet...
Weisman, Leonard E; Leeming, Angela H; Kong, Lingkun
Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model. Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated. MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains. We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.
Neubert, T.; Laursen, S.; Rasmussen, I. L.
During the northern hemisphere summer of 2003, from July 18 to September 18, a sprite observation campaign was conducted with measurements from Southern Europe, coordinated with measurements from the magnetically conjugate region in South Africa. The goal of the campaign was to investigate...... emissions. The presentation will give an overview of the campaign, the meteorological conditions, and present some first results....
Mohamed El-Saied El-Shafie
Full Text Available Early identification of sepsis and its differentiation from non-infective SIRS are important for sepsis outcome. We intended to evaluate the use of presepsin in differentiating sepsis from noninfectious SIRS and its prognostic value compared to CRP. We included 31 patients (median age 60 year old, 16 males admitted with SIRS to El-Sahel Teaching Hospital, Egypt after excluding 21 patients with preadmission corticosteroids therapy, blood transfusion, immunosuppressive illness, and ICU length of stay (ICU-LOS less than 24-hours. Patients were classified into non-infective SIRS group (13 patients and sepsis group (18 patients. Presepsin, CRP and SOFA score were measured on admission and on days 2 and 4 of admission. The outcome parameters studied were ICU-LOS and in-hospital survival. Apart from temperature and AST which were significantly higher in sepsis group, the two groups were comparable. All the presepsin levels and CRP on days 2 and 4 were significantly higher in sepsis than in SIRS groups. The ICU-LOS was positively correlated with all the presepsin levels and with the CRP levels on days 2 and 4. All presepsin values were significantly higher in survivors while none of the CRP levels were significantly different in survivors and non-survivors. The decrease of presepsin over time was significantly associated with better survival. It was found to be 70% sensitive and 91% specific for predicting survival in SIRS patients. This relation was not found in CRP levels. We concluded that the presepsin can be used for early differentiation between sepsis and non-infectious SIRS and predict higher mortality.
Battle, Ceri E; Davies, Gareth; Evans, Phillip A
Survivors of sepsis report persistent problems that can last years after hospital discharge. The main aim of this study was to investigate long-term health-related quality of life in survivors of SIRS and sepsis compared with Welsh normative data, controlling for age, length of stay and pre-existing conditions. The second aim was to investigate any differences in long-term health-related quality of life specifically with the patients categorised into three groups; SIRS, uncomplicated sepsis and severe sepsis/septic shock. A prospective study design was used in order to investigate all sepsis patients either presenting to the Emergency Department or admitted to the Intensive Care Unit of a regional trauma centre. Baseline demographics, clinical characteristics and outcomes were collected and surviving patients were sent a SF-12v2 survey at between six months to two years post-hospital discharge. Quality of life was significantly reduced in all patients when compared to local normative data (all pquality of life were more pronounced in severe sepsis/septic shock patients when compared to uncomplicated sepsis and SIRS patients, when controlling for age, pre-existing conditions, hospital and ICU length of stay. This is the first observational study to specifically focus on the different groups of SIRS and sepsis patients to assess long-term quality of life. Local population norms were used for comparison, rather than UK-wide norms that fail to reflect the intricacies of a country's population.
Full Text Available Sepsis is a syndrome related to severe infections. It is defined as the systemic host response to microorganisms in previously sterile tissues and is characterized by end-organ dysfunction away from the primary site of infection. The normal host response to infection is complex and aims to identify and control pathogen invasion, as well as to start immediate tissue repair. Both the cellular and humoral immune systems are activated, giving rise to both anti-inflammatory and proinflammatory responses. The chain of events that leads to sepsis is derived from the exacerbation of these mechanisms, promoting massive liberation of mediators and the progression of multiple organ dysfunction. Despite increasing knowledge about the pathophysiological pathways and processes involved in sepsis, morbidity and mortality remain unacceptably high. A large number of immunomodulatory agents have been studied in experimental and clinical settings in an attempt to find an efficacious anti-inflammatory drug that reduces mortality. Even though preclinical results had been promising, the vast majority of these trials actually showed little success in reducing the overwhelmingly high mortality rate of septic shock patients as compared with that of other critically ill intensive care unit patients. Clinical management usually begins with prompt recognition, determination of the probable infection site, early administration of antibiotics, and resuscitation protocols based on "early-goal" directed therapy. In this review, we address the research efforts that have been targeting risk factor identification, including genetics, pathophysiological mechanisms and strategies to recognize and treat these patients as early as possible.
Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.
IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need
Full Text Available Sepsis is a lethal syndrome with a high incidence and a weighty economy burden. The pathophysiology of sepsis includes inflammation, immune dysfunction, and dysfunction of coagulation, while sepsis-induced cardiomyopathy (SIC, defined as a global but reversible dysfunction of both sides of the heart induced by sepsis, plays a significant role in all of the aspects above in the pathogenesis of sepsis. The complex pathogenesis of SIC involves a combination of dysregulation of inflammatory mediators, mitochondrial dysfunction, oxidative stress, disorder of calcium regulation, autonomic nervous system dysregulation, and endothelial dysfunction. The treatments for SIC include the signal pathway intervention, Chinese traditional medicine, and other specific therapy. Here, we reviewed the latest literatures on the mechanisms and treatments of SIC and hope to provide further insights to researchers and create a new road for the therapy of sepsis.
Full Text Available Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool's development, which is not complete 8 weeks after secondary immunization.
Kempker, Jordan A; Wang, Henry E; Martin, Greg S
There is a paradigm shift happening for sepsis. Sepsis is no longer solely conceptualized as problem of individual patients treated in emergency departments and intensive care units but also as one that is addressed as public health issue with population- and systems-based solutions. We offer a conceptual framework for sepsis as a public health problem by adapting the traditional model of primary, secondary, and tertiary prevention.
Wang, Dawei; Yin, Yimei; Yao, Yongming
Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS), and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs), hepatocytes and liver sinusoidal endothelial cells (LSECs). In additi...
Rebello, Alex; Thabah, Molly Mary; Dutta, Tarun Kumar; Bobby, Zachariah; Harish, B N; Mehalingam, Vadivelan
Procalcitonin has been found to be a good marker for the diagnosis of sepsis. However, data on procalcitonin levels to predict the clinical outcome in patients with sepsis are limited. The aim of our study was to estimate serum procalcitonin levels in patients with sepsis and to identify its relationship with the clinical outcome. This was a prospective observational study conducted on 112 patients with sepsis admitted to the medical wards and medical intensive care unit of a tertiary care teaching hospital. Serum procalcitonin was measured at baseline before antibiotic administration and on day 5. The clinical outcome studied was death or survival on day 28. Baseline mean serum procalcitonin was highest in patients with septic shock and lowest in patients having sepsis without organ dysfunction. Mean values of procalcitonin at baseline and on day 5 were significantly higher in non-survivors when compared with survivors. There was a significant difference in the change in procalcitonin levels from baseline to day 5 between survivors and non-survivors, with survivors having declining values on day 5 while non-survivors had increasing values from baseline. The baseline APACHE II and SOFA scores also showed a significant correlation with the baseline procalcitonin level. Declining values of procalcitonin therefore indicate a favourable clinical outcome in patients with sepsis.
Wiersinga, W. Joost
Sepsis continues to be a leading cause of ICU death. This review summarizes current knowledge on sepsis pathogenesis and new therapeutical strategies. Although systemic inflammatory response syndrome predominates in early sepsis, the compensatory anti-inflammatory response syndrome causes
河村, 直幸; Kawamura, Naoyuki
The aim of this research paper is to introduce a political campaign strategy. A political campaign should do on a scientific system and needs effective strategy. Before political campaign begin, a candidate and its campaigner needs to analyze election district and sample voter opinion. An election campaign needs campaign theme. The creation of campaign theme needs careful and elaborate planning. A style of campaign varies according to incumbent or challenger. The developing of an effective po...
Klainbart, Sigal; Agi, Limor; Bdolah-Abram, Tali; Kelmer, Efrat; Aroch, Itamar
OBJECTIVE To characterize clinical and laboratory findings in cats with naturally occurring sepsis, emphasizing hemostasis-related findings, and evaluate these variables for associations with patient outcomes. DESIGN Prospective, observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control cats. PROCEDURES Data collected included history; clinical signs; results of hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome (survival vs death during hospitalization or ≤ 30 days after hospital discharge). Differences between cats with and without sepsis and associations between variables of interest and death were analyzed statistically. RESULTS The sepsis group included cats with pyothorax (n = 10), septic peritonitis (7), panleukopenia virus infection (5), bite wounds (5), abscesses and diffuse cellulitis (3), and pyometra (1). Common clinical abnormalities included dehydration (21 cats), lethargy (21), anorexia (18), pale mucous membranes (15), and dullness (15). Numerous clinicopathologic abnormalities were identified in cats with sepsis; novel findings included metarubricytosis, hypertriglyceridemia, and high circulating muscle enzyme activities. Median activated partial thromboplastin time and plasma D-dimer concentrations were significantly higher, and total protein C and antithrombin activities were significantly lower, in the sepsis group than in healthy control cats. Disseminated intravascular coagulopathy was uncommon (4/22 [18%] cats with sepsis). None of the clinicopathologic abnormalities were significantly associated with death on multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis had multiple hematologic, biochemical, and hemostatic abnormalities on hospital admission, including several findings suggestive of hemostatic derangement. Additional research including larger numbers of cats is needed to further investigate these findings and explore associations with outcome.
Wang, Te; Liu, Changdong; Wei, Pihong; Lv, Lili; Yang, Zaiqi
This study aims to explore the effect of intravenous anesthesia on the adrenal gland functions of rats with sepsis as well as on their lungs and adrenal gland tissues in order to provide a theoretical reference for the cure of sepsis. Female Sprague Dawley (SD) rats were taken as the research objects in this study. Venous channels of rats were constructed by catheterization through the external jugular vein, and the cecal ligation and puncture technique was adopted to duplicate the sepsis rat models. The level of tumor necrosis factor-α (TNF-α) in serum was detected using enzyme-linked immunosorbent assay (ELISA), and necrocytosis was observed by the fluorescent staining method. The results showed that the survival rates of groups A, B, C, and D were 100%, 60%, 60%, and 50%, respectively, while their concentrations of TNF-α in serum were101.26 ± 43.38, 1398.68 ± 178.56, 451.16 ± 78.68, and 649.83 ± 98.56 pg/mL, respectively. Results of fluorescent staining showed that the number of living cells per unit view in group A was 1428 ± 166 and those of groups B, C and D were 175 ± 56, 618 ± 76, and 468 ± 55, respectively. Besides, it was found that changes of inflammatory pathology of lung tissues of each group were significant. In conclusion, etomidate does not affect the survival of sepsis rats and does not exacerbate lung tissue inflammation in sepsis rats. Instead, it can inhibit TNF-α in serum of sepsis rats, as well as the apoptosis of adrenal cells in sepsis rats.
Peña, Geber; Cai, Bolin; Liu, Jun; van der Zanden, Esmerij P.; Deitch, Edwin A.; de Jonge, Wouter J.; Ulloa, Luis
The role of STAT3 in infectious diseases remains undetermined, in part because unphosphorylated STAT3 has been considered an inactive protein. Here, we report that unphosphorylated STAT3 contributes to cholinergic anti-inflammation, prevents systemic inflammation, and improves survival in sepsis.
Full Text Available It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis.In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis.In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1ß and TNF-α concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement.In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice.
Full Text Available Sepsis can sometimes be difficult to substantiate, and its distinction from non-infectious conditions in critically ill patients is often a challenge. Serum procalcitonin (PCT assay is one of the biomarkers of sepsis. The present study was aimed to assess the usefulness of PCT assay in critically ill patients with suspected sepsis. The study included 40 patients from the intensive care unit with suspected sepsis. Sepsis was confirmed clinically and/or by positive blood culture. Serum PCT was assayed semi-quantitatively by rapid immunochromatographic technique (within 2 hours of sample receipt. Among 40 critically ill patients, 21 had clinically confirmed sepsis. There were 12 patients with serum PCT ≥10 ng/ml (8, blood culture positive; 1, rickettsia; 2, post-antibiotic blood culture sterile; and 1, non-sepsis; 7 patients with PCT 2-10 ng/ml (4, blood culture positive; 1, falciparum malaria; 2, post-antibiotic blood culture sterile; 3 patients with PCT of 0.5 to 2 ng/ml (sepsis in 1 patient; and 18 patients with PCT < 0.5 ng/ml (sepsis in 2 patients. Patients with PCT ≥ 2 ng/ml had statistically significant correlation with the presence of sepsis (P<0.0001. The PCT assay revealed moderate sensitivity (86% and high specificity (95% at a cut-off ≥ 2 ng/ml. The PCT assay was found to be a useful biomarker of sepsis in this study. The assay could be performed and reported rapidly and provided valuable information before availability of culture results. This might assist in avoiding unwarranted antibiotic usage.
Full Text Available The aim of this study is to evaluate additional hospitalisation costs and intangible costs (mortality in patients with sepsis (intended as severe sepsis or sepsis shock in Italy. The evaluation is based on clinical data from the Italian Sepsis Study, a prospective, multicentre study conducted in 99 Intensive Care Units (ICUslocated across Italy. Each ICU enrolled the first two (or three patients admitted each month, during the year April 1993 to March 1994. In particular, data collected included the Average Length Of Stay (ALOS in ICU and later in the regular ward, and the mortality within four weeks and in hospital. Out of the 2,946 patients enrolled, 2,641 never developed sepsis and were considered as the control group (comparability was confirmed based on gender, age, and comorbidity. The additional (respective to the control group ALOSs of the patients with sepsis were valued in monetary terms using per diem full costs, inflated to 2000: 1,033.43 Euro for l day in ICU (published data and 299.54 Euro for l day in the regular ward (estimated data based on published materials. Statistical significance was tested with Student t test. The hospitalisation cost of a patient with sepsis (21,571.88 Euro is significantly higher (+86% than that patient without sepsis (11,590.84 Euro, due to a longer (+ 163% stay in the expensive ICU, not balanced by shorter stay in the regular ward. Also intangible costs are significantly higher: the risk for an ICU patient with sepsis to die in hospital is 3 times higher than that of an ICU patient without sepsis. In particular, those patients developing sepsis after admission are more costly and with a higher mortality risk.
Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P
Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.
Zhou, Yu; Song, Yan; Shaikh, Zahir; Li, Hui; Zhang, Haiju; Caudle, Yi; Zheng, Shouhua; Yan, Hui; Hu, Dan; Stuart, Charles; Yin, Deling
Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP). The effect of miR-155 on CLP-induced cardiac dysfunction was explored in late sepsis. We found that increased expression of miR-155 in the myocardium protected against cardiac dysfunction in late sepsis evidenced by attenuating sepsis-reduced cardiac output and enhancing left ventricular systolic function. We also observed that miR-155 markedly reduced the infiltration of macrophages and neutrophils into the myocardium and attenuated the inflammatory response via suppression of JNK signaling pathway. Moreover, overexpression of β-arrestin 2 (Arrb2) exacerbated the mice mortality and immunosuppression in late sepsis. Furthermore, transfection of miR-155 mimic reduced Arrb2 expression, and then restored immunocompetence and improved survival in late septic mice. We conclude that increased miR-155 expression through systemic administration of miR-155 mimic attenuates cardiac dysfunction and improves late sepsis survival by targeting JNK associated inflammatory signaling and Arrb2 mediated immunosuppression.
Full Text Available Among hospitalized patients, lactic acidosis represents the most common cause of metabolic acidosis. Lactate is not just a metabolic product of anaerobic glycolysis but is triggered by a variety of metabolites even before the onset of anaerobic metabolism as part of an adaptive response to a hypermetabolic state. On the basis of such considerations, lactic acidosis is divided into two classes: inadequate tissue oxygenation (type A and absence of tissue hypoxia (type B. Lactic acidosis is characterized by non-specific symptoms but it should be suspected in all critical patients who show hypovolemic, hypoxic, in septic or cardiogenic shock or if in the presence of an unexplained high anion gap metabolic acidosis. Lactic acidosis in sepsis and septic shock has traditionally been explained as a result of tissue hypoxia when whole-body oxygen delivery fails to meet whole body oxygen requirements. In sepsis lactate levels correlate with increased mortality with a poor prognostic threshold of 4 mmol/L. In hemodynamically stable patients with sepsis, hyperlactatemia might be the result of impaired lactate clearance rather than overproduction. In critically ill patients the speed at which hyperlactatemia resolves with appropriate therapy may be considered a useful prognostic indicator. The measure of blood lactate should be performed within 3 h of presentation in acute care setting. The presence of lactic acidosis requires early identification of the primary cause of shock for the best appropriate treatment. Since most cases of lactic acidosis depend on whole-body oxygen delivery failure, the maximization of systemic oxygen delivery remains the primary therapeutic option. When initial resuscitation does not substantially or completely correct lactic acidosis, it is also essential to consider other causes. The treatment of acidosis with buffering agents (specifically bicarbonate is generally advocated only in the setting of severe acidosis. Ongoing
Muady, Gassan Fuad; Bitterman, Haim; Laor, Arie; Vardi, Moshe; Urin, Vitally; Ghanem-Zoubi, Nesrin
Acute reduction in hemoglobin levels is frequently seen during sepsis. Previous studies have focused on the management of anemia in patients with septic shock admitted to intensive care units (ICU's), including aggressive blood transfusion aiming to enhance tissue oxygenation. To study the changes in hemoglobin concentrations during the first week of sepsis in the setting of Internal Medicine (IM) units, and their correlation to survival. Observational prospective study. We recorded hemoglobin values upon admission and throughout the first week of hospital stay in a consecutive cohort of septic patients admitted to IM units at a community hospital, the patients were enrolled into a prospective registry. Data on blood transfusions was also collected, we examined the correlation between hemoglobin concentrations during the first week of sepsis and survival, the effect of blood transfusion was also assessed. Eight hundred and fifteen patients (815) with sepsis were enrolled between February 2008 to January 2009. More than 20 % of them had hemoglobin levels less than 10g/dL on admission, a rate that was doubled during the first week of sepsis. Overall, 68 (8.3 %) received blood transfusions, 14 of them (20.6 %) due to bleeding. Typically, blood transfusion was given to older patients with a higher rate of malignancy and lower hemoglobin levels. While hemoglobin concentration on admission had strong correlation with in-hospital mortality (O.R-0.83 [95 % C.I. 0.74-0.92], blood transfusion was not found to be an independent predicting factor for mortality. Anemia is very common in sepsis. While hemoglobin level on admission exhibit independent correlation with survival, blood transfusion do not.
Barrett, Orit; Abramovich, Ella; Dreiher, Jacob; Novack, Victor; Abu-Shakra, Mahmoud
Severe infections and sepsis are common among patients with rheumatoid arthritis (RA) and are associated with increased morbidity and mortality risks. To determine whether RA is an independent risk factor for short- and long-term mortality in patients admitted to an Intensive Care Unit (ICU) with sepsis. A retrospective age- and sex-matched cohort study, based on data of the SEPSIS-ISR Registry, an ongoing study that collects data on all patients admitted with the diagnosis of sepsis to the ICUs of 7 large hospitals during the period 2002-2012. The primary outcomes of the study were the 30-day and 3-years survival rates. A total of 124 RA patients and 248 non-RA patients (mean age 71 years; 64.5% female) were included. Primary site of infection as well as pathogens distributions were similar between the two groups. Severe sepsis and septic shock were diagnosed in 92% vs. 84% (p = 0.03) and 50% versus 39% (p = 0.06) of the RA patients and non-RA, respectively. 30-day survival rates were similar between groups, whereas 3-year survival rate in 30-day survivors was significantly lower among RA patients (34.9%) compared to non-RA patients (55.7%) (p = 0.01). In multivariate Cox proportional hazards regression, RA was found to be a significant independent risk factor for 3-year mortality in 30-day survivors (hazard ratio 1.63 95% confidence interval 1.03-1.63; p = 0.04). RA is an independent risk factor for 3-year mortality, but not short-term mortality following ICU admission with sepsis.
Angus, Derek C.; van der Poll, Tom
To the Editor: We would like to address two potentially confusing issues concerning venous oxygen saturation (Svo(2)) as presented in Table 1 of the review by Angus and van der Poll (Aug. 29 issue).(1) First, Table 1 suggests that Svo(2) is raised in sepsis, severe sepsis, and septic shock.
Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M
Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding...
This 60 second public service announcement is based on the August 2016 CDC Vital Signs report. Sepsis is a medical emergency and can happen quickly. Learn the signs of sepsis and how to prevent it. Created: 8/23/2016 by National Center for Injury Prevention and Control (NCIPC). Date Released: 8/23/2016.
Banerjee, Debasree; Opal, Steven M
We report on the increasingly important need to diagnose and care for the elderly with sepsis as a distinct patient population. We share an overview of age-related changes in sepsis physiology and the potential role of exercise.See related research by Tyml et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1783-1.
Dvojnykh, V.P.; Palagin, E.K.
The results of treatment of 23 patients with acute surgical sepsis were analysed. It was shown that the X-ray examination must be obligatory in surveillance of patients with purulent foci. Two roentgenological variants are possible in surgical sepsis: central and perepheric. X-ray examinations of chest organs should be conducted every 2-3 day
Kim, Mitchell; Watase, Taketo; Jablonowski, Karl D; Gatewood, Medley O; Henning, Daniel J
Many patients meeting criteria for severe sepsis are not given a sepsis-related diagnosis by emergency physicians (EP). This study 1) compares emergency department (ED) interventions and in-hospital outcomes among patients with severe sepsis, based on the presence or absence of sepsis-related diagnosis, and 2) assesses how adverse outcomes relate to three-hour sepsis bundle completion among patients fulfilling severe sepsis criteria but not given a sepsis-related diagnosis. We performed a retrospective cohort study using patients meeting criteria for severe sepsis at two urban, academic tertiary care centers from March 2015 through May 2015. We included all ED patients with the following: 1) the 1992 Consensus definition of severe sepsis, including two or more systemic inflammatory response syndrome criteria and evidence of organ dysfunction; or 2) physician diagnosis of severe sepsis or septic shock. We excluded patients transferred to or from another hospital and those <18 years old. Patients with an EP-assigned sepsis diagnosis created the "Physician Diagnosis" group; the remaining patients composed the "Consensus Criteria" group. The primary outcome was in-hospital mortality. Secondary outcomes included completed elements of the current three-hour sepsis bundle; non-elective intubation; vasopressor administration; intensive care unit (ICU) admission from the ED; and transfer to the ICU in < 24 hours. We compared proportions of each outcome between groups using the chi-square test, and we also performed a stratified analysis using chi square to assess the association between failure to complete the three-hour bundle and adverse outcomes in each group. Of 418 patients identified with severe sepsis we excluded 54, leaving 364 patients for analysis: 121 "Physician Diagnosis" and 243 "Consensus Criteria." The "Physician Diagnosis" group had a higher in-hospital mortality (12.4% vs 3.3%, P < 0.01) and compliance with the three-hour sepsis bundle (52.1% vs 20.2%, P
Johansen, Maria Egede
The sepsis syndrome represents a disease continuum, including severe sepsis and septic shock associated with high mortality. One of the main problems in severe sepsis and septic shock, resulting in organ failure and death, are disturbances in the hemostasis due to sepsis-related coagulopathy. Sepsis-related coagulopathy affects not only traditional coagulation factors, but also the platelets and endothelium. Functional testing of the hemostatic system has found application in critical illness. Thrombelastography (TEG) provides an overview of the hemostatic system allowing for an evaluation of interactions between coagulation factors and platelets. Additionally, the role of the endothelium during sepsis can be explored through testing of biomarkers of endothelial damage. The three studies comprising this PhD thesis all investigate important aspects of the disturbed hemostasis during sepsis, including endothelial damage. Together, the specific findings from the three studies improve the existing understanding of sepsis-related coagulopathy, and the possible influences of some of the treatments offered these patients. The first study investigates the occurrence of antimicrobial-induced thrombocytopenia among critically ill patients. In sepsis, thrombocytopenia is a predictor of poor outcome, and reports, of mainly casuistic nature, have previously hypothesized that specific antimicrobial agents could induce in sepsis-related thrombocytopenia. This hypothesis was tested using a randomized designed set-up, encompassing 1147 critically ill patients, and no significant difference in risk of thrombocytopenia was observed among patients receiving large amounts of antimicrobials vs. patients receiving standard-of-care. As a consequence, the risk of antimicrobial-induced thrombocytopenia in the general population of critically ill patients seemingly does not represent a substantial problem and thrombocytopenia during critical illness is most likely due to other factors such
Arnone, Enrico; Berg, Peter; Boberg, Fredrik
In this report we give an overview of the Eurosprite observation programme and present the results of the Eurosprite 2005 campaign. These campaigns search for occurrences of transient luminous events, such as red sprites, above thunderstorms in France, Spain, northern Italy, Switzerland and south...
Your readers may be interested in knowing that VSO will be holding a publicity campaign in Scotland in November and December. The campaign is a chance for people to come and talk to us about the opportunities available to them to work in Third World countries. We have a wide range of interesting and challenging jobs in long-term development in health work.
Coffey, J Calvin
Tolerization with bacterial lipoprotein (BLP) affords a significant survival benefit in sepsis. Given that high mobility group box protein-1 (HMGB1) is a recognized mediator of sepsis-related lethality, we determined if tolerization with BLP leads to alterations in HMGB1. In vitro, BLP tolerization led to a reduction in HMGB1 gene transcription. This was mirrored at the protein level, as HMGB1 protein expression and release were reduced significantly in BLP-tolerized human THP-1 monocytic cells. BLP tolerance in vivo led to a highly significant, long-term survival benefit following challenge with lethal dose BLP in C57BL\\/6 mice. This was associated with an attenuation of HMGB1 release into the circulation, as evidenced by negligible serum HMGB1 levels in BLP-tolerized mice. Moreover, HMGB1 levels in peritoneal macrophages from BLP-tolerized mice were reduced significantly. Hence, tolerization with BLP leads to a down-regulation of HMGB1 protein synthesis and release. The improved survival associated with BLP tolerance could thus be explained by a reduction in HMGB1, were the latter associated with lethality in BLP-related sepsis. In testing this hypothesis, it was noted that neutralization of HMGB1, using anti-HMGB1 antibodies, abrogated BLP-associated lethality almost completely. To conclude, tolerization with BLP leads to a down-regulation of HMGB1, thus offering a novel means of targeting the latter. HMGB1 is also a mediator of lethality in BLP-related sepsis.
No Abstract. Keywords: minimally invasive surgery, sclerotherapy, transfusion, HIV, occupational exposure. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...
Poeze, Martijn; Ramsay, Graham; Gerlach, Herwig; Rubulotta, Francesca; Levy, Mitchel
Background To be able to diagnose and treat sepsis better it is important not only to improve the knowledge about definitions and pathophysiology, but also to gain more insight into specialists' perception of, and attitude towards, the current diagnosis and treatment of sepsis. Methods The study was conducted as a prospective, international survey by structured telephone interview. The subjects were intensive care physicians and other specialist physicians caring for intensive care unit (ICU) patients. Results The 1058 physicians who were interviewed (including 529 intensivists) agreed that sepsis is a leading cause of death on the ICU and that the incidence of sepsis is increasing, but that the symptoms of sepsis can easily be misattributed to other conditions. Physicians were concerned that this could lead to under-reporting of sepsis. Two-thirds (67%) were concerned that a common definition is lacking and 83% said it is likely that sepsis is frequently missed. Not more than 17% agreed on any one definition. Conclusion There is a general awareness about the inadequacy of the current definitions of sepsis. Physicians caring for patients with sepsis recognise the difficulty of defining and diagnosing sepsis and are aware that they miss the diagnosis frequently. PMID:15566585
... that may be done include: Blood differential Blood gases Kidney function tests Platelet count and fibrin degradation ... 2018, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...
Weber, Stefan U; Schewe, Jens-Christian; Lehmann, Lutz E; Müller, Stefan; Book, Malte; Klaschik, Sven; Hoeft, Andreas; Stüber, Frank
In transgenic animal models of sepsis, members of the Bcl-2 family of proteins regulate lymphocyte apoptosis and survival of sepsis. This study investigates the gene regulation of pro-apoptotic and anti-apoptotic members of the Bcl-2 family of proteins in patients with early stage severe sepsis. In this prospective case-control study, patients were recruited from three intensive care units (ICUs) in a university hospital. Sixteen patients were enrolled when they fulfilled the criteria of severe sepsis. Ten critically ill but non-septic patients and 11 healthy volunteers served as controls. Blood samples were immediately obtained at inclusion. To confirm the presence of accelerated apoptosis in the patient groups, caspase-3 activation and phosphatidylserine externalisation in CD4+, CD8+ and CD19+ lymphocyte subsets were assessed using flow cytometry. Specific mRNAs of Bcl-2 family members were quantified from whole blood by real-time PCR. To test for statistical significance, Kruskal-Wallis testing with Dunn's multiple comparison test for post hoc analysis was performed. In all lymphocyte populations caspase-3 (p < 0.05) was activated, which was reflected in an increased phosphatidylserine externalisation (p < 0.05). Accordingly, lymphocyte counts were decreased in early severe sepsis. In CD4+ T-cells (p < 0.05) and B-cells (p < 0.001) the Bcl-2 protein was decreased in severe sepsis. Gene expression of the BH3-only Bim was massively upregulated as compared with critically ill patients (p < 0.001) and 51.6-fold as compared with healthy controls (p < 0.05). Bid was increased 12.9-fold compared with critically ill patients (p < 0.001). In the group of mitochondrial apoptosis inducers, Bak was upregulated 5.6-fold, while the expression of Bax showed no significant variations. By contrast, the pro-survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis (p < 0.001 and p < 0.05, respectively). In early severe sepsis a gene expression pattern with
Serbanescu, Mara A; Ramonell, Kimberly M; Hadley, Annette; Margoles, Lindsay M; Mittal, Rohit; Lyons, John D; Liang, Zhe; Coopersmith, Craig M; Ford, Mandy L; McConnell, Kevin W
CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69 + CD25 int CD62L HI ) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain "unactivated" (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44 HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis. © Society for Leukocyte Biology.
Admiraal, Marjolein M.; Gilmore, Emily J.; Van Putten, Michel J.A.M.; Zaveri, Hitten P.; Hirsch, Lawrence J.; Gaspard, Nicolas
Purpose: To investigate heart rate and EEG variability and their coupling in patients with sepsis and determine their relationship to sepsis severity and severity of sepsis-Associated brain dysfunction. Methods: Fifty-Two patients with sepsis were prospectively identified, categorized as comatose (N
The Bachelor Paper contains proposal and realization advertising campaign, including make charge for cost amount. The advertising campaign is made for chosen product of firm. Advertising campaign is planning by the medium of broadsheet and advertising on the Internet.
