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Sample records for sepsis outcome acute

  1. Post–Acute Care Use and Hospital Readmission after Sepsis

    PubMed Central

    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.

    2015-01-01

    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 < 0.001), with the highest rate observed after severe sepsis. Readmission rates at 7, 30, and 90 days were higher postsepsis (P < 0.001). Compared with nonsepsis hospitalizations (15.6% readmitted within 30 d), the increased readmission risk was present regardless of sepsis severity (27.3% after sepsis and 26.0–26.2% after severe sepsis). After controlling for presepsis characteristics, the readmission risk was found to be 1.51 times greater (95% CI, 1.38–1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more likely to result in death or transition to hospice care (6.1% vs. 13.3% after sepsis; P < 0.001). Independent risk factors associated with 30-day readmissions after sepsis hospitalizations included age, malignancy diagnosis, hospitalizations in the year prior to the index hospitalization, nonelective index admission type, one or more procedures during the index hospitalization, and low hemoglobin and high red cell distribution width at discharge. 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

  2. The Coagulopathy of Acute Sepsis

    PubMed Central

    Simmons, Jeff; Pittet, Jean-Francois

    2015-01-01

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

  3. Sepsis and Acute Respiratory Distress Syndrome: Recent Update

    PubMed Central

    Kim, Won-Young

    2016-01-01

    Severe sepsis or septic shock is characterized by an excessive inflammatory response to infectious pathogens. Acute respiratory distress syndrome (ARDS) is a devastating complication of severe sepsis, from which patients have high mortality. Advances in treatment modalities including lung protective ventilation, prone positioning, use of neuromuscular blockade, and extracorporeal membrane oxygenation, have improved the outcome over recent decades, nevertheless, the mortality rate still remains high. Timely treatment of underlying sepsis and early identification of patients at risk of ARDS can help to decrease its development. In addition, further studies are needed regarding pathogenesis and novel therapies in order to show promising future treatments of sepsis-induced ARDS. PMID:27066082

  4. Sepsis-Associated Acute Kidney Injury

    PubMed Central

    Alobaidi, Rashid; Basu, Rajit K.; Goldstein, Stuart L.; Bagshaw, Sean M.

    2015-01-01

    Summary Acute kidney injury (AKI) is an epidemic problem. Sepsis has long been recognized as a foremost precipitant of AKI. Sepsis-associated AKI (SA-AKI) portends a high burden of morbidity and mortality in both children and adults with critical illness. Although our understanding of its pathophysiology is incomplete, SA-AKI likely represents a distinct subset of AKI contributed to by a unique constellation of hemodynamic, inflammatory, and immune mechanisms. SA-AKI poses significant clinical challenges for clinicians. To date, no singular effective therapy has been developed to alter the natural history of SA-AKI. Rather, current strategies to alleviate poor outcomes focus on clinical risk identification, early detection of injury, modifying clinician behavior to avoid harm, early appropriate antimicrobial therapy, and surveillance among survivors for the longer-term sequelae of kidney damage. Recent evidence has confirmed that patients no longer die with AKI, but from AKI. To improve the care and outcomes for sufferers of SA-AKI, clinicians need a robust appreciation for its epidemiology and current best-evidence strategies for prevention and treatment. PMID:25795495

  5. Improving management of severe sepsis and uptake of sepsis resuscitation bundle in an acute setting

    PubMed Central

    Kafle, Sumitra; Nath, Navdeep

    2014-01-01

    Severe sepsis still remains a major cause of morbidity and mortality, claiming between 36,000 to 64,000 lives annually in the UK, with a mortality rate of 35%.[1,2] The project aims to measure the management of severely septic patients in acute medical unit (AMU) in a district general hospital against best practice guidelines, before and after a set of interventions aiming to optimise patient management and outcomes. All new admissions who met the criteria for sepsis in AMU over a two week period were evaluated. Those who met the criteria for severe sepsis were further analysed. The criteria evaluated were time to first administration of oxygen, intravenous fluids, antibiotics, the taking of blood cultures, other relevant bloods tests (including lactate) and urine output monitoring. A re-audit was completed after the introduction of a set of interventions which included a “sepsis box.” A total of 32 patients (19 Males, 13 Females) were identified in the pre-intervention group. Twenty-two of these patients met the criteria for severe sepsis. Only 15 out of 32 (47%) had their lactate measured. Ten out of 22 (45%) received fluids within an hour. Twelve out of 22 (55%) had their blood culture sample taken after administration of antibiotics and only 12 out of 22 (55%) had antibiotics administrated within an hour of medical assessment. Post-intervention the results however improved dramatically. A total of 30 patients were identified in the post-intervention group (12 Males, 18 Females). Antibiotics administration within an hour went up by 22%. Lactate was performed in 26/30 (87%) patients presented with sepsis compared to 47% in the pre-intervention group. Similarly, identification of severe sepsis, and administration of intravenous fluids also showed improvement ultimately improving patient safety. Following the initial success, the trial was repeated over three months period, which showed sustainable improvement. PMID:26734299

  6. Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis.

    PubMed

    Osuchowski, Marcin F; Craciun, Florin; Weixelbaumer, Katrin M; Duffy, Elizabeth R; Remick, Daniel G

    2012-11-01

    The paradigm of systemic inflammatory response syndrome-to-compensatory anti-inflammatory response syndrome transition implies that hyperinflammation triggers acute sepsis mortality, whereas hypoinflammation (release of anti-inflammatory cytokines) in late sepsis induces chronic deaths. However, the exact humoral inflammatory mechanisms attributable to sepsis outcomes remain elusive. In the first part of this study, we characterized the systemic dynamics of the chronic inflammation in dying (DIE) and surviving (SUR) mice suffering from cecal ligation and puncture sepsis (days 6-28). In the second part, we combined the current chronic and previous acute/chronic sepsis data to compare the outcome-dependent inflammatory signatures between these two phases. A composite cytokine score (CCS) was calculated to compare global inflammatory responses. Mice were never sacrificed but were sampled daily (20 μl) for blood. In the first part of the study, parameters from chronic DIE mice were clustered into the 72, 48, and 24 h before death time points and compared with SUR of the same post-cecal ligation and puncture day. Cytokine increases were mixed and never preceded chronic deaths earlier than 48 h (3- to 180-fold increase). CCS demonstrated simultaneous and similar upregulation of proinflammatory and anti-inflammatory compartments at 24 h before chronic death (DIE 80- and 50-fold higher versus SUR). In the second part of the study, cytokine ratios across sepsis phases/outcomes indicated steady proinflammatory versus anti-inflammatory balance. CCS showed the inflammatory response in chronic DIE was 5-fold lower than acute DIE mice, but identical to acute SUR. The systemic mixed anti-inflammatory response syndrome-like pattern (concurrent release of proinflammatory and anti-inflammatory cytokines) occurs irrespective of the sepsis phase, response magnitude, and/or outcome. Although different in magnitude, neither acute nor chronic septic mortality is associated with a

  7. Sepsis.

    PubMed

    Dean, Erin

    2016-09-01

    Essential facts [Figure: see text] Sepsis, a clinical syndrome caused by the body's immune and coagulation systems being switched on by an infection, is believed to cause about 44,000 deaths a year. If not recognised early and treated promptly, sepsis can lead to shock, multiple organ failure and death. Major reports (UK parliamentary and health service ombudsman enquiry in 2013 and the UK National Confidential Enquiry into Patient Outcome and Death in 2015) have highlighted sepsis as being a leading cause of avoidable death that kills more people than breast, bowel and prostate cancer combined. PMID:27615338

  8. Sepsis.

    PubMed

    Dean, Erin

    2016-09-01

    Essential facts Sepsis, a clinical syndrome caused by the body's immune and coagulation systems being switched on by an infection, is believed to cause about 44,000 deaths a year. If not recognised early and treated promptly, sepsis can lead to shock, multiple organ failure and death. Major reports (UK parliamentary and health service ombudsman enquiry in 2013 and the UK National Confidential Enquiry into Patient Outcome and Death in 2015) have highlighted sepsis as being a leading cause of avoidable death that kills more people than breast, bowel and prostate cancer combined. PMID:27581906

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

    PubMed Central

    Bodkin, Jennifer Victoria; Fernandes, Elizabeth Soares

    2013-01-01

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

  10. Acute Placental Villitis as Evidence of Fetal Sepsis: An Autopsy Case Report.

    PubMed

    Bae, Go Eun; Yoon, Nara; Choi, Misun; Hwang, Soohyun; Hwang, Hyewon; Kim, Jung-Sun

    2016-01-01

    Acute placental villitis is very rare and believed to reflect overwhelming fetal sepsis in utero, commonly caused by Escherichia coli or group B streptococci. We present a case of intrauterine fetal death associated with acute placental villitis and acute necrotizing chorioamnionitis by early-onset group B streptococcal infection. A 36-year-old woman presented with decreased fetal movement and fever at 21 weeks of gestation. Ultrasound demonstrated intrauterine fetal death. After delivery, the placenta revealed multifocal neutrophilic infiltration in chorionic villi, most prominently beneath the trophoblast basement membrane, which was also accompanied by acute necrotizing chorioamnionitis. Gram-positive microorganisms were detected in villous vessels as well as in the major organs of the fetus, which was consistent with Streptococcus agalactiae (group B) cultured from maternal blood. Acute placental villitis should be recognized as evidence of fetal sepsis that often has lethal clinical outcome, as compared to intra-amniotic infection associated with acute chorioamnionitis alone. PMID:26457860

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

    PubMed Central

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

    2015-01-01

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

  12. Australian Enterococcal Sepsis Outcome Progamme, 2011.

    PubMed

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

    2014-09-01

    From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ≤ 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium. PMID:25391408

  13. Improving Sepsis Management in the Acute Admissions Unit

    PubMed Central

    Adcroft, Laura

    2014-01-01

    Sepsis is a common condition with a major impact on healthcare resources and expenditure. We therefore wanted to investigate and improve how the acute admission unit (AAU) at the Great Western Hospital (GWH) is managing patients who present directly to the unit with sepsis. In order to obtain this information, an audit was undertaken against the College of Emergency Medicine standards used by the emergency department within GWH and across the UK. Data was retrospectively collected for 30 patients with a diagnosis of severe sepsis or septic shock. The notes were scrutinized with regard to the implementation of College of Emergency Medicine standards for the management of sepsis. This meant that performance in the AAU was compared against the emergency department at GWH and national figures. The data collected shows performance is below national standards with regard to documentation of high flow oxygen use (AAU: 24%, ED 100%; national median: 50%; CEM standard 95%), crystalloid fluid boluses (AAU: 52%; ED: 90%; national median: 83%; CEM standard 100%), lactate measurements (AAU: 66%, ED: 93%; national median: 80%; CEM standard 95%), and obtainment of blood cultures (AAU: 52%; ED 73%; national median: 77%; CEM standard: 95%). Only 3% of patients received all six parts of the sepsis bundle. Since auditing in 2012/2013 we have introduced a sepsis proforma based on a current proforma being used within Severn Deanery. This proforma uses the ‘Sepsis Six’ bundle appropriate to ward based care. We have raised awareness of sepsis implications and management through the creation of a ‘sepsis working group’ to educate both junior doctors and nurses. In turn, this has led to education through the use of posters, pocket reference cards, and teaching sessions. Re-audit shows significant improvement in administering all parts of the Sepsis Six bundle and an 8% improvement in patients receiving all six of the bundle. PMID:26734269

  14. Early diverting colostomy for perianal sepsis in children with acute leukemia.

    PubMed

    Pini Prato, Alessio; Castagnola, Elio; Micalizzi, Concetta; Dufour, Carlo; Avanzini, Stefano; Pio, Luca; Guida, Edoardo; Mattioli, Girolamo; Jasonni, Vincenzo; Disma, Nicola; Mameli, Leila; Montobbio, Giovanni; Buffa, Piero

    2012-10-01

    Perineal sepsis is a life-threatening complication of acute leukemia. Although conservative management (antibiotics, incision, and drainage, alone or in combination) is considered the criterion standard, it provides an outcome that is not fully satisfactory, with an overall mortality of roughly 30%. This report presents a case series of 4 children who underwent early defunctioning colostomy for the treatment of perineal sepsis during leukemia. This management proved to be successful and allowed prompt reestablishment of chemotherapy, thus improving overall results. Routine application of this "aggressive" management in these cases will presumably increase overall survival of children with leukemia. PMID:23084226

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

    PubMed Central

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

    2016-01-01

    Objective: To establish a baseline for the incidence of sepsis by severity and presence on admission in acute care hospital settings before implementation of a broad sepsis screening and response initiative. Methods: A retrospective cohort study using hospital discharge abstracts of 5672 patients, aged 18 years and above, with sepsis-associated stays between February 2012 and January 2013 at an academic medical center and 5 community hospitals in Texas. Results: Sepsis was present on admission in almost 85% of cases and acquired in-hospital in the remainder. The overall inpatient death rate was 17.2%, but was higher in hospital-acquired sepsis (38.6%, medical; 29.2%, surgical) and Stages 2 (17.6%) and 3 (36.4%) compared with Stage 1 (5.9%). Patients treated at the academic medical center had a higher death rate (22.5% vs. 15.1%, P<0.001) and were more costly ($68,050±184,541 vs. $19,498±31,506, P<0.001) versus community hospitals. Conclusions: Greater emphasis is needed on public awareness of sepsis and the detection of sepsis in the prehospitalization and early hospitalization period. Hospital characteristics and case mix should be accounted for in cross-hospital comparisons of sepsis outcomes and costs. PMID:26759980

  16. Sepsis

    MedlinePlus

    ... Symptoms In sepsis, blood pressure drops, resulting in shock . Major organs and body systems, including the kidneys, ... RS, Suffredini AF. Spesis, severe sepsis, and septic shock. In: Bennett JE, Dolin R, Mandell GL, eds. ...

  17. Sepsis

    MedlinePlus

    ... pressure drops and the heart weakens, leading to septic shock. Anyone can get sepsis, but the risk is higher in People with ... severe burn or physical trauma Common symptoms of sepsis are fever, chills, rapid breathing and heart rate, ...

  18. Sepsis

    MedlinePlus

    ... the episode 3 , 4 . What is the economic cost of sepsis? Treatment for sepsis often involves a ... care unit and complex therapies, which incur high costs. The Agency for Healthcare Research and Quality lists ...

  19. Sepsis

    MedlinePlus

    Sepsis is an illness in which the body has a severe response to bacteria or other germs. ... The symptoms of sepsis are not caused by the germs themselves. Instead, chemicals the body releases cause the response. A bacterial infection anywhere ...