Maurya, Harikesh; Mangal, Vaishali; Gandhi, Sanjay; Prabhu, Kathiresan; Ponnudurai, Kathiresan
Present study is to investigate the effect of Gallic acid pretreatment on survival of septic animals and oxidative stress in different organs like lungs, liver, kidney, spleen, and vascular dysfunction of mice. Sepsis was induced by cecal ligation and puncture (CLP) in healthy adult male albino mice (25–30 g) and was divided into 3 groups each consisting of 6 animals, that is, sham-operated (SO group (Group I), SO + sepsis (Group II), and Gallic acid + sepsis (Group III)). Group III animals were pretreated with Gallic acid at the dose rate of 20 mg/kg body weight for 2 days before induction of sepsis. Animals were sacrificed on 8th day and the tissue samples were obtained for further investigation on lipid peroxidation (LPO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH). Gallic acid pretreatment significant (P Gallic acid pretreated mice showed significant improvement in SOD activity of kidney and spleen when compared to septic mice. Finally, the beneficial effects of Gallic acid pretreatment in sepsis are evident from the observations that Gallic acid partially restored SOD and catalase activity and completely reversed lipid peroxidation. Further studies are required to find out the possible mechanisms underlying the beneficial effects of Gallic acid on large population. PMID:25018890
Full Text Available The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism. Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L, calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.
Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio
The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.
Chatre, Laurent; Verdonk, Franck; Rocheteau, Pierre; Crochemore, Clément; Chrétien, Fabrice; Ricchetti, Miria
Sepsis is an acute systemic inflammatory response of the body to microbial infection and a life threatening condition associated with multiple organ failure. Survivors may display long-term disability with muscle weakness that remains poorly understood. Recent data suggest that long-term myopathy in sepsis survivors is due to failure of skeletal muscle stem cells (satellite cells) to regenerate the muscle. Satellite cells impairment in the acute phase of sepsis is linked to unusual mitochondrial dysfunctions, characterized by a dramatic reduction of the mitochondrial mass and hyperactivity of residual organelles. Survivors maintain the impairment of satellite cells, including alterations of the mitochondrial DNA (mtDNA), in the long-term. This condition can be rescued by treatment with mesenchymal stem cells (MSCs) that restore mtDNA alterations and mitochondrial function in satellite cells, and in fine their regenerative potential. Injection of MSCs in turn increases the force of isolated muscle fibers and of the whole animal, and improves the survival rate. These effects occur in the context of reduced inflammation markers that also raised during sepsis. Targeting muscle stem cells mitochondria, in a context of reduced inflammation, may represent a valuable strategy to reduce morbidity and long-term impairment of the muscle upon sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.
Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M
The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.
Regional tissue distress caused by microcirculatory dysfunction and mitochondrial depression underlies the condition in sepsis and shock where, despite correction of systemic oxygen delivery variables, regional hypoxia and oxygen extraction deficit persist. We have termed this condition
Christoffersen, Christina; Nielsen, Lars Bo
Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship...... to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence...... on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation....
Haase, Nicolai; Ostrowski, Sisse Rye; Wetterslev, Jørn
PURPOSE: To investigate the association between consecutively measured thromboelastographic (TEG) tracings and outcome in patients with severe sepsis. METHODS: Multicentre prospective observational study in a subgroup of the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial (NCT00962156......) comparing hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate for fluid resuscitation in severe sepsis. TEG (standard and functional fibrinogen) was measured consecutively for 5 days, and clinical data including bleeding and death was retrieved from the trial database. Statistical analyses included Cox...... bleeding [HR 2.43 (1.16-5.07)] and possibly explained the excess bleeding with HES in the 6S trial. CONCLUSIONS: In our cohort of patients with severe sepsis, progressive hypocoagulability defined by TEG variables was associated with increased risk of death and increased risk of bleeding....
O'Hare, Fiona M
Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.
Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M
The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.
Wang, Yan-Hong; Li, Tie-Hua; Wu, Ben-Quan; Liu, Hui; Shi, Yun-Feng; Feng, Ding-Yun
The fruit of Xanthium strumarium L. (Asteraceae) has been used for the treatment of various inflammatory diseases. This study investigates the protective effect of caffeoylxanthiazonoside (CYXD) isolated from fruits of X. strumarium on sepsis mice in vitro and in vivo. Cecal ligation and puncture (CLP) operation was used to establish the sepsis mice model, and sham mice were also performed. CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then the survival rate was measured in 96 h. Additionally, sepsis mice were induced by injection LPS (2 mg/kg); CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then mice were sacrificed, and serum levels of TNF-α and IL-6 were determined by ELISA assay. Furthermore, the ability of CYXD to neutralize LPS was measured by using the LAL test, and expressions of TNF-α, IL-6 were determined by using real-time fluorogenic PCR. Results indicated that CYXD significantly elevated survival rates of sepsis mice induced by CLP (p < 0.05) with survival rates of 35%, 45%, and 65%. Furthermore, the LPS level was decreased obviously by CYXD (1, 2, and 4 mg/L) (p < 0.05). Additionally, CYXD (10, 20, and 40 mg/kg) can not only significantly decrease TNF-α and IL-6 levels induced by LPS in mice's serum (p < 0.05), but also inhibit mRNA expressions of TNF-α and IL-6 induced by LPS in RAW 264.7 cells at doses of 20, 40, and 80 μg/mL (p < 0.05). Our study demonstrated that CYXD has significant protective effects on sepsis mice.
Wang, Bin; Jiang, Junli; Yang, Jun; Chen, Jun; Zhu, Zhaoqiong; Liu, Jin; Zhang, Wensheng
ET-26 hydrochloride (ET-26 HCl) is a promising sedation-hypnotic compound with stable hemodynamic features that elicits virtually no adrenocortical suppression. However, whether it preserves better pharmacologic characteristics in a rat model of sepsis is not known. This study compared the survival rate, levels of corticosterone and pro-inflammatory cytokines, and histologic injury in the lungs and kidneys of rats suffering from sepsis treated with ET-26 HCl, etomidate, or normal saline (NS). Rats were given lipopolysaccharide (1mg/kg body weight, i.v.) to establish a sepsis model. Thirty minutes after lipopolysaccharide administration, ET-26 HCl, etomidate or NS were given as a bolus injection at equivalent doses. Plasma levels of corticosterone, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α were measured 1, 2, 4, 6 and 24h after administration. Histologic injury was observed at the time of death or 24h after drug administration. The survival rate for rats in the etomidate, ET-26 HCl and NS groups was 40%, 90% and 90%, respectively. Corticosterone concentrations in the etomidate group were lower than those in the other groups 1h after administration of hypnotic compounds. Concentrations of pro-inflammatory cytokines in the ET-26 HCl group and NS group were not significantly different, but were significantly lower than those in the etomidate group. The injury scores of kidneys and lungs in the etomidate group were higher than those in ET-26 HCl and NS groups. ET-26 HCl showed virtually no suppression of corticosterone synthesis, lower concentrations of pro-inflammatory cytokines, higher survival rate, and less organ injury in rats suffering from sepsis compared with the etomidate group. It may be safer to induce anesthesia using ET-26 HCl, rather than etomidate, in patients suffering from sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.
García-Gigorro, Renata; Molina-Collado, Zaira; Sáez-de la Fuente, Ignacio; Sanchez-Izquierdo, José Ángel; Montejo González, Juan Carlos
After the publication of the new definition for sepsis and septic shock, our objective is to analyse the evolution of patients admitted to ICU with an infection process using the previous and new recommendations. This is a sub-analysis of a previous observational prospective study. We included 98 patients admitted to ICU from the emergency department due to infection during an 18-month period. We studied the clinical evolution during ICU admission and hospital mortality. According to Sepsis-2 definition, 78% percent had septic shock and using Sepsis-3 criteria, 52%; hospital mortality was 29 and 41%, respectively. The RR of hospital mortality of septic shock was 10.3 (95% CI: 2.8-37.5) compared to patients without shock. The 30-day probability survival of patients with sepsis and septic shock were 78% and 68%, respectively (long rank definition could help improve the evaluation of risk of hospital death. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.
Eissa, D; Carton, E G; Buggy, D J
Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.
Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C
Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock
Shahidi Bonjar MR
Full Text Available Mohammad Rashid Shahidi Bonjar,1 Leyla Shahidi Bonjar2 1School of Dentistry, 2College of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran Abstract: The present paper proposes a prospective auxiliary treatment for sepsis. There exists no record in the published media on the subject. As an auxiliary therapy, efficacious extracorporeal removal of sepsis-causing bacterial antigens and their toxins (BATs from the blood of septic patients is discussed. The principal component to this approach is a bacterial polyvalent antibody-column (BPVAC, which selectively traps wide spectrum of BATs from blood in an extracorporeal circuit, and detoxified blood returns back to the patient’s body. BPVAC treatment would be a device of targeted medicine. Detoxification is performed under supervision of trained personnel using simple blood-circulating machines in which blood circulates from the patient to BPVAC and back to the patient aseptically. BPVACs’ reactive sites consist of carbon nanotubes on which a vast spectra of polyvalent BATs-antibodies are bond to. The devise acts as a biological filter that selectively immobilizes harmful BATs from intoxicated blood; however, no dialysis is involved. For effective neutralization, BPVAC provides large contact surface area with blood. BPVAC approach would have advantages of: 1 urgent neutralization of notorious BATs from blood of septic patients; 2 applicability in parallel with conventional treatments; 3 potential to minimize side effects of the malady; 4 applicability for a vast range of BATs; 5 potential to eliminate contact of BATs with internal tissues and organs; 6 tolerability by patients sensitive to antiserum injections; 7 capability for universal application; 8 affectivity when antibiotic-resistant bacteria are involved and the physician has no or limited access to appropriate antibiotics; and 10 being a single-use, disposable, and stand-alone device. Before using it for clinical trials in
This article examines the contemporary knowledge and uncertainties about the burden of pregnancy-associated severe sepsis (PASS), and its manifestations, management, and outcomes. There are relatively sparse data on PASS, related in part to infrequent reports and varying use of terminology and case definitions. PASS remains rare, although its incidence appears to be rapidly rising in some high-resource countries, affecting especially women with limited resources, minorities, and those with chronic illness. High level of clinician vigilance and rapid initiation of appropriate antimicrobial therapy, coupled with effective systemic support for organ dysfunction and correction of occult and overt hypoperfusion are the keys to limit adverse outcomes. However, timely diagnosis and provision of effective care remain a challenge, with reported prevalent delay in recognition and delivery of time-sensitive care interventions among maternal decedents. The mortality rate of PASS has been rising and its case fatality, although relatively low, has remained unchanged, in contrast to the outcome gains in the general population. The long-term sequelae of PASS remain unknown. The relatively limited contemporary data on PASS suggest a rising public health hazard in the obstetric population in high-resource countries, with ongoing challenges in assuring consistent provision of time-sensitive care.
Korošec Jagodič, Helena; Jagodič, Klemen; Podbregar, Matej
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 ...
Full Text Available Following the publication of the new definition of sepsis (Sepsis-3, a plethora of articles have been published in medical journals. Recognizing the epidemiological importance of the previous definitions, first issued in 1992 (Sepsis-1, and subsequently revised in 2001 (Sepsis-2, the most recent opinion emphasizes the failure “to provide adequate groups of patients with homogenous aetiologies, presentations and outcomes”, and blamed one of the causes “for the failure of several randomized controlled trials (RCTs, that tested the efficacy of adjuvant sepsis therapies”. This review summarizes the recent advances in sepsis definition.
Full Text Available We sought to create a screening tool with improved predictive value for pediatric severe sepsis and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric Emergency Department (ED. Gold standard severe sepsis cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over two months. The tool’s identification of severe sepsis was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool’s predictive value based on receiver operating curve (ROC characteristics. Age-specific normal and abnormal values for heart rate (HR and respiratory rate (RR were empirically derived from 143,603 children seen in a second pediatric ED over three years. Univariate analyses were performed for each measure in the tool to assess its association with severe sepsis and to characterize it as an early or late indicator of severe sepsis. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool’s positive predictive value was 48.7%, a significant, nearly three-fold improvement over the original ICCPS tool. False positive Systemic Inflammatory Response Syndrome (SIRS identifications were nearly six-fold lower.
Klaus, Daniel A; Motal, Michael C; Burger-Klepp, Ursula; Marschalek, Corinna; Schmidt, Elisabeth M; Lebherz-Eichinger, Diana; Krenn, Claus G; Roth, Georg A
Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae's zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity. Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR). Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51-9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14-5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14-4.14) (P = 0.008). We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS.
Bibhuti B Mishra
Full Text Available Sepsis is a complex immune disorder with a mortality rate of 20-50% and currently has no therapeutic interventions. It is thus critical to identify and characterize molecules/factors responsible for its development. We have recently shown that pulmonary infection with Francisella results in sepsis development. As extensive cell death is a prominent feature of sepsis, we hypothesized that host endogenous molecules called alarmins released from dead or dying host cells cause a hyperinflammatory response culminating in sepsis development. In the current study we investigated the role of galectin-3, a mammalian β-galactoside binding lectin, as an alarmin in sepsis development during F. novicida infection. We observed an upregulated expression and extracellular release of galectin-3 in the lungs of mice undergoing lethal pulmonary infection with virulent strain of F. novicida but not in those infected with a non-lethal, attenuated strain of the bacteria. In comparison with their wild-type C57Bl/6 counterparts, F. novicida infected galectin-3 deficient (galectin-3(-/- mice demonstrated significantly reduced leukocyte infiltration, particularly neutrophils in their lungs. They also exhibited a marked decrease in inflammatory cytokines, vascular injury markers, and neutrophil-associated inflammatory mediators. Concomitantly, in-vitro pre-treatment of primary neutrophils and macrophages with recombinant galectin-3 augmented F. novicida-induced activation of these cells. Correlating with the reduced inflammatory response, F. novicida infected galectin-3(-/- mice exhibited improved lung architecture with reduced cell death and improved survival over wild-type mice, despite similar bacterial burden. Collectively, these findings suggest that galectin-3 functions as an alarmin by augmenting the inflammatory response in sepsis development during pulmonary F. novicida infection.
Castro, C.L. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Aguiar-Nemer, A.S. [Departamento de Nutrição, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG (Brazil); Castro-Faria-Neto, H.C. [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ (Brazil); Barros, F.R. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Rocha, E.M.S. [Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Silva-Fonseca, V.A. [Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ (Brazil)
The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.
Castro, C.L.; Aguiar-Nemer, A.S.; Castro-Faria-Neto, H.C.; Barros, F.R.; Rocha, E.M.S.; Silva-Fonseca, V.A.
The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression
Lyons, John D; Mittal, Rohit; Fay, Katherine T; Chen, Ching-Wen; Liang, Zhe; Margoles, Lindsay M; Burd, Eileen M; Farris, Alton B; Ford, Mandy L; Coopersmith, Craig M
Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered. C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival. Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003). Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury. Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on the models used.
John D Lyons
Full Text Available Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered.C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival.Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003. Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury.Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on
Clark, Jessica A; Clark, Andrew T; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M
Epidermal growth factor (EGF) is a cytoprotective peptide that has healing effects on the intestinal mucosa. We sought to determine whether systemic administration of EGF after the onset of sepsis improved intestinal integrity and decreased mortality. FVB/N mice were subjected to either sham laparotomy or 2 x 23 cecal ligation and puncture (CLP). Septic mice were further randomized to receive injection of either 150 microg kg(-1) d(-1) (i.p.) EGF or 0.9% saline (i.p.). Circulating EGF levels were decreased after CLP compared with sham animals but were unaffected by giving exogenous EGF treatment. In contrast, intestinal EGF levels increased after CLP and were further augmented by exogenous EGF treatment. Intestinal EGF receptor was increased after CLP, whether assayed by immunohistochemistry, real-time polymerase chain reaction, or Western blot, and exogenous EGF treatment decreased intestinal EGF receptor. Villus length decreased 2-fold between sham and septic animals, and EGF treatment resulted in near total restitution of villus length. Sepsis decreased intestinal proliferation and increased intestinal apoptosis. This was accompanied by increased expression of the proapoptotic proteins Bid and Fas-associated death domain, as well as the cyclin-dependent kinase inhibitor p21 cip1/waf Epidermal growth factor treatment after the onset of sepsis restored both proliferation and apoptosis to levels seen in sham animals and normalized expression of Bid, Fas-associated death domain, and p21 cip1/waf . To determine whether improvements in gut homeostasis were associated with a decrease in sepsis-induced mortality, septic mice with or without EGF treatment after CLP were followed 7 days for survival. Mortality decreased from 60% to 30% in mice treated with EGF after the onset of sepsis (P < 0.05). Thus, EGF may be a potential therapeutic agent for the treatment of sepsis in part due to its ability to protect intestinal integrity.
Adina Claudia NEAMŢU
Full Text Available Campaign and especially advertising campaign represents one of the variables of the marketing mix, an important one, being difficult to separate its contribution from the one of the other elements. Irrespective of the specific object that is behind an advertising company, the investment will be retrieved only if the right information is transmitted to the right persons in the right way. This is difficult to accomplish if the advertising responsible in that firm do not understand appropriately: the market nature; the product nature; the distribution channels nature; the communication channels nature – available advertising supports and their features
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.
Rationale: The epidemiology of post–acute care use and hospital readmission after sepsis remains largely unknown. Objectives: 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. Methods: 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. Measurements and Main Results: 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 Readmission rates at 7, 30, and 90 days were higher postsepsis (P 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 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. Conclusions: 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. PMID:25751120
Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M
Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis
Mortality of severe sepsis remains at 40% to 50%. Intensive efforts over the past two decades have only marginally improved outcome. Improving outcome in sepsis depends on understanding its pathophysiology, which involves triggers, responses of the organism, and dysfunction. Stress, injury, or infection trigger host responses, including local and systemic orchestrated mechanisms. Dysfunction and outcome depend on both trigger and response. Blood coagulation, inflammation, immunity, and fibrinolysis are critical components of the organism's responses. Understanding their role in sepsis pathophysiology is the key to effective treatment. Relevant studies were identified by a systematic literature search, complemented by manual search of individual citations. Using PubMed, 'sepsis' yields more than 62,000 references, 'plasminogen activators' more than 21,000. The selection of citations was guided by preference for reviews that expand important threads of argumentation. Single original studies were included when relevant to critical points. This analytical review describes the essential elements of pathophysiology and the current status of sepsis treatment. Based on this context, an emerging therapeutic option will be discussed: plasminogen activators.
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
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.
A new campaign is taking shape to promote computer security. The slogan “SEC_RITY is not complete without U!” reminds users of the importance of their contribution. The campaign kicks off on 10 June with a public awareness day in the Council Chamber. The new campaign, organised by CERN’s computer security team, will focus on prevention and involving the user. “This is an education and awareness-raising campaign for all users at CERN,” explains Stefan Lueders, in charge of computer security. “Every day, we register thousands of computer attacks against CERN: there are attempts to tamper with web pages, hack into user accounts, take over servers, and much more. A successful attack could mean confidential user information being divulged, services being interrupted or data being lost. It could even affect operations at CERN. Another factor is the damage that a successful attack could inflict on the Organization’s reputation. &...
Tuesday 19 March 2002 in restaurant nr 2, from 9.00 to 16.30 hrs A blood donors campaign, organized by the Centre de Transfusion sanguine of Geneva If you already have a card giving your blood group, please bring this with you.
A blood donors campaign, organized by the Centre de Transfusion Sanguine of Geneva will be held at CERN on Tuesday 13 March 2001 in restaurant nr 2, from 9.00 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.
Wednesday 13 November 2002 in restaurant nr 2, from 8.30 to 16.30 hrs will be held a blood donors campaign, organized by the Etablissement de Transfusion de Haute-Savoie If you already have a card giving your blood group, please bring this with you.
A blood donors campaign, organized by the Établissement de Transfusion de Rhône-Alpes will be held at CERN on Tuesday 14 November 2000 in restaurant nr 2, from 8.30 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.
A blood donors campaign, organized by the Centre de Transfusion d'Annemasse will be held at CERN on Tuesday 14 November 2001 in restaurant nr 2, from 9.00 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.
Campaign finance might seem like the exclusive province of political reporters, but there are many good reasons why authors should be paying attention--both in races for education positions and in other key races at the local, state, and federal levels with implications for education. Basic math is a necessary skill and familiarity with a…
Thomsen, Frederik B; Mikkelsen, Marta K; Hansen, Rikke B
AIMS: The aims of the present study were to investigate referral patterns and the diagnosis of prostate cancer (PCa) before and after the Movember campaign was initiated in Denmark. METHODS: All men (n=2817) referred to the Department of Urology at Frederiksberg Hospital with suspicion of having ...
management of sepsis has resulted in a remarkable increase of new knowledge on the ... As sepsis progresses to septic shock, the risk of dying increases substantially. Where .... altered mental state, thrombocytopenia, raised serum lactate ...
Relationship between outcome variable and exposure variable was done using Chi ... A recent study in Ethiopia indicates that neonatal sepsis in the major newborn ... Neonatal sepsis was defined as infection that had occurred during the.
rat model of sepsis established by cercal ligation and puncture (CLP). Methods: Male Wistar ... capacity, resulting in excessive oxidants in cells. . ... Care (NIH publication no. 85-23 ..... estimates of severe sepsis in United States emergency.
Verdonk, Franck; Blet, Alice; Mebazaa, Alexandre
Based on recent clinical, epidemiological, and pathophysiological data, a third international consensus conference was carried out to define new criteria of sepsis in February 2016. This review presents the different items of this new definition, their limitations and their contribution to research and diagnosis of sepsis, in comparison with the previous definitions. Incidence, management, and pathophysiological knowledge of sepsis have improved over the past 20 years. However, sepsis still evolves to a mortal outcome, in one case out of five, with no new recent or specific therapy showing its efficacy on the patient's prognosis. These findings have led to the development of new definition. The new definition of sepsis incorporates relevant clinical and biological criteria such as SOFA score or serum lactate levels. It no longer takes into account the items of the systemic inflammatory response syndrome, which present a lack of specificity. It also simplifies the different stages of severity by deleting the term of 'severe sepsis' and by defining septic shock as a subset of sepsis. This definition, endorsed by only two international societies of intensive care, has some limitations and so merits prospective validation at different levels.
Sikora, Janusz Piotr
This work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so-called "respiratory burst" of neutrophils and the antioxidant mechanisms of the host are also discussed. The work focuses on possible approaches to the management of sepsis connected with immunotherapy. Neutralization of endotoxin lipopolysaccharide (LPS), anti-tumor necrosis factor alpha (TNF-alpha) therapy with monoclonal antibodies or pentoxifylline (PTXF), as well as soluble recombinant cytokine agonists and antagonists used in clinical trials are taken into consideration. In addition, cytokine manipulation therapy, anti-adhesion techniques, glucocorticoides and antioxidant barrier interference are also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts an aggressive examination of the immune system aimed at affecting its function.
Vallabhajosyula, Saraschandra; Kumar, Mukesh; Pandompatam, Govind; Sakhuja, Ankit; Kashyap, Rahul; Kashani, Kianoush; Gajic, Ognjen; Geske, Jeffrey B; Jentzer, Jacob C
Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.
risk of death, but not in patients with a low risk of death. Bleeding events and mortality are considerable higher in studies in the usual care setting compared to clinical trials. In a number of subgroup analyses, both retrospectively and prospectively performed, DAA was not significantly associated with improved survival. The role of concurrent therapy with heparin is unclear, as DAA was only effective in reducing mortality in patients without heparin. There was no significant long-term survival benefit associated with DAA beyond the initial 28 days. Also, there is a lack of studies assessing prospectively functional ability, health-related quality of life, and morbidity in the long-term. In the subgroup of patients with a high risk of death, therapy with DAA ranges at the top level of generally accepted costs per LYG or QALY, in the subgroup of patients with low risk of death, cost effectiveness ratios were higher than those accepted for resource allocation. Conclusion: Due to the lack of effectiveness of DAA in patients with severe sepsis and a low risk of death as well as with regard to the high bleeding rates in the usual care setting, indication for DAA therapy. In those subgroups with no significant survival benefit, prospective studies with adequate sample size are needed. With regard to the heterogeneity of severe sepsis, comorbidity and concurrent medication have to be taken into account in further studies. Studies with alternative study designs, for example studies comparing heparin alone or in combination with DAA to placebo, as well as studies conducted by different researchers are needed. Costs induced by bleeding events should also be taken into account in future studies, as bleeding events are the major complica-tion associated the DAA therapy.
V. V. Nazaretyan
Full Text Available Aim of the study: the effectiveness of concomitant use of antioxidant therapy with antioxidant 2-ethyl-6- methyl-3-hydroxypyridine succinate (mexidol and intensive nutritional support with glutamine in patients with abdominal sepsis (AS. Materials and methods. 170 patients with abdominal sepsis (AS involved in the study were separated into two groups. Patients of group 1 (control group, n=70 received basic treatment. Patients from group 2 (n=100 were divided into 2 subgroups. Patients from the subgroup 21 (n=70, in additon to the basic treatment, received intravenously, by drop infusion, mexidol (2000 mg per day and dipeptiven (27.5 g per day, patients from subgroup 22 (n=30 additionally to that received per os glutamine. Survival analysis was carried out according to the Kaplan-Meier method with using of the Cox's F-test and Mantel-Cox test for testing of statistical hypotheses. Results. Treatment outcomes analysis showed that in the basic group 2, mortality was lower than in the control group 1. A statistically significant increase of cumulative part in the survivors was revealed using mexidol and glutamine. Conclusion. Concomitant intravenous administration of medications had positive effects on treatment outcomes. Following on from the analysis results, we may suggest that the pair mexidol + dipeptiven interrupts the cascade of development of abdominal sepsis and contributes to avoiding a critical condition during sepsis.
Sarangi, Pranita P.; Hyun, Young-Min; Lerman, Yelena V.; Pietropaoli, Anthony P.; Kim, Minsoo
Aberrant activation of neutrophils during sepsis results in the widespread release of pro-inflammatory mediators, leading to multi-organ system failure and death. However, aberrant activation of neutrophils during sepsis results in the widespread release of harmful inflammatory mediators causing host tissue injuries that can lead to multi organ system failure and death. One of the pivotal components of neutrophil migration during inflammation is the expression of surface integrins. In this study, we show that administration of a cyclic analog of RGD peptide (Arg-Gly-Asp) significantly reduced the number of tissue-invading neutrophils and the degree of sepsis-induced lethality in mice as compared to control peptide. Secondly, β1 integrin (CD29) was highly up-regulated on the neutrophils isolated from both septic patients and animals. Finally, conditional genetic ablation of β1 integrin from granulocytes also improved survival and bacterial clearance in septic animals Thus, our results indicate that expression of β1 integrin is important for modulating neutrophil trafficking during sepsis, and that therapeutics designed against β1 integrins may be beneficial. PMID:22683734
Taeb, Abdalsamih M; Hooper, Michael H; Marik, Paul E
Sepsis is a clinical syndrome that results from the dysregulated inflammatory response to infection that leads to organ dysfunction. The resulting losses to society in terms of financial burden, morbidity, and mortality are enormous. We provide a review of sepsis, its underlying pathophysiology, and guidance for diagnosis and management of this common disease. Current established treatments include appropriate antimicrobial agents to target the underlying infection, optimization of intravascular volume to improve stroke volume, vasopressors to counteract vasoplegic shock, and high-quality supportive care. Appropriate implementation of established treatments combined with novel therapeutic approaches promises to continue to decrease the impact of this disease.
Baba, A.A.; McKillop, J.H.; Gray, H.W.; Cuthbert, G.F.; Neilson, W.; Anderson, J.R.
We have studied the clinical utility of indium 111 autologous leucocyte scintigraphy retrospectively in 45 patients presenting with suspected intra-abdominal sepsis. The sensitivity was 95% (21/22) and the specificity was 91% (21/23). Some 34 of the studies (17 positive and 17 negative) were considered helpful in furthering patient management (76%) and 8, unhelpful (18%). In 3, the study results were misleading and led to inappropriate treatment. Indium 111 scintigraphy, whether positive or negative, provides information in patients with suspected intra-abdominal sepsis upon which therapeutic decisions can be based. (orig.)
Seymour, Christopher W.; Liu, Vincent X.; Iwashyna, Theodore J.; Brunkhorst, Frank M.; Rea, Thomas D.; Scherag, André; Rubenfeld, Gordon; Kahn, Jeremy M.; Shankar-Hari, Manu; Singer, Mervyn; Deutschman, Clifford S.; Escobar, Gabriel J.; Angus, Derek C.
IMPORTANCE The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0–3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected
National Aeronautics and Space Administration — The GRIP Campaign Reports dataset consists of various reports filed by scientists during the GRIP campaign which took place 8/15/2010 - 9/30/2010; however, several...
Pfau, Michael; Burgoon, Michael
Posits a strategy of resistance to the influence of attack messages in political campaigns. Finds that political campaign messages can be designed to inoculate supporters of candidates against subsequent attack messages of opposing candidates. (MS)
Sepsis is the most common cause of neonatal mortality. As per National Neonatal Perinatal Database (NNPD) 2002-2003, the incidence of neonatal sepsis in India was 30 per 1000 live birth. It is 3% among intramural babies and 39.7% among extramural admissions. The early manifestations of neonatal sepsis are vague ...
Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or without accompanying bacteremia in the first month of life. The clinical signs of neonatal sepsis are neither specific nor uniform. Neonatal sepsis may present with fever, hypotonia, respiratory distress, apnea and hyperglycaemia.
Ree, Isabelle M. C.; Fustolo-Gunnink, Suzanne F.; Bekker, Vincent; Fijnvandraat, Karin J.; Steggerda, Sylke J.; Lopriore, Enrico
Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. A cohort study was carried out among all
Conclusion: Resistin levels were higher in premature newborns with sepsis and correlated with IL-6 levels, which is an indicator of neonatal sepsis. This suggests that resistin may also be used in the diagnosis of neonatal sepsis. However, it has limited value when compared with the other inflammatory markers including C-reactive protein, procalcitonin, and IL-6.
In this thesis, we examined the impact of HIV infection on the epidemiology (Part I) of sepsis, and host response (Part II) to sepsis. We studied sepsis patients in Gabon, a setting with a high prevalence of HIV, and in Dutch intensive care units (ICUs). In Part I, we found that HIV positive
Klein Klouwenberg, P.M.C.
Sepsis is a syndrome that arises when the body’s response to a severe infection injures its own tissues. It is a major and increasing cause of in-hospital morbidity and mortality. Despite recent advances in the management of sepsis, the morbidity and mortality caused by sepsis remain unacceptably
Capital campaigns are intense efforts to build the financial assets of an institution in a specified amount of time. This study provides an empirical view of how changes in leadership affected concomitant capital campaigns at ten colleges and universities. The transitions during these 10 campaigns influenced morale on campus, altered timing of the…
Wall, M.; Sudulich, M.L.; Gallagher, M.; Marsh, M.