  20. CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis.

    PubMed

    Wang, Chao-Yung; Hsieh, Ming-Jer; Hsieh, I-Chang; Shie, Shian-Sen; Ho, Ming-Yun; Yeh, Jih-Kai; Tsai, Ming-Lung; Yang, Chia-Hung; Hung, Kuo-Chun; Wang, Chun-Chieh; Wen, Ming-Shien

    2016-09-16

    Polymicrobial sepsis is a potentially fatal condition and a significant burden on health care systems. Acute lung injury is the most common complication of sepsis and results in high mortality. However, there has been no recent significant progress in the treatment of sepsis or acute lung injury induced by sepsis. Here we show that mice deficient in the circadian protein CLOCK had better survival than wild-type mice after induction of polymicrobial sepsis by cecal ligation and puncture. Inflammatory cytokine production was attenuated and bacterial clearance was improved in CLOCK-deficient mice. Moreover, acute lung injury after induction of sepsis was significantly decreased in CLOCK-deficient mice. Genome-wide profiling analysis showed that inhibin signaling was reduced in CLOCK-deficient mice. These data establish the importance of circadian CLOCK-inhibin signaling in sepsis, which may have potential therapeutic implications. PMID:27520377

  1. Sepsis.

    PubMed

    Dean, Erin

    2016-07-20

    Essential facts Sepsis is a clinical syndrome caused by the body's immune and coagulation systems being switched on by an infection and is thought to cause 44,000 deaths a year. If not recognised early, sepsis can lead to shock, multiple organ failure and death. Sepsis is a leading cause of avoidable death that kills more people than breast, bowel and prostate cancer combined. PMID:27440336

  2. Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

    PubMed Central

    Kojic, Dubravka; Siegler, Benedikt H; Uhle, Florian; Lichtenstern, Christoph; Nawroth, Peter P; Weigand, Markus A; Hofer, Stefan; Brenner, Thorsten

    2015-01-01

    Beside many efforts to improve outcome, sepsis is still one of the most frequent causes of death in critically ill patients. It is the most common condition with high mortality in intensive care units. The complexity of the septic syndrome comprises immunological aspects - i.e., sepsis induced immunosuppression - but is not restricted to this fact in modern concepts. So far, exact mechanisms and variables determining outcome and mortality stay unclear. Since there is no typical risk profile, early diagnosis and risk stratification remain difficult, which hinders rapid and effective treatment initiation. Due to the heterogeneous nature of sepsis, potential therapy options should be adapted to the individual. Biomarkers like C-reactive protein and procalcitonin are routinely used as complementary tools in clinical decision-making. Beyond the acute phase proteins, a wide bunch of promising substances and non-laboratory tools with potential diagnostic and prognostic value is under intensive investigation. So far, clinical decision just based on biomarker assessment is not yet feasible. However, biomarkers should be considered as a complementary approach. PMID:25992320

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

    PubMed Central

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

    2015-01-01

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

  4. Association between hemodynamic presentation and outcome in sepsis patients.

    PubMed

    Hwang, Sung Yeon; Shin, Tae Gun; Jo, Ik Joon; Jeon, Kyeongman; Suh, Gee Young; Lee, Tae Rim; Cha, Won Chul; Sim, Min Seob; Song, Keun Jeong; Jeong, Yeon Kwon

    2014-09-01

    We aimed to compare outcomes of sepsis patients according to their hemodynamic presentation: cryptic shock (CS), cryptic to overt shock (COS), and overt shock (OS). We analyzed the sepsis registry for adult patients who presented to the emergency department (ED) of a tertiary hospital and met the criteria for severe sepsis or septic shock between August 2008 and March 2012. We classified the patients as having CS, COS, or OS. "Cryptic shock" was defined as severe sepsis with a lactate level of 4 mmol/L or greater and normotension, "COS" was defined as initial CS that progressed to septic shock within 72 h, and "OS" was defined as septic shock on ED arrival. The primary outcome was in-hospital mortality. We performed a multivariable logistic regression analysis to assess variables related to in-hospital mortality and a multivariable Cox regression analysis to assess predictive factors for progression to OS in patients who initially showed CS. A total of 591 patients were included. We assigned 187 (31.6%) patients to the CS group, 157 (26.6%) patients to the COS group, and 247 (41.8%) patients to the OS group. There was a significant difference in unadjusted in-hospital mortality among groups (7.0% in the CS group, 27.4% in the COS group, and 21.9% in the OS group; P < 0.01). Multivariable analysis showed an odds ratio (OR) for in-hospital mortality of 0.17 (95% confidence interval, 0.07 - 0.40; P < 0.01) for the CS group and 0.83 (95% confidence interval, 0.46 - 1.49; P = 0.54) for the COS group compared with the OS group. A higher blood lactate concentration and respiratory failure were significant risk factors for progression to OS. In conclusion, CS without deterioration to hypotension during initial treatment showed significantly lower mortality than OS. The mortality from CS that progressed to apparent hypotension, however, was comparable to the mortality associated with OS. PMID:24978884

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-12-01

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

  7. Knockdown of Burton's tyrosine kinase confers potent protection against sepsis-induced acute lung injury.

    PubMed

    Zhou, Panyu; Ma, Bing; Xu, Shuogui; Zhang, Shijie; Tang, Hongtai; Zhu, Shihui; Xiao, Shichu; Ben, Daofeng; Xia, Zhaofan

    2014-11-01

    Sepsis is a common and critical complication in surgical patients that often leads to multiple organ failure syndrome (MOFS), including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Despite intensive supportive care and treatment modalities, the mortality of these patients remains high. In this study, we investigated the role of Burton's tyrosine kinase (BTK), a member of the Btk/Tec family of cytoplasmic tyrosine kinases, in the pathogenesis of sepsis, and evaluated the protective effect of in vivo Btk RNA interference in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. After intratracheal injection of Btk siRNA, the mice were then subjected to CLP to induce sepsis. The results demonstrated that this approach conferred potent protection against sepsis-induced ALI, as evidenced by a significant reduction in pathological scores, epithelial cell apoptosis, pulmonary edema, vascular permeability, and the expression of inflammatory cytokines and neutrophil infiltration in the lung tissues of septic mice. In addition, RNA interference of Btk significantly suppressed p-38 and iNOS signaling pathways in transduced alveolar macrophages in vitro. These results identify a novel role for BTK in lethal sepsis and provide a potential new therapeutic approach to sepsis and ALI. PMID:24906236

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-12-01

    From 1 January to 31 December 2013, 26 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2013 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 826 unique episodes of bacteraemia investigated, 94.6% were caused by either E. faecalis (56.1%) or E. faecium (38.5%). Ampicillin resistance was not detected in E. faecalis but was detected in over 90% of E. faecium. Vancomycin non-susceptibility was reported in 0.2% and 40.9% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Overall, 41.6% of E. faecium harboured vanA or vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium isolates consisted of 81 pulsed-field gel electrophoresis pulsotypes of which 72.3% were classified into 14 major pulsotypes containing five or more isolates. Multilocus sequence typing grouped the 14 major pulsotypes into clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. Of the 2 predominant sequence types, ST203 (80 isolates) was identified across Australia and ST555 (40 isolates) was isolated primarily in the western and central regions (Northern Territory, South Australia and Western Australia) respectively. In conclusion, the AESOP 2013 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanB E. faecium, which have limited treatment options. PMID:25631594

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

    Sepsis is a common condition that is associated with significant morbidity, mortality and health-care cost. Pulmonary and non-pulmonary sepsis are common causes of the acute respiratory distress syndrome (ARDS). The mortality from ARDS remains high despite protective lung ventilation, and currently there are no specific pharmacotherapies to treat sepsis or ARDS. Sepsis and ARDS are characterised by activation of the inflammatory cascade. Although there is much focus on the study of the dysregulated inflammation and its suppression, the associated activation of the haemostatic system has been largely ignored until recently. There has been extensive interest in the role that platelet activation can have in the inflammatory response through induction, aggregation and activation of leucocytes and other platelets. Aspirin can modulate multiple pathogenic mechanisms implicated in the development of multiple organ dysfunction in sepsis and ARDS. This review will discuss the role of the platelet, the mechanisms of action of aspirin in sepsis and ARDS, and aspirin as a potential therapy in treating sepsis and ARDS. PMID:26494395

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

    PubMed

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

    2014-05-15

    Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the Lmn group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in Lmn samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis. PMID:24619519

  13. Severe sepsis in cirrhosis.

    PubMed

    Gustot, Thierry; Durand, François; Lebrec, Didier; Vincent, Jean-Louis; Moreau, Richard

    2009-12-01

    Sepsis is physiologically viewed as a proinflammatory and procoagulant response to invading pathogens. There are three recognized stages in the inflammatory response with progressively increased risk of end-organ failure and death: sepsis, severe sepsis, and septic shock. Patients with cirrhosis are prone to develop sepsis, sepsis-induced organ failure, and death. There is evidence that in cirrhosis, sepsis is accompanied by a markedly imbalanced cytokine response ("cytokine storm"), which converts responses that are normally beneficial for fighting infections into excessive, damaging inflammation. Molecular mechanisms for this excessive proinflammatory response are poorly understood. In patients with cirrhosis and severe sepsis, high production of proinflammatory cytokines seems to play a role in the worsening of liver function and the development of organ/system failures such as shock, renal failure, acute lung injury or acute respiratory distress syndrome, coagulopathy, or hepatic encephalopathy. In addition, these patients may have sepsis-induced hyperglycemia, defective arginine-vasopressin secretion, adrenal insufficiency, or compartmental syndrome. In patients with cirrhosis and spontaneous bacterial peritonitis (SBP), early use of antibiotics and intravenous albumin administration decreases the risk for developing renal failure and improves survival. There are no randomized studies that have been specifically performed in patients with cirrhosis and severe sepsis to evaluate treatments that have been shown to improve outcome in patients without cirrhosis who have severe sepsis or septic shock. These treatments include recombinant human activated C protein and protective-ventilation strategy for respiratory failure. Other treatments should be evaluated in the cirrhotic population with severe sepsis including the early use of antibiotics in "non-SBP" infections, vasopressor therapy, hydrocortisone, renal-replacement therapy and liver support systems, and

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

  16. Effect of statins on the clinical outcomes of patients with sepsis.

    PubMed

    Goodin, J; Manrique, C; Dulohery, M; Sampson, J; Saettele, M; Dabbagh, O

    2011-11-01

    Despite numerous attempts at novel intervention and tests to aid in earlier diagnosis and improved treatment, there has been an increased incidence of overall mortality related to sepsis, despite improvements in in-hospital mortality. Statins have emerged as potential immunomodulatory and antioxidant agents that might impact on sepsis outcomes. Definitive evidence to support the routine use of statins in patients with sepsis has not yet been elicited. We retrospectively analysed data from patients who presented with sepsis, severe sepsis or septic shock, stratifiying them according to statin use into two groups (statin and no statin). Sequential Organ Failure Assessment was used to evaluate severity of illness. The primary outcome was hospital mortality. Secondary outcomes included intensive care unit (ICU) mortality, hospital and ICU length of stay, and mechanical ventilation and vasopressor therapy duration. Five hundred and sixty-eight patients were included. Patients with prior statin use (statin group) were older; more obese and had higher prevalence of smoking, diabetes and ischaemic heart disease. There was no difference in Sequential Organ Failure Assessment scores and mortality did not vary between the two groups (19.6 vs. 16.9%). Furthermore, secondary outcomes including ICU mortality, hospital and ICU length of stay, mechanical ventilation and vasopressor duration did not differ Multivariate analysis revealed age and Sequential Organ Failure Assessment score were independent predictors of survival, while history of statin use was not (p = 0.403). This current retrospective study did not find any benefit of statin use on primary and secondary outcomes of the patients admitted to an academic hospital with sepsis. PMID:22165357

  17. Targeting sepsis as a performance improvement metric: role of the nurse.

    PubMed

    Kleinpell, Ruth; Schorr, Christa A

    2014-01-01

    Sepsis is the body's systemic response to infection that can be complicated by acute organ dysfunction and is associated with high mortality rates and adverse outcomes for acute and critically ill patients. The 2012 Surviving Sepsis Campaign guidelines advocated for implementation of evidence-based practice care for sepsis, with a focus on quality improvement. Nurses are directly involved in identification and management of sepsis. Implementing performance improvement strategies aimed at early recognition and targeted treatment can further improve sepsis care and patient outcomes. This article presents an overview of the process of implementing performance improvement initiatives for sepsis care, highlighting the significant contribution of nursing care. PMID:24752031

  18. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid.

    PubMed

    Fisher, Bernard J; Kraskauskas, Donatas; Martin, Erika J; Farkas, Daniela; Wegelin, Jacob A; Brophy, Donald; Ward, Kevin R; Voelkel, Norbert F; Fowler, Alpha A; Natarajan, Ramesh

    2012-07-01

    Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis. PMID

  19. Acute Lung Injury and Fibrosis in a Baboon Model of Escherichia coli Sepsis

    PubMed Central

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

    2014-01-01

    Sepsis-induced inflammation of the lung leads to acute respiratory distress syndrome (ARDS), which may trigger persistent fibrosis. The pathology of ARDS is complex and poorly understood, and the therapeutic approaches are limited. We used a baboon model of Escherichia coli sepsis that mimics the complexity of human disease to study the pathophysiology of ARDS. We performed extensive biochemical, histological, and functional analyses to characterize the disease progression and the long-term effects of sepsis on the lung structure and function. Similar to humans, sepsis-induced ARDS in baboons displays an early inflammatory exudative phase, with extensive necrosis. This is followed by a regenerative phase dominated by proliferation of type 2 epithelial cells, expression of epithelial-to-mesenchymal transition markers, myofibroblast migration and proliferation, and collagen synthesis. Baboons that survived sepsis showed persistent inflammation and collagen deposition 6–27 months after the acute episodes. Long-term survivors had almost double the amount of collagen in the lung as compared with age-matched control animals. Immunostaining for procollagens showed persistent active collagen synthesis within the fibroblastic foci and interalveolar septa. Fibroblasts expressed markers of transforming growth factor-β and platelet-derived growth factor signaling, suggesting their potential role as mediators of myofibroblast migration and proliferation, and collagen deposition. In parallel, up-regulation of the inhibitors of extracellular proteases supports a deregulated matrix remodeling that may contribute to fibrosis. The primate model of sepsis-induced ARDS mimics the disease progression in humans, including chronic inflammation and long-lasting fibrosis. This model helps our understanding of the pathophysiology of fibrosis and the testing of new therapies. PMID:24066737

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

    PubMed Central

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

    2015-01-01

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

  1. Profile of burn sepsis challenges and outcome in an exclusive children's hospital in Chennai, India

    PubMed Central

    Ramakrishnan, K.M.; Jayaraman, V.; Mathivanan, T.; Babu, M.; Ramachandran, B.; Sankar, J.

    2012-01-01

    Summary A group of 273 paediatric patients admitted to Kanchi Kamakoti Childs Trust Hospital Burn Unit, Chennai, India between the years 2004 to 2010 were analysed retrospectively. Of these, 89 were suffering from sepsis and septic shock and 15 died. Strict adherence to antibiotic administration and to the Paediatric Intensive Care Unit (PICU) and management protocol improved the outcome, especially in 2009 and 2010. PMID:23012610

  2. Chitinase-like Proteins are Candidate Biomarkers for Sepsis-induced Acute Kidney Injury*

    PubMed Central

    Maddens, B.; Ghesquière, B.; Vanholder, R.; Demon, D.; Vanmassenhove, J.; Gevaert, K.; Meyer, E.

    2012-01-01

    Sepsis-induced acute kidney injury (AKI) is a frequent complication of critically ill patients and leads to high mortality rates. The specificity of currently available urinary biomarkers for AKI in the context of sepsis is questioned. This study aimed to discover urinary biomarkers for septic AKI by contemporary shotgun proteomics in a mouse model for sepsis and to validate these in individual urine samples of mice and human septic patients with and without AKI. At 48 h after uterine ligation and inoculation of Escherichia coli, aged mice (48 weeks) became septic. A subgroup developed AKI, defined by serum creatinine, blood urea nitrogen, and renal histology. Separate pools of urine from septic mice with and without AKI mice were collected during 12 h before and between 36–48 h after infection, and their proteome compositions were quantitatively compared. Candidate biomarkers were validated by Western blot analysis of urine, plasma, and renal tissue homogenates from individual mice, and a limited number of urine samples from human septic patients with and without AKI. Urinary neutrophil gelatinase-associated lipocalin, thioredoxin, gelsolin, chitinase 3-like protein 1 and -3 (CHI3L3) and acidic mammalian chitinase were the most distinctive candidate biomarkers selected for septic AKI. Both neutrophil gelatinase-associated lipocalin and thioredoxin were detected in urine of septic mice and increased with severity of AKI. Acidic mammalian chitinase was only present in urine of septic mice with AKI. Both urinary chitinase 3-like protein 1 and -3 were only detected in septic mice with severe AKI. The human homologue chitinase 3-like protein 1 was found to be more excreted in urine from septic patients with AKI than without. In summary, urinary chitinase 3-like protein 1 and -3 and acidic mammalian chitinase discriminated sepsis from sepsis-induced AKI in mice. Further studies of human chitinase proteins are likely to lead to additional insights in septic AKI. PMID

  3. Urgent endoscopic ultrasound-guided choledochoduodenostomy for acute obstructive suppurative cholangitis-induced sepsis.

    PubMed

    Minaga, Kosuke; Kitano, Masayuki; Imai, Hajime; Yamao, Kentaro; Kamata, Ken; Miyata, Takeshi; Omoto, Shunsuke; Kadosaka, Kumpei; Yoshikawa, Tomoe; Kudo, Masatoshi

    2016-04-28

    Acute obstructive suppurative cholangitis (AOSC) due to biliary lithiasis is a life-threatening condition that requires urgent biliary decompression. Although endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is the current gold standard for biliary decompression, it can sometimes be difficult because of failed biliary cannulation. In this retrospective case series, we describe three cases of successful biliary drainage with recovery from septic shock after urgent endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) was performed for AOSC due to biliary lithiasis. In all three cases, technical success in inserting the stents was achieved and the patients completely recovered from AOSC with sepsis in a few days after EUS-CDS. There were no procedure-related complications. When initial ERCP fails, EUS-CDS can be an effective life-saving endoscopic biliary decompression procedure that shortens the procedure time and prevents post-ERCP pancreatitis, particularly in patients with AOSC-induced sepsis. PMID:27122677

  4. Urgent endoscopic ultrasound-guided choledochoduodenostomy for acute obstructive suppurative cholangitis-induced sepsis

    PubMed Central

    Minaga, Kosuke; Kitano, Masayuki; Imai, Hajime; Yamao, Kentaro; Kamata, Ken; Miyata, Takeshi; Omoto, Shunsuke; Kadosaka, Kumpei; Yoshikawa, Tomoe; Kudo, Masatoshi

    2016-01-01

    Acute obstructive suppurative cholangitis (AOSC) due to biliary lithiasis is a life-threatening condition that requires urgent biliary decompression. Although endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is the current gold standard for biliary decompression, it can sometimes be difficult because of failed biliary cannulation. In this retrospective case series, we describe three cases of successful biliary drainage with recovery from septic shock after urgent endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) was performed for AOSC due to biliary lithiasis. In all three cases, technical success in inserting the stents was achieved and the patients completely recovered from AOSC with sepsis in a few days after EUS-CDS. There were no procedure-related complications. When initial ERCP fails, EUS-CDS can be an effective life-saving endoscopic biliary decompression procedure that shortens the procedure time and prevents post-ERCP pancreatitis, particularly in patients with AOSC-induced sepsis. PMID:27122677

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

    PubMed

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

    2013-11-01

    Ulinastatin is a potent multivalent serine protease inhibitor, which was recently found with therapeutic potentials in treating sepsis, and the most life-threatening complication of critically ill population. However, the pharmacological features and possible mechanisms need to be further elucidated in reliable and clinical relevant sepsis models. As known, sepsis induced by surgery of cecal ligation and puncture (CLP) is widely accepted as the gold standard animal model, but the inconsistency of outcomes is the most obvious problem. In the present experiments, we reported an improved rat CLP model with much more consistent outcomes using self-made three edged puncture needles in our lab. Results from this optimized model revealed that ulinastatin improved survivals of CLP rats, attenuated proinflammatory response and prevented systemic disorder and organ dysfunction. Ulinastatin was also found to be effective in ameliorating sepsis-related ALI, a syndrome most frequent and fatal in sepsis. The molecular mechanism investigation showed that ulinastatin's protection against ALI was probably related to the down-regulation of NF-κB activity and inhibition of TNF-α, IL-6 and elastase expressions in the lung tissue. In conclusion, based on a successful establishment of optimized rat CLP model ulinastatin is proved to be an effective candidate for sepsis treatment, due to its anti-inflammation and anti-protease activities that ameliorate systemic disorders, prevent organ injuries and thus improve the survival outcomes of sepsis in animals. PMID:24075864

  6. Neutropenic Sepsis in the ICU: Outcome Predictors in a Two-Phase Model and Microbiology Findings

    PubMed Central

    Kruse, Jan M.; Jenning, Thomas; Rademacher, Sibylle; Arnold, Renate; Schmitt, Clemens A.; Jörres, Achim; Enghard, Philipp; Oppert, Michael

    2016-01-01

    Objective. Patients with neutropenic sepsis have a poor prognosis. We aimed to identify outcome predictors and generate hypotheses how the care for these patients may be improved. Methods. All 12.352 patients admitted between 2006 and 2011 to the medical ICUs of our tertiary university center were screened for neutropenia; out of 558 patients identified, 102 fulfilled the inclusion criteria and were analyzed. Severity markers and outcome predictors were assessed. Results. The overall ICU mortality was 54.9%. The severity of sepsis and the number of organ failures predicted survival of the primary septic episode (APACHE II 22.8 and 29.0; SOFA 7.3 and 10.1, resp.). In the recovery phase, persistent organ damage and higher persistent C-reactive protein levels were associated with a poor outcome. Blood transfusions and CMV infection correlated with an unfavorable prognosis. Ineffective initial antibiotic therapy, fungal infections, and detection of multiresistant bacteria displayed a particularly poor outcome. Infections with coagulase-negative staphylococci and enterococci were associated with a significantly higher mortality and a high degree of systemic inflammation. Conclusion. Patients with persistent organ dysfunction show an increased mortality in the further course of their ICU stay. Early antimicrobial treatment of Gram-positive cocci may improve the outcome of these patients. PMID:27195148

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2009-04-01

    A 64-year-old man with acute myelogenous leukemia (FAB classification, M7) in remission received consolidation chemotherapy with mitoxantrone/cytosine arabinoside. WBC counts decreased to 0/microl on day 14, and fever (39.3 degrees C) and epigastralgia developed on day 15. Cefozopran was instituted for febrile neutropenia; however, on day 16, he was found to be in cardiac arrest. CT scan on day 16 revealed subarachnoid hemorrhage. Gram-positive rods were isolated from blood cultures on day 15, and were later identified as B.cereus. He recovered transiently, but eventually died on day 19. Postmortem examination demonstrated many colonies of B. cereus in the cerebrum, cerebellum, lung, and liver. Hepatocyte necrosis was also observed in the liver. Bacterial aneurysms or septic emboli were not identified in the arachnoid vessels, but necrosis of cerebral vessels was prominent, which was considered to be the cause of subarachnoid hemorrhage. Fatal subarachnoid hemorrhage has been reported to be associated with B. cereus sepsis, which developed at nadir following chemotherapy for leukemia patients. Because of the aggressive clinical course of B. cereus sepsis, including the risk for subarachnoid hemorrhage, early treatment with effective antibiotics for B. cereus sepsis would be important in the management of leukemia patients after chemotherapy. PMID:19404024

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

    PubMed Central

    2014-01-01

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

  10. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats.

    PubMed

    Wang, Peng; Huang, Jian; Li, Yi; Chang, Ruiming; Wu, Haidong; Lin, Jiali; Huang, Zitong

    2015-01-01

    Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP) to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2) was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN), kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI. PMID:26334271

  11. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats

    PubMed Central

    Wang, Peng; Huang, Jian; Li, Yi; Chang, Ruiming; Wu, Haidong; Lin, Jiali; Huang, Zitong

    2015-01-01

    Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP) to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2) was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN), kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI. PMID:26334271

  12. Accelerated Cellular Uptake and Metabolism of L-Thyroxine during Acute Salmonella typhimurium Sepsis

    PubMed Central

    DeRubertis, Frederick R.; Woeber, Kenneth A.

    1973-01-01

    The effects of acute Salmonella typhimurium sepsis on the kinetics of peripheral L-thyroxine (T4) distribution and metabolism and on serum total and free T4 concentrations were studied in rhesus monkeys inoculated i.v. with either heat-killed or viable organisms. The rate of disappearance of labeled T4 from serum was increased within 8 h after inoculation of monkeys with either heat-killed or viable Salmonella. The effects of the heat-killed organisms were transient and no longer evident by 16 h postinoculation. The monkeys inoculated with the viable Salmonella experienced a 2-3 day febrile, septic illness that was accompanied by an increase in the absolute rate of T4 disposal. In the infected monkeys, serum total T4 and endogenously labeled protein-bound iodine concentrations fell significantly during the period of acute sepsis and then rose during convalescence to values that exceeded the preinoculation values, suggesting that thyroidal secretion of hormone had increased in response to a primary depletion of the peripheral hormonal pool. Total cellular and hepatic uptakes of T4 were enhanced by 4 h after inoculation of monkeys with either heat-killed or viable Salmonella, but the increase in total cellular uptake persisted for 24 h only in the monkeys inoculated with the viable organisms. These alterations in T4 kinetics could neither be correlated with changes in the binding of T4 in plasma nor attributed to an increase in vascular permeability. Moreover, they could not be ascribed to an in vitro product of bacterial growth, suggesting that the presence of the organisms themselves was required. An acceleration of T4 disappearance was also observed during Escherichia coli and Diplococcus pucumoniae bacteremias. Our findings are consistent with a primary increase in the cellular uptake and metabolism of T4 during bacterial sepsis, possibly related to phagocytic cell function in the host. PMID:4629910

  13. Time profile of oxidative stress and neutrophil activation in ovine acute lung injury and sepsis.

    PubMed

    Lange, Matthias; Szabo, Csaba; Traber, Daniel L; Horvath, Eszter; Hamahata, Atsumori; Nakano, Yoshimitsu; Traber, Lillian D; Cox, Robert A; Schmalstieg, Frank C; Herndon, David N; Enkhbaatar, Perenlei

    2012-05-01

    The formation of oxidative stress in the lung and activation of neutrophils are major determinants in the development of respiratory failure after acute lung injury and sepsis. However, the time changes of these pathogenic factors have not been sufficiently described. Twenty-four chronically instrumented sheep were subjected to cotton smoke inhalation injury and instillation of live Pseudomonas aeruginosa into both lungs. The sheep were euthanized at 4, 8, 12, 18, and 24 h after injury. Additional sheep received sham injury and were euthanized after 24 h. Pulmonary function was assessed by determination of oxygenation index and pulmonary shunt fraction. In addition, lung tissue was harvested at the respective time points for the measurement of malondialdehyde, interleukin 6, poly(ADP ribose), myeloperoxidase, and alveolar polymorphonuclear neutrophil score. The injury induced severe respiratory failure that was associated with an early increase in lipid peroxidation and interleukin 6 expression. The injury further led to an increase in poly(ADP ribose) activity that reached its peak at 12 h after injury and declined afterward. In addition, progressive increases in markers of neutrophil accumulation in the lung were observed. The peak of neutrophil accumulation in the lung was associated with a severe depletion of circulating neutrophils. The results from our model may enhance the understanding of the pathophysiological alterations after acute lung injury and sepsis and thus be useful in exploring therapeutic interventions directed at modifying the expression or activation of inflammatory mediators. PMID:22266977

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

    PubMed Central

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

    2015-01-01

    Kallistatin, an endogenous plasma protein, exhibits pleiotropic properties in inhibiting inflammation, oxidative stress and apoptosis, as evidenced in various animal models and cultured cells. Here, we demonstrate that kallistatin levels were positively correlated with the concentration of total protein in bronchoalveolar lavage fluids (BALF) from patients with sepsis-related acute respiratory distress syndrome (ARDS), indicating a compensatory mechanism. Lower ratio of kallistatin to total protein in BALF showed a significant trend toward elevated neutrophil counts (P = 0.002) in BALF and increased mortality (P = 0.046). In lipopolysaccharide (LPS)-treated mice, expression of human kallistatin in lung by gene transfer with human kallistatin-encoding plasmid ameliorated acute lung injury (ALI) and reduced cytokine/chemokine levels in BALF. These mice exhibited attenuated lung epithelial apoptosis and decreased Fas/FasL expression compared to the control mice. Mouse survival was improved by kallistatin gene transfer or recombinant human kallistatin treatment after LPS challenge. In LPS-stimulated A549 human lung epithelial cells, kallistatin attenuated apoptosis, down-regulated Fas/FasL signaling, suppressed intracellular reactive oxygen species (ROS) and inhibited ROS-mediated NF-κB activation and inflammation. Furthermore, LPS-induced apoptosis was blocked by antioxidant N-acetylcysteine or NF-κB inhibitor via down-regulating Fas expression. These findings suggest the therapeutic potential of kallistatin for sepsis-related ALI/ARDS. PMID:26198099

  15. Rest energy expenditure is decreased during the acute as compared to the recovery phase of sepsis in newborns

    PubMed Central

    2010-01-01

    Background Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE) of newborns with bacterial sepsis during the acute and the recovery phases. Methods We studied nineteen neonates (27.3 ± 17.2 days old) with bacterial sepsis during the acute phase and recovery of their illness. REE was determined by indirect calorimetry and VO2 and VCO2 measured by gas chromatography. Results REE significantly increased from 49.4 ± 13.1 kcal/kg/day during the acute to 68.3 ± 10.9 kcal/kg/day during recovery phase of sepsis (P < 0.01). Similarly, VO2 (7.4 ± 1.9 vs 10 ± 1.5 ml/kg/min) and VCO2 (5.1 ± 1.7 vs 7.4 ± 1.5 ml/kg/min) were also increased during the course of the disease (P < 0.01). Conclusion REE was increased during recovery compared to the sepsis phase. REE of septic newborns should be calculated on individualized basis, bearing in mind their metabolic capabilities. PMID:20653967

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

    PubMed

    Li, Kehan; Yang, Jianxue; Han, Xuechang

    2016-05-01

    High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play important roles in the development of sepsis-induced acute lung injury (ALI). Ketamine is considered to confer protective effects on ALI during sepsis. In this study, we investigated the effects of ketamine on HMGB1-RAGE activation in a rat model of sepsis-induced ALI. ALI was induced in wild type (WT) and RAGE deficient (RAGE(-/-)) rats by cecal ligation and puncture (CLP) or HMGB1 to mimic sepsis-induced ALI. Rats were randomly divided to six groups: sham-operation+normal saline (NS, 10mL/kg), sham-operation+ketamine (10mg/kg), CLP/HMGB1+NS (10mL/kg), CLP/HMGB1+ketamine (5mg/kg), CLP/HMGB1+ketamine (7.5mg/kg), and CLP/HMGB1+ketamine (10mg/kg) groups. NS and ketamine were administered at 3 and 12h after CLP/HMGB1 via intraperitoneal injection. Pathological changes of lung, inflammatory cell counts, expression of HMGB1and RAGE, and concentrations of various inflammatory mediators in bronchoalveolar lavage fluids (BALF) and lung tissue were then assessed. Nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in the lung were also evaluated. CLP/HMGB1 increased the wet to dry weight ratio and myeloperoxidase activity in lung, the number of total cells, neutrophils, and macrophages in the BALF, and inflammatory mediators in the BALF and lung tissues. Moreover, expression of HMGB1and RAGE in lung tissues was increased after CLP. Ketamine inhibited all the above effects. It also inhibited the activation of IκB-α, NF-κB p65, and MAPK. Ketamine protects rats against HMGB1-RAGE activation in a rat model of sepsis-induced ALI. These effects may partially result from reductions in NF-κB and MAPK. PMID:26945830

  17. Heme oxygenase inhibition enhances neutrophil migration into the bronchoalveolar spaces and improves the outcome of murine pneumonia-induced sepsis.