The idea of an ‘internet election’ was initially put forward in 1997. However, there is little evidence to date that online campaigning has supplanted more traditional campaign practices. This is particularly true of Irish campaigns, which are hardware-rich affairs characterised by substantial
If you see this poster, stop and read it! This is the third poster produced by TIS Division as part of its information campaign on health and safety in the workplace. It provides statistics on occupational accidents at CERN. You will see that, as in the rest of Europe, falls, slips and trips continue to be the main cause of accident. So, eyes open and take care! For more information : http://safety.cern.ch/
Michels, Monique; Sonai, Beatriz; Dal-Pizzol, Felipe
Microglial polarization in response to brain inflammatory conditions is a crescent field in neuroscience. However, the effect of systemic inflammation, and specifically sepsis, is a relatively unexplored field that has great interest and relevance. Sepsis has been associated with both early and late harmful events of the central nervous system, suggesting that there is a close link between sepsis and neuroinflammation. During sepsis evolution it is supposed that microglial could exert both neurotoxic and repairing effects depending on the specific microglial phenotype assumed. In this context, here it was reviewed the role of microglial polarization during sepsis-associated brain dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.
Dendoncker, Karen; Libert, Claude
Sepsis is an acute systemic inflammatory disease. Glucocorticoids (GCs), which function by binding to the GC receptor GR have very powerful anti-inflammatory activities, yet they are hardly useful in sepsis. We can thus consider sepsis as a GC resistant disease. We here review the literature which has investigated this GC resistance, and summarize the mechanisms of GC resistance that have been observed in other diseases and in experimental models. We also discuss the importance of GC resistance in sepsis, in terms of the contribution of this phenomenon to the pathogenesis of sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.
Tonnac, Alain de
As many other companies involved in the nuclear business, Framatome was initially concentrating on corporate advertisements in business newspapers and magazines. The first goal was to concentrate on our traditional nuclear core business, while selecting the protection of the environment at large, and particularly the greenhouse effect, one of the most sensible issues of the moment. The 1997 campaign was shaped around the need to motivate European decision makers, while maintaining a domestic consensus towards nuclear power for the future resumption of constructions. The brief elaborated for Ad agencies was roughly threefold: elaborate simple messages, unquestionable, and explained with serenity; put emphasis on the benefits of nuclear power for the environment; establish a balanced comparison between nuclear and fossil fuels. A pre-test was conducted with about 100 people, half of which from the energy sector, and politicians, mainly members of the French and European Parliaments, the other half from the general public. Being accustomed to a usually discrete, if not 'ashamed' nuclear communication, people were generally surprised by such an optimistic tone about nuclear power, but agreed, on average. The campaign lasted one month (spread over June-July 97), and the three selected ads appeared successively in the form of a colour double page. Beyond nuclear magazines, the media plan included French daily newspapers le Figaro, le Monde, les Echos, Liberation, and weekly magazines: le Point, le Nouvel Observateur, I'Express, etc. All of them are intended for middle to high social class readers. In addition, some advertisements were inserted in The European Voice, a weekly publication reaching Brussels Commission and European parliament members. As an average, the campaign was perceived as dynamic (69%), and original (61%). But credibility and conviction were poor (resp 33%, 26%), probably because it was coincident with La Hague being on the carpet. On the other hand
Gessler Damian DG
Full Text Available Abstract 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.
Apr 27, 2015 ... Abstract: Introduction: Neonatal sepsis is a major cause of mortal- ity in developing countries. Accu- rate and quick diagnosis are diffi- cult because clinical presentation are non-specific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. Serum procalci-.
Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W
Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.
Ibsen, Michael; Perner, Anders
Key elements in the initial resuscitation and stabilization of the patient with sepsis are fluid therapy, vasopressor or inotropic support, administration of adequate antibiotics and source control. This review will primarily discuss fluid, vasopressor and antibiotic therapy because these have been...
Bacterial pneumonia and sepsis are a major cause of morbidity and mortality worldwide. Massive use of antibiotics promotes pathogen resistance, and, as a consequence, the incidence of drug-resistant bacteria is increasing. Therefore, it is of the utmost importance to expand our comprehension of host
The article investigates strategic, informative campaigning by two parties when politics concern redistribution. Voters are uncertain about whether parties favour special groups. Parties will target campaigns on groups where most votes are gained by informing about policies. In equilibrium......, campaigning will be most intensive in groups where the uncertainty is largest and where voters are most mobile, most likely to vote, most receptive to campaigns and relatively uninformed initially. These groups will become more informed about policy. Parties will therefore gain more votes by treating...... these groups well so these groups will gain from strategic campaigning. Welfare effects are assessed...
Quality of Life of Severe Sepsis Survivors After Hospital Discharge Calidad de vida de sobrevivientes de sepsis grave después del alta hospitalar Qualidade de vida de sobreviventes de sepse grave após alta hospitalar
Ligia Marcia Contrin
Full Text Available AIMS: to evaluate the quality of life in severe sepsis survivors, using specific QoL questionnaires: the EuroQol-5 Dimensions and the Visual Analogue Scale (EQ-VAS. METHOD: This case-control study was performed in patients discharged from a teaching hospital after being admitted to the ICU with severe sepsis. Medical records from 349 patients were retrieved from the hospital sepsis registry. Each patient with sepsis was considered as a case. Patients who were admitted immediately after the sepsis episode were considered as controls, provided that they did not have sepsis and survived the ICU admission. This specific study population included 100 patients. RESULTS: The sepsis group showed higher mortality at 1 year compared with critically ill patients. However, the control group showed no sepsis. Older patients (>60 years in the sepsis group had a significantly higher prevalence of problems. There were no differences in EQ-VAS between respondents from both groups. CONCLUSIONS: After discharge from ICU, sepsis survivors of sepsis had a higher mortality rate than critically ill patients without sepsis. Older patients with sepsis had more moderate and severe problems in all five quality of life dimensions evaluated. OBJETIVO: Evaluación de la calidad de vida de los sobrevivientes de sepsis grave con los instrumentos EuroQol-5D y la Escala Analógica Visual (EQ-VAS. MÉTODO: Estudio caso-control anidado en pacientes que recibieron alta de la unidad de cuidados intensivos (UCI de un hospital de enseñanza después de la admisión con sepsis grave. La selección fue realizada a partir del registro de sepsis conteniendo 349 pacientes y cada paciente con sepsis fue considerado como un caso y el que fue hospitalizado inmediatamente después fue seleccionado como control, desde que no tuviera sepsis y hubiera sobrevivido a la hospitalización en la UCI y la sepsis, totalizando 100 sujetos. RESULTADOS: El grupo de sepsis mostró una mayor mortalidad a 1 a
Fahila, R.; Kembaren, T.; Rahimi, A.
Sepsis can increase the amount of triglyceride as well as change the functional and structural components of lipoproteins. The triglyceride level is directly proportional to the severity of sepsis and associated with a systemic inflammatory response. The study aims to determine the correlation between the severity of bacterial sepsis with triglyceride value. An observational study with case control design from January2017 to March 2017 in 30 sepsis and 30 non-sepsis patients at H. Adam Malik General Hospital Medan. We examined Procalcitonin (PCT) and triglyceride level on the 1st, 3rd and 5th day and then analyzed using MannWhitney to assess their correlation.The triglyceride value in the sepsis group was 120 ± 5.1 mg/dl on day 1, non-sepsis 117.53 ± 36.37mg/dl. However, on the fifth day, the sepsis group of triglyceride values was 124.2±50.29mg/dl and the non-sepsis group triglyceride values 134.03±68.12mg/dl. There was no specific connection between the severity of sepsis and triglyceride value in a patient with sepsis.
Hansen, Kasper M.; Kosiara-Pedersen, Karina
The minimal effect theory of campaign studies stipulates that intense political competition during campaigns assures and reinforces the initial party choice of the electorate. We find that this reinforcement is two-fold. During the campaign, the party preference of the voters’ in-group party...... an increase in their preference for their most preferred party and a decrease for their least liked party as the campaign progresses. These trends show that the political campaign polarizes the electorate by increasing the affective distance between in-group party and out-group party preferences, thereby...... resulting in stronger political polarization after the campaign than before the campaign. The data utilized in this study is a large six-wave panel-study of Danish voters’ party preferences during the Danish parliamentary election of 2011. Thus, the analysis provides evidence of the minimal effect theory...
Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.
IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a
Ulla, Marco; Pizzolato, Elisa; Lucchiari, Manuela; Loiacono, Maria; Soardo, Flavia; Forno, Daniela; Morello, Fulvio; Lupia, Enrico; Moiraghi, Corrado; Mengozzi, Giulio; Battista, Stefania
Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock. This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records. Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival. In our
Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao
Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.
McConnell, Kevin W.; Fox, Amy C.; Clark, Andrew T.; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A.; Farris, Alton B.; Buchman, Timothy G.; Hunt, Clayton R.; Coopersmith, Craig M.
Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6–12week old) and aged (16–17 month old) HSP70−/− and wild type (WT) mice to determine if HSP70 modulated outcome in an age-dependent fashion. Young HSP70−/− and WT mice subjected to cecal ligation and puncture (CLP), Pseudomonas aeruginosa pneumonia or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70−/− mice than aged WT mice subjected to CLP (p=0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared to WT mice, aged septic HSP70−/− mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70−/−mice had increased systemic levels of TNF-α, IL-6, IL-10 and IL-1β compared to WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation. PMID:21296977
McConnell, Kevin W; Fox, Amy C; Clark, Andrew T; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A; Farris, Alton B; Buchman, Timothy G; Hunt, Clayton R; Coopersmith, Craig M
Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70(-/-) and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70(-/-) and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70(-/-) mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70(-/-) mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70(-/-) mice had increased systemic levels of TNF-α, IL-6, IL-10, and IL-1β compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation.
Full Text Available Sepsis is the major cause of death for critically ill patients. Recent progress in proteomics permits a thorough characterization of the mechanisms associated with critical illness. The purpose of this study was to screen potential biomarkers for early prognostic assessment of patients with sepsis.For the discovery stage, 30 sepsis patients with different prognoses were selected. Urinary proteins were identified using isobaric tags for relative and absolute quantitation (iTRAQ coupled with LC-MS/MS. Mass spec instrument analysis were performed with Mascot software and the International Protein Index (IPI; bioinformatic analyses were used by the algorithm of set and the Gene Ontology (GO Database. For the verification stage, the study involved another 54 sepsis-hospitalized patients, with equal numbers of patients in survivor and non-survivor groups based on 28-day survival. Differentially expressed proteins were verified by Western Blot.A total of 232 unique proteins were identified. Proteins that were differentially expressed were further analyzed based on the pathophysiology of sepsis and biomathematics. For sepsis prognosis, five proteins were significantly up-regulated: selenium binding protein-1, heparan sulfate proteoglycan-2, alpha-1-B glycoprotein, haptoglobin, and lipocalin; two proteins were significantly down-regulated: lysosome-associated membrane proteins-1 and dipeptidyl peptidase-4. Based on gene ontology clustering, these proteins were associated with the biological processes of lipid homeostasis, cartilage development, iron ion transport, and certain metabolic processes. Urinary LAMP-1 was down-regulated, consistent with the Western Blot validation.This study provides the proteomic analysis of urine to identify prognostic biomarkers of sepsis. The seven identified proteins provide insight into the mechanism of sepsis. Low urinary LAMP-1 levels may be useful for early prognostic assessment of sepsis.ClinicalTrial.gov NCT01493492.
Lambertucci, Flavia; Motiño, Omar; Villar, Silvina; Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A; Martín-Sanz, Paloma; Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar; Ronco, María Teresa
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice
Lambertucci, Flavia [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Motiño, Omar [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Villar, Silvina [Instituto de Inmunología, Facultad de Ciencias Médicas, UNR, Suipacha 531, 2000 Rosario (Argentina); Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Martín-Sanz, Paloma [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid (Spain); Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Ronco, María Teresa, E-mail: firstname.lastname@example.org [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina)
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice.
Reis, Patricia A; Alexandre, Pedro C B; D'Avila, Joana C; Siqueira, Luciana D; Antunes, Barbara; Estato, Vanessa; Tibiriça, Eduardo V; Verdonk, Franck; Sharshar, Tarek; Chrétien, Fabrice; Castro-Faria-Neto, Hugo C; Bozza, Fernando A
Acute brain dysfunction is a frequent condition in sepsis patients and is associated with increased mortality and long-term neurocognitive consequences. Impaired memory and executive function are common findings in sepsis survivors. Although neuroinflammation and blood-brain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. Experimental sepsis was induced in Swiss Webster mice by intraperitoneal injection of cecal material (5mg/kg, 500μL). Control groups (n=5/group each experiment) received 500μL of saline. Support therapy recover (saline 0.9%, 1mL and imipenem 30mg/kg) were applied (6, 24 and 48h post injection, n=5-10/group, each experiment), together or not with additive orally treatment with statins (atorvastatin/simvastatin 20mg/kg b.w.). Survival rate was monitored at 6, 24 and 48h. In a setting of experiments, animals were euthanized at 6 and 24h after induction for biochemical, immunohistochemistry and intravital analysis. Statins did not prevented mortality in septic mice, however survivors presented lower clinical score. At another setting of experiments, after 15days, mice survivors from fecal supernatant peritoneal sepsis presented cognitive dysfunction for contextual hippocampal and aversive amygdala-dependent memories, which was prevented by atorvastatin/simvastatin treatment. Systemic and brain tissue levels of proinflammatory cytokines/chemokines and activation of microglial were lower in septic mice treated with statins. Brain lipid peroxidation and myeloperoxidase levels were also reduced by statins treatment. Intravital examination of the brain vessels of septic animals revealed decreased functional capillary density and increased rolling and adhesion of leukocytes, and blood flow impairment, which were reversed by treatment with statins. In addition, treatment with statins restored the cholinergic vasodilator response
Dominguez, Jessica A; Samocha, Alexandr J; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Coopersmith, Craig M
Nuclear factor-κB is a critical regulator of cell-survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase. Prospective, randomized controlled study. Animal laboratories in university medical centers. Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkβ) and wild-type mice were subjected to sham laparotomy or cecal ligation and puncture. Animals were killed at 24 hours or followed 7 days for survival. Septic wild-type mice had decreased villus length compared with sham mice, whereas villus atrophy was further exacerbated in septic Vil-Cre/Ikkβ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared with sham mice, which was further exacerbated in Vil-Cre/Ikkβ mice. Sepsis induced intestinal hyperpermeability in wild-type mice compared with sham mice, which was further exacerbated in septic Vil-Cre/Ikkβ mice. This was associated with increased intestinal expression of claudin-2 in septic wild-type mice, which was further increased in septic Vil-Cre/Ikkβ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following cecal ligation and puncture, and interleukin 10 and monocyte chemoattractant protein-1 levels were higher in septic Vil-Cre/Ikkβ mice than in septic wild-type mice. All septic mice were bacteremic, but no differences in bacterial load were identified between wild-type and Vil-Cre/Ikkβ mice. To determine the functional significance of these results, animals were followed for survival. Septic wild-type mice had lower mortality than septic Vil-Cre/Ikkβ mice (47% vs 80%, p<0.05). Antitumor necrosis factor administration decreased intestinal apoptosis, permeability, and mortality in wild-type septic mice, and a similar improvement in intestinal integrity and survival were seen when antitumor necrosis factor was given to Vil-Cre/Ikkβ mice. Enterocyte
Dominguez, Jessica A.; Samocha, Alexandr J.; Liang, Zhe; Burd, Eileen M.; Farris, Alton B.; Coopersmith, Craig M.
Objective NF-kB is a critical regulator of cell survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase (IKK)-ß. Design Prospective, randomized, controlled study. Setting Animal laboratories in university medical centers. Subjects and Interventions Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkßf/Δ) and wild type (WT) mice were subjected to sham laparotomy or cecal ligation and puncture (CLP). Animals were sacrified at 24 hours or followed seven days for survival. Measurements and Main Results Septic WT mice had decreased villus length compared to sham mice while villus atrophy was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared to sham mice which was further exacerbated in Vil-Cre/Ikkßf/Δ mice. Sepsis induced intestinal hyperpermeability in WT mice compared to sham mice, which was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. This was associated with increased intestinal expression of claudin-2 in septic WT mice, which was further increased in septic Vil-Cre/Ikkßf/Δ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following CLP, and IL-10 and MCP-1 levels were higher in septic Vil-Cre/Ikkßf/Δ mice than septic WT mice. All septic mice were bacteremic, but no differences in bacterial load were identified between WT and Vil-Cre/Ikkßf/Δ mice. To determine the functional significance of these results, animals were followed for survival. Septic WT mice had lower mortality than septic Vil-Cre/Ikkßf/Δ mice (47% vs. 80%, p<0.05). Anti-TNF administration decreased intestinal apoptosis, permeability and mortality in WT septic mice and a similar improvement in intestinal integrity and survival were seen when anti-TNF was given to Vil-Cre/Ikkßf/Δ mice. Conclusions Enterocyte-specific NF
justification. This paper finally discusses the reason for this greening of government initiated Danish energy saving campaigns, which is seen as an indirect result of the 1987 UN report, Our Common Future. The 1988 general election in Denmark led to the formation of a new center-right government coalition...... economics and not least a significant portion of patriotism. Environmental justification was almost entirely absent throughout the 1970s and 1980s. This changed only from 1989 onwards, as government initiatives to curb the ever rising consumption of energy commenced an extensive use of environmental...
Alexander D Malkin
-24 hours, which may reduce survival to 13%. In severe sepsis, an extracorporeal treatment which modulates CXCR-1/2 levels has therapeutic potential, but also potential for harm. Further development of the computational model will help guide optimal device development and determine which patient populations should be targeted by treatment.
Storgaard, Merete; Hallas, Jesper; Gahrn-Hansen, Bente
Background: Severe sepsis and septic shock have a high 30-day mortality (10-50%), but the long-term mortality is not well described. The purpose of this study was to describe long-term mortality among patients with community-acquired severe sepsis or septic shock compared to a population-based re......Background: Severe sepsis and septic shock have a high 30-day mortality (10-50%), but the long-term mortality is not well described. The purpose of this study was to describe long-term mortality among patients with community-acquired severe sepsis or septic shock compared to a population...... extracted from the National Danish Patient Registry. We analyzed the hazard ratio for mortality at predefined intervals. Results: Absolute mortality within the first 30 days was 69/211 (33%, 95% confidence interval (CI) 25-41%), with a cumulative mortality of 121/211 (57%, 95% CI 48-69%) for the entire...... follow-up. Among septic patients who survived the first 30 days, the mortality hazard ratio was 2.7 (95% CI 1.7-4.3) until day 365, and among septic patients who survived the first year, the 1-4 y mortality hazard ratio was 2.3 (95% CI 1.7-3.3), compared to the community-based reference persons...
Huan, J N
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.
Full Text Available Sepsis is a complication of severe infection associated with high mortality and open diagnostic issues. Treatment strategies are currently limited and essentially based on prompt recognition, aggressive supportive care and early antibiotic treatment. In the last years, extensive antibiotic use has led to selection, propagation and maintenance of drug-resistant microorganisms. In this context, several biomarkers have been proposed for early identification, etiological definition, risk stratification and improving antibiotic stewardship in septic patient care. Among these molecules, only a few have been translated into clinical practice. In this review, we provided an updated overview of established and developing biomarkers for sepsis, focusing our attention on their pathophysiological profile, advantages, limitations, and appropriate evidence-based use in the management of septic patients.
Ansio, Susa; Saarenketo, Tiia
Sepsiksellä tarkoitetaan tilannetta, jolloin ihmisen verenkierrossa on bakteereita ja tämä aiheuttaa vakavia oireita. Lähes kaikki sepsiksen oireet johtuvat elimistön puolustusreaktiosta bakteeria vastaan. Sepsiksen hoito on monivaiheista ja kallista, ja siihen kuolleisuus on suurta. Ensihoidossa olisi tärkeää tunnistaa mahdollinen sepsis ja aloittaa tarvittava hoito mahdollisimman varhaisessa vaiheessa. Opinnäytetyön tarkoituksena on kuvata sepsiksen tunnistamista ensihoidossa, myöhäisem...
Full Text Available Marcello Guido,1 Maria Rosaria Tumolo,2 Antonella De Donno,1 Tiziano Verri,3 Francesca Serio,1 Francesco Bagordo,1 Antonella Zizza2 1Laboratory of Hygiene, Department of Biological and Environmental Sciences and Technologies, Faculty of Sciences, University of Salento, Lecce, Italy; 2National Research Council, Institute of Clinical Physiology, 3Laboratory of Physiology, Department of Biological and Environmental Sciences and Technologies, Faculty of Sciences, University of Salento, Lecce, ItalyAbstract: Sepsis, severe sepsis and septic shock, systemic inflammatory response, and other related manifestations represent a relevant medical problem with high morbidity and mortality, despite the improvements in diagnosis, treatment, and preventive measures over the last few decades. The limited knowledge of the pathophysiology in association with the lack of in vitro diagnostic methods for the certain and quick determination of the causative microbiological agents and their antibiotic resistance means the condition is still critical and of high impact in health care. The current gold standard method to detect the sepsis-causing pathogens, which is based on blood culture, is still insufficiently sensitive and slow. The new culture-independent molecular biology-based techniques can lead to the identification of a broad range of microorganisms and resistance markers within a few hours and with high sensitivity and specificity; nevertheless, limitations of, for example, the polymerase chain reaction-based methods still hamper their application in the clinical routine. This review summarizes the in vitro diagnostic methods and their approach in the clinical diagnosis of the bloodstream infections, and explores their advantages and disadvantages at the current state of the art. A quick analysis of the future prospective in multiplex technologies for microbiological diagnosis of sepsis is also provided. Keywords: PCR, PCR/ESI-MS, microarray, MALDI-TOF, next
A Guntur Hermawan
Full Text Available Over the past decade, sepsis has been diagnosed according to consensus guidelines established in 1991 as an infection in addition to the symptoms of systemic inflammatory response syndrome (SIRS. In addition to the previous criteria, the 2001 conference added several new diagnostic criteria for sepsis. Of particular interest was the inclusion of the biomarkers procalcitonin (PCT and C-reactive protein (CRP, despite the overall conclusion that it was premature to use biomarkers for sepsis diagnosis. The primary recommendation of the panel was the implementation of the Predisposition, insult Infection, Response, and Organ dysfunction (PIRO.The immune system has traditionally been devided into innate and adaptive components, each of which has a different role and function in defending the host against infectious agents. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. The superantigens are able to induce toxic shock syndrome and can sometimes cause multiple organ failure via adaptive immune system. The superantigenic activity of the bacterial exotoxins can be attributed to their ability to cross-link major histocompatibility complex class II molecules on antigen-presenting cells outside the peptide groove with T-cell receptors to form a trimolecular complex. This trimolecular interaction leads to uncontrolled release of a number of proinflammatory cytokines. Proinflammatory cytokines especially IFN-γ and TNF-α, the key cytokines causing toxic shock syndrome. KEYWORDS: sepsis, innate immunity, adaptive.
Petrache, Simona Magdalena; Miftode, Egidia; Vâţă, A; Petrovici, Cristina Mirela; Dorneanu, Olivia; Luca, V
The aim of our study was to analyze clinical and biological characteristics of immunocompromised patients with staphylococcal sepsis and to compare with the same data in non-immunocompromised patients. The diagnosis of sepsis was made based on Bone criteria. MiniAPI system ID 32 STAPH was used for identification and antibiotic susceptibility was assessed by ATB STAPH method and by E-test for oxacillin and vancomycin. Among the 147 patients with Staphylococcus aureus sepsis--66.67% had concomitant immunosuppressive conditions (diabetes mellitus, liver diseases, renal failure, corticotherapy, etc). We have found a significant correlation between the immunosuppressed status and MRSA (methicillin-resistant Staphylococcus aureus) involvement (p = 0.0018) and also, between this group of patients and treatment failure (p = 0.0012). Because of the high rate of MRSA involvement in systemic infections in the Eastern region of Romania first intention treatment of patients with staphylococcal infections and conditions of immunosuppression must include antibiotics effective against methicillin-resistant strains.
Foga, M.M.; McGinn, G.J.; Kroeker, M.A.; Guzman, R.
Clostridium septicum is an unusual anaerobic, gram-positive, gas-producing bacillus, which has been identified as a cause of fulminant rapidly fatal infection in humans. Infection with C. septicum usually occurs in patients with cancer, patients receiving immunosuppressive chemotherapy, or patients with a nonmalignant hematological disorder such as hemolytic uremic syndrome. C. septicum infection most commonly involves the abdomen, and a recent review article has identified 164 cases in the medical literature describing the abdominal findings in this disease. Intracranial manifestation of C. septicum infection are less common and include meningitis, cerebritis, abscess formation and pneumocephalus. There have been only 12 documented cases in the English literature describing central nervous system lesions associated with C. septicum. We present a case report of a 56-year-old man in whom septicemia due to C. septicum developed as a complication of Crohn's disease. To our knowledge, there has never been a previous report of C. septicum sepsis related to underlying Crohn's disease. Our case is also remarkable in that an intracerebral gas collection developed at the site of a mycotic infarct related to C. septicum bacteremia, Intracranial, intraparenchymal gas formation related to anaerobic infection is extremely rare; to our knowledge, this radiological finding related to C. septicum sepsis has been described in only 1 previous case report in the medical literature. We also describe the intra-abdominal manifestations of C. septicum sepsis that occurred in this patient as well as the associated radiographic and pathologic findings. (author)
Schoedinger, S. E.; Strang, C.
"Ocean Literacy is an understanding of the ocean's influence on you and your influence on the ocean." This simple statement captures the spirit of a conceptual framework supporting ocean literacy (COSEE et al., 2005). The framework comprises 7 essential principles and 44 fundamental concepts an ocean literate person would know (COSEE et al., 2005). The framework is the result of an extensive grassroots effort to reach consensus on (1) a definition for ocean literacy and (2) an articulation of the most important concepts to be understood by ocean-literate citizen (Cava et al., 2005). In the process of reaching consensus on these "big ideas" about the ocean, what began as a series of workshops has emerged as a campaign "owned" by an ever-expanding community of individuals, organizations and networks involved in developing and promoting the framework. The Ocean Literacy Framework has provided a common language for scientists and educators working together and serves as key guidance for the ocean science education efforts. This presentation will focus on the impact this Ocean Literacy Campaign has had to date as well as efforts underway to provide additional tools to enable educators and educational policy makers to further integrate teaching and learning about the ocean and our coasts into formal K-12 education and informal education. COSEE, National Geographic Society, NOAA, College of Exploration (2005). Ocean Literacy: The Essential Principles of Ocean Sciences Grades K-12, a jointly published brochure, URL: http://www.coexploration.org/oceanliteracy/documents/OceanLitChart.pdf Cava, F., S. Schoedinger , C. Strang, and P. Tuddenham (2005). Science Content and Standards for Ocean Literacy: A Report on Ocean Literacy, URL: http://www.coexploration.org/oceanliteracy/documents/OLit2004-05_Final_Report.pdf.
Søndergaard, Edith Smed; Alamili, Mahdi; Coskun, Mehmet
Purpose: Sepsis is one of the leading causes of death after admission to the intensive care unit (ICU). The discovery of small non-coding microRNAs (miRs) and their correlation to sepsis has gained increasing interest. Our aim was to systematically review the literature examining the association ...... searching the computational target prediction databases. Conclusion: Various miRs are associated with sepsis, but no corresponding predictor genes were found....
Full Text Available BACKGROUND Sepsis refers to the systemic response to serious infection. It can be response to the infection caused by any class of microorganism. The presence of bacteraemia is an indicator of disseminated infection and generally indicates a poorer prognosis when associated with localised disease. This study was undertaken to study the diagnostic and prognostic value of Procalcitonin (PCT in patients with sepsis. AIM To study the diagnostic and prognostic value of Procalcitonin (PCT in patients with sepsis. MATERIALS AND METHODS Fifty patients of age more than 18 years with sepsis admitted in KMC Hospitals, Mangalore, from August 2008 to June 2010 were subjects in the study after due permission from institution and informed consent from the patients. Diagnosis of sepsis was made according to criteria by ACCP/SCCM definition for sepsis. Definitive aetiological diagnosis requires isolation of microorganism from the blood and local site of infection, Gram stain and culture of the material from the primary site of infection for the microbial aetiology was taken. Other appropriate laboratory investigations depending upon requirement were done as mentioned in the investigations. RESULTS Out of total 50 patients, 23 patients were in group of sepsis, 14 were in group of severe sepsis while 13 had septic shock. Maximum number of the study patients were in the age group of 51-60 years. 52% of the study patients were male and 48% were female. Most common symptom in patients with sepsis was fever. Most common sign in the patient with sepsis is tachycardia followed by high temperature and then tachypnoea. Most common source of sepsis was respiratory infection followed by UTI. CONCLUSION Our data suggest the possibility that the addition of Procalcitonin into the standard workup of critically ill patients with suspected sepsis could increase diagnostic certainty and improve patient management.
Sepsis and subsequent organ failure remain the major cause of mortality in intensive care units in spite of significant research efforts. The lung is the most vulnerable organ affected by early hyper-inflammatory immune response in septic patients. On the other hand, the septic insult induces immune dysfunction in later phases of sepsis which in turn increases susceptibility to infections. The aim of this thesis was to investigate early and late inflammatory mechanisms in abdominal sepsis ind...