    PubMed

    Czaikoski, Paula Giselle; Nascimento, Daniele Carvalho; Sônego, Fabiane; de Freitas, Andressa; Turato, Walter Miguel; de Carvalho, Michel A; Santos, Raquel Souza; de Oliveira, Gisele Pena; dos Santos Samary, Cynthia; Tefe-Silva, Cristiane; Alves-Filho, José C; Ferreira, Sérgio Henrique; Rossi, Marcos Antonio; Rocco, Patricia Rieken Macedo; Spiller, Fernando; Cunha, Fernando Queiroz

    2013-04-01

    A reduction of the neutrophil migration into the site of infection during cecal ligation and puncture-induced sepsis increases host mortality. Inhibition of heme oxygenase (HO) prevents this neutrophil paralysis and improves host survival in the cecal ligation and puncture model. Taking into account that almost 50% of all sepsis cases are a consequence of pneumonia, we designed the present study to determine the role of HO in an experimental model of pneumonia-induced sepsis. The objective of this study was to evaluate whether the inhibition of HO improves the outcome and pathophysiologic changes of sepsis induced by an intratracheal instillation of Klebsiella pneumoniae. The pretreatment of mice subjected to pneumonia-induced sepsis with ZnDPBG (zinc deuteroporphyrin 2,4-bis glycol), a nonspecific HO inhibitor, increased the number of neutrophils in the bronchoalveolar spaces, reduced the bacterial load at the site of infection, and prevented the upregulation of CD11b and the downregulation of CXCR2 on blood neutrophils. Moreover, the pretreatment with ZnDPBG decreased alveolar collapse, attenuating the deleterious changes in pulmonary mechanics and gas exchanges and, as a consequence, improved the survival rate of mice from 0% to ∼20%. These results show that heme oxygenase is involved in the pathophysiology of pneumonia-induced sepsis and suggest that HO inhibitors could be helpful for the management of this disease. PMID:23481491

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

    PubMed Central

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

    2016-01-01

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

  19. Role of kidney injury in sepsis.

    PubMed

    Doi, Kent

    2016-01-01

    Kidney injury, including acute kidney injury (AKI) and chronic kidney disease (CKD), has become very common in critically ill patients treated in ICUs. Many epidemiological studies have revealed significant associations of AKI and CKD with poor outcomes of high mortality and medical costs. Although many basic studies have clarified the possible mechanisms of sepsis and septic AKI, translation of the obtained findings to clinical settings has not been successful to date. No specific drug against human sepsis or AKI is currently available. Remarkable progress of dialysis techniques such as continuous renal replacement therapy (CRRT) has enabled control of "uremia" in hemodynamically unstable patients; however, dialysis-requiring septic AKI patients are still showing unacceptably high mortality of 60-80 %. Therefore, further investigations must be conducted to improve the outcome of sepsis and septic AKI. A possible target will be remote organ injury caused by AKI. Recent basic studies have identified interleukin-6 and high mobility group box 1 (HMGB1) as important mediators for acute lung injury induced by AKI. Another target is the disease pathway that is amplified by pre-existing CKD. Vascular endothelial growth factor and HMGB1 elevations in sepsis were demonstrated to be amplified by CKD in CKD-sepsis animal models. Understanding the role of kidney injury as an amplifier in sepsis and multiple organ failure might support the identification of new drug targets for sepsis and septic AKI. PMID:27011788

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

    PubMed Central

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

    2016-01-01

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

  1. Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis.

    PubMed

    Weber, Georg F; Chousterman, Benjamin G; He, Shun; Fenn, Ashley M; Nairz, Manfred; Anzai, Atsushi; Brenner, Thorsten; Uhle, Florian; Iwamoto, Yoshiko; Robbins, Clinton S; Noiret, Lorette; Maier, Sarah L; Zönnchen, Tina; Rahbari, Nuh N; Schölch, Sebastian; Klotzsche-von Ameln, Anne; Chavakis, Triantafyllos; Weitz, Jürgen; Hofer, Stefan; Weigand, Markus A; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K

    2015-03-13

    Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis. Using a mouse model of abdominal sepsis, we showed that innate response activator B cells produce IL-3, which induces myelopoiesis of Ly-6C(high) monocytes and neutrophils and fuels a cytokine storm. IL-3 deficiency protects mice against sepsis. In humans with sepsis, high plasma IL-3 levels are associated with high mortality even after adjusting for prognostic indicators. This study deepens our understanding of immune activation, identifies IL-3 as an orchestrator of emergency myelopoiesis, and reveals a new therapeutic target for treating sepsis. PMID:25766237

  2. Coagulation abnormalities in sepsis.

    PubMed

    Tsao, Cheng-Ming; Ho, Shung-Tai; Wu, Chin-Chen

    2015-03-01

    Although the pathophysiology of sepsis has been elucidated with the passage of time, sepsis may be regarded as an uncontrolled inflammatory and procoagulant response to infection. The hemostatic changes in sepsis range from subclinical activation of blood coagulation to acute disseminated intravascular coagulation (DIC). DIC is characterized by widespread microvascular thrombosis, which contributes to multiple organ dysfunction/failure, and subsequent consumption of platelets and coagulation factors, eventually causing bleeding manifestations. The diagnosis of DIC can be made using routinely available laboratory tests, scoring algorithms, and thromboelastography. In this cascade of events, the inhibition of coagulation activation and platelet function is conjectured as a useful tool for attenuating inflammatory response and improving outcomes in sepsis. A number of clinical trials of anticoagulants were performed, but none of them have been recognized as a standard therapy because recombinant activated protein C was withdrawn from the market owing to its insufficient efficacy in a randomized controlled trial. However, these subgroup analyses of activated protein C, antithrombin, and thrombomodulin trials show that overt coagulation activation is strongly associated with the best therapeutic effect of the inhibitor. In addition, antiplatelet drugs, including acetylsalicylic acid, P2Y12 inhibitors, and glycoprotein IIb/IIIa antagonists, may reduce organ failure and mortality in the experimental model of sepsis without a concomitant increased bleeding risk, which should be supported by solid clinical data. For a state-of-the-art treatment of sepsis, the efficacy of anticoagulant and antiplatelet agents needs to be proved in further large-scale prospective, interventional, randomized validation trials. PMID:25544351

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

    PubMed Central

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

    2014-01-01

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

  4. Glycyrrhizic Acid Attenuates Sepsis-Induced Acute Kidney Injury by Inhibiting NF-κB Signaling Pathway

    PubMed Central

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

    2016-01-01

    Glycyrrhizic acid (GA) is a major active ingredient in licorice. In our study, the effects of GA on acute kidney injury (AKI) in rats and its underlying molecular mechanisms were investigated. The sepsis model was produced by caecal ligation and puncture (CLP) in rats. The molecular and histological experiments were performed in the kidney tissues and serum samples of rats. According to the results obtained, GA alleviated sepsis-induced AKI by improving the pathological changes, decreasing the levels of blood urea nitrogen (BUN), creatinine (Cre), and increasing the survival rate of rats with AKI significantly. The production of inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, was markedly inhibited by GA. Moreover, treatment with GA inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and expression levels of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in kidney tissues. Furtherly, the apoptosis in kidney tissue induced by AKI was suppressed by GA. Finally, GA could inhibit the activation of NF-κB signaling pathway. Our study suggests that GA alleviates sepsis-induced AKI by inhibiting the NF-κB signaling pathway, which provides a strong evidence for a new approach for treating sepsis-induced AKI. PMID:26904148

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

    PubMed

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

    2016-01-01

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

  6. MITOCHONDRIAL FUNCTION IN SEPSIS.

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults.

    PubMed

    McGill, F; Heyderman, R S; Michael, B D; Defres, S; Beeching, N J; Borrow, R; Glennie, L; Gaillemin, O; Wyncoll, D; Kaczmarski, E; Nadel, S; Thwaites, G; Cohen, J; Davies, N W S; Miller, A; Rhodes, A; Read, R C; Solomon, T

    2016-04-01

    Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients. PMID:26845731

  10. Hemodynamic changes in the kidney in a pediatric rat model of sepsis-induced acute kidney injury.

    PubMed

    Seely, Kathryn A; Holthoff, Joseph H; Burns, Samuel T; Wang, Zhen; Thakali, Keshari M; Gokden, Neriman; Rhee, Sung W; Mayeux, Philip R

    2011-07-01

    Sepsis is a leading cause of acute kidney injury (AKI) and mortality in children. Understanding the development of pediatric sepsis and its effects on the kidney are critical in uncovering new therapies. The goal of this study was to characterize the development of sepsis-induced AKI in the clinically relevant cecal ligation and puncture (CLP) model of peritonitis in rat pups 17-18 days old. CLP produced severe sepsis demonstrated by time-dependent increase in serum cytokines, NO, markers of multiorgan injury, and renal microcirculatory hypoperfusion. Although blood pressure and heart rate remained unchanged after CLP, renal blood flow (RBF) was decreased 61% by 6 h. Renal microcirculatory analysis showed the number of continuously flowing cortical capillaries decreased significantly from 69 to 48% by 6 h with a 66% decrease in red blood cell velocity and a 57% decline in volumetric flow. The progression of renal microcirculatory hypoperfusion was associated with peritubular capillary leakage and reactive nitrogen species generation. Sham adults had higher mean arterial pressure (118 vs. 69 mmHg), RBF (4.2 vs. 1.1 ml·min(-1)·g(-1)), and peritubular capillary velocity (78% continuous flowing capillaries vs. 69%) compared with pups. CLP produced a greater decrease in renal microcirculation in pups, supporting the notion that adult models may not be the most appropriate for studying pediatric sepsis-induced AKI. Lower RBF and reduced peritubular capillary perfusion in the pup suggest the pediatric kidney may be more susceptible to AKI than would be predicted using adults models. PMID:21511700

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

    PubMed Central

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

    2016-01-01

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

  12. Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study

    PubMed Central

    2013-01-01

    Introduction Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis. Methods We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis. Results Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI. Conclusions The findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis. PMID:24330815

  13. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation.

    PubMed

    Campos, Renata; Shimizu, Maria Heloísa Massola; Volpini, Rildo Aparecido; de Bragança, Ana Carolina; Andrade, Lucia; Lopes, Fernanda Degobbi Tenório Quirino Dos Santos; Olivo, Clarice; Canale, Daniele; Seguro, Antonio Carlos

    2012-04-01

    Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/l in drinking water), underwent cecal ligation and puncture (CLP) 2 days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control + NAC, CLP, and CLP + NAC. All animals were submitted to low-tidal-volume mechanical ventilation. We evaluated respiratory mechanics, the sodium cotransporters Na-K-2Cl (NKCC1) and the α-subunit of the epithelial sodium channel (α-ENaC), polymorphonuclear neutrophils, the edema index, oxidative stress (plasma thiobarbituric acid reactive substances and lung tissue 8-isoprostane), and glomerular filtration rate. The CLP rats developed AKI, which was ameliorated in the CLP + NAC rats. Sepsis-induced alterations in respiratory mechanics were also ameliorated by NAC. Edema indexes were lower in the CLP + NAC group, as was the wet-to-dry lung weight ratio. In CLP + NAC rats, α-ENaC expression was upregulated, whereas that of NKCC1 was downregulated, although the difference was not significant. In the CLP + NAC group, oxidative stress was significantly lower and survival rates were significantly higher than in the CLP group. The protective effects of NAC (against kidney and lung injury) are likely attributable to the decrease in oxidative stress, suggesting that NAC can be useful in the treatment of sepsis. PMID:22268121

  14. Anti-inflammatory mechanisms of apolipoprotein A-I mimetic peptide in acute respiratory distress syndrome secondary to sepsis.

    PubMed

    Sharifov, Oleg F; Xu, Xin; Gaggar, Amit; Grizzle, William E; Mishra, Vinod K; Honavar, Jaideep; Litovsky, Silvio H; Palgunachari, Mayakonda N; White, C Roger; Anantharamaiah, G M; Gupta, Himanshu

    2013-01-01

    Acute respiratory distress syndrome (ARDS) due to sepsis has a high mortality rate with limited treatment options. High density lipoprotein (HDL) exerts innate protective effects in systemic inflammation. However, its role in ARDS has not been well studied. Peptides such as L-4F mimic the secondary structural features and functions of apolipoprotein (apo)A-I, the major protein component of HDL. We set out to measure changes in HDL in sepsis-mediated ARDS patients, and to study the potential of L-4F to prevent sepsis-mediated ARDS in a rodent model of lipopolysaccharide (LPS)-mediated acute lung injury, and a combination of primary human leukocytes and human ARDS serum. We also analyzed serum from non-lung disease intubated patients (controls) and sepsis-mediated ARDS patients. Compared to controls, ARDS demonstrates increased serum endotoxin and IL-6 levels, and decreased HDL, apoA-I and activity of anti-oxidant HDL-associated paraoxanase-1. L-4F inhibits the activation of isolated human leukocytes and neutrophils by ARDS serum and LPS in vitro. Further, L-4F decreased endotoxin activity and preserved anti-oxidant properties of HDL both in vitro and in vivo. In a rat model of severe endotoxemia, L-4F significantly decreased mortality and reduces lung and liver injury, even when administered 1 hour post LPS. Our study suggests the protective role of the apoA-I mimetic peptide L-4F in ARDS and gram-negative endotoxemia and warrant further clinical evaluation. The main protective mechanisms of L-4F are due to direct inhibition of endotoxin activity and preservation of HDL anti-oxidant activity. PMID:23691230

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

    PubMed

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

    2016-01-01

    Sepsis is a frequent cause of death in very-low-birthweight infants and often results in neurological impairment. Its attributable risk of sequelae has not been systematically assessed. To establish an outcome tree for mapping the burden of neonatal sepsis, we performed systematic literature searches to identify systematic reviews addressing sequelae of neonatal sepsis. We included cohort studies and performed meta-analyses of attributable risks. Evidence quality was assessed using GRADE. Two systematic reviews met inclusion criteria. The first included nine cohort studies with 5,620 participants and five outcomes (neurodevelopmental impairment, cerebral palsy, vision impairment, hearing impairment, death). Pooled risk differences varied between 4% (95% confidence interval (CI):2-10) and 13% (95% CI:5-20). From the second review we analysed four studies with 472 infants. Positive predictive value of neurodevelopmental impairment for later cognitive impairment ranged between 67% (95% CI:22-96) and 83% (95% CI:36-100). Neonatal sepsis increases risk of permanent neurological impairment. Effect size varies by outcome, with evidence quality being low to very low. Data were used to construct an outcome tree for neonatal sepsis. Attributable risk estimates for sequelae following neonatal sepsis are suitable for burden estimation and may serve as outcome parameters in interventional studies. PMID:26940884

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

    PubMed Central

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

    2016-01-01

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

  17. Gender-related outcome difference is related to course of sepsis on mixed ICUs: a prospective, observational clinical study

    PubMed Central

    2011-01-01

    Introduction Impact of gender on severe infections is in highly controversial discussion with natural survival advantage of females described in animal studies but contradictory to those described human data. This study aims to describe the impact of gender on outcome in mixed intensive care units (ICUs) with a special focus on sepsis. Methods We performed a prospective, observational, clinical trial at Charité University Hospital in Berlin, Germany. Over a period of 180 days, patients were screened, undergoing care in three mainly surgical ICUs. In total, 709 adults were included in the analysis, comprising the main population ([female] n = 309, [male] n = 400) including 327 as the sepsis subgroup ([female] n = 130, [male] n = 197). Results Basic characteristics differed between genders in terms of age, lifestyle factors, comorbidities, and SOFA-score (Sequential Organ Failure Assessment). Quality and quantity of antibiotic therapy in means of antibiotic-free days, daily antibiotic use, daily costs of antibiotics, time to antibiotics, and guideline adherence did not differ between genders. ICU mortality was comparable in the main population ([female] 10.7% versus [male] 9.0%; P = 0.523), but differed significantly in sepsis patients with [female] 23.1% versus [male] 13.7% (P = 0.037). This was confirmed in multivariate regression analysis with OR = 1.966 (95% CI, 1.045 to 3.701; P = 0.036) for females compared with males. Conclusions No differences in patients' outcome were noted related to gender aspects in mainly surgical ICUs. However, for patients with sepsis, an increase of mortality is related to the female sex. PMID:21693012

  18. Australian Group on Antimicrobial Resistance Australian Enterococcal Sepsis Outcome Programme annual report, 2014.

    PubMed

    Coombs, Geoffrey W; Daley, Denise A; Thin Lee, Yung; Pang, Stanley; Pearson, Julie C; Robinson, J Owen; Johnson, Paul Dr; Kotsanas, Despina; Bell, Jan M; Turnidge, John D

    2016-01-01

    From 1 January to 31 December 2014, 27 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2014 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 952 unique episodes of bacteraemia investigated, 94.4% were caused by either E. faecalis (54.9%) or E. faecium (39.9%). Ampicillin resistance was detected in 0.6% of E. faecalis and in 89.4% of E. faecium. Vancomycin non-susceptibility was reported in 0.2% and 46.1% of E. faecalis and E. faecium respectively. Overall 51.1% of E. faecium harboured vanA or vanB genes. For the vanA/B positive E. faecium isolates, 81.5% harboured vanB genes and 18.5% vanA genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium consisted of 113 pulsed-field gel electrophoresis pulsotypes of which 68.9% of isolates were classified into 14 major pulsotypes containing 5 or more isolates. Multilocus sequence typing grouped the 14 major pulsotypes into clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. The geographical distribution of the 4 predominant sequence types (ST203, ST796, ST555 and ST17) varied with only ST203 identified across most regions of Australia. Overall 74.7% of isolates belonging to the four predominant STs harboured vanA or vanB genes. In conclusion, the AESOP 2014 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanA or vanB E. faecium, which have limited treatment options. PMID:27522135

  19. A Comparative Study to Assess the Determinants and Outcomes of Sepsis Treated in Medical Wards and ICU in an Indian Teaching Hospital

    PubMed Central

    Gautom, Debdutta; Nath, Neena; Saikia, Hiranya

    2016-01-01

    Introduction Sepsis is the primary cause of death from infection worldwide. In resource-limited countries, increasing number of sepsis is managed in non-ICU settings, in Medical Wards (MW). Aim To compare the burden, aetiology and short term outcome of sepsis treated in MW with ICU. Materials and Methods Prospective, observational, analytical study in sepsis patients in general MW and medical ICU in a tertiary care hospital. Two hundred forty five sepsis patients (MW=150, ICU=95), ≥18 years, selected randomly, were studied to compare aetiology, co-morbidities, clinical & microbiological profile and short-term outcome between MW and ICU sepsis. Sepsis following surgery, trauma, those transferred to/from ICU, those with other life threatening diseases were excluded. Chi-square test/Fisher’s-exact test was used for comparing ratios. A ’p-value’ <0.05 was considered statistically significant. Results Sepsis was more common in elderly males, both in MW and ICU (median age: 56.7, 59.2 years; male: female ratios = 1.34:1, 1.63:1 respectively). Frequency of presenting symptoms, co-morbidities and sources of sepsis were similar in both groups (p>0.05). Frequency of positive microbiological culture, pattern of microbial flora and antimicrobial resistance patterns were similar in both groups (p>0.05). Number of antibiotics used was significantly higher in ICU compared to MW (p<0.01); multi-organ dysfunction and mortality were significantly higher in ICU settings (55.8% vs. 38.7%, p=0.04; 48.4% vs. 32.6%, p=0.041 respectively). While sepsis and severe sepsis were significantly higher in MW (34.6% vs. 22.1 %, p=0.03; 47.3% vs. 26.3%, p<0.01 respectively), septic shock was significantly higher in ICU (51.6% vs. 18.0%, p<0.01). Mortality in both settings was highest in septic shock (55.5% and 61.2%, p>0.05) and multi-organ dysfunction (55.1% and 64.2%, p>0.05). Duration of hospital stay was significantly shorter in MW than ICU (7.3 vs. 11.0 days, p<0.01). Conclusion Our

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

    PubMed

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

    2016-06-15

    Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. The aim of our study was to investigate the molecular mechanism involved in the protective effects of GA in lipopolysaccharide (LPS) stimulated rat mesangial cells (HBZY-1) and septic rats. Sepsis model was established by injection of 5mg/kg LPS in rats or incubation with 1μg/ml LPS for 24h in HBZY-1 cells. A variety of molecular biological experiments were carried out to assess the effects of GA on inflammation, apoptosis, and oxidative stress. First we found that GA alleviated sepsis-induced kidney injury in vivo. Furthermore, GA suppressed inflammatory response in vivo and in vitro. Additionally, GA inhibited cell apoptosis and the changes in expressions of apoptosis related proteins induced by LPS. Moreover, GA markedly inhibited oxidative stress induced by LPS via activation of ERK signaling pathway. Finally GA could inhibit the activation of NF-κ B induced by LPS. Our present study indicates that GA has a protective effect against sepsis-induced inflammatory response, apoptosis, and oxidative stress damage, which provides a molecular basis for a new medical treatment of septic acute kidney injury. PMID:27063444

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

    PubMed

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

    2016-07-15

    Both quality improvement and clinical research efforts over the past few decades have focused on consensus definition of sepsis and acute respiratory distress syndrome (ARDS). Although clinical definitions based on readily available clinical data have advanced recognition and timely use of broad supportive treatments, they likely hinder the identification of more targeted therapies that manipulate select biological mechanisms underlying critical illness. Sepsis and ARDS are by definition heterogeneous, and patients vary in both their underlying biology and their severity of illness. We have long been able to identify subtypes of sepsis and ARDS that confer different prognoses. The key is that we are now on the verge of identifying subtypes that may confer different response to therapy. In this perspective, inspired by a 2015 American Thoracic Society International Conference Symposium entitled "Lumpers and Splitters: Phenotyping in Critical Illness," we highlight promising approaches to uncovering patient subtypes that may predict treatment responsiveness and not just differences in prognosis. We then discuss how this information can be leveraged to improve the success and translatability of clinical trials by using predictive enrichment and other design strategies. Last, we discuss the challenges and limitations to identifying biomarkers and endotypes and incorporating them into routine clinical practice. PMID:27244481

  2. Clinical outcomes of acute myocarditis in childhood

    PubMed Central

    Lee, K; McCrindle, B; Bohn, D; Wilson, G; Taylor, G; Freedom, R; Smallhorn, J; Benson, L

    1999-01-01

    OBJECTIVE—To describe clinical outcomes of a paediatric population with histologically confirmed lymphocytic myocarditis.
DESIGN—A retrospective review between November 1984 and February 1998.
SETTING—A major paediatric tertiary care hospital.
PATIENTS—36 patients with histologically confirmed lymphocytic myocarditis.
MAIN OUTCOME MEASURES—Survival, cardiac transplantation, recovery of ventricular function, and persistence of dysrhythmias.
RESULTS—Freedom from death or cardiac transplantation was 86% at one month and 79% after two years. Five deaths occurred within 72 hours of admission, and one late death at 1.9 years. Extracorporeal membrane oxygenation support was used in four patients, and three patients underwent heart replacement. 34 patients were treated with intravenous corticosteroids. In the survivor/non-cardiac transplantation group (n = 29), the median follow up was 19 months (range 1.2-131.6 months), and the median period for recovery of a left ventricular ejection fraction to > 55% was 2.8 months (range 0-28 months). The mean (SD) final left ventricular ejection and shortening fractions were 66 (9)% and 34 (8)%, respectively. Two patients had residual ventricular dysfunction. No patient required antiarrhythmic treatment. All survivors reported no cardiac symptoms or restrictions in physical activity.
CONCLUSIONS—Our experience documents good outcomes in paediatric patients presenting with acute heart failure secondary to acute lymphocytic myocarditis treated with immunosuppression. Excellent survival and recovery of ventricular function, with the absence of significant arrhythmias, continued cardiac medications, or restrictions in physical activity were the normal outcomes.


Keywords: myocarditis; paediatric cardiology; immunosuppression PMID:10409542

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. Curcumin protects against sepsis-induced acute lung injury in rats.

    PubMed

    Xiao, Xuefei; Yang, Mingshi; Sun, Dao; Sun, Shenghua

    2012-07-01

    The present study aimed to investigate the effect of curcumin on sepsis-induced acute lung injury (ALI) in rats, and explore its possible mechanisms. Male Sprague-Dawley rats were randomly divided into the following five experimental groups (n = 20 per group): animals undergoing a sham cecal ligature puncture (CLP) (sham group); animals undergoing CLP (control group); or animals undergoing CLP and treated with vehicle (vehicle group), curcumin at 50 mg/kg (low-dose curcumin [L-Cur] group), or curcumin at 200 mg/kg (high-dose curcumin [H-Cur] group).At 6, 12, 24 h after CLP, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level, and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathologic changes in lungs. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, as well as superoxidase dismutase (SOD) activity were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interluekin-8 (IL-8), and macrophage migration inhibitory factor (MIF) were determined in the BALF. Survival rates were recorded at 72 h in the five groups in another experiment. Treatment with curcumin significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung W/D ratio, protein concentration, and the accumulation of the inflammatory cells in the BALF, as well as pulmonary MPO activity. This was supported by the histopathologic examination, which revealed marked attenuation of CLP-induced ALI in curcumin treated rats. In addition, curcumin significantly increased SOD activity with significant decrease in MDA content in the lung. Also, curcumin caused down-regulation of the inflammatory cytokines TNF-α, IL-8, and MIF levels in the lung. Importantly, curcumin improved the survival rate of rats by 40%-50% with CLP-induced ALI. Taken together, these results

  6. The Association of Lacking Insurance With Outcomes of Severe Sepsis: Retrospective Analysis of an Administrative Database

    PubMed Central

    Kumar, Gagan; Taneja, Amit; Majumdar, Tilottama; Jacobs, Elizabeth R.; Whittle, Jeff; Nanchal, Rahul

    2016-01-01

    Objective Patients with severe sepsis have high mortality that is improved by timely, often expensive, treatments. Patients without insurance are more likely to delay seeking care; they may also receive less intense care. Design We performed a retrospective analysis of administrative database—Healthcare Costs and Utilization Project’s Nationwide Inpatient Sample—to test whether mortality is more likely among uninsured patients hospitalized for severe sepsis. Patients None. Interventions We used International Classification of Diseases—9th Revision, Clinical Modification, codes indicating sepsis and organ system failure to identify hospitalizations for severe sepsis among patients aged 18–64 between 2000 and 2008. We excluded patients with end-stage renal disease or solid organ transplants because very few are uninsured. We performed multivariate logistic regression modeling to examine the association of insurance status and in-hospital mortality, adjusted for patient and hospital characteristics. We performed subgroup analysis to examine whether the impact of insurance status varied by geographical region; by patient age, sex, or race; or by hospital characteristics such as teaching status, size, or ownership. We used similar methods to examine the impact of insurance status on the use of certain procedures, length of stay, and discharge destination. Measurements and Main Results There were 1,600,269 discharges with severe sepsis from 2000 through 2008 in the age group 18–64 years. Uninsured people, who accounted for 7.5% of admissions with severe sepsis, had higher adjusted odds of mortality (odds ratio, 1.43; 95% CI, 1.37–1.47) than privately insured people. The higher mortality in uninsured was present in all subgroups and was similar in each year from 2000 to 2008. After adjustment, uninsured individuals had a slightly shorter length of stay than insured people and were less likely to receive five of the six interventions we examined. They were

  7. Ghrelin attenuates sepsis-associated acute lung injury oxidative stress in rats.

    PubMed

    Zeng, Mian; He, Wanmei; Li, Lijun; Li, Bin; Luo, Liang; Huang, Xubin; Guan, Kaipan; Chen, Weiling

    2015-04-01

    This study investigated the effect of ghrelin on oxidative stress in septic rat lung tissue. Male Sprague-Dawley rats were divided into sham-operation, sepsis, and ghrelin groups. Sepsis was induced by cecal ligation and puncture. Ghrelin was administered intraperitoneally at 3 and 15 h post-operation. Bronchoalveolar lavage was performed to collect alveolar macrophages (AMs). Inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression in alveolar macrophages and iNOS protein levels were measured by reverse transcription PCR (RT-PCR) and Western blot. Pulmonary pathology was analyzed and nitrotyrosine expression was examined by immunohistochemistry. Plasma superoxide dismutase (SOD) and lung wet/dry weight were measured. In the sepsis group, iNOS mRNA expression in AMs was 1.33 ± 0.05, 1.44 ± 0.08, and 1.57 ± 0.11 at 6, 12, and 20 h post-surgery, respectively, and were higher compared with the sham-operation group (p<0.05). No increase was observed at longer time points. iNOS mRNA expression in the sepsis group was lower compared with the ghrelin group (2.27 ± 0.37) (p<0.05) at 20 h post-surgery. iNOS protein levels in the ghrelin group (0.87 ± 0.03, p<0.05) were lower than in the sepsis group at 20 h. Ghrelin group pathological scores were lower than in the sepsis group (p<0.05). Plasma SOD was slightly non-significantly decreased in the ghrelin group. No difference was observed in lung wet/dry weight ratios between sepsis and ghrelin groups. iNOS mRNA expression in AMs was elevated between 6 and 20 h after cecal ligation and puncture (CLP), but did not progress. Ghrelin attenuated pulmonary iNOS protein expression and tended to increase plasma SOD activity. Ghrelin suppressed pulmonary nitrosative stress in septic rats, but did not improve lung wet/dry weight ratios. PMID:25037094

  8. [Sepsis in Emergency Medicine].

    PubMed

    Christ, Michael; Geier, Felicitas; Bertsch, Thomas; Singler, Katrin

    2016-07-01

    Sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host-response to infection". Presence of organ dysfunction is associated with a mortality of 10% and higher in hospitalized sepsis patients.Introduction of standards in diagnosis and treatment of sepsis in intensive care units has not considerably reduced sepsis mortality. About 80% of patients with sepsis are transferred to intensive care units from usual care wards and emergency departments. Thus, it is tempting to speculate whether opportunities for further improvement of sepsis management exist outside of intensive care units. Performing a "quick sequential organ assessment" (qSOFA; two of following criteria have to be present: respiratory rate >22/min; sytolic blood pressure <100mmHg; altered mental status) supports to identify patients with suspicion of an infection and an increased risk of death within the hospital. Subsequent treatment according to current guidelines on sepsis management will reduce in-hospital mortality of sepsis patients. Indeed, we were able to show a substantial decrease of in-hospital mortality of about 20% in patients presenting with community acquired pneumonia to the emergency department.In summary, decision of further management of sepsis patients has to be done outside intensive care units at the time of initial presentation to professional care givers. Sepsis management in acute care settings should include a structured and standardized protocol to further improve survival in affected patients with even mild organ dysfunction. PMID:27464279

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

    PubMed

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

    2015-01-01

    Pregnancy-associated acute kidney injury (PAKI) is encountered frequently in developing countries. We evaluated the maternal, fetal and renal outcomes in women with PAKI who needed at least one session of dialysis. Of the total of 98 cases (mean age 28.85 ± 5.13 years; mean parity 2.65 ± 1.28) of PAKI, the most common cause of PAKI was postabortal sepsis. Eighteen patients died; those with oligoanuria, sepsis and central nervous system (CNS) involvement were at greater risk of mortality. The relative risk (RR) of neonatal mortality was lower after with full-term delivery (RR: 0.17, 95% confidence interval (CI): 0.03-0.96, P = 0.02) compared to preterm delivery. Of the 80 surviving patients, 60 (75%) patients achieved complete recovery of renal function at the end of 3 months; and of the remaining 14 had presumed (n = 4) or, biopsy-proven (n = 10) acute patchy cortical necrosis. The RR of non-recovery of renal function was high (RR: 24.7, 95% CI: 3.4- 179.5) in patients who did not recover at 6 weeks. Of the 14 patients with cortical necrosis, 3 (21.42%) became independent of dialysis at 6 months. PAKI patients should be watched for dialysis independency for 6 months. PMID:25838643

  10. [Patients with sepsis].