Phillips, Gary S; Osborn, Tiffany M; Terry, Kathleen M; Gesten, Foster; Levy, Mitchell M; Lemeshow, Stanley
In accordance with Rory's Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment. Retrospective evaluation of prospectively collected data. Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated. Prospective data were submitted to a database from January 1, 2015, to December 31, 2015. None. Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765-0.775) and 0.773 (95% CI, 0.758-0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate. The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult
Pseudomonas aeruginosa. Furthermore, nanostructures did not show hemolytic activity. In vivo sepsis bioassays were performed using C57BL6 mice strain inoculated with a polymicrobial suspension. Assays led to 100% survival rate under sub-lethal sepsis assays and 40% under lethal sepsis assays in the presence of nanoformulated clavanin A until the seventh day of the experiment. Data here reported indicated that nanostructured clavanin A form shows improved antimicrobial activity and has the potential to be used to treat polymicrobial infections. Keywords: peptides, antimicrobial, nanoparticles, nanobiotechnology
Chen, J; Wang, L H; Ouyang, B; Chen, M Y; Wu, J F; Liu, Y J; Liu, Z M; Guan, X D
Objective: To observe the effect of sepsis single-disease manage system on the improvement of sepsis treatment and the value in predicting mortality in patients with sepsis. Methods: A retrospective study was conducted. Patients with sepsis admitted to the Department of Surgical Intensive Care Unit of Sun Yat-Sen University First Affiliated Hospital from September 22, 2013 to May 5, 2015 were enrolled in this study. Sepsis single-disease manage system (Rui Xin clinical data manage system, China data, China) was used to monitor 25 clinical quality parameters, consisting of timeliness, normalization and outcome parameters. Based on whether these quality parameters could be completed or not, the clinical practice was evaluated by the system. The unachieved quality parameter was defined as suspicious parameters, and these suspicious parameters were used to predict mortality of patients with receiver operating characteristic curve (ROC). Results: A total of 1 220 patients with sepsis were enrolled, included 805 males and 415 females. The mean age was (59±17) years, and acute physiology and chronic health evaluation (APACHE Ⅱ) scores was 19±8. The area under ROC curve of total suspicious numbers for predicting 28-day mortality was 0.70; when the suspicious parameters number was more than 6, the sensitivity was 68.0% and the specificity was 61.0% for predicting 28-day mortality. In addition, the area under ROC curve of outcome suspicious number for predicting 28-day mortality was 0.89; when the suspicious outcome parameters numbers was more than 1, the sensitivity was 88.0% and the specificity was 78.0% for predicting 28-day mortality. Moreover, the area under ROC curve of total suspicious number for predicting 90-day mortality was 0.73; when the total suspicious parameters number was more than 7, the sensitivity was 60.0% and the specificity was 74.0% for predicting 90-day mortality. Finally, the area under ROC curve of outcome suspicious numbers for predicting 90
Zoila del S. López Díaz
Full Text Available Se realiza un estudio retrospectivo y longitudinal de la sepsis cervicomaxilofacial en los neonatos ingresados en nuestra unidad de cuidados intensivos en un período de 10 años. Encontramos una incidencia promedio de 1,20 por cada 100 ingresos, y el predominio del grupo de edades entre 7 y 27 días de vida (sepsis tardía, del sexo femenino y del color blanco de la piel. La celulitis facial fue ocasionada por trauma obstétrico y fue el diagnóstico más frecuente. No encontramos relación entre la presencia de sepsis y la edad gestacional, el conteo de Apgar o el peso al nacer, pues en el mayor número de niños estos resultados estuvieron dentro de límites normales. El tratamiento más utilizado fue la antibioticoterapia con asociación de 2 o más antibióticos, y entre estas la más socorrida fue la asociación de penicilina y gentamicina. Cuando la sepsis tuvo una repercusión sistémica muy grave, se utilizó además inmunoglobulinoterapia. La evolución fue satisfactoria en el 100 % de los casos, la mayoría de los cuales necesitó internación hospitalaria hasta los 7 días. No hubo fallecidos.A retrospective and longitudinal study of cervicomaxillofacial sepsis in the neonates admitted in our intensive care unit in a period of 10 years was conducted. An average incidence of 1.20 per 100 admissions, as well as the predominance of white female infants aged 7-27 days old (late sepsis were observed. Facial cellulitis was caused by obstetric trauma and it was the most frequent diagnosis. No relation between the presence of sepsis and gestational age, Apgar score, or birth weight, was found, since in most of the children these results were within the normal limits. The most used treatment was the antibiotic therapy with the association of 2 or more antibiotics. The combination of penicillin and gentamicin was the most common treatment. In those cases, among whom the sepsis had a very severe systemic repercussion, immunoglobulin therapy was
Full Text Available Sepsis, a dysregulated host response to infection that causes life-threatening organ dysfunction, is a highly heterogeneous syndrome with no specific treatment. Although sepsis can be caused by a wide variety of pathogenic organisms, endothelial dysfunction leading to vascular leak is a common mechanism of injury that contributes to the morbidity and mortality associated with the syndrome. Perturbations to the angiopoietin (Ang/Tie2 axis cause endothelial cell activation and contribute to the pathogenesis of sepsis. In this review, we summarize how the Ang/Tie2 pathway is implicated in sepsis and describe its prognostic as well as therapeutic utility in life-threatening infections.
Bohl, Daniel D; Iantorno, Stephanie E; Saltzman, Bryan M; Tetreault, Matthew W; Darrith, Brian; Della Valle, Craig J
Sepsis after hip fracture typically develops from one of the 3 potential infectious sources: urinary tract infection (UTI), pneumonia, and surgical site infection (SSI). The purpose of this investigation is to determine (1) the proportion of cases of sepsis that arises from each of these potential infectious sources; (2) baseline risk factors for developing each of the potential infectious sources; and (3) baseline risk factors for developing sepsis. The National Surgical Quality Improvement Program database was searched for geriatric patients (aged >65 years) who underwent surgery for hip fracture during 2005-2013. Patients subsequently diagnosed with sepsis were categorized according to concomitant diagnosis with UTI, SSI, and/or pneumonia. Multivariate regression was used to test for associations while adjusting for baseline characteristics. Among the 466 patients who developed sepsis (2.4% of all patients), 157 (33.7%) also had a UTI, 135 (29.0%) also had pneumonia, and 36 (7.7%) also had SSI. The rate of sepsis was elevated in patients who developed UTI (13.0% vs 1.7%; P sepsis (21.0% vs 3.8%; P Sepsis occurs in about 1 in 40 patients after geriatric hip fracture surgery. Of these septic cases, 1 in 3 is associated with UTI, 1 in 3 with pneumonia, and 1 in 15 with SSI. The cause of sepsis is often unknown on clinical diagnosis, and this distribution of potential infectious sources allows clinicians for direct identification and treatment. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available Sepsis is a common complication after severe trauma and burn, and also one of the main causes of death. Recently, although some new progresses were seen in antibiotic therapy, the mortality of sepsis is still on the rise, and the death rate as a result of sepsis is higher than a total of that of prostate cancer, breast cancer and AIDS. Therefore, sepsis has obviously become one of the serious ailments threatening human health. The present paper introduced the international definition of sepsis, severe sepsis and septic shock, the current researches on diagnosis and therapy, and proposed that we should not only pay attention to pathogenesis and treatment, but also to sepsis prevention in sepsis researches, and we should try to find out the breakthrough in the interaction and dynamic balance between human being and pathogenic factors. Researches on the strategies to revert strong toxicity of infectious agents to non-toxic or weak pathogenic factors, and to conduct further research concerning biological characteristics of microorganisms and mechanism of drug resistance in order to render them to lose the drug resistance ability, or to increase its sensitivity to the drugs. The above suggested approaches might form the future strategies for preventing and controlling sepsis.
Wiens, Matthew O; Kumbakumba, Elias; Kissoon, Niranjan; Ansermino, J Mark; Ndamira, Andrew; Larson, Charles P
Sepsis represents the progressive underlying inflammatory pathway secondary to any infectious illness, and ultimately is responsible for most infectious disease-related deaths. Addressing issues related to sepsis has been recognized as an important step towards reducing morbidity and mortality in developing countries, where the majority of the 7.5 million annual deaths in children under 5 years of age are considered to be secondary to sepsis. However, despite its prevalence, sepsis is largely neglected. Application of sepsis definitions created for use in resource-rich countries are neither practical nor feasible in most developing country settings, and alternative definitions designed for use in these settings need to be established. It has also been recognized that the inflammatory state created by sepsis increases the risk of post-discharge morbidity and mortality in developed countries, but exploration of this issue in developing countries is lacking. Research is urgently required to characterize better this potentially important issue.
Turnbull, Isaiah R; Clark, Andrew T; Stromberg, Paul E; Dixon, David J; Woolsey, Cheryl A; Davis, Christopher G; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M
Aging is associated with increased inflammation following sepsis. The purpose of this study was to determine whether this represents a fundamental age-based difference in the host response or is secondary to the increased mortality seen in aged hosts. Prospective, randomized controlled study. Animal laboratory in a university medical center. Young (6-12 weeks) and aged (20-24 months) FVB/N mice. Mice were subjected to 2 x 25 or 1 x 30 cecal ligation and puncture (CLP). Survival was similar in young mice subjected to 2 x 25 CLP and aged mice subjected to 1 x 30 CLP (p = 0.15). Young mice subjected to 1 x 30 CLP had improved survival compared with the other groups (p < 0.05). When injury was held constant but mortality was greater, both systemic and peritoneal levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and monocyte chemotactic protein-1 were elevated 24 hours after CLP in aged animals compared with young animals (p < 0.05). When mortality was similar but injury severity was different, there were no significant differences in systemic cytokines between aged mice and young mice. In contrast, peritoneal levels of tumor necrosis factor-alpha, IL-6, and IL-10 were higher in aged mice subjected to 1 x 30 CLP than young mice subjected to 2 x 25 CLP despite their similar mortalities (p < 0.05). There were no significant differences in either bacteremia or peritoneal cultures when animals of different ages sustained similar injuries or had different injuries with similar mortalities. Aged mice are more likely to die of sepsis than young mice when subjected to an equivalent insult, and this is associated with increases in both systemic and local inflammation. There is an exaggerated local but not systemic inflammatory response in aged mice compared with young mice when mortality is similar. This suggests that systemic processes that culminate in death may be age independent, but the local inflammatory response may be greater with aging.
Turnbull, Isaiah R.; Clark, Andrew T.; Stromberg, Paul E.; Dixon, David J.; Woolsey, Cheryl A.; Davis, Christopher G.; Hotchkiss, Richard S.; Buchman, Timothy G.; Coopersmith, Craig M.
Objective Aging is associated with increased inflammation following sepsis. The purpose of this study was to determine if this represents a fundamental age-based difference in the host response or is secondary to the increased mortality seen in aged hosts. Design Prospective, randomized controlled study. Setting Animal laboratory in a university medical center. Subjects Young (6–12 week) and aged (20–24 month) FVB/N mice. Interventions Mice were subjected to 2×25 or 1×30 cecal ligation and puncture (CLP). Measurements and Main Results Survival was similar in young mice subjected to 2×25 CLP and aged mice subjected to 1×30 CLP (p=0.15). Young mice subjected to 1×30 CLP had improved survival compared to both other groups (p<0.05). When injury was held constant but mortality was greater, both systemic and peritoneal levels of TNF-α, IL-6, IL-10 and MCP-1 were elevated 24 hours after CLP in aged animals compared to young animals (p<0.05). When mortality was similar but injury severity was different, there were no significant differences in systemic cytokines between aged mice and young mice. In contrast, peritoneal levels of TNF-α, IL-6, and IL-10 were higher in aged mice subjected to 1×30 CLP than young mice subjected to 2×25 CLP despite their similar mortalities (p<0.05). There were no significant differences in either bacteremia or peritoneal cultures when animals of different ages sustained similar injuries or had different injuries with similar mortalities. Conclusions Aged mice are more likely to die from sepsis than young mice when subjected to an equivalent insult, and this is associated with increases in both systemic and local inflammation. There is an exaggerated local but not systemic inflammatory response in aged mice compared to young mice when mortality is similar. This suggests that systemic processes that culminate in death may be age-independent, but the local inflammatory response may be greater with aging. PMID:19237912
Full Text Available Objective To investigate the prevalence and risk factors of post-traumatic sepsis, and to evaluate the rationality of the 1992, 2001 and 2012 international sepsis definitions in diagnosing post-traumatic sepsis in a trauma intensive care unit (ICU in China. Methods A one-day cross-sectional survey of trauma patients who met the inclusion criteria was conducted from 8:00 a.m., June 16, 2014 to 8:00 a.m., June 17, 2014 in the trauma ICU of Daping Hospital. The survey data included demographic information, clinical characteristics, pertinent scores (APACHE Ⅱ, SOFA, GCS, ISS and injury mechanism. According to the definition of sepsis as depicted in the 1992, 2001, and 2012 "International Guideline of Sepsis", the patients were divided into A, B and C groups. The infection site, infection pathogens, and key medical treatment were recorded, the infection identified, and the 28day mortality recorded. A positive pathogen culture of respiratory and urinary tracts, blood, cerebrospinal fluid, and wound secretion was adopted as the diagnostic "gold standard" for septic infection. The diagnostic sensitivity and specificity of the three versions of the guidelines were statistically analyzed and the diagnostic feasibility of each definition was assessed. Results A total of 30 trauma patients were enrolled, twenty-three patients met the 1992 sepsis criteria, 22 met the 2001 criteria, and 20 met the 2012 criteria. The prevalence rates were 76.7%, 73.3%, and 66.7%, respectively, and there was no significant statistical difference. Four patients died within 28 days, which was in line with the diagnostic criteria of the three versions of the sepsis criteria. The 28-day mortality in the three sepsis guidelines groups was 17.4%, 18.2%, and 25.0%, respectively, indicating no statistical difference. By adopting culture-positive pathogens as the "gold standard" of septic infection, the diagnostic sensitivity and specificity of the group A was 77.8% and 25
Student research campaigns (forskningskampanjer) have been an annual event in connection to Research Days (Forskningsdagene) since 2003 in Norway. The campaigns invite students from all over the country to participate in a common scientific research event, always connected to a special environmentally related theme - for example Air Quality in the Classroom (2003), Pollution along Roads (2004), Bacteria in Drinking Water (2005), and The Rain Check (2006). The year 2008, as with previous years, was overshadowed by the topic of climate change, and the specific role of humans. The research campaign theme for 2008 fit well into this focus: the potential benefits of solar energy as an alternative energy source. The campaign also was aligned with the Research Days theme of alternative energy sources and technologies. The campaign included the hands-on activity of assembling a solar panel and taking measurements with the device to determine efficiency, as well as a questionnaire to record the results and ask deeper questions regarding alternative energy and climate change. The results gained from data analysis of the campaign show that students were able to gain maximum efficient solar power from the devices they constructed, which gave them a solid understanding of solar power technology. Analysis of the campaign questionnaire in regards to the activity shows that students believe that solar energy should be better utilized as an energy source in Norway. (Also in Norwegian OR 24/2009). (Author)
Ismail, Amid I; Jedele, Jenefer M; Lim, Sungwoo; Tellez, Marisol
Organizers of the Detroit Oral Cancer Prevention Project at the University of Michigan, Ann Arbor, launched a multifaceted media campaign targeted toward a high-risk population to raise awareness about oral cancer, educate the public regarding the importance of early detection and increase screening rates. The authors present data about the effectiveness of the campaign with regard to the screening behaviors of medical and dental providers. Before the start of the campaign and during each of the three years of the campaign, the authors mailed surveys to random samples of physicians and dentists practicing in targeted and non-targeted areas. More dentists than physicians reported screening patients routinely, and dentists reported that they referred more patients for biopsy or further evaluation compared with physicians. A larger proportion of dentists and physicians in the targeted area than in the nontargeted area reported that their patients had seen or heard the advertisements. A larger proportion of dentists in the targeted area than in the nontargeted area reported an increase in patients' questions and requests for screening, even after the authors accounted for demographic characteristics (adjusted odds ratio = 2.47). The survey findings show that the media campaign was effective in influencing providers' screening for signs and symptoms of oral cancer. An increase in patients' requests for screening as a result of the implementation of mass media campaigns may promote oral cancer screening and improve patients' chances of survival.
Full Text Available Abstract Background Signs of serious clinical events overlap with those of sepsis. We hypothesised that any education on severe sepsis/septic shock may affect the outcome of all hospital patients. We designed this study to assess the trend of the mortality rate of adults admitted to hospital for at least one night in relationship with a hospital staff educational program dedicated to severe sepsis/septic shock. Methods This study was performed in six Italian hospitals in the same region. Multidisciplinary Sepsis Teams members were selected by each hospital management among senior staff. The education included the following steps: i the Teams were taught about adult learning, problem based learning, and Surviving Sepsis guidelines, and provided with educational material (literature, electronic presentations, scenarios of clinical cases for training and booklets; ii they started delivering courses and seminars each to their own hospital staff in the last quarter of 2007. To analyse mortality, we selected adult patients, admitted for at least one night to the wards or units present in all the study hospitals and responsible for 80% of hospital deaths. We fitted a Poisson model with monthly hospital mortality rates from December 2003 to August 2009 as dependent variable. The effect of the educational program on hospital mortality was measured as two dummy variables identifying a first (November 2007 to December 2008 and a second (January to August 2009 education period. The analysis was adjusted for a linear time trend, seasonality and monthly average values of age, Charlson score, length of stay in hospital and urgent/non-urgent admission. Results The hospital staff educated reached 30.6% at the end of June 2009. In comparison with the pre-education period, the Relative Risk of death of the patient population considered was 0.93 (95% confidence interval [CI] 0.87-0.99; p 0.025 for in-patients in the first, and 0.89 (95% CI 0.81-0.98; p 0.012 for
Lee, Sung Kyun; Park, Yoo Jung; Ko, Min Jung; Wang, Ziyu; Lee, Ha Young; Choi, Young Whan; Bae, Yoe-Sik
Sepsis is a serious, life-threatening, infectious disease. In this study, we demonstrate that sucrose methyl 3-formyl-4-methylpentanoate (SMFM), a novel natural compound isolated from garlic (Allium sativum L.), markedly enhances survival rates by inhibiting lung inflammation in a cecal ligation and puncture (CLP) experimental polymicrobial sepsis model. SMFM strongly reduced bacterial colony units from peritoneal fluid in CLP mice by stimulating the generation of reactive oxygen species. Lymphocyte apoptosis in spleens from CLP mice was also markedly decreased by SMFM administration. SMFM also significantly inhibited the production of proinflammatory cytokines, such as TNF-α, interleukin-1β (IL-1β) and IL-6, in CLP mice. Lipopolysaccharide-stimulated production of TNF-α and IL-6 were also strongly inhibited by SMFM in mouse bone marrow-derived macrophages. Taken together, our results indicate that SMFM has therapeutic effects against polymicrobial sepsis that are mediated by enhanced microbial killing and blockage of cytokine storm. Copyright © 2015 Elsevier Inc. All rights reserved.
Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu
Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditionings with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in opposite to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a novel mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.
Full Text Available Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditioning with super-low or low dose endotoxin lipopolysaccharide (LPS cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP. This is in contrast to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.
Scicluna, Brendon P; van Vught, Lonneke A; Zwinderman, Aeilko H; Wiewel, Maryse A; Davenport, Emma E; Burnham, Katie L; Nürnberg, Peter; Schultz, Marcus J; Horn, Janneke; Cremer, Olaf L; Bonten, Marc J; Hinds, Charles J; Wong, Hector R; Knight, Julian C; van der Poll, Tom
Host responses during sepsis are highly heterogeneous, which hampers the identification of patients at high risk of mortality and their selection for targeted therapies. In this study, we aimed to identify biologically relevant molecular endotypes in patients with sepsis. This was a prospective observational cohort study that included consecutive patients admitted for sepsis to two intensive care units (ICUs) in the Netherlands between Jan 1, 2011, and July 20, 2012 (discovery and first validation cohorts) and patients admitted with sepsis due to community-acquired pneumonia to 29 ICUs in the UK (second validation cohort). We generated genome-wide blood gene expression profiles from admission samples and analysed them by unsupervised consensus clustering and machine learning. The primary objective of this study was to establish endotypes for patients with sepsis, and assess the association of these endotypes with clinical traits and survival outcomes. We also established candidate biomarkers for the endotypes to allow identification of patient endotypes in clinical practice. The discovery cohort had 306 patients, the first validation cohort had 216, and the second validation cohort had 265 patients. Four molecular endotypes for sepsis, designated Mars1-4, were identified in the discovery cohort, and were associated with 28-day mortality (log-rank p=0·022). In the discovery cohort, the worst outcome was found for patients classified as having a Mars1 endotype, and at 28 days, 35 (39%) of 90 people with a Mars1 endotype had died (hazard ratio [HR] vs all other endotypes 1·86 [95% CI 1·21-2·86]; p=0·0045), compared with 23 (22%) of 105 people with a Mars2 endotype (HR 0·64 [0·40-1·04]; p=0·061), 16 (23%) of 71 people with a Mars3 endotype (HR 0·71 [0·41-1·22]; p=0·19), and 13 (33%) of 40 patients with a Mars4 endotype (HR 1·13 [0·63-2·04]; p=0·69). Analysis of the net reclassification improvement using a combined clinical and endotype model
The best protection from AIDS is prevention, and this fact makes AIDS awareness campaigns a high priority. Since there are cases of well informed groups that still do not alter their sexual behavior (i.e. teenagers in the UK and San Francisco), fact forcing campaigns cannot be the method of AIDS education. Facts along with behavioral motivation are needed. AIDS awareness campaigns must recognize denial factors that must be overcome before the campaign is even taken seriously. On the other end of the spectrum, exaggerated fears leading to irrational behavior and stigmatization must be prevented by supplying counselling programs to dispel these fears. A campaign must build trust and not underestimate its target population so that their self respect remains high enough to motivate them towards assertive action. Cultural problems, such as women who cannot discuss sexual options for fear of being socially stigmatized, need to have programs that instruct as well as develop a environment that supports change. School women's groups, work places, clinics, community networks, and religious organizations know a local temperament and beliefs, and therefore should be consulted on designing messages that best fit their peers language, literacy, and economic circumstances. Their is no single answer for an AIDS awareness campaign, but a mixture of facts, explanation, persuasion, and reassurance for each targeted community must be well planned. Since each campaign is an experiment, it should be carefully regulated.
Liu, Chang-Feng; Shi, Xin-Ping; Chen, Yun; Jin, Ye; Zhang, Bing
The survival rate of septic patients mainly depends on a rapid and reliable diagnosis. A rapid, broad range, specific and sensitive quantitative diagnostic test is the urgent need. Thus, we developed a TaqMan-Based Multiplex real-time PCR assays to identify bloodstream pathogens within a few hours. Primers and TaqMan probes were designed to be complementary to conserved regions in the 16S rDNA gene of different kinds of bacteria. To evaluate accurately, sensitively, and specifically, the known bacteria samples (Standard strains, whole blood samples) are determined by TaqMan-Based Multiplex real-time PCR. In addition, 30 blood samples taken from patients with clinical symptoms of sepsis were tested by TaqMan-Based Multiplex real-time PCR and blood culture. The mean frequency of positive for Multiplex real-time PCR was 96% at a concentration of 100 CFU/mL, and it was 100% at a concentration greater than 1000 CFU/mL. All the known blood samples and Standard strains were detected positively by TaqMan-Based Multiplex PCR, no PCR products were detected when DNAs from other bacterium were used in the multiplex assay. Among the 30 patients with clinical symptoms of sepsis, 18 patients were confirmed positive by Multiplex real-time PCR and seven patients were confirmed positive by blood culture. TaqMan-Based Multiplex real-time PCR assay with highly sensitivity, specificity and broad detection range, is a rapid and accurate method in the detection of bacterial pathogens of sepsis and should have a promising usage in the diagnosis of sepsis. © 2017 Wiley Periodicals, Inc.
Full Text Available Introduction. Deescalation refers to either discontinuation or a step-down of antimicrobials. Despite strong recommendations in the Surviving Sepsis Guidelines (2012 to deescalate, actual practices can vary. Our objective was to identify variables that are associated with deescalation failure. Methods. In this prospective study of patients with sepsis/septic shock, patients were categorized into 4 groups based on antibiotic administration: no change in antibiotics, deescalation, escalation (where antibiotics were changed to those with a broader spectrum of antimicrobial coverage, or mixed changes (where both escalation to a broader spectrum of coverage and discontinuation of antibiotics were carried out. Results. 395 patients were studied; mean APACHE II score was 24±7.8. Antimicrobial deescalation occurred in 189 (48% patients; no changes were made in 156 (39% patients. On multivariate regression analysis, failure to deescalate was significantly predicted by hematologic malignancy OR 3.3 (95% CI 1.4–7.4 p<0.004, fungal sepsis OR 2.7 (95% CI 1.2–5.8 p=0.011, multidrug resistance OR 2.9 (95% CI 1.4–6.0 p=0.003, baseline serum procalcitonin OR 1.01 (95% CI 1.003–1.016 p=0.002, and SAPS II scores OR 1.01 (95% CI 1.004–1.02 p=0.006. Conclusions. Current deescalation practices reflect physician reluctance when dealing with complicated, sicker patients or with drug-resistance or fungal sepsis. Integrating an antibiotic stewardship program may increase physician confidence and provide support towards increasing deescalation rates.
Fox, Amy C; Robertson, Charles M; Belt, Brian; Clark, Andrew T; Chang, Katherine C; Leathersich, Ann M; Dominguez, Jessica A; Perrone, Erin E; Dunne, W Michael; Hotchkiss, Richard S; Buchman, Timothy G; Linehan, David C; Coopersmith, Craig M
Whereas most septic patients have an underlying comorbidity, most animal models of sepsis use mice that were healthy before the onset of infection. Malignancy is the most common comorbidity associated with sepsis. The purpose of this study was to determine whether mice with cancer have a different response to sepsis than healthy animals. Prospective, randomized controlled study. Animal laboratory in a university medical center. C57Bl/6 mice. Animals received a subcutaneous injection of either 250,000 cells of the transplantable pancreatic adenocarcinoma cell line Pan02 (cancer) or phosphate-buffered saline (healthy). Three weeks later, mice given Pan02 cells had reproducible, nonmetastatic tumors. Both groups of mice then underwent intratracheal injection of either Pseudomonas aeruginosa (septic) or 0.9% NaCl (sham). Animals were killed 24 hrs postoperatively or followed-up 7 days for survival. Mice with cancer and healthy mice appeared similar when subjected to sham operation, although cancer animals had lower levels of T- and B-lymphocyte apoptosis. Septic mice with cancer had increased mortality compared to previously healthy septic mice subjected to the identical injury (52% vs. 28%; p = .04). This was associated with increased bacteremia but no difference in local pulmonary infection. Septic mice with cancer also had increased intestinal epithelial apoptosis. Although sepsis induced an increase in T- and B-lymphocyte apoptosis in all animals, septic mice with cancer had decreased T- and B-lymphocyte apoptosis compared to previously healthy septic mice. Serum and pulmonary cytokines, lung histology, complete blood counts, and intestinal proliferation were similar between septic mice with cancer and previously healthy septic mice. When subjected to the same septic insult, mice with cancer have increased mortality compared to previously healthy animals. Decreased systemic bacterial clearance and alterations in intestinal epithelial and lymphocyte apoptosis may
Vallabhajosyula, Saraschandra; Sakhuja, Ankit; Geske, Jeffrey B; Kumar, Mukesh; Kashyap, Rahul; Kashani, Kianoush; Jentzer, Jacob C
To evaluate the clinical features and outcomes of acute cardiorenal syndrome type-5 in patients with severe sepsis and septic shock. Historical cohort study of all adult patients with severe sepsis and septic shock admitted to the intensive care units (ICU) at Mayo Clinic Rochester from January 1, 2007 through December 31, 2014. Patients with prior renal or cardiac dysfunction were excluded. Patients were divided into groups with and without cardiorenal syndrome type-5. Acute Kidney Injury (AKI) was defined by both serum creatinine and urine output criteria of the AKI Network and the cardiac injury was determined by troponin-T levels. Outcomes included in-hospital mortality, ICU and hospital length of stay, and one-year survival. Of 602 patients meeting the study inclusion criteria, 430 (71.4%) met criteria for acute cardiorenal syndrome type-5. Patients with cardiorenal syndrome type-5 had higher severity of illness, greater vasopressor and mechanical ventilation use. Cardiorenal syndrome type-5 was associated higher unadjusted in-hospital mortality, ICU and hospital lengths of stay, and lower one-year survival. When adjusted for age, gender, severity of illness and mechanical ventilation, cardiorenal syndrome type-5 was independently associated with 1.7-times greater odds of in-hospital mortality (p = .03), but did not predict one-year survival (p = .06) compared to patients without cardiorenal syndrome. In sepsis, acute cardiorenal syndrome type-5 is associated with worse in-hospital mortality compared to patients without cardiorenal syndrome.
The Orthopedic Hospital of Oklahoma is a 25-bed inpatient and outpatient center with one focus: Orthopedics. To acquaint people with its services and build brand awareness to drive market share, the hospital launched a print campaign featuring actual patients.
Full Text Available Emphysematous cystitis (EC is a rare, rapidly progressive infection characterized by gas formation within the bladder wall. Gas production is mainly due to fermentation of glucose or albumin by the pathogenic organisms. We present the case of a patient with EC who presented with severe sepsis of unknown origin. He was also found to have two vesical calculi and a horseshoe kidney. EC was diagnosed on ultrasonography which showed circumferential, acoustic shadowing around the bladder wall. Computed tomography (CT confirmed the diagnosis. Rapid healing could be achieved with appropriate antibiotics and bladder drainage. Endoscopic disintegration of the stones was performed three weeks later, and follow-up was uneventful.
Hansen, Kasper Møller; Kosiara-Pedersen, Karina
sites and Facebook sites are popular among candidates but other features such as blogs, feeds, newsletter, video uploads, SMS and twitter are used by less than half the candidates. Second, only age and possibly education seem to matter when explaining the uptake of cyber-campaigning. The prominent...... candidates are not significantly more likely to use cyber-campaigning tools and activities. Third, the analysis of the effect of cyber-campaigning shows that the online score has an effect on the inter-party competition for personal votes, but it does not have a significant effect when controlling for other...
Strange, Michael Stewart
The article traces the complex series of relations that are constitutive of transnational campaigning through empirical research, focusing on political campaigning critical of the WTO's General Agreement on Trade-in-Services. Applying the methodology of post-structuralist discourse theory......, as developed by Laclau and Mouffe, the article is able to move beyond the search for a ‘Global Civil Society' or ‘Transnational Advocacy Network', and instead focus on the articulatory process in which the relations central to transnational campaigning are produced. This empowers an analysis that is able...
Wang, Rui-lan; Kang, Fu-xin
Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide (pro-ANP) and pro-adrenomedullin (pro-ADM) levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores. Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value of pro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation (APACHE) II scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay. On admission, 25 patients had systemic inflammatory response syndrome (SIRS), 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels (ng/ml) of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock. With the increasing severity of disease, the levels of pro-ANP and pro-ADM were gradually increased. On admission, the circulating levels of pro-ANP and pro-ADM in patients with sepsis, severe sepsis, or septic shock were significantly higher in non-survivors than in survivors (P less than 0.05). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve (AUCs) for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE II scores. Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients.
Skibsted, Simon; Jones, Alan E; Puskarich, Michael A
and mortality in sepsis and that (ii) soluble fms-like tyrosine kinase 1 (sFlt-1) holds promise as a novel prognostic marker in sepsis. METHODS: This was a prospective, multicenter, observational study of a convenience sample of emergency department (ED) patients with a suspected infection presenting to one...
Neonatal sepsis is a clinical syndrome consisting of nonspecific symptoms and signs of infection, accompanied by a bacteraemia in the first 28 days of life. The risk of neonatal sepsis and death increases with decreasing birth weight and gestational age. South African data have reported the overall incidence of neonatal ...
Fernando Rodrigues Coelho
Full Text Available OBJECTIVE: Sepsis is a common condition encountered in hospital environments. There is no effective treatment for sepsis, and it remains an important cause of death at intensive care units. This study aimed to discuss some methods that are available in clinics, and tests that have been recently developed for the diagnosis of sepsis. METHODS: A systematic review was performed through the analysis of the following descriptors: sepsis, diagnostic methods, biological markers, and cytokines. RESULTS: The deleterious effects of sepsis are caused by an imbalance between the invasiveness of the pathogen and the ability of the host to mount an effective immune response. Consequently, the host's immune surveillance fails to eliminate the pathogen, allowing it to spread. Moreover, there is a pro-inflammatory mediator release, inappropriate activation of the coagulation and complement cascades, leading to dysfunction of multiple organs and systems. The difficulty achieve total recovery of the patient is explainable. There is an increased incidence of sepsis worldwide due to factors such as aging population, larger number of surgeries, and number of microorganisms resistant to existing antibiotics. CONCLUSION: The search for new diagnostic markers associated with increased risk of sepsis development and molecules that can be correlated to certain steps of sepsis is becoming necessary. This would allow for earlier diagnosis, facilitate patient prognosis characterization, and prediction of possible evolution of each case. All other markers are regrettably constrained to research units.