    PubMed

    Oppert, M

    2016-05-01

    Sepsis is still the leading cause of mortality in noncardiac intensive care units. The new definition of sepsis emphasizes the importance of organ dysfunction. The Sepsis-related Organ Failure Assessment (SOFA) score is an indicator for organ dysfunction. The diagnosis of sepsis is for the most part made on clinical parameters with an altered mental status being a very sensitive indicator. Microbiological work-up is essential and two sets of blood cultures are the recommended minimum. Management includes prompt initiation of adequate antibiotic treatment and swift fluid resuscitation. Overinfusion is to be avoided as this itself can have a negative impact on patient outcome. PMID:27160262

  11. TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis.

    PubMed

    Xu, Chang; Chang, Anthony; Hack, Bradley K; Eadon, Michael T; Alper, Seth L; Cunningham, Patrick N

    2014-01-01

    Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration permselectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower, whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-α activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse. PMID:23903370

  12. The Effect of Statins Use on the Risk and Outcome of Acute Bacterial Infections in Adult Patients

    PubMed Central

    Ghorbani, Raheb; Afshar, Reza Kiaee

    2015-01-01

    Background Beyond their lipid-lowering abilities, statins have anti-inflammatory and immunomodulatory properties. In view of these effects, a growing interest has emerged in the possible role of statins, in preventing or decreasing morbidity and mortality from infection. Objectives The aim of this study was to determine whether previous statin use is associated with reduced risk of acute bacterial infections and better outcome of these infections. Materials and Methods In this historical cohort study, consecutive adult patients admitted with acute bacterial infection were enrolled. Control group were selected from adult outpatient and without history of acute bacterial infections. Acute bacterial infections included in this study were; pneumonia, acute pyelonephritis, cellulitis and sepsis with unknown origin. Data about baseline characteristics, co-morbidities and statins use of two groups was obtained. Results Finally 144 patients met inclusion criteria and were enrolled. Same numbers of controls were selected. Two groups were matched based on most baseline characteristics and co-morbidities. The patients’ categories were as follows: pneumonia 42.3%, acute pyelonephritis 23.6%, cellulitis 16% and sepsis 18%. From all participants 29.9% of patients and 45.8% controls were statin users. There was significant association between previous statin use and reduced risk of acute bacterial infections (Mantel Haenszel Weighted Odds Ratio=0.51, 95% CI: 0.30-0.85, p=0.009). Duration of hospitalization was significantly shorter in statin users (p=0.002). Hospital mortality rate was lower (14.6%) in statins users when compared with non-users (18.8%) with significant difference (p=0.028). Conclusion Prior therapy with statins is associated with considerably reduced onset of acute bacterial infections and better outcome in adult patients. PMID:26676277

  13. Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury

    PubMed Central

    2010-01-01

    Introduction Recruitment maneuvers (RMs) seem to be more effective in extrapulmonary acute lung injury (ALI), caused mainly by sepsis, than in pulmonary ALI. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. Since the interaction between volemic status and RMs is not well established, we investigated the effects of RMs on lung and distal organs in the presence of hypovolemia, normovolemia, and hypervolemia in a model of extrapulmonary lung injury induced by sepsis. Methods ALI was induced by cecal ligation and puncture surgery in 66 Wistar rats. After 48 h, animals were anesthetized, mechanically ventilated and randomly assigned to 3 volemic status (n = 22/group): 1) hypovolemia induced by blood drainage at mean arterial pressure (MAP)≈70 mmHg; 2) normovolemia (MAP≈100 mmHg), and 3) hypervolemia with colloid administration to achieve a MAP≈130 mmHg. In each group, animals were further randomized to be recruited (CPAP = 40 cm H2O for 40 s) or not (NR) (n = 11/group), followed by 1 h of protective mechanical ventilation. Echocardiography, arterial blood gases, static lung elastance (Est,L), histology (light and electron microscopy), lung wet-to-dry (W/D) ratio, interleukin (IL)-6, IL-1β, caspase-3, type III procollagen (PCIII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) mRNA expressions in lung tissue, as well as lung and distal organ epithelial cell apoptosis were analyzed. Results We observed that: 1) hypervolemia increased lung W/D ratio with impairment of oxygenation and Est,L, and was associated with alveolar and endothelial cell damage and increased IL-6, VCAM-1, and ICAM-1 mRNA expressions; and 2) RM reduced alveolar collapse independent of volemic status. In hypervolemic animals, RM improved oxygenation above the levels observed with the use of positive-end expiratory pressure (PEEP), but increased lung injury and led to higher inflammatory and fibrogenetic

  14. Late mortality after sepsis: propensity matched cohort study

    PubMed Central

    Osterholzer, John J; Langa, Kenneth M; Angus, Derek C; Iwashyna, Theodore J

    2016-01-01

    Objectives To determine whether late mortality after sepsis is driven predominantly by pre-existing comorbid disease or is the result of sepsis itself. Deign Observational cohort study. Setting US Health and Retirement Study. Participants 960 patients aged ≥65 (1998-2010) with fee-for-service Medicare coverage who were admitted to hospital with sepsis. Patients were matched to 777 adults not currently in hospital, 788 patients admitted with non-sepsis infection, and 504 patients admitted with acute sterile inflammatory conditions. Main outcome measures Late (31 days to two years) mortality and odds of death at various intervals. Results Sepsis was associated with a 22.1% (95% confidence interval 17.5% to 26.7%) absolute increase in late mortality relative to adults not in hospital, a 10.4% (5.4% to 15.4%) absolute increase relative to patients admitted with non-sepsis infection, and a 16.2% (10.2% to 22.2%) absolute increase relative to patients admitted with sterile inflammatory conditions (P<0.001 for each comparison). Mortality remained higher for at least two years relative to adults not in hospital. Conclusions More than one in five patients who survives sepsis has a late death not explained by health status before sepsis. PMID:27189000

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

    PubMed Central

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

    2016-01-01

    BACKGROUND: Whether early goal-directed therapy (EGDT) improves outcome in severe sepsis and septic shock remains unclear. We performed a meta-analysis of existing clinical trials to examine whether EGDT improved outcome in the resuscitation of adult sepsis patients compared with control care. METHODS: We searched for eligible studies using MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials, and Web of Science databases. Studies were eligible if they compared the effects of EGDT versus control care on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Data including mortality, sample size of the patients with severe sepsis and septic shock, and resuscitation end points were extracted. Data were analyzed using methods recommended by the Cochrane Collaboration Review Manager 4.2 software. Random errors were evaluated by trial sequential analysis (TSA). RESULTS: Nine studies compared EGDT with control care, and 5202 severe sepsis and septic shock patients were included. A nonsignificant trend toward reduction in the longest all-cause mortality was observed in the EGDT group compared with control care (relative risk, 0.89; 99% confidence interval, 0.74–1.07; P = 0.10). However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients (relative risk, 0.72; 99% confidence interval, 0.57–0.90; P = 0.0002). TSA indicated lack of firm evidence for a beneficial effect. CONCLUSIONS: In this meta-analysis, a nonsignificant trend toward reduction in the longest all-cause mortality in patients resuscitated with EGDT was noted. However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients. TSA indicated a lack of firm evidence for the results. More powered, randomized controlled trials are needed to determine the effects. PMID:27049857

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

    PubMed

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

    2015-01-01

    Acute kidney injury (AKI) is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%). Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases), hemorrhagic shock (six cases) and septic events (five cases). We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6%) cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care. PMID:26022044

  17. Predictors of Acute Hemodynamic Decompensation in Early Sepsis: An Observational Study

    PubMed Central

    Lee, Young Im; Smith, Robert L.; Gartshteyn, Yevgeniya; Kwon, Sophia; Caraher, Erin J.; Nolan, Anna

    2016-01-01

    Background The study of sepsis is hindered by its heterogeneous time course and evolution. A subgroup of patients with severe sepsis develops shock soon after the initiation of treatment while others present hypotensive. We sought to determine the incidence of hypotension after the initiation of treatment for sepsis, and characterize their clinical features and course. Methods A retrospective review of electronic medical record of all septic patients (n = 542) that met the definition of septic shock within 24 hours of admission (2011 - 2012) at an urban Veteran Affairs Hospital was performed. Subjects either had 1) initial normotension (INT) with hypotension developing within 24 hours or 2) initial hypotension (IH). Logistic regression was used to model associated factors of INT/IH. Results INT occurred in 62 patients (11%) with average initial blood pressure of 120/71 mm Hg and developed hypotension to 79/48 mm Hg. IH was identified in 52 patients (10%) with average presenting blood pressure of 81/46 mm Hg. INT showed evidence of increased sympathetic tone with significantly higher heart rate, blood pressure and temperature. INT patients were younger, more frequently on alpha-blockers, and more likely septic from pneumonia compared to IH patients. INT and IH patients had similar timing of antibiotic initiation, amount of 24-hour fluid resuscitation, vasopressor use, organ dysfunction and mortality at 28 days. Using alpha-blockers, being Caucasian, and having higher temperatures were independent predictors of INT. Conclusion INT is a distinctive presentation of septic shock characterized by rapid deterioration during early treatment. By further studying this subgroup, mediators of septic shock may be identified that clarify pathophysiology and provide timely targeted treatment. PMID:27429677

  18. Presepsin is an early monitoring biomarker for predicting clinical outcome in patients with sepsis.

    PubMed

    Ali, Fahmy T; Ali, Mohamed A M; Elnakeeb, Mostafa M; Bendary, Heba N M

    2016-09-01

    Despite their undoubted helpfulness in diagnosing sepsis, increased blood C-reactive protein (CRP) and procalcitonin (PCT) levels have been described in many noninfectious conditions. Presepsin is a soluble fragment of the cluster of differentiation 14 involved in pathogen recognition by innate immunity. We aimed to investigate the diagnostic and prognostic performance of presepsin in comparison to PCT and CRP in patients presenting with systemic inflammatory response syndrome (SIRS) and suspected sepsis. Seventy-six subjects were enrolled in this study, including 51 patients with SIRS as well as 25 healthy subjects. Plasma presepsin, PCT and CRP levels were serially measured on admission and at days 1, 3, 7 and 15. Presepsin and PCT yielded similar diagnostic accuracy, whereas presepsin performed significantly better than CRP. Presepsin and PCT showed comparable performance for predicting 28-day mortality, and both biomarkers performed significantly better than CRP. In septic patients, presepsin revealed earlier concentration changes over time when compared to PCT and CRP. Presepsin and PCT could differentiate between septic and non-septic patients with comparable accuracy and both biomarkers showed similar performance for predicting 28-day mortality. Early changes in presepsin concentrations might reflect the appropriateness of the therapeutic modality and could be useful for making effective treatment decisions. PMID:27353646

  19. Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury

    PubMed Central

    Chen, Hong-Hwa; Chang, Chia-Lo; Lin, Kun-Chen; Sung, Pei-Hsun; Chai, Han-Tan; Zhen, Yen-Yi; Chen, Yi-Ching; Wu, Ying-Chung; Leu, Steve; Tsai, Tzu-Hsien; Chen, Chih-Hung; Chang, Hsueh-Wen; Yip, Hon-Kan

    2014-01-01

    This study investigated whether combining melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) was superior to ADMSC alone in ameliorating sepsis-induced acute lung injury. Adult male Sprague-Dawley rats (n=50) were randomized equally into five groups: sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating interleukin (IL)-6 at 6, 18, and 72 hrs, were highest in CLP and lowest in SC groups, higher in CLP-melatonin than CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, higher in CLP-A-ADMSC than CLP-melatonin-A-ADMSC groups (all p<0.001). Immune reactivity (indicated by circulating cytotoxic-, and regulatory-T cells) and WBC count at 72 h exhibited the same pattern as that of circulating IL-6 (all p<0.001). Changes in histological scoring of lung parenchyma and the number of CD68+ and CD14+ cells showed a similar pattern compared to that of IL-6 level in all groups (all p<0.001). Changes in protein expressions of inflammatory (oxidative stress, RANTES, TNF-α, NF-κB, MMP-9, MIP-1, IL-1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-β) markers and those of reactive-oxygen-species (NOX-1, NOX-2) displayed an identical pattern compared to that of circulating IL-6 in all groups (all p<0.001). Anti-oxidative capacities (GR+, GPx+, HO-1, NQO-1+) and angiogenesis marker (CXCR4+ cells) were lowest in SC group but highest in CLP-melatonin-A-ADMSC group, lower in CLP than CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin than CLP-A-ADMSC groups (all p<0.001). In conclusion, combined melatonin and A-ADMSC were superior to A-ADMSC alone in protecting the lung from sepsis-induced injury. PMID:25360211

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

    PubMed Central

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

    2013-01-01

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

  1. The TFPI-2 Derived Peptide EDC34 Improves Outcome of Gram-Negative Sepsis

    PubMed Central

    Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E.; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

    2013-01-01

    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. PMID:24339780

  2. Serum Neutrophil Gelatinase Associated Lipocalin (NGAL) Outperforms Serum Creatinine in Detecting Sepsis-Induced Acute Kidney Injury, Experiments on Bilateral Nephrectomy and Bilateral Ureter Obstruction Mouse Models.

    PubMed

    Leelahavanichkul, Asada; Somparn, Poorichaya; Issara-Amphorn, Jiraphorn; Eiam-Ong, Somchai; Avihingsanon, Yingyos; Hirankarn, Nattiya; Srisawat, Nattachai

    2016-05-01

    Serum neutrophil gelatinase associated lipocalin (sNGAL), a promising acute kidney injury (AKI) biomarker produced by renal and non-renal tissues, might be affected by sepsis. We evaluated sNGAL in zero glomerular filtration rate models [bilateral ureter obstruction (BUO) and bilateral nephrectomy (BiNx)] with subsequent cecal ligation and puncture (CLP)-induced sepsis in 6 to 8-week-old ICR mice. We found that sNGAL increased earlier than serum creatinine (Scr) in BiNx/BUO with and without CLP. The earliest time-point of increased sNGAL in BiNx+CLP was 1 h after surgery. Scr, but not sNGAL, was lower at 18 h after BiNx/BUO+CLP compared with BiNx/BUO alone. Compared with BUO, BiNx had higher, and equal sNGAL at 1 to 18 h and 36 h, respectively. Additionally, similar NGAL expression in internal organs (heart, lung, liver, and spleen) and survival rates indicated the comparable severity of BiNx and BUO. Serum interleukin (IL)-6 was increased and correlated with sNGAL in BiNx/BUO with and without sepsis. In summary, we demonstrated: sNGAL is an early AKI biomarker, which is not affected by sepsis; sNGAL is mainly produced by extrarenal sources as demonstrated by the comparable sNGAL in BiNx and BUO; the saturation of renal NGAL re-absorption in BUO is demonstrated by lower sNGAL in BUO at 1 to 18 h, but not at 36 h when compared with BiNx; and a correlation of sNGAL and IL-6 implied sNGAL is a good sepsis prognostic biomarker. Therefore, sNGAL is a more beneficial sepsis-AKI biomarker than Scr. PMID:26863120

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

    PubMed Central

    2014-01-01

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

  4. Biomarkers in sepsis.

    PubMed

    Walley, Keith R

    2013-10-01

    There is much enthusiasm and interest in sepsis biomarkers, particularly because sepsis is a highly lethal condition, its diagnosis is challenging, and even simple treatment with antibiotics has led to serious adverse consequences such as emergence of resistant pathogens. Yet development of a sepsis biomarker requires many more steps than simply finding an association between a particular molecule and a clinical state or outcome. Demonstration of improvement of therapeutic practice using receiver-operating characteristic and other analyses is important. Validation in independent, prospective and, preferably, multicenter trials is essential. Many promising candidate sepsis biomarkers have recently been proposed. While procalcitonin (PCT) is currently the most studied sepsis biomarker, evidence of potential value has been found for a wide array of blood biomarkers including proteins, mRNA expression in whole blood or leukocytes, micro-RNAs (miRNA), pathogen and host DNA, pathogen and host genetic variants and metabolomic panels, and even in the novel use of currently available clinical data. While the most common early reports link putative sepsis biomarker levels to severity of illness and outcome (prognostic), this is not anticipated to be their primary use. More important is the distinction between infection and noninfectious inflammatory responses (diagnostic) and the use of sepsis biomarkers to direct therapy (predictive). PMID:23975686

  5. Neonatal sepsis

    MedlinePlus

    ... and some strains of streptococcus. Group B streptococcus (GBS) has been a major cause of neonatal sepsis. ... an infant's risk of early-onset bacterial sepsis: GBS colonization during pregnancy Preterm delivery Water breaking (rupture ...