Background. It has recently been suggested that procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. This study was to evaluate the role of PCT as a single early marker of neonatal sepsis. Setting. Neonatal Unit, Johannesburg Hospital, and Microbiology Laboratory, National Health ...
Developing countries suffer from a huge burden of neonatal sepsis. Neonatal mortality and long term sequelae or morbidity portends huge costs for the poor Nigerian economy. We identified trends in bacterial agents implicated in neonatal sepsis and their antibiotic susceptibility profiles at the National Hospital Abuja over ...
The incidence and mortality of sepsis and severe sepsis in hospitalised patients is seasonal and consistently highest during the winter. The primary aim of this study was to measure the seasonal variation in the prevalence of emergency department (ED) patients with sepsis. This cross-sectional study was performed over two four-week periods in the summer and in the winter, respectively. The clinical records of all patients presenting to the ED during the study periods were retrospectively screened to determine if they met the criteria for “uncomplicated” sepsis and severe sepsis or septic shock. The prevalence of “uncomplicated” sepsis was higher in the winter (43.9 per 1000) compared to the summer (30.7 per 1000). The prevalence of severe sepsis or septic shock was also higher in the winter (17.7 per 1000) compared to the summer (11.7 per 1000). This quantitatively demonstrates the increased ED burden of sepsis in the winter that can be used to inform healthcare planning and resource allocation.
Brocklehurst, Peter; Farrell, Barbara; King, Andrew
Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...
Zeerleder, S.; Zürcher Zenklusen, R.; Hack, C. E.; Wuillemin, W. A.
We report on a man (age: 49 years), who died from severe meningococcal sepsis with disseminated intravascular coagulation (DIC), multiple organ dysfunction syndrome and extended skin necrosis. We discuss in detail the pathophysiology of the activation of coagulation and fibrinolysis during sepsis.
I have read the article published by Guclu et al. with a great interest.1 They examined platelet indices in patients with sepsis. Mean platelet volume (MPV) and platelet distribution width (PDW) were significantly higher in patients with sepsis than in controls. MPV and PDW were significantly higher in patients with severe ...
This article describes a man who presented to the ED in acute distress with signs and symptoms of sepsis, pneumonia, and a new petechial rash on his chest. He was eventually diagnosed with Rocky Mountain spotted fever. Aggressive treatment of sepsis and timely administration of empiric antibiotics were lifesaving in this situation.
Korosec Jagodic, Helena; Jagodic, Klemen; Podbregar, Matej
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. 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. 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 Trauma patients stayed longer on the general ward (35 +/- 44 days versus 17 +/- 24 days; P 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 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. 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.
Ashauer, Roman; Albert, Carlo; Augustine, Starrlight
The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...
Slate, Andrea R; Bandyopadhyay, Sheila; Francis, Kevin P; Papich, Mark G; Karolewski, Brian; Hod, Eldad A; Prestia, Kevin A
We examined the efficacy of enrofloxacin administered by 2 different routes in a mouse model of sepsis. Male CD1 mice were infected with a bioluminescent strain of enteropathogenic Escherichia coli and treated with enrofloxacin either by injection or in drinking water. Peak serum levels were evaluated by using HPLC. Mice were monitored for signs of clinical disease, and infections were monitored by using bioluminescence imaging. Serum levels of enrofloxacin and the active metabolite ciprofloxacin were greater in the group treated by injection than in controls or the groups treated by administration in drinking water. Survival of the group treated with enrofloxacin injection was greater than that of controls and groups treated with enrofloxacin in the drinking water. Bioluminescence in the group treated with enrofloxacin injection was less than that in the groups treated with oral administration at 12 h and in the groups treated orally and the control group at 16 h. According to these findings, we recommend the use of injectable enrofloxacin at 5 mg/kg SC for mice with systemic infections.
Rita Mey Rina
21.0 U/L vs -2.0 (ranged -167 .0 - 85.0 U/L; P= 0.730, median aspartate aminotransferase (AST levels [ 43 .0 (range 14.0-297 .0 U/L vs 150.0 (range 24.0-840.0 U/L; P=0.081, and median gamma-glutamyl transpeptidase (GGf levels [125.0 (48.0-481.0 U/L vs 235.0 (56.0-456.0 U/L; P=0.108. Five neonates in control group died compared to two in the UDCA group (P=0.232. In addition, UDCA did not significantly lengthen the survival time (hazard ratio/HR 3.62; 95%CI 0.69 to 18.77 . Conclusion Ursodeoxycholic acid tends to improve total bilirubin, direct bilirubin, and AST levels in sepsis associated cholestasis .
The Indian government's plan to introduce the new long-acting contraceptive Norplant in the National Family Planning Program under pressure from the US government is opposed because Norplant has not been adequately tested. The government has reduced the funding for the national program for eradication of malaria and tuberculosis, but it is proposing to finance a Norplant based population project for the State of Uttar Pradesh. The powers that can turn a deaf ear to the possible hazards of Norplant. Implanted in the arm of a woman, the chemical is released into the bloodstream providing contraception for 5 years. Severe adverse reactions include depression, heart disease thromboembolism, high blood pressure, and ovarian cysts. Many such long-acting contraceptives are being developed including injectables, vaccines, nasal sprays, and vaginal rings with potential permanent impairment to fertility. One of the major objectives of the Family Planning Program is the improvement of the health status of women, but the introduction of Norplant would harm healthy young women. Therefore, the group Saheli and others in the campaign demand: 1) that plans for introduction of Norplant in the Family Planning Program be halted immediately; 2) that the introduction of any other long acting invasive contraceptive such as Net-En, vaginal ring, nasal spray, and anti-fertility vaccine be banned, both on the grounds of inadequacy of the health services and loss of user controls; 3) that information on the safety aspects of Norplant and the basis on which the Drugs Controller has granted his approval be made public; 4) that each and every one of the hundreds of women who still have the implant should be located, and the implant removed; and 5) that all hormonal contraceptive preparations be banned in the social marketing program as their use involves extensive monitoring.
The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model
Williams, Paul T
Test whether inadequate exercise is related to sepsis mortality. Mortality surveillance of an epidemiological cohort of 155,484 National Walkers' and Runners' Health Study participants residing in the United States. Deaths were monitored for an average of 11.6-years using the National Death index through December 31, 2008. Cox proportional hazard analyses were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths occurring within one year of the baseline survey were excluded. Sepsis was the underlying cause in 54 deaths (sepsis(underlying)) and a contributing cause in 184 deaths (sepsis(contributing)), or 238 total sepsis-related deaths (sepsis(total)). Inadequate exercise was associated with 2.24-fold increased risk for sepsis(underlying) (95%CI: 1.21 to 4.07-fold, P = 0.01), 2.11-fold increased risk for sepsis(contributing) (95%CI: 1.51- to 2.92-fold, P<10(-4)), and 2.13-fold increased risk for sepsis(total) (95%CI: 1.59- to 2.84-fold, P<10(-6)) when adjusted for age, sex, race, and cohort. The risk increase did not differ significantly between runners and walkers, by sex, or by age. Sepsis(total) risk was greater in diabetics (P = 10(-5)), cancer survivors (P = 0.0001), and heart attack survivors (P = 0.003) and increased with waist circumference (P = 0.0004). The sepsis(total) risk associated with inadequate exercise persisted when further adjusted for diabetes, prior cancer, prior heart attack and waist circumference, and when excluding deaths with cancer, or cardiovascular, respiratory, or genitourinary disease as the underlying cause. Inadequate exercise also increased sepsis(total) risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8-fold, P = 0.0001) when adjusted, which was significantly greater (P = 0.03) than the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46-fold, P = 0
Chen, Ching-Wen; Mittal, Rohit; Klingensmith, Nathan J; Burd, Eileen M; Terhorst, Cox; Martin, Greg S; Coopersmith, Craig M; Ford, Mandy L
Sepsis is a leading cause of death in the United States, but the mechanisms underlying sepsis-induced immune dysregulation remain poorly understood. 2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8 + T cells that has been shown to regulate T cell function in models of viral infection and autoimmunity. In this article, we show that 2B4 signaling mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased on CD4 + T cells in septic animals and human patients at early time points. Importantly, genetic loss or pharmacologic inhibition of 2B4 significantly increased survival in a murine cecal ligation and puncture model. Further, CD4-specific conditional knockouts showed that 2B4 functions on CD4 + T cell populations in a cell-intrinsic manner and modulates adaptive and innate immune responses during sepsis. Our results illuminate a novel role for 2B4 coinhibitory signaling on CD4 + T cells in mediating immune dysregulation. Copyright © 2017 by The American Association of Immunologists, Inc.
Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier
Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462
EPA developed the Collision Repair Campaign to focus on meaningful risk reduction in the Collision Repair source sector to complement ongoing community air toxics work and attain reductions at a faster rate.
Pousttchi, Key; Wiedemann, Dietmar Georg
The result of this contribution is a categorization and thus a description model for mobile advertising campaigns using the morphological method. For identification of the characteristics 32 case studies were analysed and relevant literature was sighted.
Goggs, Robert; Milloway, Matthew; Troia, Roberta; Giunti, Massimo
Sepsis, the life-threatening organ dysfunction caused by a dysregulated host response to infection, is difficult to identify and to prognosticate for. In people with sepsis, procalcitonin (PCT) measurement aids diagnosis, enables therapeutic monitoring and improves prognostic accuracy. This study used a commercial canine PCT assay to measure plasma PCT concentrations in dogs with gastric dilatation volvulus (GDV) syndrome and in dogs with sepsis. It was hypothesised that dogs with GDV syndrome and with sepsis have greater plasma PCT concentrations than healthy dogs and that dogs with sepsis have greater PCT concentrations than dogs with GDV syndrome. Before analysing canine plasma samples, the ability of the assay to identify canine PCT, in addition to assay imprecision and the lower limit of detection were established. The assay had low imprecision with coefficients of variation ≤4.5 per cent. The lower limit of detection was 3.4 pg/ml. Plasma PCT concentrations were measured in 20 dogs with sepsis, in 32 dogs with GDV syndrome and in 52 healthy dogs. Median (IQR) PCT concentration in dogs with sepsis 78.7 pg/ml (39.1–164.7) was significantly greater than in healthy dogs 49.8 pg/ml (36.2–63.7) (P=0.019), but there were no significant differences between PCT concentrations in dogs with GDV syndrome and controls (P=0.072) or between dogs with sepsis and GDV syndrome (P=1.000). Dogs with sepsis have significantly increased plasma PCT concentrations compared with healthy dogs, although considerable overlap between these populations was identified. Future investigations should confirm this finding in other populations and evaluate the diagnostic and prognostic value of PCT in dogs with sepsis. PMID:29682292
Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki
Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease.
Mansfield, Sara; Grießl, Marion; Gutknecht, Michael; Cook, Charles H
Cytomegalovirus (CMV) reactivation in non-immune-suppressed critically ill patients is an area of increasing interest. CMV has long been appreciated as a pathogen in immunocompromised hosts. CMV reactivates in approximately one-third of latently infected non-immune-suppressed hosts during critical illness; however, its role as a pathogen in these patients remains unclear. CMV reactivation has been linked to bacterial sepsis and likely results from inflammation, transient immune compromise, and viral epigenetic changes. While CMV may improve immune response to some bacterial infections, other data suggest that CMV induces exaggerated responses to severe infections that may be harmful to latently infected hosts. These results also suggest that previous infection history may explain significant differences seen between human septic responses and murine models of sepsis. While critically ill human hosts clearly have worse outcomes associated with CMV reactivation, determining causality remains an area of investigation, with randomized control trials currently being performed. Here we review the current literature and highlight areas for future investigation.
Aragones, Enriqueta; Palfrey, Thomas R.; Postlewaite, Andrew
We analyze conditions under which candidates' reputations may affect voters' beliefs over what policy will be implemented by the winning candidate of an election. We develop a model of repeated elections with complete information in which candidates are purely ideological. We analyze an equilibrium in which voters' strategies involve a credible threat to punish candidates who renege on their campaign promises and in which all campaign promises are believed by voters and honored by candidates....
Vincent A Traag
Full Text Available Money is central in US politics, and most campaign contributions stem from a tiny, wealthy elite. Like other political acts, campaign donations are known to be socially contagious. We study how campaign donations diffuse through a network of more than 50,000 elites and examine how connectivity among previous donors reinforces contagion. We find that the diffusion of donations is driven by independent reinforcement contagion: people are more likely to donate when exposed to donors from different social groups than when they are exposed to equally many donors from the same group. Counter-intuitively, being exposed to one side may increase donations to the other side. Although the effect is weak, simultaneous cross-cutting exposure makes donation somewhat less likely. Finally, the independence of donors in the beginning of a campaign predicts the amount of money that is raised throughout a campaign. We theorize that people infer population-wide estimates from their local observations, with elites assessing the viability of candidates, possibly opposing candidates in response to local support. Our findings suggest that theories of complex contagions need refinement and that political campaigns should target multiple communities.
Traag, Vincent A
Money is central in US politics, and most campaign contributions stem from a tiny, wealthy elite. Like other political acts, campaign donations are known to be socially contagious. We study how campaign donations diffuse through a network of more than 50,000 elites and examine how connectivity among previous donors reinforces contagion. We find that the diffusion of donations is driven by independent reinforcement contagion: people are more likely to donate when exposed to donors from different social groups than when they are exposed to equally many donors from the same group. Counter-intuitively, being exposed to one side may increase donations to the other side. Although the effect is weak, simultaneous cross-cutting exposure makes donation somewhat less likely. Finally, the independence of donors in the beginning of a campaign predicts the amount of money that is raised throughout a campaign. We theorize that people infer population-wide estimates from their local observations, with elites assessing the viability of candidates, possibly opposing candidates in response to local support. Our findings suggest that theories of complex contagions need refinement and that political campaigns should target multiple communities.
Gabillaud Poillion, Florence
In line with the approaches already adopted in France during the 90's on various sites where research and/or radium-extraction activities were mostly conducted in the past, the French public authorities wish from now on to pursue their prevention and site-rehabilitation approach inherited from the French craftsman and medical sectors that used that radioelement. As a matter of fact, radium has been in use in several medical activities, notably in the initial methods of cancer therapy. Similarly, it was also used in some craftsman activities, such as the clock industry, for its radioluminescent properties, the fabrication of lightning conductors or cosmetics until the 60's. Those activities have generated various traces of pollution that have remained today. On the basis of the different inventories of industrial sites where radium may have been held or used, and notably the inventory updated by the French Institute for Radiation Protection and Nuclear Safety (Institut de radioprotection et de surete nucleaire - IRSN) in 2007 at the request of the French Nuclear Safety Authority (Autorite de surete nucleaire - ASN), French State services have potentially identified 134 sites that hosted radium-related activities in France. The radiological status of those sites is either unknown or very partially known by State services. Sites include both dwellings or commercial premises and derelict lands. The 'Radium Diagnosis Campaign' (Operation Diagnostic Radium), consists of a radiological survey carried out by the IRSN. In cases where traces of radium are detected, plans call for the implementation of precautionary measures and of a medical follow-up of the relevant populations. Lastly, radium-contaminated sites are rehabilitated by the French National Radioactive Waste Management Agency (Agence nationale pour la gestion des dechets radioactifs - Andra). That voluntary and positive approach on the part of public authorities is fully financed by public funds, and consequently
Wang, Zenggeng; Wu, Qinghua; Nie, Xiangbi; Guo, Jinghua; Yang, Chunli
As a β-adrenoceptor antagonist (β-blocker), esmolol can reduce cardiac output and the phosphodiesterase III inhibitor milrinone has been shown to improve heart contractility in patients with septic shock. This study was performed to assess the effects of esmolol combined with milrinone in patients with severe sepsis. This prospective randomized study was conducted in patients with severe sepsis in the intensive care unit of the Jiangxi Provincial People's Hospital (Nanchang, Jiangsu, China) between June 2013 and June 2014. Patients were randomly divided into control (C), milrinone (M), and milrinone-esmolol (ME) groups. The primary outcome was the rate of controlling the heart rate (HR) to achieve target levels. Secondary outcomes included the 28-day survival rate and changes in hemodynamic variables, organ function variables, myocardial injury markers, and the serum levels of proinflammatory factors. A total of 90 patients with severe sepsis were included in this study (30 per group). The HR in the ME group was lower than in the M and C groups after 12 h. The rate of successful HR control during the first 96 h was significantly higher in the ME group (60.0 vs. 33.3 % in the M group, vs. 26.7 % in the C group). Also, patients in the ME group had higher 28-day overall survival compared with the M (Log rank statistic = 5.452; P = 0.020) and C groups (Log rank statistic = 10.206; P = 0.001). Additionally, several variables showed significant improvement in the ME group 96 h after treatment compared with the M and C groups (P milrinone and esmolol could improve cardiac function and the 28-day survival rate in patients with severe sepsis.
Pepper, Dominique J; Jaswal, Dharmvir; Sun, Junfeng; Welsh, Judith; Natanson, Charles; Eichacker, Peter Q
This article has been corrected. To see what has changed, please read the Letter to the Editor and the authors' response. The original version (PDF) is appended to this article as a Supplement. The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1), the sepsis performance measure introduced in 2015 by the Centers for Medicare & Medicaid Services (CMS), requires the reporting of up to 5 hemodynamic interventions, as many as 141 tasks, and 3 hours to document for a single patient. To evaluate whether moderate- or high-level evidence shows that use of the 2015 SEP-1 or its hemodynamic interventions improves survival in adults with sepsis. PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov from inception to 28 November 2017 with no language restrictions. Randomized and observational studies of death among adults with sepsis who received versus those who did not receive either the entire SEP-1 bundle or 1 or more SEP-1 hemodynamic interventions, including serial lactate measurements; a fluid infusion of 30 mL/kg of body weight; and assessment of volume status and tissue perfusion with a focused examination, bedside cardiovascular ultrasonography, or fluid responsiveness testing. Two investigators independently extracted study data and assessed each study's risk of bias; 4 authors rated level of evidence by consensus using CMS criteria published in 2013. High- or moderate-level evidence required studies to have no confounders and low risk of bias. Of 56 563 references, 20 studies (18 reports) met inclusion criteria. One single-center observational study reported lower in-hospital mortality after implementation of the SEP-1 bundle. Sixteen studies (2 randomized and 14 observational) reported increased survival with serial lactate measurements or 30-mL/kg fluid infusions. None of the 17 studies were free of confounders or at low risk of bias. In 3 randomized trials, fluid responsiveness testing did not alter survival. Few trials, poor-quality and
Full Text Available Introduction: Clostridium (C perfringens and Klebsiella (K oxytoca are pathogenous human bacteria. Due to the production of several toxins C. perfringens is virulent by causing i.a. the necrotizing fasciitis, gas gangrene and hepatic abscess. K. oxytoca mostly causes infections of the respiratory and gastrointestinal tract. Presentation of case: We are presenting the case of a male patient at the age of 64, who suffered from nausea and progressive pain in the right upper abdomen. A computer tomography of the abdomen revealed a 7 × 5,6 cm sized entrapped air in liver segment VII. Later the patient developed a multiorgan failure. We then performed an explorative laparotomy. Intraoperatively it became clear that the liver was destructed presenting an open liver abscess (LA cavity of segment VII. The gallbladder was found inflamed. We successfully conducted the consistent debridement of segment VII and removed the gallbladder. Microbiological examination isolated C. perfringens and K. oxytoca. The patient survived undergoing antimicrobial and multimodal sepsis therapy. Discussion: The LA is a severe disease in surgery. In literature an overall mortality of 6–14% is described. Mostly bacterial infections of the biliary tract and the gallbladder are responsible for a LA. Abscesses with sepsis caused by both, C. perfringens and K. oxytoca, are highly perilous but rarely described in literature. Conclusion: When diagnosing an LA caused by C. perfringens an immediate surgical debridement and antimicrobial treatment is mandatory for the patient’s survival. Keywords: Liver abscess, Sepsis, Clostridium perfringens, Klebsiella oxytoca, Gas gangrene
Wakefield, Melanie A; Loken, Barbara; Hornik, Robert C
Mass media campaigns are widely used to expose high proportions of large populations to messages through routine uses of existing media, such as television, radio, and newspapers. Exposure to such messages is, therefore, generally passive. Such campaigns are frequently competing with factors, such as pervasive product marketing, powerful social norms, and behaviours driven by addiction or habit. In this Review we discuss the outcomes of mass media campaigns in the context of various health-risk behaviours (eg, use of tobacco, alcohol, and other drugs, heart disease risk factors, sex-related behaviours, road safety, cancer screening and prevention, child survival, and organ or blood donation). We conclude that mass media campaigns can produce positive changes or prevent negative changes in health-related behaviours across large populations. We assess what contributes to these outcomes, such as concurrent availability of required services and products, availability of community-based programmes, and policies that support behaviour change. Finally, we propose areas for improvement, such as investment in longer better-funded campaigns to achieve adequate population exposure to media messages. Copyright © 2010 Elsevier Ltd. All rights reserved.
... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Campaign schedule. 950.801 Section 950... VOLUNTARY ORGANIZATIONS CFC Timetable § 950.801 Campaign schedule. (a) The Combined Federal Campaign will be.../International and International parts of the Charity List to all local campaigns by a date to be determined by...
Chaussade, Jean-Pierre; Ansel, Philippe
'Today, some 75 % of France's electricity is generated by nuclear plants'. This was the theme of the advertising campaign launched for the second time in May 1992 by Electricite de France in national daily newspapers and magazines, in regional publications, on cinema and on TV. Compared to 1991 the second campaign was a new step in communication: first, was the wish to inform better the public. A Minitel program '3614 EDF' was created and connected by general public including a lot of information about nuclear energy and the way to visit a nuclear plant; secondly, was the use of TV media to target a larger population. The TV spot, 'the nuclear drill', uses humor to get more impact on the public. The campaign received an encouraging reception from the press, which admired its boldness and originality. As far as the general public is concerned, the campaign achieved its goals, as illustrated by the results of post-campaign surveys carried out to measure its effect. The segment of population targeted by campaign was mainly the so called 'pragmatics'. 'Pragmatics', who account for 25 % of the French population, are young, have a good education and are well informed. This category was selected as it shows a subtle attitude towards nuclear power, with more doubts than certainties. Moreover, this segment of the population has proven to be open to information issued by EDF and also plays a key role in influencing social trends. 63% of the segment targeted by the campaign (pragmatics) and 56% of the whole french population saw the ads
Full Text Available La sepsis afecta al 40% de los pacientes críticos, siendo su mortalidad de aproximadamente un 30% en el caso de la sepsis grave, y de 75% con injuria renal aguda, la cual sucede en el 20-51% de los casos. Se realizó un estudio prospectivo, observacional, longitudinal, en 80 pacientes sépticos graves en el lapso de 1 año para determinar el desarrollo de injuria renal aguda y su relación con la mortalidad; correlacionar antecedentes clínicos y variaciones del laboratorio con la mortalidad; determinar la tasa de mortalidad de la sepsis grave; relacionar óbito y foco séptico primario; evaluar la predictibilidad de mortalidad según niveles de creatinina de ingreso y sus variaciones finales. Se definieron dos grupos: Obito (n = 25 y No-óbito (n = 55. Analizados según la creatinina de ingreso, 39 tenían valores normales de creatinina (10 óbitos y 41 la presentaban elevada (15 óbitos; según la creatinina de egreso, 48 presentaron creatinina normal y fallecieron 7, mientras que 32 tenían daño renal agudo, de los cuales 18 fallecieron. De los 25 pacientes fallecidos, el 72% presentaron daño renal. De éstos, 7 pacientes vivos y 2 fallecidos requirieron hemodiálisis. El foco primario más frecuente fue el respiratorio (26.4%. El desarrollo de daño renal es un alto predictor de mortalidad en la sepsis, independientemente de los valores iniciales de creatinina. Edad más avanzada, hipertensión arterial, score APACHE más elevado, anemia más grave, hipoalbuminemia, hiperfosfatemia e hiperkalemia se asociaron a mayor mortalidad. La mortalidad global fue 31.3%. La imposibilidad de identificar el foco séptico primario se asoció a mayor mortalidad. El foco respiratorio se relacionó a mayor riesgo de requerir hemodiálisis.Sepsis affects 40% of critically ill patients, with a reported mortality of approximately 30% in severe sepsis, raising to 75% when acute kidney injury ensues, which occurs in about 20-51% of cases. The present study
Pang, Xiaoqing; Kozlowski, Natascha; Wu, Sulong; Jiang, Mei; Huang, Yongbo; Mao, Pu; Liu, Xiaoqing; He, Weiqun; Huang, Chaoyi; Li, Yimin; Zhang, Haibo
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.
Li, Binjie; Zeng, Qiyi
Sepsis is a leading killer of children worldwide with numerous differentially expressed genes reported to be associated with sepsis. Identifying core pathways in an individual is important for understanding septic mechanisms and for the future application of custom therapeutic decisions. Samples used in the study were from a control group (n=18) and pediatric sepsis group (n=52). Based on Kauffman's attractor theory, differentially expressed pathways associated with pediatric sepsis were detected as attractors. When the distribution results of attractors are consistent with the distribution of total data assessed using support vector machine, the individualized pathway aberrance score (iPAS) was calculated to distinguish differences. Through attractor and Kyoto Encyclopedia of Genes and Genomes functional analysis, 277 enriched pathways were identified as attractors. There were 81 pathways with Ppathways with Ppathway clusters and four sample clusters. Thus, in the majority pediatric sepsis samples, core pathways can be detected as different from accumulated normal samples. In conclusion, a novel procedure that identified the dysregulated attractors in individuals with pediatric sepsis was constructed. Attractors can be markers to identify pathways involved in pediatric sepsis. iPAS may provide a correlation score for each of the signaling pathways present in an individual patient. This process may improve the personalized interpretation of disease mechanisms and may be useful in the forthcoming era of personalized medicine.
Garrido Alejandra G.
Full Text Available Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.
Full Text Available In elderly population sepsis is one of the leading causes of intensive care unit (ICU admissions in the United States. Sepsis-induced delirium (SID is the most frequent cause of delirium in ICU (1. Together delirium and SID represent under recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143 to 152 billion dollars per year (2. The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (3-4. Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium.This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis?
To determine the frequency of early onset neonatal sepsis in newborn with various duration of preterm premature rupture of membranes (PPROM). Study Design: Cross sectional study. Place and Duration of Study: Neonatal Intensive Care Unit Combined Military Hospital, Lahore from November 2009 to November 2010. Material and Methods: Neonates of singleton pregnancies complicated by preterm premature rupture of the membranes (PPROM) with delivery between 30 and 36 weeks gestation were included in the study. The overall frequency of neonatal sepsis was calculated on clinical and serological basis. Comparison of the frequency of sepsis among groups with varying duration of rupture of membranes was done. Results: Out of 164 babies, 84 (51.2%) were female and 80 (48.8%) were male. Mean maternal age was 23 years (range: 18-36 years). Mean gestational age was 33 weeks (range: 30-36 weeks). Sepsis was suspected in 41(25%) babies on clinical grounds. C-reactive protein was raised in 36 (22%) neonates. There was statistically insignificant difference between clinical versus serological diagnosis (p=0.515). Frequency of neonatal sepsis was significantly higher in mothers with longer duration of rupture of membrane (p < 0.001). Conclusion: Frequency of neonatal sepsis was observed to be 22%. PPROM is an important risk factor for early onset neonatal sepsis. (author)
Full Text Available Neonatal sepsis is a clinical syndrome consisting of nonspecific symptoms and signs of infection, accompanied by a bacteraemia in the first 28 days of life. The risk of neonatal sepsis and death increases with decreasing birth weight and gestational age. South African data have reported the overall incidence of neonatal sepsis to be 8.5 - 10%, with late-onset sepsis accounting for most of these infections. The diagnosis of neonatal sepsis is not always straightforward, and the initiation and continuation of antimicrobials in these situations relies on good clinical judgment. The need for empirical antimicrobials is driven by the existence of risk factors for early-onset sepsis and clinical symptoms and signs of late-onset sepsis. Antimicrobial stewardship programmes should be in place to guide clinicians to either stop, change, or continue antimicrobials. Institution-specific knowledge of the most common pathogens and the antimicrobial susceptibility pattern is important to prevent the emergence of further antimicrobial resistance.
Sepsis is a major public health problem as well as one of the leading causes of preventable death in children because of failure to recognise the early signs and symptoms and to resuscitate rapidly. Blood lactate levels are used to assess the severity of sepsis and the effectiveness of resuscitation. Lactate levels are easily obtainable and should be checked in all patients admitted with suspected sepsis within six hours of presentation. The test should be repeated four and eight-hours post-diagnosis of sepsis. For the diagnosis of sepsis, patients' clinical symptoms, along with the combined analysis of partial pressure of oxygen, carbon dioxide and lactate levels, should be used. A multitude of factors can cause elevated lactate levels and so clinicians should use elevated levels cautiously by considering all other aetiologies. This article, which focuses on practice in Australia but makes reference to the UK, discusses the importance of measuring lactate levels in sepsis, the pathophysiology of lactate production, causes of elevated lactate levels, lactate measurement, nursing management of patients with elevated lactate levels, limitations of using lactate as a biomarker for diagnosing sepsis and implications for practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.
Troìa, Roberta; Gruarin, Marta; Foglia, Armando; Agnoli, Chiara; Dondi, Francesco; Giunti, Massimo
Systemic inflammatory response syndrome (SIRS) and sepsis can be challenging to diagnose in cats. Retrospectively, we investigated the diagnostic and prognostic potential of serum amyloid A (SAA), a major feline acute-phase protein (APP), in a population of critically ill cats with SIRS related to trauma or sepsis. A total of 56 SIRS cats (trauma n = 27; sepsis n = 29) were included and compared with healthy controls ( n = 18). SAA concentration was significantly increased in SIRS cats compared to controls, confirming its potential for the detection of systemic inflammation in this species. Significantly higher values of SAA were detected in cats belonging to the sepsis group; however, according to the results of the receiver operating characteristic curve analysis, the value of using SAA (>81 mg/L) to discriminate septic cats was only moderate (AUC = 0.76). Additionally, cats with sepsis had significantly higher serum bilirubin concentrations and toxic neutrophil changes compared to the trauma group. Overall, 38 of 56 cats were survivors; 18 of 56 were non-survivors, with 83% of the non-survivors (15 of 18) belonging to the sepsis group. Serum bilirubin concentration, but not SAA, was able to predict outcome. Prospective studies are needed to assess the potential of SAA in the diagnosis of feline sepsis and outcome prediction.