  6. Severe sepsis and septic shock

    PubMed Central

    Schorr, Christa A; Zanotti, Sergio; Dellinger, R Phillip

    2014-01-01

    Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical care outcomes, has led to the development of clinical practice guidelines in a variety of areas related to infection and sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and Septic Shock were first published in 2004, revised in 2008, and recently revised again and published in 2013. The first part of this manuscript is a summary of the 2013 guidelines with some editorial comment. The second part of the manuscript characterizes hospital based sepsis performance improvement programs and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key component of such a program. PMID:24335487

  7. Sepsis: pathophysiology and clinical management.

    PubMed

    Gotts, Jeffrey E; Matthay, Michael A

    2016-01-01

    Sepsis, severe sepsis, and septic shock represent increasingly severe systemic inflammatory responses to infection. Sepsis is common in the aging population, and it disproportionately affects patients with cancer and underlying immunosuppression. In its most severe form, sepsis causes multiple organ dysfunction that can produce a state of chronic critical illness characterized by severe immune dysfunction and catabolism. Much has been learnt about the pathogenesis of sepsis at the molecular, cell, and intact organ level. Despite uncertainties in hemodynamic management and several treatments that have failed in clinical trials, investigational therapies increasingly target sepsis induced organ and immune dysfunction. Outcomes in sepsis have greatly improved overall, probably because of an enhanced focus on early diagnosis and fluid resuscitation, the rapid delivery of effective antibiotics, and other improvements in supportive care for critically ill patients. These improvements include lung protective ventilation, more judicious use of blood products, and strategies to reduce nosocomial infections. PMID:27217054

  8. Determinants of hepcidin levels in sepsis-associated acute kidney injury: Impact on pAKT/PTEN pathways?

    PubMed

    Schaalan, Mona F; Mohamed, Walid A

    2016-09-01

    The antimicrobial β-defensin-like role of hepcidin (HEPC) has been increasingly investigated for its potential role in acute kidney injury (AKI). In sepsis-induced AKI, there is a complex interplay between positive and negative regulation of HEPC, with consequently altered distributions of iron caused by changes in HEPC levels. The aim of the current research was to assess serum HEPC levels in a cohort of septic patients with AKI and investigate the regulatory impact of hypoxia-inducing factor (HIF)-1α, erythropoietin (EPO) and inflammation on HEPC levels and related signal cascades in these patients. Baseline, higher levels of SCr (2.3-fold), blood urea nitrogen (BUN) (1.8-fold), uric acid (2.3-fold) and white blood cell (2.3-fold) were noted in septic AKI patients, along with decreased levels of albumin (15.7%), creatinine (44.7%) and BUN/creatinine ratios (23.8%), compared to in normal subjects. These hosts also had increased serum levels of TNFα (4.4-times) and TGFβ1 (3.2-times) compared to controls (p < 0.05). Further, HEPC and HIF-1α levels were also increased (8.8- and 3.6-times control levels), while EPO levels were decreased (77.8%) from control levels. After 12 weeks of antibiotic therapy, all septic AKI patients showed significant improvement of the altered markers of kidney dysfunction. In line with significant reductions in serum TNFα and TGFβ1 (25.5% and 26.2%, respectively), HEPC and HIF-1α levels were significantly decreased (31.6% and 19.3%), and EPO levels increased (1.9-fold) compared to pretreatment values. There was a significant positive correlation between HEPC levels and kidney function markers (SCr and BUN), inflammatory TNFα and TGFβ1 and serum HIF-1α and pAKT in septic AKI patients before and after treatment. Based on the results here, we conclude that HEPC, EPO and HIF-1α are involved in the pathogenesis of sepsis-induced AKI and confirm the dominating effects of inflammatory determinants over hypoxia

  9. Neurodevelopmental and Behavioral Outcomes in Children With Sepsis-Associated Encephalopathy Admitted to Pediatric Intensive Care Unit: A Prospective Case Control Study.

    PubMed

    Kaur, Jasmine; Singhi, Pratibha; Singhi, Sunit; Malhi, Prahbhjot; Saini, Arushi Gahlot

    2016-05-01

    The authors prospectively compared the neurodevelopmental and behavioral outcomes in 50 consecutive children with sepsis-associated encephalopathy admitted to intensive care unit with healthy controls. Children with sepsis-associated encephalopathy had significantly worse mean verbal IQ, full-scale IQ, General Development Score, and its physical, adaptive, social-emotional, cognitive, and communication subscales. Significant proportion of cases (52% vs 32% in controls) had low intelligence. Decline in school performance (44%), disobedience (28%), and stubbornness/irritable behavior (26%) were the most common behavior changes. Children with Glasgow Coma Scale score ≤10 and ≤8 had impairments in full-scale IQ even though overall Glasgow Coma Scale score did not show significant correlation with developmental outcomes. In conclusion, children with sepsis-associated encephalopathy have delayed neurodevelopment, low verbal IQ, decline in school performance and low intelligence at short-term follow-up. Irritability, shock and duration of sedation are associated with poor behavioral outcomes, especially scholastic performance. PMID:26500243

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

    PubMed Central

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

    2015-01-01

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

  11. Gadolinium chloride attenuates sepsis-induced pulmonary apoptosis and acute lung injury.

    PubMed

    Kishta, Osama A; Goldberg, Peter; Husain, Sabah N A

    2012-01-01

    Gadolinium chloride (GdCl3), a Kupffer cells inhibitor, attenuates acute lung injury; however, the mechanisms behind this effect are not completely elucidated. We tested the hypothesis that GdCl3 acts through the inhibition of lung parenchymal cellular apoptosis. Two groups of rats were injected intraperitoneally with saline or E. coli lipopolysaccharide. In two additional groups, rats were injected with GdCl3 24 hrs prior to saline or LPS administration. At 12 hrs, lung injury, inflammation, and apoptosis were studied. Lung water content, myeloperoxidase activity, pulmonary apoptosis and mRNA levels of interleukin-1 β , -2, -5, -6, -10 and TNF- α rose significantly in LPS-injected animals. Pretreatment with GdCl3 significantly reduced LPS-induced elevation of pulmonary water content, myeloperoxidase activity, cleaved caspase-3 intensity, and attenuated pulmonary TUNEL-positive cells. GdCl3 pre-treatment upregulated IL-1 β , -2 and -10 pulmonary gene expression without significantly affecting the others. These results suggest that GdCl3 attenuates acute lung injury through its effects on pulmonary parenchymal apoptosis. PMID:24049647

  12. The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis

    PubMed Central

    Sterling, Sarah A.; Miller, W. Ryan; Pryor, Jason; Puskarich, Michael A.; Jones, Alan E.

    2015-01-01

    Objectives We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. Data Sources and Study Selection A comprehensive search was performed using a pre-defined protocol. Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to ED triage and/or shock recognition, and mortality. Exclusion criteria: immunosuppressed populations, review article, editorial, or non-human studies. Data Extraction Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of ED triage; 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds Ratios (OR) were calculated using a random effect model. The primary outcome was mortality. Data Synthesis 1123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from ED triage. Patients who received antibiotics more than 3 hours after ED triage (< 3 hours reference), had a pooled OR for mortality of 1.16 (0.92 to 1.46, p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hour reference) had a pooled OR for mortality of 1.46 (0.89 to 2.40, p = 0.13). There was no increased mortality in the pooled ORs for each hourly delay from <1 to >5 hours in antibiotic administration from severe sepsis/shock recognition. Conclusion Using the available pooled data we found no significant mortality benefit of administering antibiotics within 3 hours of ED triage or within 1 hour of shock recognition in severe sepsis and septic shock

  13. Induction of hepatocyte lipopolysaccharide binding protein in models of sepsis and the acute-phase response.

    PubMed

    Geller, D A; Kispert, P H; Su, G L; Wang, S C; Di Silvio, M; Tweardy, D J; Billiar, T R; Simmons, R L

    1993-01-01

    Lipopolysaccharide binding protein (LBP) is a serum glycoprotein that complexes with lipopolysaccharide (LPS) to facilitate macrophage response to endotoxin. To determine the conditions that stimulate LBP production in vivo, we measured the induction of LBP in models of inflammation produced by LPS, Corynebacterium parvum, and turpentine injection. Plasma aspartate aminotransferase and alanine aminotransferase concentrations and hepatocyte fibrinogen synthesis were elevated in all models. Northern blot analysis revealed 17-, 14-, and 20-fold upregulation of hepatocyte LBP mRNA following treatment with LPS, C parvum, and turpentine, respectively. Peritoneal macrophage interleukin 6 and tumor necrosis factor production following endotoxin stimulation was augmented by cultured hepatocyte supernatants, suggesting increased LBP synthesis in these groups. The results show that LBP mRNA is induced during hepatic inflammation and suggest that LBP is an acute-phase protein important in regulating the in vivo response to endotoxin. PMID:8418776

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2013-07-01

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

  16. Reduced Production of Creatinine Limits Its Use as Marker of Kidney Injury in Sepsis

    PubMed Central

    Doi, Kent; Yuen, Peter S.T.; Eisner, Christoph; Hu, Xuzhen; Leelahavanichkul, Asada; Schnermann, Jürgen; Star, Robert A.

    2009-01-01

    Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-α. Serum creatinine, however, was significantly lower in septic animals than in animals subjected to bilateral nephrectomy and sham cecal ligation and puncture. Under these conditions treatment with chloroquine decreased nonrenal organ injury markers but paradoxically increased serum creatinine. Sepsis dramatically decreased production of creatinine in nephrectomized mice, without changes in body weight, hematocrit, or extracellular fluid volume. In conclusion, sepsis reduces production of creatinine, which blunts the increase in serum creatinine after sepsis, potentially limiting the early detection of acute kidney injury. This may partially explain why small absolute increases in serum creatinine levels are associated with poor clinical outcomes. These data support the need for new biomarkers that provide better measures of renal injury, especially in patients with sepsis. PMID:19389851

  17. Improving the Outcome of Acute Pancreatitis.

    PubMed

    Bruno, Marco J

    2016-01-01

    Acute pancreatitis (AP) is the most common indication for hospital admission and its incidence is rising. It has a variable prognosis, which is mainly dependent upon the development of persistent organ failure and infected necrotizing pancreatitis. In the past few years, based on large-scale multicenter randomized trials, some novel insights regarding clinical management have emerged. In patients with infected pancreatic necrosis, a step-up approach of percutaneous catheter drainage followed by necrosectomy only when the patient does not improve, reduces new-onset organ failure and prevents the need for necrosectomy in about a third of patients. A randomized pilot study comparing surgical to endoscopic necrosectomy in patients with infected necrotizing pancreatitis showed a striking reduction of the pro-inflammatory response following endoscopic necrosectomy. These promising results have recently been tested in a large multicenter randomized trial whose results are eagerly awaited. Contrary to earlier data from uncontrolled studies, a large multicenter randomized trial comparing early (within 24 h) nasoenteric tube feeding compared with an oral diet after 72 h, did not show that early nasoenteric tube feeding was superior in reducing the rate of infection or death in patients with AP at high risk for complications. Although early ERCP does not have a role in the treatment of predicted mild pancreatitis, except in the case of concomitant cholangitis, it may ameliorate the disease course in patients with predicted severe pancreatitis. Currently, a large-scale randomized study is underway and results are expected in 2017. PMID:27336312

  18. Improving Alcohol Withdrawal Outcomes in Acute Care

    PubMed Central

    Melson, Jo; Kane, Michelle; Mooney, Ruth; McWilliams, James; Horton, Terry

    2014-01-01

    Context Excessive alcohol consumption is the nation’s third leading cause of preventable deaths. If untreated, 6% of alcohol-dependent patients experience alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT), when they stop drinking. Without routine screening, patients often experience DT without warning. Objective: Reduce the incidence of alcohol withdrawal advancing to DT, restraint use, and transfers to the intensive care unit (ICU) in patients with DT. Design: In October 2009, the alcohol withdrawal team instituted a care management guideline used by all disciplines, which included tools for screening, assessment, and symptom management. Data were obtained from existing datasets for three quarters before and four quarters after implementation. Follow-up data were analyzed and showed a great deal of variability in transfers to the ICU and restraint use. Percentage of patients who developed DT showed a downward trend. Main Outcome Measures: Incidence of alcohol withdrawal advancing to DT and, in patients with DT, restraint use and transfers to the ICU. Results: Initial data revealed a decrease in percentage of patients with alcohol withdrawal who experienced DT (16.4%–12.9%). In patients with DT, restraint use decreased (60.4%–44.4%) and transfers to the ICU decreased (21.6%–15%). Follow-up data indicated a continued downward trend in patients with DT. Changes were not statistically significant. Restraint use and ICU transfers maintained postimplementation levels initially but returned to preimplementation levels by third quarter 2012. Conclusion: Early identification of patients for potential alcohol withdrawal followed by a standardized treatment protocol using symptom-triggered dosing improved alcohol withdrawal management and outcomes. PMID:24867561

  19. Requisite Role of the Cholinergic α7 Nicotinic Acetylcholine Receptor Pathway in Suppressing Gram-Negative Sepsis-Induced Acute Lung Inflammatory Injury

    PubMed Central

    Su, Xiao; Matthay, Michael A.; Malik, Asrar B.

    2010-01-01

    Although activation of the α7 nicotinic acetylcholine receptor (α7 nAChR) modulates the response to sepsis, the role of this pathway in the development of sepsis-induced acute lung injury (ALI) is not known. In this study, we addressed the contribution of α7 nAChR in mediating endotoxin- and live Escherichia coli–induced ALI in mice. Because we found that α7 nAChR+ alveolar macrophages and neutrophils were present in bronchoalveolar lavage and injured lungs of mice, we tested whether acetylcholine released by lung vagal innervation stimulated these effector cells and thereby down-regulated proinflammatory chemokine/cytokine generation. Administration of α7 nAChR agonists reduced bronchoalveolar lavage MIP-2 production and transalveolar neutrophil migration and reduced mortality in E. coli pneumonia mice, whereas vagal denervation increased MIP-2 production and airway neutrophil accumulation and increased mortality. In addition, α7 nAChR−/− mice developed severe lung injury and had higher mortality compared with α7 nAChR+/+ mice. The immunomodulatory cholinergic α7 nAChR pathway of alveolar macrophages and neutrophils blocked LPS- and E. coli–induced ALI by reducing chemokine production and transalveolar neutrophil migration, suggesting that activation of α7 nAChR may be a promising strategy for treatment of sepsis-induced ALI. PMID:19949071

  20. Effects of Fluid Resuscitation With 0.9% Saline Versus a Balanced Electrolyte Solution on Acute Kidney Injury in a Rat Model of Sepsis*

    PubMed Central

    Zhou, Feihu; Peng, Zhi-Yong; Bishop, Jeffery V.; Cove, Matthew E.; Singbartl, Kai; Kellum, John A.