American Civil War produced several campaigns and characters replete with all the drama, comedy , sacrifice, and tragedy of a Shake- spearean play. From...Grant’s army, though slowed and bloodied, inexorably moved through the meatgrinder that culminated in the horrors of trench warfare 5 at Petersburg...poured a murderous fire into McCausland’s hapless men. The cavalrymen who survived that initial volley fled in horror . Complaining that they had been
Full Text Available Context: There is a logical connection with biomarkers, trauma, and sepsis. This review paper provides new information and clinical practice implications. Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Stress management both in trauma is based upon the notion that stress causes an immune imbalance in susceptible individuals. Evidence Acquisition: Data sources included studies indexed in PubMed, a meta- analysis, predictive values, research strategies, and quality assessments. A recent paper by one of the authors stated marked increase in serum procalcitonin during the course of a septic process often indicates an exacerbation of the illness, and a decreasing level is a sign of improvement. A review of epidemiologic studies on pediatric soccer patients was also addressed. Keywords for searching included biomarkers, immunity, trauma, and sepsis. Results: Of 50 reviewed articles, 34 eligible articles were selected including biomarkers, predictive values for procalcitonin, identifying children at risk for intra-abdominal injuries, blunt trauma, and epidemiology, a meta-analysis. Of neonatal associated sepsis, the NF-kappa B pathway by inflammatory stimuli in human neutrophils, predictive value of gelsolin for the outcomes of preterm neonates, a meta-analysis interleukin-8 for neonatal sepsis diagnosis. Conclusions: Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms, and physiological functions of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Various topics were covered such as biomarkers, trauma, sepsis, inflammation, innate immunity, role of neutrophils and IL-8, reactive oxygen species
Rochwerg, Bram; Oczkowski, Simon; Siemieniuk, Reed Alexander; Menon, Kusum; Szczeklik, Wojciech; English, Shane; Agoritsas, Thomas; Belley-Cote, Emilie; D'Aragon, Frédérick; Alhazzani, Waleed; Duan, Erick; Gossack-Keenan, Kira; Sevransky, Jon; Vandvik, Per; Venkatesh, Bala; Guyatt, Gordon; Annane, Djillali
Sepsis is associated with a dysregulated host response to infection and impaired endogenous corticosteroid metabolism. As such, therapeutic use of exogenous corticosteroids is a promising adjunctive intervention. Despite a large number of trials examining this research question, uncertainty persists regarding the effect of corticosteroids on survival in sepsis. Several large randomised controlled trials have been published recently prompting a re-evaluation of the available literature. A rigorous and reproducible search and screening process from a Cochrane review on the same topic was comprehensive to October 2014. We will search MEDLINE, EMBASE, LILACS, the Cochrane trial registry and clinicaltrials.gov for eligible randomised controlled trials investigating the use of corticosteroids in patients with sepsis from September 2014. Outcomes have been chosen by a semi-independent guideline panel, created in the context of a parallel BMJ Rapid Recommendation on the topic. This panel includes clinicians, content experts, methodologists and patient representatives, who will help identify patient-important outcomes that are critical for deciding whether to use or not use corticosteroids in sepsis. Two reviewers will independently screen and identify eligible studies; a third reviewer will resolve any disagreements. We will use RevMan to pool effect estimates from included studies for each outcome using a random-effect model. We will present the results as relative risk with 95% CI for dichotomous outcomes and as mean difference or standardised mean difference for continuous outcomes with 95% CI. We will assess the certainty of evidence at the outcome level using the Grading of Recommendations, Assessment, Development and Evaluation approach. We will conduct a priori subgroup analyses, which have been chosen by the parallel BMJ Rapid Recommendation panel. The aim of this systematic review is to summarise the updated evidence on the efficacy and safety of corticosteroids
Arvela, H.; Valmari, T.; Reisbacka, H.; Niemelae, H.; Oinas, T.; Maekelaeinen, I.; Laitinen-Sorvari, R.
Radon campaigns aim at activating citizens to make indoor radon measurements and remediation as well as increasing the common awareness of indoor radon questions. Indoor radon increases the risk of lung cancer. Through radon campaigns Radiation and Nuclear Safety Authority (STUK) also promotes the attainment of those goals that the Ministry of Social Affairs and Health has set for municipal authorities in Finland for prevention of the harmful effects of radon. The Ministry of Social Affairs and Health supports this campaign. Radon campaigns were started in autumn 2003. By autumn 2008 the campaigns have been organised already in 64 regions altogether in 160 municipalities. In some municipalities they have already arranged two campaigns. Altogether 14 100 houses have been measured and in 2 100 of these the action limit of radon remediation 400 Bq / m 3 has been exceeded. When participating in radon campaigns the house owners receive a special offer on radon detectors with a reduced price. In 2008 a new practice was introduced where the campaign advertisements were distributed by mail to low-rise residential houses in a certain region. The advertisement includes an order / deposit slip with postage paid that the house owner can send directly to STUK to easily make an order for radon measurement. In the previous radon campaigns in 2003 - 2007 the municipal authorities collected the orders from house owners and distributed later the radon detectors. The radon concentrations measured in the campaign regions have exceeded the action limit of 400 Bq / m 3 in 0 - 39% of houses, depending on the region. The total of 15% of all measurements made exceeded this limit. The remediation activities have been followed by sending a special questionnaire on remedies performed to the house owners. In 2006 - 2007 a questionnaire was sent to those households where the radon concentration of 400 Bq / m 3 was exceeded during the two first campaign seasons. Among the households that replied
Bond, Christopher M; Djogovic, Dennis; Villa-Roel, Cristina; Bullard, Michael J; Meurer, David P; Rowe, Brian H
Sepsis is a potentially life-threatening condition that requires urgent management in an Emergency Department (ED). Evidence-based guidelines for managing sepsis have been developed; however, their integration into routine practice is often incomplete. Care maps may help clinicians meet guideline targets more often. To determine if electronic clinical practice guidelines (eCPGs) improve management of patients with severe sepsis and septic shock (SS/SS). The impact of an eCPG on the management of patients presenting with SS/SS over a 3-year period at a tertiary care ED was evaluated using retrospective case-control design and chart review methods. Cases and controls, matched by age and sex, were chosen from an electronic database using physician sepsis diagnoses. Data were compared using McNemar tests or paired t-tests, as appropriate. Overall, 51 cases and controls were evaluated; the average age was 62 years, and 60% were male. eCPG patients were more likely to have a central venous pressure and central venous oxygen saturation measured; however, lactate measurement, blood cultures, and other investigations were similarly ordered (all p > 0.05). The administration of antibiotics within 3 h (63% vs. 41%; p = 0.03) and vasopressors (45% vs. 20%; p = 0.02) was more common in the eCPG group; however, use of corticosteroids and other interventions did not differ between the groups. Overall, survival was high and similar between groups. A sepsis eCPG experienced variable use; however, physicians using the eCPG achieved more quality-of-care targets for SS/SS. Strategies to increase the utilization of eCPGs in Emergency Medicine seem warranted. Copyright © 2013 Elsevier Inc. All rights reserved.
Ahmad, M. S.; Waheed, A.
Objective: To determine frequency of thrombocytopenia and thrombocytosis, the MPV (mean platelet volume) and PDW (platelet distribution width) in patients with probable and culture proven neonatal sepsis and determine any association between platelet counts and mortality rate. Study Design: Descriptive analytical study. Place and Duration of Study: NICU, Fazle Omar Hospital, from January 2011 to December 2012. Methodology: Cases of culture proven and probable neonatal sepsis, admitted in Fazle Omar Hospital, Rabwah, were included in the study. Platelet counts, MPV and PDW of the cases were recorded. Mortality was documented. Frequencies of thrombocytopenia ( 450000/mm3) were ascertained. Mortality rates in different groups according to platelet counts were calculated and compared by chi-square test to check association. Results: Four hundred and sixty nine patients were included; 68 (14.5%) of them died. One hundred and thirty six (29%) had culture proven sepsis, and 333 (71%) were categorized as probable sepsis. Thrombocytopenia was present in 116 (24.7%), and thrombocytosis was present in 36 (7.7%) cases. Median platelet count was 213.0/mm3. Twenty eight (27.7%) patients with thrombocytopenia, and 40 (12.1%) cases with normal or raised platelet counts died (p < 0.001). Median MPV was 9.30, and median PDW was 12.30. MPV and PDW of the patients who died and who were discharged were not significantly different from each other. Conclusion: Thrombocytopenia is a common complication of neonatal sepsis. Those with thrombocytopenia have higher mortality rate. No significant difference was present between PDW and MPV of the cases who survived and died. (author)
Gong, Yuanqi; Lan, Haibing; Yu, Zhihong; Wang, Meng; Wang, Shu; Chen, Yu; Rao, Haiwei; Li, Jingying; Sheng, Zhiyong; Shao, Jianghua
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.
Cyril Jacob Chacko
Conclusion: There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.
Peach, Brian C
The Society of Critical-Care Medicine and the European Society of Intensive Care Medicine recently announced a marked change in the sepsis definition. A task force of 19 sepsis clinicians and researchers made the change based on advances in the pathobiological understanding of the septic process. The task force determined that there were numerous justifications for a revision of the sepsis definition, which are outlined in this article. The systemic inflammatory response criteria have been replaced by the Sequential Organ Failure Assessment (SOFA) score in the newly operationalized definition (Singer et al., 2016). In addition to the definition change, the task force recommended using the new quick SOFA (qSOFA) score in non-ICU settings, as a risk stratification tool to identify patients who may be septic or be at risk of developing sepsis. The change in definition will likely have a negative impact on sepsis research in the short-term as hospitals adjust their coding for the new definition, but may result in less misclassification bias and improved research data in the long-term. While the intent of the SCCM/ESICM task force was to better define sepsis for coding and epidemiological research purposes, there is the potential for improved patient outcomes if clinicians are better able to differentiate between sepsis and inflammatory events. The qSOFA tool may also aid clinicians in recognizing sepsis in a quicker manner, leading to more timely treatment, and potentially better outcomes. While the new operationalized Sepsis-3 definition appears on the surface to be an improvement over the previous iterations, it remains to be seen if research data will be more robust using the new criteria. There is the potential for better patient outcomes if clinicians are better able to differentiate sepsis from inflammatory events with the new definition, and if sepsis cases are recognized sooner with qSOFA. Future research on the impact of this definition change on research and
We report seven patients in whom five dropped surgical clips and two gallstones were visualized in the peritoneal cavity, on radiological studies. In two, subphrenic abscesses and empyemas developed as a result of dropped clips into the peritoneal cavity during or following laparoscopic cholecystectomy. In one of these two, a clip was removed surgically from the site of an abscess. In two other patients dropped gallstones, and in three, dropped clips led to no complications. These were seen incidentally on studies done for other indications. Abdominal abscess secondary to dropped gallstones is a well-recognized complication of laparoscopic cholecystectomy (LC). We conclude that even though dropped surgical clips usually do not cause problems, they should be considered as a risk additional to other well-known causes of post-LC abdominal sepsis
Weber, Martin W; Carlin, John B; Gatchalian, Salvacion; Lehmann, Deborah; Muhe, Lulu; Mulholland, E Kim
Neonatal infections are a major cause of death worldwide. Simple procedures for identifying infants with infection that need referral for treatment are therefore of major public health importance. We investigated 3303 infants Ethiopia, The Gambia, Papua New Guinea and The Philippines, using a standardized approach. Historical factors and clinical signs predicting sepsis, meningitis, hypoxemia, deaths and an ordinal scale indicating severe disease were investigated by logistic regression, and the performance of simple combination rules was explored. In multivariable analysis, reduced feeding ability, no spontaneous movement, temperature >38 degrees C, being drowsy/unconscious, a history of a feeding problem, history of change in activity, being agitated, the presence of lower chest wall indrawing, respiratory rate >60 breaths/min, grunting, cyanosis, a history of convulsions, a bulging fontanel and slow digital capillary refill were independent predictors of severe disease. The presence of any 1 of these 14 signs had a sensitivity for severe disease (defined as sepsis, meningitis, hypoxemia, or radiologically proven pneumonia) of 87% and a specificity of 54%. More stringent combinations, such as demanding 2 signs from the list, resulted in a considerable loss of sensitivity. By contrast only slight loss of sensitivity and considerable gain of specificity resulted from reducing the list to 9 signs. Requiring the presence of fever and any other sign produced a diagnostic rule with extremely low sensitivity (25%). Physical signs can be used to identify young infants at risk of severe disease, however with limited specificity, resulting in large numbers of unnecessary referrals. Further studies are required to validate and refine the prediction of severe disease, especially in the first week of life, but there appear to be limits on the accuracy of prediction that is achievable.
Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki
Purpose: Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. Methods: In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Results: Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. Conclusion: The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease. PMID:28974828
Thompson, L.; Ouzounian, T.J.; Webber, M.M.; Amstutz, H.C.
This study evaluated the accuracy and utility of the In-111 labeled WBC imaging in a series of patients who were suspected of having musculoskeletal sepsis. The labeling of the WBCs was patterned after a method previously described, in which the WBCs are labeled with In-111 oxine in plasma. The WBCs from 100 ml of blood are separated and incubated with In-111 oxine complex, and then 500 μCi. of the labeled cells were reinjected into the patient. Images of the areas in question were obtained at 24 hrs. In some instances, 48 hour images were also obtained. Images were interpreted using consistent criteria. Forty imaging procedures were done on 39 patients. These included 39 total joint protheses, and 17 other images to evaluate possible osteomyelitis, septic arthritis or deep abscesses. Of these studies, 15 were positive, and 42 negative. The findings were then correlated with operative culture and pathology in 21, aspiration cultures and gram stains in 14, and with clinical findings in the remaining 21. This correlation showed 41 true negatives, 12 true positives, 1 false negative, and 2 false positives. The sensitivity was 92.9% and the specificity was 95.2%l. The false negative occurred in a patient on chronic suppressive antibiotic therapy for an infected total hip replacement. The false positive images occurred in a patient with active rheumatoid arthritis and in a patient imaged one month post operative placement of the prosthesis. These images were very useful in several septic patients who had many possible sites of infection. The authors conclude that In-III imaging is an accurate and useful non-invasive method of evaluating musculoskeletal sepsis
Jafarzadeh, S Reza; Thomas, Benjamin S; Marschall, Jonas; Fraser, Victoria J; Gill, Jeff; Warren, David K
To quantify the coinciding improvement in the clinical diagnosis of sepsis, its documentation in the electronic health records, and subsequent medical coding of sepsis for billing purposes in recent years. We examined 98,267 hospitalizations in 66,208 patients who met systemic inflammatory response syndrome criteria at a tertiary care center from 2008 to 2012. We used g-computation to estimate the causal effect of the year of hospitalization on receiving an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis code for sepsis by estimating changes in the probability of getting diagnosed and coded for sepsis during the study period. When adjusted for demographics, Charlson-Deyo comorbidity index, blood culture frequency per hospitalization, and intensive care unit admission, the causal risk difference for receiving a discharge code for sepsis per 100 hospitalizations with systemic inflammatory response syndrome, had the hospitalization occurred in 2012, was estimated to be 3.9% (95% confidence interval [CI], 3.8%-4.0%), 3.4% (95% CI, 3.3%-3.5%), 2.2% (95% CI, 2.1%-2.3%), and 0.9% (95% CI, 0.8%-1.1%) from 2008 to 2011, respectively. Patients with similar characteristics and risk factors had a higher of probability of getting diagnosed, documented, and coded for sepsis in 2012 than in previous years, which contributed to an apparent increase in sepsis incidence. Copyright © 2016 Elsevier Inc. All rights reserved.
Hamed, Sonja; Behnes, Michael; Pauly, Dominic; Lepiorz, Dominic; Barre, Max; Becher, Tobias; Lang, Siegfried; Akin, Ibrahim; Borggrefe, Martin; Bertsch, Thomas; Hoffmann, Ursula
Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. NCT01535534 . Registered 14.02.2012.
Need to start a new installation and worried about safety aspects? Or are you newly responsible for safety matters in a CERN building? Perhaps you're simply interested in how to make the working environment safer for yourself and your colleagues. Whatever the case, a new information campaign launched by TIS this week can help. The most visible aspects of the new campaign will be posters distributed around the Laboratory treating a different subject each month. The Web site - http://safety.cern.ch/ - which provides all safety related information. But these are not the only aspects of the new campaign. Members of the TIS/GS group, whose contact details can be found on the safety web site, are available to give information and advice on a one-to-one basis at any time. The campaign's launch has been timed to coincide with European Safety Week, organized by the European Agency for Safety and Health at Work and the subject treated in the first posters is safety inspection. This particular topic only concerns thos...
As sepsis progresses to septic shock, the risk of dying increases ... Jantjie Taljaard's current fields of interests are general internal medicine, antibiotic stewardship, HIV/HBV co-infection, drug-related .... infections (infection control) and stress.
Barkhausen, J.; Stoeblen, F.; Mueller, R.D.
Purpose: To evaluate the diagnostic relevance of CT in patients with sepsis of unknown origin. Material and Methods: Sixty-three consecutive intensive care patients with suspicion of an abscess and negative or inconclusive previous radiological examinations were included. CT was performed using the helical technique. A total of 45 abdominal and 38 chest examinations were evaluated. Results: 5/38 examinations of the chest revealed the source of sepsis (pleural empyema 2, lung abscess 1, mediastinitis 1, retrosternal abscess 1). 7/45 abdominal CT examinations showed the source of sepsis (intraabdominal abscess 2, hepatic abscess 3, intestinal perforation 1, gangrenous colitis 1). Conclusion: CT is useful for the evaluation of patients with fever or sepsis without a known source. Due to the detection of a spetic focus by CT, 19% of the patients in our study could be immediately referred to causal therapy as percutaneous drainage or surgery. (orig.)
Barkhausen, J.; Stoeblen, F.; Mueller, R.D. [University Hospital Essen (Germany). Dept. of Radiology; Dominguez-Fernandez, E. [University Hospital Essen (Germany). Dept. of General Surgery; Henseke, P. [Nycomed-Amersham Arzneimittel GmbH, Muenchen (Germany)
Purpose: To evaluate the diagnostic relevance of CT in patients with sepsis of unknown origin. Material and Methods: Sixty-three consecutive intensive care patients with suspicion of an abscess and negative or inconclusive previous radiological examinations were included. CT was performed using the helical technique. A total of 45 abdominal and 38 chest examinations were evaluated. Results: 5/38 examinations of the chest revealed the source of sepsis (pleural empyema 2, lung abscess 1, mediastinitis 1, retrosternal abscess 1). 7/45 abdominal CT examinations showed the source of sepsis (intraabdominal abscess 2, hepatic abscess 3, intestinal perforation 1, gangrenous colitis 1). Conclusion: CT is useful for the evaluation of patients with fever or sepsis without a known source. Due to the detection of a spetic focus by CT, 19% of the patients in our study could be immediately referred to causal therapy as percutaneous drainage or surgery. (orig.)
Evangelatos, Nikolaos; Bauer, Pia; Reumann, Matthias; Satyamoorthy, Kapaettu; Lehrach, Hans; Brand, Angela
Sepsis, with its often devastating consequences for patients and their families, remains a major public health concern that poses an increasing financial burden. Early resuscitation together with the elucidation of the biological pathways and pathophysiological mechanisms with the use of "-omics" technologies have started changing the clinical and research landscape in sepsis. Metabolomics (i.e., the study of the metabolome), an "-omics" technology further down in the "-omics" cascade between the genome and the phenome, could be particularly fruitful in sepsis research with the potential to alter the clinical practice. Apart from its benefit for the individual patient, metabolomics has an impact on public health that extends beyond its applications in medicine. In this review, we present recent developments in metabolomics research in sepsis, with a focus on pneumonia, and we discuss the impact of metabolomics on public health, with a focus on free/libre open source software. © 2018 S. Karger AG, Basel.
Buwalda, Mattijn; Ince, Can
Objective: A prominent feature of sepsis is dysfunction of the microcirculation, with impaired perfusion and regional tissue oxygenation causing a deficit in oxygen extraction. If shunting of oxygen transport past closed hypoxic microcirculatory beds is responsible for this, vasodilator therapy,
Davis, Anna; Henderson, James; Langmack, Gill
Severe sepsis is a major cause of morbidity and mortality in the UK. This article describes the collaborative development and implementation of an interactive online learning package to understand the key role nurses have in recognising and then starting to apply the Sepsis Six care bundle in clinical practice. The e-learning package, developed in a UK teaching hospital, uses a case study approach to address the knowledge that is required to be able to recognise sepsis, to understand the processes that occur and the ongoing care and treatment required. The package is relevant to final-year student nurses, newly registered nurses in preceptorship and other health professionals involved in assessing and treating patients who may be developing sepsis.
count has a poor positive predictive value for neonatal sepsis and is ... Division of Neonatology, Department of Paediatrics and Child Health, School of Medicine, University ... infections (UTIs) in neonates, many clinicians use the following.
Charles E Bane
Full Text Available Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/- mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-α and IL-10 and delayed IL-1β and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI-/- mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI-/- animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.
Molitoris, Bruce A
The clinical complexity of sepsis and the regional variability in renal blood flow present a difficult challenge for the clinician or investigator in understanding the role and clinical importance of reduced blood flow in the pathophysiology of sepsis-induced acute renal failure. Understanding the role of regional microvasculature flow and interactions between endothelium and white blood cells in the local delivery of oxygen and substrates is of critical importance. Therefore, measuring total...
multi- faceted approach to the management of sepsis. Rapid pro- vision of broad-spectrum antibiotic coverage is coupled with aggressive organ support...setting of sepsis may include (1) exposure to infectious agents, (2) immunocompromise , (3) injury or illness, (4) genetic abnormalities, or (5) under- lying...assays 2. Obtain culture panel (blood, respiratory, urine, wound) 3. Prompt administration of broad-spectrum antibiotics 4. Manage organ dysfunction
Heffernan, D S; Monaghan, S F; Ayala, Alfred
Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3 + T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3 + T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3 + T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3 + CD29 + T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.
Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François
Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia 10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.
Jones, Caroline N; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Hassell, Bryan A; Warren, H Shaw; Tompkins, Ronald G; Fagan, Shawn P; Irimia, Daniel
Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns.
Raul de Pablo
Full Text Available Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.
Sang Hoon Lee
Full Text Available Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n=19] and septic shock [n=98] who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG, high-density lipoprotein (HDL, low-density lipoprotein (LDL, free fatty acid (FFA, and apolipoprotein (Apo A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p=0.043, p=0.020, p=0.005, and p=0.015, resp.. According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p=0.018 and p=0.008, resp.. Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients.
This paper investigates the role of campaign advertising and the opportunity of legal restrictions on it. An electoral race is modeled as a signalling game with three classes of players: a continuum of voters, two candidates, and one interest group. The group has non-verifiable insider information
Hansen, Kasper Møller
between the theoretical considerations and empirical data. Finally, the paper presents how these models are operationalized in the questionnaires and experiments of the project Online Panel of Electoral Campaigning (OPEC). The paper is part of a five years research project, OPEC, which is set out...
Grover, Stuart R.
Twenty five years ago, few community or technical colleges considered launching capital campaigns. They lacked community standing, professional fundraising staff, and the related institutional foundation structure to manage charitable efforts. Gradually, as public funding eroded, bond issues became harder to pass, and colleges recognized the need…
The Advanced Fuels Campaign (AFC) under the Fuel Cycle Research and Development (FCRD) program is responsible for developing fuels technologies to support the various fuel cycle options defined in the DOE Nuclear Energy Research and Development Roadmap, Report to Congress, April 2010. The fiscal year 2012 (FY 2012) accomplishments are highlighted below. Kemal Pasamehmetoglu is the National Technical Director for AFC.
Sang Hoon Lee
Full Text Available Background Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1 has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA. Results Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively. Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029. Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038. IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.
Full Text Available OBJECTIVE: Septic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the activation of leukocytes and microvascular endothelium resulting in cardiovascular instability, lung injury and renal dysfunction. Due to the primary role of leukocyte activation in the sepsis syndrome, a synthetic biomimetic membrane, called a selective cytopheretic device (SCD, was developed to bind activated leukocytes. The incorporation of the SCD along an extracorporeal blood circuit coupled with regional anticoagulation with citrate to lower blood ionized calcium was devised to modulate leukocyte activation in sepsis. DESIGN: Laboratory investigation. SETTING: University of Michigan Medical School. SUBJECTS: Pigs weighing 30-35 kg. INTERVENTIONS: To assess the effect of the SCD in septic shock, pigs were administered 30×10(10 bacteria/kg body weight of Escherichia coli into the peritoneal cavity and within 1 hr were immediately placed in an extracorporeal circuit containing SCD. MEASUREMENTS AND MAIN RESULTS: In this animal model, the SCD with citrate compared to control groups without the SCD or with heparin anticoagulation ameliorated the cardiovascular instability and lung sequestration of activated leukocytes, reduced renal dysfunction and improved survival time compared to various control groups. This effect was associated with minimal elevations of systemic circulating neutrophil activation. CONCLUSIONS: These preclinical studies along with two favorable exploratory clinical trials form the basis of an FDA-approved investigational device exemption for a pivotal multicenter, randomized control trial currently underway.
Full Text Available This study aimed to investigate the protective effects of oridonin (ORI on cecal ligation and puncture (CLP-induced sepsis in mice. Male C57BL/6 mice weighing 22–30 g and aged 8–10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 μg/kg was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin–eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6, and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05. Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05. The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05. Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.
Madonna, G.S.; Ledney, G.D.; Moore, M.M.; Elliott, T.B.; Brook, I.
Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. We recently showed that injection of synthetic trehalose dicorynomycolate (S-TDCM) significantly augments resistance to infection and increases survival of mice compromised either by whole-body irradiation with gamma radiation or equal mixtures of fission neutron and gamma radiation. In this study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an open wound (15% total body surface area [TBSA]) 1 hr later while anesthetized. Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than mice exposed to radiation alone, and died from natural wound infection and sepsis within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or ofloxacin for 10 days significantly increased survival time compared with untreated irradiated/wounded mice (p less than 0.01). Combination therapy with topical gentamicin cream and systemic oxacillin increased survival from 0% to 100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and systemic gentamicin increased survival compared with antibiotic treatment alone. These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics augments resistance to infection in immunocompromised mice. The data suggest that therapies which combine stimulation of nonspecific host defense mechanisms with antibiotics may increase survival of irradiated patients inflicted with accidental or surgical trauma
Madonna, G.S.; Ledney, G.D.; Moore, M.M.; Elliott, T.B.; Brook, I. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))
Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. We recently showed that injection of synthetic trehalose dicorynomycolate (S-TDCM) significantly augments resistance to infection and increases survival of mice compromised either by whole-body irradiation with gamma radiation or equal mixtures of fission neutron and gamma radiation. In this study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an open wound (15% total body surface area (TBSA)) 1 hr later while anesthetized. Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than mice exposed to radiation alone, and died from natural wound infection and sepsis within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or ofloxacin for 10 days significantly increased survival time compared with untreated irradiated/wounded mice (p less than 0.01). Combination therapy with topical gentamicin cream and systemic oxacillin increased survival from 0% to 100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and systemic gentamicin increased survival compared with antibiotic treatment alone. These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics augments resistance to infection in immunocompromised mice. The data suggest that therapies which combine stimulation of nonspecific host defense mechanisms with antibiotics may increase survival of irradiated patients inflicted with accidental or surgical trauma.
Pedersen, Rasmus Tue
that news coverage of negative campaigning does apply the strategic game frame to a significantly larger degree than articles covering positive campaigning. This finding has significant implications for campaigning politicians and for scholars studying campaign and media effects.......News media coverage of election campaigns is often characterized by use of the strategic game frame and a focus on politicians’ use of negative campaigning. However, the exact relationship between these two characteristics of news coverage is largely unexplored. This article theorizes that consumer...... demand and norms of journalistic independence might induce the news media outlets to cover negative campaigning with a strategic game frame. A comprehensive content analysis based on several newspaper types, several election campaigns, and several different measurements of media framing confirms...
... Bar Home Current Issue Past Issues Cover Story Heart Health The Heart Truth Campaign 2009 Past Issues / Winter 2009 Table ... one of the celebrities supporting this year's The Heart Truth campaign. Both R&B singer Ashanti (center) ...
Absolute counts of peripheral blood leukocyte subpopulations in intraabdominal sepsis and pneumonia-derived sepsis: a pilot study Absolute counts of peripheral blood leukocyte subpopulations in intraabdominal sepsis and pneumonia-derived sepsis: a pilot study
Grazyna Anna Hoser
Full Text Available The leading pathophysiological changes during sepsis include systemic abnormalities in the immune
response. Due to the general character of these disturbances, sepsis is usually studied as a homogenous clinical
condition. We aimed to compare the immune response in intraabdominal sepsis (IAS and pneumonia-derived
sepsis (PDS. The following cell populations were examined: white blood cell count (WBC, monocytes, lymphocytes:
CD3+, CD4+ and CD8+ T cells, B cells, and NK cells. In both studied groups (i.e. IAS and PDS, the
WBC was elevated. However, it was significantly higher in the IAS group than in the PDS group. The difference
was due to a lower granulocyte count, as well as a lower monocyte count in PDS. We found no significant
correlation between the total lymphocyte number and CD3+CD8+ T cells in either form of sepsis. Similarly, we
observed no correlation between the total lymphocyte number and the NK cells subset in IAS. However, the
numbers of CD3+CD8+ and NK cells correlated similarly in both types of sepsis. Both studied types of sepsis
induced profound lymphocytopenia, with marked loss of CD8+ T cells and the NK cells. However, the similar
relation between them, which was independent of the infection type, suggests that the NK and CD3+CD8+ cells
have shared mechanisms of regulation. The primary site of infection has an impact on the global immune reaction.
These alternations include especially myeloid cells: granulocytes and monocytes which disappear from peripheral
blood during PDS, but increase in IAS.
The leading pathophysiological changes during sepsis include systemic abnormalities in the immune
response. Due to the general character of these disturbances, sepsis is usually studied as a homogenous clinical
condition. We aimed to compare the immune response in intraabdominal sepsis (IAS and pneumonia-derived
sepsis (PDS. The following cell
Miguel Angel Rodríguez-Weber
Full Text Available OBJETIVO: Comparar el comportamiento de un grupo de recién nacidos sépticos que fallecieron contra un grupo de recién nacidos sépticos vivos. MATERIAL Y MÉTODOS: Revisión retrospectiva de expedientes de un grupo de recién nacidos con sepsis neonatal, atendidos en el Instituto Nacional de Pediatría, de la Secretaría de Salud de México, en la Ciudad de México, D.F., entre 1992 y 2000, los cuales se dividieron en recién nacidos sépticos vivos y fallecidos a los 90 días de seguimiento máximo. Se compararon las variables entre los grupos a través de U de Mann Whitney en el caso de variables numéricas, y ji cuadrada o prueba exacta de Fisher en el caso de variables categóricas. Las variables significativas en el análisis bivariado se incluyeron en uno de riesgos proporcionales de Cox. En todos los análisis se consideró como significativo un valor de pOBJECTIVE: To compare the epidemiological, clinical and microbiological profiles between patients with neonatal sepsis who lived or died. MATERIAL AND METHODS: The medical records of patients with neonatal sepsis were retrospectively reviewed at Instituto Nacional de Pediatría (National Pediatric Institute of Secretaría de Salud (Ministry of Health in Mexico City, between 1992 and 2000. Neonatal sepsis cases were classified as surviving or not after 90 days of postnatal follow-up. The survivor and deceased groups were compared using Mann-Whitney's U test for continuous variables, and the chi-squared test or the Fisher's exact test for categorical variables. Significantly associated variables were included in a Cox proportional hazards model. A p-value <0.05 was considered statistically significant for all analyses. RESULTS: A total of 116 patients with neonatal sepsis were included (65 live and 51 dead. Multivariate analysis showed that fetal distress, respiratory distress, a delayed capillary fill up, a low platelet count, and a positive hemoculture for Klebsiella pneumoniae were
Liu, Vincent X; Fielding-Singh, Vikram; Greene, John D; Baker, Jennifer M; Iwashyna, Theodore J; Bhattacharya, Jay; Escobar, Gabriel J
Prior sepsis studies evaluating antibiotic timing have shown mixed results. To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration. Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors. The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock. In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.
Chacko, Cyril Jacob; Gopal, Shameer
We proposed a review of present literature and systematic analysis of present literature to summarize the evidence on the use of β-blockers on the outcome of a patient with severe sepsis and septic shock. Medline, EMBASE, Cochrane Library were searched from 1946 to December 2013. The bibliography of all relevant articles was hand searched. Full-text search of the grey literature was done through the medical institution database. The database search identified a total of 1241 possible studies. The citation list was hand searched by both the authors. A total of 9 studies were identified. Most studies found a benefit from β-blocker administration in sepsis. This included improved heart rate (HR) control, decreased mortality and improvement in acid-base parameters. Chronic β-blocker usage in sepsis was also associated with improved mortality. The administration of β-blockers during sepsis was associated with better control of HR. The methodological quality of all the included studies, however, was poor. There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.
Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei
Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627
Low survival rate of trees planted during annual planting campaigns is often reported in many parts of the country and there is need to understand why and propose adequate solutions to improve survival rate of trees in plantation. The study was conducted in three sectors of Huye District namely Mukura, Tumba and Ngoma ...
This Stabilization Blend Plan documents the material to be processed and the processing order for the FY95 Ash Stabilization Campaign. The primary mission of this process is to reduce the inventory of unstable plutonium bearing ash. The source of the ash is from Rocky Flats and the 232-Z incinerator at the Plutonium Finishing Plant (PFP). The ash is currently being stored in Room 235B and Vault 174 in building 234-5Z. The sludge is to be thermally stabilized in a glovebox in room 230A of the 234-5Z building and material handling for the process will be done in room 230B of the same building. The campaign is scheduled for approximately 12--16 weeks. A total of roughly 4 kg of Pu will be processed
Ha, Sang Ook; Park, Sang Hyuk; Hong, Sang Bum; Jang, Seongsoo
Disseminated intravascular coagulation (DIC) is a major complication in sepsis patients. We compared the performance of five DIC diagnostic criteria, focusing on the prediction of mortality. One hundred patients with severe sepsis or septic shock admitted to intensive care unit (ICU) were enrolled. Routine DIC laboratory tests were performed over the first 4 days after admission. The overall ICU and 28-day mortality in DIC patients diagnosed from five criteria (International Society on Thrombosis and Haemostasis [ISTH], the Japanese Association for Acute Medicine [JAAM], the revised JAAM [R-JAAM], the Japanese Ministry of Health and Welfare [JMHW] and the Korean Society on Thrombosis and Hemostasis [KSTH]) were compared. Both KSTH and JMHW criteria showed superior performance than ISTH, JAAM and R-JAAM criteria in the prediction of overall ICU mortality in DIC patients (odds ratio 3.828 and 5.181, P = 0.018 and 0.006, 95% confidence interval 1.256-11.667 and 1.622-16.554, respectively) when applied at day 1 after admission, and survival analysis demonstrated significant prognostic impact of KSTH and JMHW criteria on the prediction of 28-day mortality (P = 0.007 and 0.049, respectively) when applied at day 1 after admission. In conclusion, both KSTH and JMHW criteria would be more useful than other three criteria in predicting prognosis in DIC patients with severe sepsis or septic shock.
Cassiano Felippe Gonçalves-de-Albuquerque
Full Text Available Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA, a monounsaturated fatty acid (MUFA. We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP. OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A mRNA levels were increased, while uncoupling protein 2 (UCP2 liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA.
Chen, Longwang; Lu, Yang; Zhao, Linjun; Hu, Lili; Qiu, Qiaomeng; Zhang, Zhuoling; Li, Mengfang; Hong, Guangliang; Wu, Bing; Zhao, Guangju; Lu, Zhongqiu
Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4 + CD25 + regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. The levels of Foxp3 were detected by Western blot and real-time PCR and cytokine levels were determined by enzyme-linked immunosorbent assay. We found that the administration of curcumin significantly alleviated inflammatory injury of the lung and kidney in septic mice. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with curcumin. Furthermore, the secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with curcumin and administration with curcumin could improve survival after CLP. These data suggest that curcumin could be used as a potential therapeutic agent for sepsis. Copyright © 2018 Elsevier B.V. All rights reserved.
Full Text Available Matthew O Wiens,1 Elias Kumbakumba,2 Niranjan Kissoon,3 J Mark Ansermino,4 Andrew Ndamira,2 Charles P Larson51School of Population and Public Health, University of British Columbia, Vancouver, Canada; 2Department of Pediatrics, Mbarara University of Science and Technology, Mbarara, Uganda; 3Department of Pediatrics, BC Children's Hospital and University of British Columbia, Vancouver, Canada; 4Department of Anesthesia, BC Children's Hospital and University of British Columbia, Vancouver, Canada; 5Department of Pediatrics and School of Population and Public Health, University of British Columbia, Vancouver, CanadaAbstract: Sepsis represents the progressive underlying inflammatory pathway secondary to any infectious illness, and ultimately is responsible for most infectious disease-related deaths. Addressing issues related to sepsis has been recognized as an important step towards reducing morbidity and mortality in developing countries, where the majority of the 7.5 million annual deaths in children under 5 years of age are considered to be secondary to sepsis. However, despite its prevalence, sepsis is largely neglected. Application of sepsis definitions created for use in resource-rich countries are neither practical nor feasible in most developing country settings, and alternative definitions designed for use in these settings need to be established. It has also been recognized that the inflammatory state created by sepsis increases the risk of post-discharge morbidity and mortality in developed countries, but exploration of this issue in developing countries is lacking. Research is urgently required to characterize better this potentially important issue.Keywords: children, pediatric sepsis, developing countries
Pregnancy is associated with an increased risk of infection related to its associated mechanical and physiological changes. Sepsis remains among the top causes of maternal death worldwide and is associated with substantial maternal morbidity. However, there are sparse data on pregnancy-associated severe sepsis (PASS), related in part to infrequent reports, varying case definitions and methodological approach, small cohort size, and often limited focus on severe sepsis in selected phases of pregnancy outcomes. Available reports vary, but indicate that PASS is a rare but likely increasing complication, and it is more likely to develop with increased maternal age, among minority women, the poor, those lacking health insurance, those with chronic illness or pregnancy-associated complications, and following invasive procedures. Obstetric sites of infection are the most prevalent, but non-obstetric infections often underlie pregnancy-associated severe sepsis, though the source of infection is often not readily apparent during initial care. Women with PASS can have a rapidly fatal course and require heightened clinician vigilance for early diagnosis and timely effective intervention. Nevertheless, available reports raise concerns about prevalent substandard care of these patients, contributing to adverse outcomes. The case fatality of PASS appears lower than that in the general population with severe sepsis, while the long-term outcomes of survivors remain unknown.
S. L. Kan
Full Text Available Objective: to evaluate the microcirculation system in critical conditions caused by abdominal sepsis for a further differentiated approach to intensive care. Subjects and methods. Twenty-four patients with abdominal sepsis (mean age 42.9±0.9 years were examined; a control group consisted of 35 apparently healthy individuals (mean age 40.1±2.1 years. Over 11 days, the microcirculatory bed was evaluated by cutaneous laser Doppler flowmetry by means of a ЛАКК-02 laser capillary blood flow analyzer made in the Russian Federation (LAZMA Research-and-Production Association, by using a basic light guide for percutaneous microcirculation studies. Results. Throughout the study, tissue blood perfusion remained in the patients with sepsis due to the higher effect of mainly active components of vascular tone regulation on the microvascular bed. In a poor outcome, there was a reduction in both active and passive regulatory effects on tissue perfusion chiefly due to local (myogenic factors. Conclusion. The findings suggest that the patients with sepsis have microcirculatory regulation changes aimed at maintaining tissue perfusion. A follow-up of the microcirculation may be useful in choosing intensive care tactics and predicting disease outcome. Key words: sepsis, microcirculation, microvascular bed, micro blood flow, tissue perfusion.
Xu, Zhiheng; Huang, Yongbo; Mao, Pu; Zhang, Jianrong; Li, Yimin
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
Gwadry-Sridhar, Femida; Lewden, Benoit; Mequanint, Selam; Bauer, Michael
Sepsis is a significant cause of mortality and morbidity and is often associated with increased hospital resource utilization, prolonged intensive care unit (ICU) and hospital stay. The economic burden associated with sepsis is huge. With advances in medicine, there are now aggressive goal oriented treatments that can be used to help these patients. If we were able to predict which patients may be at risk for sepsis we could start treatment early and potentially reduce the risk of mortality and morbidity. Analytic methods currently used in clinical research to determine the risk of a patient developing sepsis may be further enhanced by using multi-modal analytic methods that together could be used to provide greater precision. Researchers commonly use univariate and multivariate regressions to develop predictive models. We hypothesized that such models could be enhanced by using multiple analytic methods that together could be used to provide greater insight. In this paper, we analyze data about patients with and without sepsis using a decision tree approach and a cluster analysis approach. A comparison with a regression approach shows strong similarity among variables identified, though not an exact match. We compare the variables identified by the different approaches and draw conclusions about the respective predictive capabilities,while considering their clinical significance.
The history of the nuclear industry in the UK has been dominated by Sellafield reprocessing site in west Cumbria. The site, formerly owned by the United Kingdom Atomic Energy Authority was transferred to the newly-formed British Nuclear Fuels plc in 1971. Although trade union representation existed at Sellafield before the emergence of BNFL, it is only after this date that collective trade union activity began to emerge. In 1977, after a long running dispute with management about the issue of radiation dose uptake, the workforce went on strike, forcing the management to question their previous 'need to know' attitude and to improve industrial relations. In 1984, it was recognised that the lobbying influence of trade unions within politics, and especially the Labour party could be used to greater effect to challenge potentially -damaging influence of anti-nuclear campaigners. The National Campaign for the Nuclear Industry (NCNI) was born, combining nine industrial and non-industrial trade unions within the nuclear industry. Its task during the last ten years has been to put forward the interests of its members collectively and to secure the, role of nuclear power. within a balanced energy policy in the political arena. In dome so, it has gained a credible voice within both the trade union movement and the Labour party. The new Thermal Oxide Reprocessing Plant (THORP) received strong support from the NCNI during its construction and commissioning phases. When it became clear that the anti-nuclear lobby had gained the upper hand and were beginning to seriously delay the necessary legal instruments required to start the plant, the power of collective action was once again recognised, and the TRUST US campaign was born. The campaign was run and organised by a clerks committee and fronted by the Trade Unions at Sellafield., and turned out to be one of the most successful] trade union campaigns in recent history. The first task involved getting, the entire workforce on
This management project looks at four recent social marketing campaigns in the field of health in the UK to determine whether such campaigns work. The project critically analyses the marketing campaigns used, and aims to determine the range of factors that create a successful social marketing campaign in health. There is analysis of four case studies undertaken after secondary research into social marketing campaigns run by a range of different organisations. The case studies are the ...
Miller, Rupert G
A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.
Kesimpulan. Sepsis salah satu penyebab utama kematian neonatus yang dipengaruhi oleh berat lahir rendah, prematuritas, resistensi kuman terhadap antibiotik empirik dan jenis kuman. Penyebab sepsis neonatus terbanyak adalah kuman Gram negatif yang berkontribusi terhadap angka mortalitas
Vallabhajosyula, S; Pruthi, S; Shah, S; Wiley, B M; Mankad, S V; Jentzer, J C
Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.
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
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
Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur
Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2). This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections.
Chin, Y T; Scattergood, N; Thornber, M; Thomas, S
Sepsis is a major healthcare problem and leading cause of death worldwide. UK hospital mortality statistics and payments for patient episodes of care are calculated on clinical coding data. The accuracy of these data depends on the quality of coding. This study aimed to investigate whether patients with significant bacteraemia are coded for sepsis and to estimate the financial costs of miscoding. Of 54 patients over a one-month period with a significant bacteraemia, only 19% had been coded for sepsis. This is likely to lead to falsely high calculated hospital mortality. Furthermore, this resulted in an underpayment of £21,000 for one month alone. Copyright © 2016 The Healthcare Infection Society. All rights reserved.
Full Text Available Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC. There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant system, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.
Astrup, Lærke Boye; Iburg, Tine Moesgaard; Nielsen, Ole Lerberg
Introduction: Sepsis is a major problem in humans and both the incidence and mortality is increasing. Multiple microabcesses can be found in the brain of septic patients. Staphylococcus aureus is one of the most common causes of sepsis and brain abscesses. S. aureus is also a frequent cause...... of spontaneous porcine pyemia including endocarditis and associated brain lesions. We present a porcine model of haematogenous S. aureus induced brain infection. Materials and Methods: Twelve pigs received an intravenous injection of S. aureus of 108 CFU/kg body weight once at 0h or twice at 0h and 12h. Four...... pigs were kept as controls. The pigs were euthanized in groups of four at either 6, 12, 24 or 48 h post infection. The brain was collected from all the animals and examined histologically. Results: All the inoculated pigs developed sepsis and 7 out of 12 animals had microabscesses in the prosencephalon...
A. P. Berdnikov
Full Text Available Objective: to define the prognostic value of intracranial pressure (ICP changes in highvolume hemofiltration (HVHF in patients with severe sepsis and normal preperfusion ICP.Subjects and methods. A retrospective study was conducted in 50 patients (a total of 134 sessions with severe sepsis and normal baseline ICP who received ther apy using HVHF for extrarenal indications. Based on ICP changes before and after HVHF, the investigators identified 2 groups: 1 no ICP changes (n=81; 2 elevated ICP (n=53.Conclusion. HVHF is ineffective when the normal preperfusion ICP is increased in patients with severe sepsis who have a concurrence of an arteriovenous carbon dioxide difference of more than 8 mm Hg and a Glasgow coma score of less than 10.
Rayes, Julie; Lax, Siân; Wichaiyo, Surasak; Watson, Stephanie K; Di, Ying; Lombard, Stephanie; Grygielska, Beata; Smith, Stuart W; Skordilis, Kassiani; Watson, Steve P
Platelets play a critical role in vascular inflammation through the podoplanin and collagen/fibrin receptors, C-type-lectin-like-2 (CLEC-2) and glycoprotein VI (GPVI), respectively. Both receptors regulate endothelial permeability and prevent peri-vascular bleeding in inflammation. Here we show that platelet-specific deletion of CLEC-2 but not GPVI leads to enhanced systemic inflammation and accelerated organ injury in two mouse models of sepsis-intra-peritoneal lipopolysaccharide and cecal ligation and puncture. CLEC-2 deficiency is associated with reduced numbers of podoplanin-expressing macrophages despite increased cytokine and chemokine levels in the infected peritoneum. Pharmacological inhibition of the interaction between CLEC-2 and podoplanin regulates immune cell infiltration and the inflammatory reaction during sepsis, suggesting that activation of podoplanin underlies the anti-inflammatory action of platelet CLEC-2. We suggest podoplanin-CLEC-2 as a novel anti-inflammatory axis regulating immune cell recruitment and activation in sepsis.
Djuang, M. H.; Ginting, F.; Hariman, H.
Sepsis is an infection-induced syndrome, mostly caused by bacteria, of organ dysfunctions that caused by host response dysregulations. One of the simplest sepsis-indicator is platelet and its indexes. A new platelet parameter called immature platelet count (IPF) became theinterest in this study. The study aims to see whether IPF could assess sepsis severity by procalcitonin (PCT).Sixty-four of seventy-one patients with increased PCT were included in this cross-sectional study and separated into three groups based on their PCT levels. IPF showed no significance among the three groups (p-value>0.05) while platelet count was significant (p-valuesepsis severity based on PCT showed larger platelet count, as the result of platelet destructions caused by pro-inflammatory cytokines and endotoxins.
Sasaguri, K.; Yamaguchi, K.; Nakazono, T.; Mizuguchi, M.; Irie, H.
Aim: To evaluate renal volume and attenuation changes in patients with sepsis on contrast-enhanced computed tomography (CT) with respect to the severity of sepsis. Materials and methods: Forty-four patients with sepsis who underwent CT before and after the onset of sepsis were retrospectively analysed. Renal volume and CT attenuation value of the renal cortex on contrast-enhanced CT were measured for each patient and changes in renal volume and CT attenuation value from before to after the onset of sepsis were calculated. The changes were correlated with the severity of sepsis (Sepsis-related Organ Failure Assessment [SOFA] score). The time course of the renal volume and CT attenuation changes were also evaluated. Results: Renal volume increased by 17.6% and CT attenuation value decreased by 19% after the onset of sepsis with statistically significant differences (p<0.001 for both renal volume and CT attenuation changes). The renal volume and CT attenuation changes had significant correlations with the SOFA score (r=0.36, p=0.018 and −0.43, p=0.005, respectively). The time course of the renal volume and CT attenuation changes seemed to be gradual compared to that of the SOFA score and to lag behind the peak of the SOFA score. Conclusion: In patients with sepsis, the renal volume increases and the CT attenuation value decreases in proportion to the severity of sepsis. The changes may lag behind the peak of severity of sepsis and can be observed for a relatively long time after a patient's recovery from sepsis. - Highlights: • The renal volume increases and the renal enhancement on contrast-enhanced CT decreases in patients with sepsis. • The degrees of these changes are correlated with severity of sepsis. • These changes may lag behind the peak of severity of sepsis and last for a long time after a patient's recovery from sepsis.
Full Text Available Objective To investigate the distribution characteristics of organs with liquid sequestration during fluid resuscitation in rats with sepsis. Methods Fifty male Wistar rats were randomly divided into five groups: control group (n=10, sepsis group (n=10, crystalloid group (n=10, albumin group (n=10, and artificial colloid (HAES group (n=10. The sepsis model was reproduced by cecal ligation and puncture. The mean arterial pressure was monitored with carotid artery intubation. Twelve hours after fluid infusion by micro-infusion pump via the femoral vein, tissues from the heart, liver, lungs, kidney (right, and small intestine were harvested to observe the pathological changes and calculate the tissue water content. Results The water content of every visceral tissue was higher in the sepsis group than in the control group (P < 0.05; the water content in the heart, liver, and lung tissues was higher in the albumin group than in the crystalloid group (P < 0.05. The water content in both albumin and crystalloid groups was higher than that in the sepsis group (P < 0.05. Moreover, the water content in the heart, liver, and lungs in the HAES group was lower than that in the crystalloid and albumin groups (P < 0.05. Cellular injuries were more severe in the heart, liver, and lungs than in the intestine and kidney in the crystalloid group and albumin group under electron-microscope. Conclusion Liquid sequestration exists mainly in the lungs, heart, and liver of rats with sepsis during fluid resuscitation. The phenomenon is less evident in the kidney and small intestine. Artificial colloid can reduce capillary leak with a good volume expansion effect.
Wang, Yu; Kong, Bing-Bing; Yang, Wen-Ping; Zhao, Xin; Zhang, Rong
Sepsis-triggered immune paralysis including T-cell dysfunction increase susceptibility to infection. Gamma interferon (IFNg) exert beneficial effects in patients with sepsis. Herein, we speculated that IFNg may attenuate T-cell dysfunction induced by sepsis, although the mechanisms remain elusive. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pretreated with recombinant human IFNg (0.01μg/g of body weight) before CLP. The immunophenotyping of cell surface receptor expression, and regulatory T cells (CD4+CD25+Foxp3+) were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of IFNg and interleukin 4 (IL-4) in the spleen and plasma levels of TNF-α, IL-6, high-mobility group box 1 (HMGB1) were determined using enzyme-linked immunosorbent assay. IFNg markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. IFNg-treated mices had significantly decreased percentages of programmed cell death 1 (PD-1) receptors, increased the percentages of positive costimulatory receptor CD28 on CD4 T cells expressing. IFNg markedly reduced T-cell apoptosis through upregulating the expression of Bcl-2. CLP-induced formation of regulatory T cells in the spleen was abolished in IFNg -treated mices. Moreover, IFNg treatment reduced plasma levels of TNF-α, IL-6, HMGB1. IFNg can be a powerful regulator of immune function under sepsis conditions. Therefore, targeted immune-enhancement with IFNg may be a valid therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.
Yang, Chun-Hua; Zhou, Tian-Biao
This article has been included in a multiple retraction: Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei
Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M
Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment
Dolente, Brett A; Lindborg, Susan; Palmer, Jonathan E; Wilkins, Pamela A
There is limited literature on neonatal bacterial sepsis in New World (NW) camelids. Bacterial culture-positive crias have clinical differences based on the specific bacterial genera isolated. Bacterial culture-positive NW camelid crias blood gas abnormalities, potentially complicating diagnosis. Affected crias may not have localizing signs at presentation and are not usually febrile, although hypothermia, tachypnea, and tachycardia are relatively common. Total protein concentration was not a substitute for immunoglobulin G measurement in septic crias in this study. Familiarity with the clinical presentation and common pathogens isolated should improve early recognition and treatment and ultimately outcome of crias with sepsis.
Steiner, Jennifer L; Lang, Charles H
Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ∼24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions, and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the nonstimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 (mammalian target of rapamycin [mTOR] complex 1) substrates S6K1 (70-kd ribosomal protein S6 kinase 1) Thr (8-fold), S6K1 ThrSer (7-fold) and 4E-BP1 Ser (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr (67%), S6K1 ThrSer (46%), and 4E-BP1 Ser (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr phosphorylation was decreased similarly by muscle contraction in both groups. Mitogen-activated protein kinase signaling was discordant following contraction in septic muscle; phosphorylation of extracellular signal-regulated kinase ThrTyr and p38 ThrTyr was increased similarly in both CON and CLP mice, while sepsis prevented the contraction-induced phosphorylation of JNK ThrTyr and c-JUN Ser. The expression of interleukin 6 and tumor necrosis factor α (TNF-α) mRNA in muscle was increased by sepsis, and contraction increased TNF-α to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent.
This PhD-thesis is based on work performed at Clinical Research Centre and Department of Infectious Diseases at Copenhagen University Hospital, Hvidovre, and includes a review, a method development study, and two clinical studies. The background of the thesis is, that timely and accurate diagnosis...... of sepsis is of great importance for choice of treatment, level of monitoring and prognosis. In this biomarkers could be a significant aid, and thus the search for and application of "new" sepsis biomarkers is of great importance. The thesis reviews the definitions and the epidemiology, and gives...
Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek
Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels. Copyright © 2016 Elsevier Inc. All rights reserved.
de Stoppelaar, Sacha F.; van 't Veer, Cornelis; Claushuis, Theodora A. M.; Albersen, Bregje J. A.; Roelofs, Joris J. T. H.; van der Poll, Tom
Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median
Skibsted, Simon; Filbin, Michael; Hou, Peter
-acuity sepsis patients. The hypothesis was that patients with sepsis, but without hypotension, will demonstrate signs of flow abnormalities compared to noninfected control patients. Methods This was a prospective, observational study in a convenience sample of patients with sepsis and noninfected controls...
Full Text Available 18086373 Role of Toll-like receptor responses for sepsis pathogenesis. Weighardt H,... of Toll-like receptor responses for sepsis pathogenesis. PubmedID 18086373 Title Role of Toll-like receptor... responses for sepsis pathogenesis. Authors Weighardt H, Holzmann B. Publication
Sepsis is a systemic inflammatory response syndrome in the presence of suspected or proven infection, and it may progress to or encompass organ failure (severe sepsis) and hypotension (septic shock). Clinicians possess an arsenal of supportive measures to combat severe sepsis and septic shock, and some success, ...
van Vught, L.A.
Sepsis is a life-threatening syndrome that arises when a dysbalanced patient response to an infection causes damage to the body’s own organs and tissues. Sepsis is, to date, still a major cause of morbidity and mortality worldwide. A detailed understanding of the pathogenesis of sepsis is likely to
Chanrion, Olivier Arnaud; Crosby, Norma; Armone, Enrico
The four year "Coupling of Atmospheric Layers (CAL)" EU FP5 Research Training Network project studied unanswered questions related to transient luminous events (sprites, jets and elves) in the upper atmosphere. Consisting of ten scientific work-packages CAL also included intensive training and ou......, to develop their organisational skills, and to enhance their ability to communicate their activities. The campaign was a unique opportunity to train and strengthen skills that will be an asset to their future careers and, overall, was most successful....
De Vries, M.L.
This sludge stabilization blend plan documents the material to be processed and the order of processing for the FY95 Sludge Stabilization Campaign. The primary mission of this process is to reduce the inventory of unstable plutonium bearing sludge. The source of the sludge is residual and glovebox floor sweepings from the production of material at the Plutonium Finishing Plant (PFP). The reactive sludge is currently being stored in various gloveboxes at PFP. There are two types of the plutonium bearing material that will be thermally stabilized in the muffle furnace: Plutonium Reclamation Facility (PRF) sludge and Remote Mechanical C (RMC) Line material
Grant, J P
Growth monitoring charts, packets of oral rehydration salts (ORS), and vaccines, are inexpensive, life-saving, growth-protecting technologies which can enable parents to protect their children against the worst effects of poverty. Similarly, a matrix of current and easily understandable information about pregnancy, breast feeding, weaning, feeding during and immediately after illness, child spacing, and preparing and using home-made oral rehydration solutions, also could empower parents to protect the lives and the health of their children. The question arises as to how can these technologies and this information be put at the disposal of millions of families in the low-income world. The initial task of the Child Survival and Development Revolution is the communication of what is now possible, yet little is known about how to communicate information whose principal value is to the poor. There are 2 large-scale precedents: the Green Revolution, which in many instances succeeded in putting into the hands of thousands of small and large farmers the techniques and the knowledge which enabled them to double and treble the yields from their lands; and the campaign to put the knowledge and the means of family planning at the disposal of many millions of people. There are 2 lessons to be learned from these precedents: they have shown that the way to promote a people's technology and to put information at the disposal of the majority is by mobilizing all possible resources and working through all possible channels both to create the demand and to meet it; and neither the Green Revolution nor the family planning movement rally took off until they were viewed as political and economic priorities and given the full support of the nation's political leadership. Nowhere are these 2 lessons more clearly illustrated than in present-day Indonesia. Because the campaign for family planning was given high personal and political priority by the President, and because 85% of all family
Lyons, John D; Chen, Ching-Wen; Liang, Zhe; Zhang, Wenxiao; Chihade, Deena B; Burd, Eileen M; Farris, Alton B; Ford, Mandy L; Coopersmith, Craig
Patients with cancer who develop sepsis have a markedly higher mortality than patients who were healthy prior to the onset of sepsis. Potential mechanisms underlying this difference have previously been examined in two preclinical models of cancer followed by sepsis. Both pancreatic cancer/pneumonia and lung cancer/cecal ligation and puncture (CLP) increase murine mortality, associated with alterations in lymphocyte apoptosis and intestinal integrity. However, pancreatic cancer/pneumonia decreases lymphocyte apoptosis and increases gut apoptosis while lung cancer/CLP increases lymphocyte apoptosis and decreases intestinal proliferation. These results cannot distinguish the individual roles of cancer versus sepsis since different models of each were used. We therefore created a new cancer/sepsis model to standardize each variable. Mice were injected with a pancreatic cancer cell line and three weeks later cancer mice and healthy mice were subjected to CLP. Cancer septic mice had a significantly higher 10-day mortality than previously healthy septic mice. Cancer septic mice had increased CD4 T cells and CD8 T cells, associated with decreased CD4 T cell apoptosis 24 hours after CLP. Further, splenic CD8+ T cell activation was decreased in cancer septic mice. In contrast, no differences were noted in intestinal apoptosis, proliferation or permeability, nor were changes noted in local bacterial burden, renal, liver or pulmonary injury. Cancer septic mice thus have consistently reduced survival compared to previously healthy septic mice, independent of the cancer or sepsis model utilized. Changes in lymphocyte apoptosis are common to cancer model and independent of sepsis model whereas gut apoptosis is common to sepsis model and independent of cancer model. The host response to the combination of cancer and sepsis is dependent, at least in part, on both chronic co-morbidity and acute illness.
CHEN Hao; HE Ming-yan; LI Yu-min
Background Tradition treatment of sepsis and new therapies, including high dose corticosteroids and non-steroidal anti-inflammatory drugs, have proven unsuccessful in improving survival. This study aimed to evaluate the potential efficacy of immunomodulating therapy using Ulinastatin (UTI) plus Thymosin α1 (Tα1) for improving organ function and reducing mortality in patients with severe sepsis.Methods A prospective study was carried out with randomized and controlled clinical analysis of 114 patients conforming to the enrollment standard. All patients had severe sepsis and received standard supportive care and antimicrobial therapy. Fifty-nine patients were also administered UTI plus Tα1 (defined as Group A), 55 patients were given a placebo (defined as Group B). Clinical parameters were determined by evaluation with the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ), multiple organ failure (MOF) and the Glasgow Coma Scores (GCS) on entry and after therapy on the 3rd, 8th, and 28th day. By flow cytometery and ELISA lymphocyte subsets and cytokines were analyzed. Survival analysis was determined by the Kaplan-Meier method at 28, 60, and 90 days. Results Based on comparison of the two groups, patients in Group A exhibited a better performance in organ failure scores which was noticeable soon after initiation of treatment. Patients in Group A also demonstrated a better resolution of pre-existing organ failures during the observation period. After initiation of treatment, significant improvements in the CD4+/CD8+ ratio, a quicker balance between proinflammatory mediators such as tumor necrosis factor a, interleukin 6 and anti-inflammatory cytokines including interleukin 4 and interleukin 10 were found. This was followed by cumulative survival increases of 17.3% at 28 days, 28.9% at 60 days, and 31.4% at 90 days in Group A. The reduction in mortality was accompanied by a considerably shorter stay in the ICU and a shorter length of supportive
Bonet, Mercedes; Nogueira Pileggi, Vicky; Rijken, Marcus J; Coomarasamy, Arri; Lissauer, David; Souza, João Paulo; Gülmezoglu, Ahmet Metin
There is a need for a clear and actionable definition of maternal sepsis, in order to better assess the burden of this condition, trigger timely and effective treatment and allow comparisons across facilities and countries. The objective of this study was to review maternal sepsis definitions and identification criteria and to report on the results of an expert consultation to develop a new international definition of maternal sepsis. All original and review articles and WHO documents, as well as clinical guidelines providing definitions and/or identification criteria of maternal sepsis were included. A multidisciplinary international panel of experts was surveyed through an online consultation in March-April 2016 on their opinion on the existing sepsis definitions, including new definition of sepsis proposed for the adult population (2016 Third International Consensus Definitions for Sepsis and Septic Shock) and importance of different criteria for identification of maternal sepsis. The definition was agreed using an iterative process in an expert face-to-face consensus development meeting convened by WHO and Jhpiego. Standardizing the definition of maternal sepsis and aligning it with the current understanding of sepsis in the adult population was considered a mandatory step to improve the assessment of the burden of maternal sepsis by the expert panel. The literature review and expert consultation resulted in a new WHO consensus definition "Maternal sepsis is a life-threatening condition defined as organ dysfunction resulting from infection during pregnancy, child-birth, post-abortion, or post-partum period". Plans are in progress to validate the new WHO definition of maternal sepsis in a large international population. The operationalization of the new maternal sepsis definition requires generation of a set of practical criteria to identify women with sepsis. These criteria should enable clinicians to focus on the timely initiation of actionable elements of
Aragonés, Enriqueta; Postlewaite, Andrew
We analyze conditions under which a candidate's campaign rhetoric may affect the beliefs of the voters over what policy the candidate will implement in case he wins the election. We develop a model of repeated elections with complete information in which candidates are purely ideological. Voter's strategies involve a credible threat to punish candidates that renege of their campaign promises, and in equilibrium all campaign promises are believed by voters, and honore...
Olenick, Evelyn M; Zimbro, Kathie S; DʼLima, Gabrielle M; Ver Schneider, Patricia; Jones, Danielle
The Sepsis "Sniffer" Algorithm (SSA) has merit as a digital sepsis alert but should be considered an adjunct to versus an alternative for the Nurse Screening Tool (NST), given lower specificity and positive predictive value. The SSA reduced the risk of incorrectly categorizing patients at low risk for sepsis, detected sepsis high risk in half the time, and reduced redundant NST screens by 70% and manual screening hours by 64% to 72%. Preserving nurse hours expended on manual sepsis alerts may translate into time directed toward other patient priorities.
Javadi, Pardis; Buchman, Timothy G; Stromberg, Paul E; Turnbull, Isaiah R; Vyas, Dinesh; Hotchkiss, Richard S; Karl, Irene E; Coopersmith, Craig M
Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels. Hfe-/- mice (a murine homologue of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24-26 months) or mature (16-18 months) Hfe-/- mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 h later and assessed for apoptosis and cytokine levels. Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe-/- mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe-/- mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe-/- mice than septic mature Hfe-/- animals. Interleukin-6 was elevated in septic aged Hfe-/- mice compared to sham mice. Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe-/- mice are able to mount an inflammatory response following CLP and mature Hfe-/- mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation.
Aso Omer Rashid
Conclusion: DM, staghorn stones, degree of hydronephrosis, duration of the operation and number of tracts are risk factors for post PCNL fever, while number of stones, intraoperative blood loss, duration of the operation and residual stones are risk factors for post PCNL sepsis.
Schröttner, Percy; Heidrich, Katharina; Rudolph, Wolfram W; Stölzel, Friedrich; Jacobs, Enno; Gunzer, Florian
We report on a 62 year old patient who developed sepsis due to an infection caused by Porphyromonas pogonae, a recently described species of the bacterial genus Porphyromonas. This is the first case of an invasive infection with this pathogen. Copyright © 2017 Elsevier Ltd. All rights reserved.
Alebouyeh, M; Gooran Orimi, P; Azimi-rad, M; Tajbakhsh, M; Tajeddin, E; Jahani Sherafat, S; Nazemalhosseini mojarad, E; Zali, MR
An immunosuppressed man was admitted to hospital with diarrhea and a history of urinary tract infection. He was subjected to treatment with antibiotics. The patient died of putative severe sepsis. The etiological agent was a carbapenemase producing isolate of Bacillus circulans with resistance to all prescribed antimicrobial agents.
Adib, Minoo; Bakhshiani, Zahra; Navaei, Fakhri; Saheb Fosoul, Fereshteh; Fouladi, Salomeh; Kazemzadeh, Hamidreza
Objective(s) In the last few years, serum procalcitonin has been proposed as an early marker of infections in neonates, with varying results. In this study, we aimed to investigate the value of procalcitonin, and C- reactive protein in establishing the diagnosis of neonatal sepsis. Materials and Methods Blood samples were collected at admission from 69 neonates with suspected infection (admitted to the Neonatal Intensive Care Units at Alzahra and Dr Beheshti Hospital in and Fatema-Zahra in Najafabad from May 2005 to April 2006). Patients were categorized in different groups according to clinical symptoms of sepsis, bacteriological and laboratory results. Group I consisted of 20 newborns with positive blood cultures and other biological tests which suggested infection. Group II consisted of 49 neonates with negative blood cultures but had two or three of clinical signs of sepsis. The control group included 18 healthy neonates with physiological hyperbilirubinemia and no clinical and biological data of infection, referred to the hospital for bilirubin determination. Procalcitonin and C-reactive protein (CRP) were determined by immunoluminometric assay and nephlometry method respectively. Results Mean levels of procalcitonin and CRP in septic neonates (group I) were significantly higher than the other two groups (P< 0.005). Sensitivity, specificity, positive predictive value and negative predictive value were determined for all markers and compared with each other. Conclusion We conclude that procalcitonin is a better marker than CRP in the diagnosis of neonatal sepsis. PMID:23493845
Zhang, Zhibo; Huang, Ying; Wang, Dajia; Su, Pengjun
Tubular rectal duplication is a very rare congenital anomaly. We report a case of tubular rectal duplication in a newborn baby who presented with perianal sepsis. The diagnosis was confirmed by barium enema, magnetic resonance imaging, and at operation. We performed total mucosectomy through a posterior sagittal incision combined with laparotomy. The patient was doing quite well at 17-month follow-up examination.
Rosalina D Roeslani
Kesimpulan.Pada neonatus yang lahir di RSCM Jakarta apabila terdapat faktor risiko prematur (usia gestasi <37 minggu, dan atau nilai APGAR rendah maka harus dilakukan skrining sepsis, pemantauan ketat terhadap timbulnya SNAD, bila melakukan tindakan intervensif maka harus dengan tindakan septik-antiseptik yang ideal,serta pemberian antibiotik empiris dapat dipertimbangkan.
O. M. Shevtsova
Full Text Available Objective: to evaluate the efficiency of extracorporeal detoxification techniques in patients with abdominal sepsis. Subjects and methods. Three hundred and seventy-nine patients with acute generalized peritonitis were examined. Extracorporeal detoxifying techniques were used during conventional therapy in Group 1 (n=319; the other patients received only traditional therapy (a control group. The time course of changes in the parameters of toxemia, a hemostasiogram, and an immunogram were examined. Results. The study indicated significantly reduced endotoxemia and better blood aggregation resulting from the use of plasmapheresis, cryoplasmasorption, and plasmasorption, as well as stimulated immunity when the above techniques were combined with autoblood photomodification and extracorporeal immunopharmacotherapy in patients with abdominal sepsis. In severe abdominal sepsis and infectious-toxic shock, there was regression of multiple organ dysfunction and lower mortality when venovenous hemofiltration was applied. Conclusion. A differential approach to using active detoxifying techniques is needed, by taking into account the severity of the disease. Key words: abdominal sepsis, detoxifying techniques.
Full Text Available Authors report a fatal neonatal sepsis caused by Listeria monocytogenes. While the diagnostic procedure aimed to identify the microrganism is described, it is emphasized the importance to recover Streptococcus agalactiae (GBS and L. monocytogenes by means of vaginal-rectal swab culture. The intrapartum screening for L. monocytogenes, by Polymerase Chain Reaction (PCR providing results in 75 minutes is also evaluated.
of 3.5 to 8 cases per 1,000 live births; and mortality rate 16 to 30%. Cytokines, produced by ... 40 weeks with a picture of early onset neonatal sepsis within 48 hours of life admitted to neonatal ..... Infect Dis J 2000;19 (9):879-87. 5. Gonzalez BE ...
Wynn, James L; Wong, Hector R; Shanley, Thomas P; Bizzarro, Matthew J; Saiman, Lisa; Polin, Richard A
To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. The review focused primarily on pediatric literature relevant to the topic of interest. Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates.
Cribbs, Sushma K; Matthay, Michael A; Martin, Greg S
Sepsis and acute lung injury continue to be major causes of morbidity and mortality worldwide despite advances in our understanding of pathophysiology and the discovery of new management strategies. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the potential use of endogenous adult tissue-derived stem cells in sepsis and acute lung injury as prognostic markers and also as exogenous cell-based therapy. A directed systematic search of the medical literature using PubMed and OVID, with particular emphasis on the time period after 2002, was done to evaluate topics related to 1) the epidemiology and pathophysiology of sepsis and acute lung injury; and 2) the definition, characterization, and potential use of stem cells in these diseases. DATA SYNTHESIS AND FINDINGS: When available, preferential consideration was given to prospective nonrandomized clinical and preclinical studies. Stem cells have shown significant promise in the field of critical care both for 1) prognostic value and 2) treatment strategies. Although several recent studies have identified the potential benefit of stem cells in sepsis and acute lung injury, further investigations are needed to more completely understand stem cells and their potential prognostic and therapeutic value.
Introduction: Neonatal sepsis is a major cause of mortality in developing countries. Accurate and quick diagnosis are difficult because clinical presentation are non-specific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. Serum procalcitonin (PCT) has been proposed as an ...
This is a report on a case of neonatal sepsis and clinical management with multiple antibiotic therapy in a neonatal intensive care unit (NICU) in Brazil. A preterm baby boy was born by caesarean section at. 34 weeks and two days of gestation from an oligodramnious pregnancy with intrauterine growth restriction.
Kalbitz, Miriam; Grailer, Jamison J; Fattahi, Fatemeh; Jajou, Lawrence; Herron, Todd J; Campbell, Katherine F; Zetoune, Firas S; Bosmann, Markus; Sarma, J Vidya; Huber-Lang, Markus; Gebhard, Florian; Loaiza, Randall; Valdivia, Hector H; Jalife, José; Russell, Mark W; Ward, Peter A
The purpose of this study was to define the relationship in polymicrobial sepsis (in adult male C57BL/6 mice) between heart dysfunction and the appearance in plasma of extracellular histones. Procedures included induction of sepsis by cecal ligation and puncture and measurement of heart function using echocardiogram/Doppler parameters. We assessed the ability of histones to cause disequilibrium in the redox status and intracellular [Ca(2+)]i levels in cardiomyocytes (CMs) (from mice and rats). We also studied the ability of histones to disturb both functional and electrical responses of hearts perfused with histones. Main findings revealed that extracellular histones appearing in septic plasma required C5a receptors, polymorphonuclear leukocytes (PMNs), and the Nacht-, LRR-, and PYD-domains-containing protein 3 (NLRP3) inflammasome. In vitro exposure of CMs to histones caused loss of homeostasis of the redox system and in [Ca(2+)]i, as well as defects in mitochondrial function. Perfusion of hearts with histones caused electrical and functional dysfunction. Finally, in vivo neutralization of histones in septic mice markedly reduced the parameters of heart dysfunction. Histones caused dysfunction in hearts during polymicrobial sepsis. These events could be attenuated by histone neutralization, suggesting that histones may be targets in the setting of sepsis to reduce cardiac dysfunction. © FASEB.
Ibrahim, Hiba; Barrow, Paul; Foster, Neil
Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.
Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...
Neonatal Septicaemia (NNS) remains an important cause of morbidity and mortality in Nigeria. This prospective cross- sectional study was carried out to determine the relationship between exclusive breastfeeding and incidence and outcome of neonatal sepsis in population of Nigerian newborns. Subjects were babies ...
The Resistable Rise of Surgical Sepsis in Malawi. C Lavy, C Schmidt, E Kalau, J Phuka. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about ...
To determine the commonest organism cultured from the blood of children suspected to have bacterial sepsis and their antibiogram sensitivity using the commonly used antibiotics in a private practice and see if there are differences from established data from other areas. Children beyond neonatal age presenting to a ...
Toft, P; Lillevang, S T; Tønnesen, Else Kirstine
Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes...
Salmonella sepsis in African children. SM Graham. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's ...
Background: Puerperal sepsis is a common pregnancy related complication and is one of the leading causes of maternal morbidity and mortality in Sub Saharan Africa. There is paucity of regional data on the antibiogram and risk factors associated with this condition, Aim: To determine the risk factors, aetiological organisms ...
Waheed, M.; Laeeq, A.; Maqbool, S.
Objective: To study the patterns of causative bacteria and antibiotic resistance in neonatal sepsis. Results: Among 228 cases included in the study, the male to female ratio was 2.1 to 1. The gestational age was less than 36 weeks in 68 (30%) cases and low birth weight babies were 143 (62.6%). History of birth asphyxia was present in 103 (45%) cases. There were 142 (62.3%) cases of early onset ( 7 days). Out of 233 positive blood cultures Escherichia coli was found to be commonest (47.8%, n =111, p<0.05) both in early onset (47.8%, n=68, p <0.05) and late onset sepsis (47.3%,n=43, p<0.05). Staphylococcus aureus was the most common among gram positive organism. Resistance to cefotaxime, ceftazidime and amikacin was 34% to 80% and to ciprofloxacin 13% to 72%. A total of 64 cases (28%) died. Mortality was four times higher in early onset sespis. Conclusion: Gram negative bacteria are the commenst cause of neonatal sepsis. The resistance to the commonly used antibiotics is alarmingly high. Mortality is four times higher in early one set sepsis. (author)
Background and objectives. Delayed presentation of haematogenous bone and joint sepsis is common in our childhood population and leads to a large burden of avoidable morbidity extending into adult life. We set out to determine causative factors in these delays. Design. A prospective study was undertaken over a 1- ...
Bowton, D.L.; Bertels, N.H.; Prough, D.S.; Stump, D.A.
The relationship between sepsis-induced CNS dysfunction and changes in brain blood flow remains unknown, and animal studies examining the influence of sepsis on cerebral blood flow (CBF) do not satisfactorily address that relationship. We measured CBF and cerebrovascular reactivity to CO 2 in nine patients with sepsis syndrome using the 133 Xe clearance technique. Mean CBF was 29.6 +/- 15.8 (SD) ml/100 g.min, significantly lower than the normal age-matched value in this laboratory of 44.9 +/- 6.2 ml/100 g.min (p less than .02). This depression did not correlate with changes in mean arterial pressure. Despite the reduction in CBF, the specific reactivity of the cerebral vasculature to changes in CO 2 was normal, 1.3 +/- 0.9 ml/100 g.min/mm Hg. Brain blood flow is reduced in septic humans; the contribution of this reduction to the metabolic and functional changes observed in sepsis requires further study
Diana González Rangel
Conclusión. La procalcitonina tiene un buen rendimiento diagnóstico como marcador de sepsis en niños —con mayor utilidad cuando toma valores negativos— y buen valor pronóstico al relacionarse con mortalidad.
Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C
Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation. ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2
Kofoed, Kristian; Schneider, Uffe Vest; Scheel, Troels
Sepsis is a common and often fatal disease. Because sepsis can be caused by many different organisms, biomarkers that can aid in diagnosing sepsis and monitoring treatment efficacy are highly warranted. New sepsis markers may provide additional information to complement the currently used markers....
McCoy, R. P.; Bristow, W. A.; Fallen, C. T.
Experiments in HF ionospheric heating using the Highfrequency Active Auroral Research Program (HAARP) facilities have tremendous potential for informing our investigation of the Earth's upper atmosphere, ionosphere, and magnetosphere. They provide a unique opportunity for quantifying and modeling the multiscale coupled processes that characterize the interactions between the plasma in nearEarth space, the Earth's magnetic field, and the neutral gasses of the atmosphere. Physical parameters of the region are often difficult to measure with groundbased instruments, and the measurements that are possible are often poorly resolved in range or time or unavailable outside narrow altitude regimes. HF ionospheric modification experiments allow us to measure ionospheric and thermospheric state parameters more systematically and over a broader range of conditions than would otherwise be possible. HAARP is the world's most powerful and most flexible HF transmitting facility, capable of generating 3.6 MW of RF power over a frequency range from about 2 MHz to about 10 MHz. The electronic phased array antenna provides the ability to direct the RF energy to a large region of the sky above Alaska. HAARP was constructed through a research program managed by the Air Force Research Laboratory (AFRL), and the Office of Naval Research (ONR). It was jointly funded by AFRL, ONR, and the Defense Advanced Projects Research Agency (DARPA). These agencies ended of their program of HAARP research in 2014, and donated the site equipment to the University of Alaska, Fairbanks (UAF), in the summer of 2015, who now operate the facility as an international observatory for radio plasma heating and subauroral physics. Since taking control of HAARP, UAF has carried out research campaigns in February 2017, and September 2017. The topics investigated in the campaigns included the physics of ionospheric irregularities (FAI), the stimulated electromagnetic emissions (SEE), generation of optical
Full Text Available Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called “cytopathic hypoxia,” perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs. In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system (“immunoparalysis” translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.
Breen, Sarah-Jane; Rees, Sharon
To identify the barriers to implementation of the Sepsis Six pathway. Research has suggested that compliance with the Sepsis Six pathway remains low. A convenience sample of doctors and nurses from one emergency department, two medical wards and two surgical wards were asked to complete a survey questionnaire. Data from 108 respondents were available for analysis. Doctors and nurses agreed that lack of sepsis recognition during observation rounds and failure to associate sepsis with deranged temperature and blood results acted as barriers to the identification of sepsis. Doctors and nurses agreed that nursing delays and knowledge deficits were the top barriers leading to delay in sepsis treatment. Knowledge deficits, lack of resources and practical issues were barriers identified in this survey. This will inform the educational and process needs of both doctors and nurses in order to improve sepsis care.
Hjortrup, Peter Buhl; Haase, Nicolai; Wetterslev, Jørn
PURPOSE: Fluid resuscitation is a key intervention in patients with sepsis and circulatory impairment. The recommendations for continued fluid therapy in sepsis are vague, which may result in differences in clinical practice. We aimed to evaluate associations between hospital and patient characte....... The data indicate variations in clinical practice not explained by patient characteristics emphasizing the need for RCTs assessing fluid resuscitation volumes fluid in patients with sepsis.......PURPOSE: Fluid resuscitation is a key intervention in patients with sepsis and circulatory impairment. The recommendations for continued fluid therapy in sepsis are vague, which may result in differences in clinical practice. We aimed to evaluate associations between hospital and patient...... characteristics and fluid resuscitation volumes in ICU patients with severe sepsis. METHODS: We explored the 6S trial database of ICU patients with severe sepsis needing fluid resuscitation randomised to hydroxyethyl starch 130/0.42 vs. Ringer's acetate. Our primary outcome measure was fluid resuscitation volume...
Vallone, Donna M; Ilakkuvan, Vinu; Xiao, Haijun; Cantrell, Jennifer; Rath, Jessica; Hair, Elizabeth
Mass media campaigns have been found to shape the public's knowledge, attitudes, beliefs, and behavior around tobacco. This study examines the influence of contextual factors with respect to awareness of the national truth® campaign, a mass media, branded tobacco use prevention campaign, among a sample of young adults (n = 2,804) aged 24-34 years old; these respondents were within the age range for both the primary and secondary targets of the campaign during the period (2000-2007) when the campaign was airing television advertising at consistently high levels. Mulitvariable models reveal lower educational attainment and Hispanic ethnicity as significant contextual factors predictive of lower campaign awareness, controlling for media use. In contrast, gender, state tobacco control policy, sensation-seeking, current smoking status, and community-level SES variables were not significantly associated with campaign awareness. Further research is needed to identify the mechanisms through which public education campaigns operate, particularly among disadvantaged communities.
Levy, Michaël; Le Sache, Nolwenn; Mokhtari, Mostafa; Fagherazzi, Guy; Cuzon, Gaelle; Bueno, Benjamin; Fouquet, Virginie; Benachi, Alexandra; Eleni Dit Trolli, Sergio; Tissieres, Pierre
Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly and remains among the most challenging ICU-managed disease. Beside severe pulmonary hypertension, lung hypoplasia and major abdominal surgery, infective complications remain major determinants of outcome. However, the specific incidence of sepsis as well as associated risk factors is unknown. This prospective, 4-year observational study took place in the pediatric intensive care and neonatal medicine department of the Paris South University Hospitals (Le Kremlin-Bicêtre, France), CDH national referral center and involved 62 neonates with CDH. During their ICU stay, 28 patients (45%) developed 38 sepsis episodes. Ventilator-associated pneumonia (VAP: 23/38; 31.9 VAP per 1000 days of mechanical ventilation) and central line-associated blood stream infections (CLABSI: 5/38; 5.5 per 1000 line days) were the most frequently encountered infections. Multivariate analysis showed that gestational age at birth and intra-thoracic position of liver were significantly associated with the occurrence of sepsis. Infected patients had longer duration of mechanical and noninvasive ventilation (16.2 and 5.8 days, respectively), longer delay to first feeding (1.2 days) and a longer length of stay in ICU (23 days), but there was no difference in mortality. Healthcare-associated infections, and more specifically VAP, are the main infective threat in children with CDH. Sepsis has a significant impact on the duration of ventilator support and ICU length of stay but does not impact mortality. Low gestational age and intra-thoracic localization of the liver are two independent risk factors associated with sepsis.
Khilnani, Praveen; Singhi, Sunit; Lodha, Rakesh; Santhanam, Indumathi; Sachdev, Anil; Chugh, Krishan; Jaishree, M.; Ranjit, Suchitra; Ramachandran, Bala; Ali, Uma; Udani, Soonu; Uttam, Rajiv; Deopujari, Satish
Justification: Pediatric sepsis is a commonly encountered global issue. Existing guidelines for sepsis seem to be applicable to the developed countries, and only few articles are published regarding application of these guidelines in the developing countries, especially in resource-limited countries such as India and Africa. Process: An expert representative panel drawn from all over India, under aegis of Intensive Care Chapter of Indian Academy of Pediatrics (IAP) met to discuss and draw guidelines for clinical practice and feasibility of delivery of care in the early hours in pediatric patient with sepsis, keeping in view unique patient population and limited availability of equipment and resources. Discussion included issues such as sepsis definitions, rapid cardiopulmonary assessment, feasibility of early aggressive fluid therapy, inotropic support, corticosteriod therapy, early endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, glycemic control, and role of immunoglobulin, blood, and blood products. Objective: To achieve a reasonable evidence-based consensus on the basis of published literature and expert opinion to formulating clinical practice guidelines applicable to resource-limited countries such as India. Recommendations: Pediatric sepsis guidelines are presented in text and flow chart format keeping resource limitations in mind for countries such as India and Africa. Levels of evidence are indicated wherever applicable. It is anticipated that once the guidelines are used and outcomes data evaluated, further modifications will be necessary. It is planned to periodically review and revise these guidelines every 3–5 years as new body of evidence accumulates. PMID:20606908
Four aims are included in the Draft Declaration about the Champaign for The Biosphere; 1) education and allied activities, 2) scientific understanding, 3) practical activities, and 4) accommodation of humanity to The Biosphere. There is a strong case for application to practical affairs of what is already known. The campaign might focus initially on problems that illustrate changing attitudes which are the result of research and experience. Examples include the Green revolution in agriculture and, in engineering, the swing of changing attitudes to the primary and ancillary effects of large projects for hydro-power and irrigation. The need for conservation of natural resources by rational, ecologically wise use is stressed. Educational and medical programs for planned parenthood are already available. The problem will be to boost them to top priority in the countries that need them most. (JMT)
The purpose of the Advanced Fuels Campaign (AFC) Execution Plan is to communicate the structure and management of research, development, and demonstration (RD&D) activities within the Fuel Cycle Research and Development (FCRD) program. Included in this document is an overview of the FCRD program, a description of the difference between revolutionary and evolutionary approaches to nuclear fuel development, the meaning of science-based development of nuclear fuels, and the “Grand Challenge” for the AFC that would, if achieved, provide a transformational technology to the nuclear industry in the form of a high performance, high reliability nuclear fuel system. The activities that will be conducted by the AFC to achieve success towards this grand challenge are described and the goals and milestones over the next 20 to 40 year period of research and development are established.
The purpose of the Advanced Fuels Campaign (AFC) Execution Plan is to communicate the structure and management of research, development, and demonstration (RD&D) activities within the Fuel Cycle Research and Development (FCRD) program. Included in this document is an overview of the FCRD program, a description of the difference between revolutionary and evolutionary approaches to nuclear fuel development, the meaning of science-based development of nuclear fuels, and the 'Grand Challenge' for the AFC that would, if achieved, provide a transformational technology to the nuclear industry in the form of a high performance, high reliability nuclear fuel system. The activities that will be conducted by the AFC to achieve success towards this grand challenge are described and the goals and milestones over the next 20 to 40 year period of research and development are established.
Full Text Available Abstract Background Patients with sepsis syndromes in comparison to general intensive care patients can have worse outcomes for physical function, quality of life and survival. Early intensive care rehabilitation can improve the outcome in general Intensive Care Unit (ICU patients, however no investigations have specifically looked at patients with sepsis syndromes. The 'i-PERFORM Trial' will investigate if early targeted rehabilitation is both safe and effective in patients with sepsis syndromes admitted to ICU. Methods/Design A single-centred blinded randomized controlled trial will be conducted in Brisbane, Australia. Participants (n = 252 will include those ≥ 18 years, mechanically ventilated for ≥ 48 hours and diagnosed with a sepsis syndrome. Participants will be randomised to an intervention arm which will undergo an early targeted rehabilitation program according to the level of arousal, strength and cardiovascular stability and a control group which will receive normal care. The primary outcome measures will be physical function tests on discharge from ICU (The Acute Care Index of Function and The Physical Function ICU Test. Health-related quality of life will be measured using the Short Form-36 and the psychological component will be tested using The Hospital Anxiety and Depression Scale. Secondary measures will include inflammatory biomarkers; Interleukin-6, Interleukin-10 and Tumour Necrosis Factor-α, peripheral blood mitochondrial DNA content and lactate, fat free muscle mass, tissue oxygenation and microcirculatory flow. Discussion The 'i-PERFORM Trial' will determine whether early rehabilitation for patients with sepsis is effective at improving patient outcomes with functional and physiological parameters reflecting long and short-term effects of early exercise and the safety in its application in critical illness. Trial Registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12610000808044
Dominguez, Jessica A.; Xie, Yan; Dunne, W. Michael; Yoseph, Benyam P.; Burd, Eileen M.; Coopersmith, Craig M.; Davidson, Nicholas O.
Background The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the “motor” of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO), which exhibit a block in chylomicron assembly together with lipid malabsorption. Methodology/Principal Findings Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%) dying compared to 5/17 (29%) control mice (p<0.05). This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL) levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice. Conclusions/Significance These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by
Jessica A Dominguez
Full Text Available The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the "motor" of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO, which exhibit a block in chylomicron assembly together with lipid malabsorption.Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0% dying compared to 5/17 (29% control mice (p<0.05. This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice.These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by metabolic and physiological adaptations in both intestinal and
Septimus, Edward J; Coopersmith, Craig M; Whittle, Jessica; Hale, Caleb P; Fishman, Neil O; Kim, Thomas J
The Center for Medicare and Medicaid Services adopted the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital Inpatient Quality Reporting Program in July 2015 to help address the high mortality and high cost associated with sepsis. The SEP-1 performance measure requires, among other critical interventions, timely administration of antibiotics to patients with sepsis or septic shock. The multistakeholder workgroup recognizes the need for SEP-1 but strongly believes that multiple antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the use of these antibiotics, as called for in the SEP-1 measure, is not in alignment with prudent antimicrobial stewardship. To promote the appropriate use of antimicrobials and combat antimicrobial resistance, the workgroup provides recommendations for appropriate antibiotics for the treatment of sepsis. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: email@example.com.
Full Text Available Electrical vagus nerve (VN stimulation during sepsis attenuates tumor necrosis factor (TNF production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36 on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP. The septic rats were subsequently treated with EA-ST36 (CLP+ST36, and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P<0.05, and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms.
Holmberg, K.; Hellsten, I.
In this article, we analyzed campaigning on Twitter around the publication of the fifth Intergovernmental Panel for Climate Change (IPCC) Working Group 1 report in September, 2013. In particular, we analyzed how participation in a specific campaign and use of hashtags connected to the campaign
... 11 Federal Elections 1 2010-01-01 2010-01-01 false Allocation of expenses between campaign and non-campaign related travel. 106.3 Section 106.3 Federal Elections FEDERAL ELECTION COMMISSION GENERAL ALLOCATIONS OF CANDIDATE AND COMMITTEE ACTIVITIES § 106.3 Allocation of expenses between campaign and non...
Ranzani, Otavio T; Prina, Elena; Menéndez, Rosario; Ceccato, Adrian; Cilloniz, Catia; Méndez, Raul; Gabarrus, Albert; Barbeta, Enric; Bassi, Gianluigi Li; Ferrer, Miquel; Torres, Antoni
The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown. To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia. This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality. Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the "treat-all" strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality. qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile.
Kangozhinova, Kalamkas; Abentayeva, Botakoz; Repa, Andreas; Baltabayeva, Assem; Erwa, Wolfgang; Stauffer, Friedrich
Newborn sepsis is one of the major public health concerns worldwide. Also in our neonatal care unit, it is one of the major problems and especially infections with Enterobacteriaceae were noted to pose an increasing problem in the last years. Data collection was done retrospectively for 2011. Early onset sepsis was defined as having a positive blood culture within 72 h and late onset sepsis after 72 h of delivery. Out of 599 patients being admitted, 58 newborns were assessed having a neonatal sepsis. Of these 58 newborns with sepsis, 11 were diagnosed within 72 h post delivery (early onset) and 47 were diagnosed after 72 h post delivery (late onset). The percentage of Enterobacteriaceae causing late onset sepsis was 57.5 %. Among these, Klebsiella pneumoniae could be isolated in 29.8 %, Enterobacter cloacae in 12.8 %, Enterobacter aerogenes in 8.5 %, and Escherichia coli in 6.4 % of late onset sepsis. Majority of the strains showed a resistance to antibiotics used in empiric treatment. Antibiotic prophylaxis/treatment from birth until the onset of late onset sepsis could be analyzed in 20 out of 27 newborns with late onset sepsis caused by Enterobacteriaceae. A regimen of empirical antibiotic treatment containing aminopenicillin and/or gentamicin was administered in 16 newborns and that of cephalosporin in 14 out of 20 newborns for at least 5 days before onset of sepsis. The association of empiric long-term antibiotic treatment and the high number of late onset sepsis with often multiresistant Enterobacteriaceae might be causal and urges for a change in general antibiotic prophylaxis/treatment in newborns admitted to the neonatal care unit of our hospital.
Worley, Debra A.
Argues for a Campaign Planning Course in the undergraduate public relations major. Discusses nine course objectives. Describes five phases of campaign planning and implementation, how the phase approach includes important course topics, and how it fulfills course objectives. Describes how student groups work with actual clients throughout the…