    2014-01-01

    Objective To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Design Controlled laboratory experiment. Setting University laboratory. Subjects Sixty adult, male Sprague-Dawley rats. Interventions We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals. Measurements and Main Results Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury. Conclusion Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short

  1. The Italian SEPSIS study: preliminary results on the incidence and evolution of SIRS, sepsis, severe sepsis and septic shock.

    PubMed

    Salvo, I; de Cian, W; Musicco, M; Langer, M; Piadena, R; Wolfler, A; Montani, C; Magni, E

    1995-11-01

    This prospective, multicenter, epidemiological study was carried out in 99 Italian ICUs, distributed throughout the country, from April 1993 to March 1994. In the study, we applied the new ACCP/SCCM classification system for sepsis (SIRS, sepsis, severe sepsis and septic shock) and determined the prevalence, incidence, evolution and outcome of these categories in critically ill patients. The preliminary analysis of 1101 patients showed that on admission SIRS accounted for about half of the diagnoses (52%) with sepsis, severe sepsis and septic shock accounting for 4.5%, 2.1% and 3% of patients, respectively. Patients with severe sepsis or septic shock more frequently had high SAPS scores than patients without sepsis. Mortality rates were similar in patients with SIRS (26.5%) and without SIRS or infection (24%), but rose to 36% in patients with sepsis, to 52% in those with severe sepsis and to 81.8% in those with septic shock. Sepsis, severe sepsis and septic shock were more common in patients with medical diagnoses, and neither severe sepsis nor septic shock was observed in trauma patients. With respect to evolution, the incidence of septic shock was progressively higher in patients admitted with more severe "sepsis-related" diagnoses, while only a trivial difference in rates of incidence was observed between SIRS patients and those admitted without SIRS or any septic disorder (nil). The breakdown of the various ACCP/SCCM "sepsis-related" diagnoses at any time during the study was: SIRS in 58% of the population, sepsis in 16.3%, severe sepsis in 5.5% and septic shock in 6.1%. It seems reasonable to expect from the final evaluation of our study answers to the questions raised by the ACCP/SCCM Consensus Conference about the correlations between "sepsis-related" diagnosis, severity score, organ dysfunction score and outcome. PMID:8636531

  2. Bench-to-bedside review: the role of nitric oxide in sepsis.

    PubMed

    De Cruz, Sharon J; Kenyon, Nicholas J; Sandrock, Christian E

    2009-10-01

    Sepsis is a state of systemic inflammation directed at microbes or their toxins in blood or tissues. Nitric oxide (NO) is one of many vasoactive molecules released from a variety of cell types during sepsis. Almost two decades ago, NO emerged as a potential therapeutic target in sepsis. NO produced by the constitutive NO synthase (NOS) isoform (endothelial NOS and neuronal NOS) in the vascular endothelium and elsewhere acts as a nonadrenergic, noncholinergic neurotransmitter, an inhibitor of platelet aggregation and a vasodilator. During sepsis, activation of inducible NOS (iNOS) in the lung epithelium and other organs occurs, leading to NO overproduction. The result of excessive circulating NO is enhanced bacterial destruction, but also profound vasodilatation, activation of inflammatory cascades and depression of cardiac function. Trials of nonselective NOS inhibitors have shown increased mean arterial pressure, but also increased pulmonary artery pressure and reduced cardiac output. Small animal studies of iNOS selective inhibition have produced dichotomous results, but larger clinical studies assessing mortality are lacking. Inhaled NO has been touted as a therapeutic option to improve systemic oxygenation in the acute lung injury of sepsis (hypoxic pulmonary vasoconstriction and pulmonary hypertension); however, studies of inhaled NO in acute respiratory distress syndrome have not shown survival efficacy. Further investigation into the role of NO in human sepsis, and the development of methods to assess NO balance in patients with sepsis is essential in this field. In this review, we outline the effects of NO in sepsis, and summarize the therapeutic outcomes of NOS inhibitors, and inhaled NO in sepsis and acute respiratory distress syndrome. PMID:20477340

  3. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome

    PubMed Central

    Romeo, M G; Romeo, D M; Trovato, L; Oliveri, S; Palermo, F; Cota, F; Betta, P

    2011-01-01

    Objective: To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by Candida species, of late-onset sepsis and neurological outcome in preterm newborns. Study Design: A prospective study was conducted in 249 preterms who were subdivided into three groups: one group (n=83) was supplemented with Lactobacillus (L.) reuteri, one group with L. rhamnosus (n=83) and the other with no supplementation (n=83). The fungal colonization in the gastrointestinal tract, the late onset of sepsis and clinical parameters were recorded. A neurological structured assessment was further performed at 1 year of age. Result: Candida stool colonization was significantly higher (P<0.01) in the control group than in the groups treated with probiotics. The L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups. Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group. Conclusion: The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by Candida, in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms. PMID:20410904

  4. Outcomes and Predictors of Mortality for Patients with Acute Leukemia Admitted to the Intensive Care Unit

    PubMed Central

    Croucher, Danielle; Christian, Michael; Ibrahimova, Narmin; Kumar, Vikram; Jacob, Gabriella; Kiss, Alex

    2016-01-01

    Purpose. The objectives were to describe the management and outcomes of acute leukemia (AL) patients admitted to the ICU and to identify predictors of ICU mortality. Methods. Data was retrospectively collected from the medical records of all patients with AML or ALL admitted to the Mount Sinai Hospital ICU from August 2009 to December 2012. Results. 151 AL patients (117 AML, 34 ALL) were admitted to the ICU. Mean age was 54 (SD 15) years, median APACHE II score was 27 (IQR 22–33), and 50% were female. While in ICU, 128 (85%) patients had sepsis and 56 (37%) had ARDS. The majority of patients required invasive organ support: 94 (62%) required mechanical ventilation while 23 (15%) received renal replacement therapy. Multivariable analysis identified SOFA score (OR 1.18, 95% CI 1.01–1.38) and invasive ventilation (OR 9.64, 95% CI 3.39–27.4) as independent predictors of ICU mortality. Ninety-four (62%) patients survived to ICU discharge. Only 39% of these 94 patients discharged were alive 12 months after ICU admission. Conclusions. AL patients admitted to the ICU had a 62% ICU survival rate; yet only 25% of cohort patients were alive 12 months after ICU admission. Higher admission SOFA scores and invasive ventilation are independently associated with a greater risk of dying in the ICU. PMID:27445524

  5. Removal of regulatory T cells prevents secondary chronic infection but increases the mortality of subsequent sub-acute infection in sepsis mice

    PubMed Central

    Wang, Xiaoya; Zhao, Yong; Wang, Yi; Zhao, Xiaomin; Chang, Lingling; Liu, Shan-lu; Tong, Dewen; Zhang, Hai; Huang, Yong

    2016-01-01

    The immunosuppression following initial septic insult impairs resistance to secondary infection. Modulation of lymphocytes population may help to develop an effective therapeutic strategy. In this study, lipopolysaccharide (LPS)-induced endotoxemia was employed as the initial septic insult. 24 hours later, mice underwent cecal ligation and puncture to induce chronic or sub-acute peritonitis. Potential usefulness of T regs deletion antibody (anti-CD25) in improving LPS-induced immunosuppression and the survival of subsequent different infections were evaluated. LPS injection induced lymphocyte loss and led to decreased IL-6, TNF-α and IFN-γ, and weakened bacteria clearance upon chronic peritonitis at 24 h post-LPS, whereas reconstitution with lymphocytes reversed these changes. LPS-induced T regs expansion contributed to T and NK cells decrease in number and activity during sepsis. Depletion of T regs using anti-CD25 antibodies partly prevented lymphocyte loss and increased the responses of T and NK cells to subsequent stimulation, resulting in significantly increased bacterial clearance and survival in a 2-hit model of chronic peritonitis, but which significantly increased early mortality upon subsequently sub-acute infection. Yet, using lower dosage of anti-CD25 antibodies to moderate down-regulate T regs levels could partly improve bacterial clearance and survival in either chronic or sub-acute infection. These results demonstrate that using anti-CD25 antibodies to deplete T regs can ameliorate immunosuppression through increasing T cells and NK cells responses in sepsis, which is beneficial for preventing subsequently chronic infection, but will probably bring some deleterious effects for subsequent sub-acute infection. PMID:26918357

  6. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes

    PubMed Central

    Graham, Garth

    2016-01-01

    In the USA and internationally, women experience farranging differences with respect to acute coronary syndrome (ACS) and myocardial infarction (MI). Women suffer from more comorbidities than men, such as smoking, obesity, hypertension, diabetes, and poor mental health. They some-times exhibit atypical MI presentation symptoms and are overall less likely to present with chest pain. Women are more likely than men to encounter delays between the onset of symptoms and arrival at the hospital or to guideline treatment. The use of various surgical and pharmacological treatments, including revascularization approaches, also differs. Women, on average, have worse outcomes than men following MI, with more complications, higher mortality rates, and poorer recovery. Internationally, outcomes are similar despite various differences in health care and culture in non-US countries. In this review, we detail differences regarding ACS and MI in women, describing their complex correlations and discussing their possible causes. Educational approaches that are tailored to women might help to reduce the incidence of ACS and MI, as well as outcomes following hospitalization. Although outcomes following acute MI have been improving over the years, women may require special consideration in order to see continued improvement. PMID:26884685

  7. Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load.

    PubMed

    Choudhury, Soumen; Kandasamy, Kannan; Maruti, Bhojane Somnath; Addison, M Pule; Kasa, Jaya Kiran; Darzi, Sazad A; Singh, Thakur Uttam; Parida, Subhashree; Dash, Jeevan Ranjan; Singh, Vishakha; Mishra, Santosh Kumar

    2015-10-15

    Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro-inflammatory cytokines (IL-1β and TNFα) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice. PMID:26375251

  8. Demographic diversity, value congruence, and workplace outcomes in acute care.

    PubMed

    Gates, Michael G; Mark, Barbara A

    2012-06-01

    Nursing scholars and healthcare administrators often assume that a more diverse nursing workforce will lead to better patient and nurse outcomes, but this assumption has not been subject to rigorous empirical testing. In a study of nursing units in acute care hospitals, the influence of age, gender, education, race/ethnicity, and perceived value diversity on nurse job satisfaction, nurse intent to stay, and patient satisfaction were examined. Support was found for a negative relationship between perceived value diversity and all outcomes and for a negative relationship between education diversity and intent to stay. Additionally, positive relationships were found between race/ethnicity diversity and nurse job satisfaction as well as between age diversity and intent to stay. From a practice perspective, the findings suggest that implementing retention, recruitment, and management practices that foster a strong shared value system among nurses may lead to better workplace outcomes. PMID:22377771

  9. Cytomegalovirus infection in patients with sepsis due to bloodstream infections: lower risk and better outcomes in new versus already hospitalised intensive care unit admissions.

    PubMed

    R, Osawa; M, Wagener; Ns, Singh

    2016-09-01

    Few studies have examined cytomegalovirus (CMV) reactivation exclusively in immunocompetent patients with sepsis due to bloodstream infections. In a cohort of CMV-seropositive critically ill otherwise non-immunosuppressed patients with sepsis due to bloodstream infection, weekly testing for CMV viraemia was performed. Outcomes were assessed at 30 days or until death/discharge from the intensive care unit (ICU). CMV viraemia developed in 20% (20/100) of the patients. Age (P=0.044) and blood transfusions (P=0.022) were significantly associated with CMV viraemia. There was no difference in the primary endpoint (mortality and/or multi-organ failure) between patients with and without CMV viraemia (P=0.49). However, CMV viraemia was associated with significantly fewer ICU-free days (P=0.023) and fewer ventilator-free days (P=0.031). Patients hospitalised in the ICU for more than 48 hours prior to the onset of bloodstream infection were more likely to develop CMV viraemia (P=0.006), have high-grade viraemia (P=0.010), and fewer ICU-free days (P=0.018) and ventilator-free days (P=0.029) than those admitted within 48 hours of bloodstream infection. Thus, CMV reactivation was associated with fewer ICU- and ventilator-free days, however overall mortality was not affected. Patients already in the ICU at the onset of sepsis had higher risk of CMV reactivation and worse outcomes than new ICU-bound patients suggesting that a targeted approach for interventions for CMV could conceivably be directed towards those with a more protracted course of illness. PMID:27608339

  10. Sepsis-Associated Encephalopathy

    PubMed Central

    Cotena, Simona; Piazza, Ornella

    2012-01-01

    Summary Sepsis-associated encephalopathy (SAE) is defined as a diffuse or multifocal cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct brain infection. Its pathogenesis is multifactorial. SAE generally occurs early during severe sepsis and precedes multiple-organ failure. The most common clinical feature of SAE is the consciousness alteration which ranges from mildly reduced awareness to unresponsiveness and coma. Diagnosis of SAE is primarily clinical and depends on the exclusion of other possible causes of brain deterioration. Electroencephalography (EEG) is almost sensitive, but it is not specific for SAE. Computed Tomography (CT) head scan generally is negative in case of SAE, while Magnetic Resonance Imaging (MRI) can show brain abnormalities in case of SAE, but they are not specific for this condition. Somatosensitive Evoked Potentials (SEPs) are sensitive markers of developing cerebral dysfunction in sepsis. Cerebrospinal fluid (CBF) analysis is generally normal, a part an inconstant elevation of proteins concentration. S100B and NSE have been proposed like biomarkers for diagnosis of SAE, but the existing data are controversial. SAE is reversible even if survivors of severe sepsis have often long lasting or irreversible cognitive and behavioral sequel; however the presence of SAE can have a negative influence on survival. A specific therapy of SAE does not exist and the outcome depends on a prompt and appropriate treatment of sepsis as whole. PMID:23905041

  11. Pediatric sepsis

    PubMed Central

    Randolph, Adrienne G; McCulloh, Russell J

    2014-01-01

    Sepsis is the leading cause of death in children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics. This article highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. We review how the capacity of the immune system to respond to infection develops over early life. We also bring attention to primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms. The management of pediatric sepsis must be tailored to the child’s age and immune capacity, and to the site, severity, and source of the infection. It is important for clinicians to be aware of infection-related syndromes that primarily affect children. Although children in developed countries are more likely to survive severe infections than adults, many survivors have chronic health impairments. PMID:24225404

  12. The interplay between microbiota and inflammation: lessons from peritonitis and sepsis

    PubMed Central

    Lobo, Leandro A; Benjamim, Claudia F; Oliveira, Ana Carolina

    2016-01-01

    Mammals harbor a complex gut-associated microbiota, comprising bacteria that provide immunological, metabolic and neurological benefits to the host, and contribute to their well-being. However, dysregulation of the microbiota composition, known as dysbiosis, along with the associated mucosal immune response have a key role in the pathogenesis of many inflammatory diseases, including inflammatory bowel diseases (IBDs), type 1 and type 2 diabetes, asthma, multiple sclerosis, among others. In addition, outside the gut lumen, bacteria from microbiota are the causative agent of peritoneal inflammation, abdominal sepsis and systemic sepsis. Critical care interventions during sepsis by antibiotics induce dysbiosis and present acute and long-term poor prognosis. In this review, we discuss immunomodulatory effects of the microbial molecules and products, highlighting the role of Bacteroides fragilis, a human commensal with ambiguous interactions with the host. Moreover, we also address the impact of antibiotic treatment in sepsis outcome and discuss new insights for microbiota modulation. PMID:27525063

  13. Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis.

    PubMed

    Cheng, Shih-Chin; Scicluna, Brendon P; Arts, Rob J W; Gresnigt, Mark S; Lachmandas, Ekta; Giamarellos-Bourboulis, Evangelos J; Kox, Matthijs; Manjeri, Ganesh R; Wagenaars, Jori A L; Cremer, Olaf L; Leentjens, Jenneke; van der Meer, Anne J; van de Veerdonk, Frank L; Bonten, Marc J; Schultz, Marcus J; Willems, Peter H G M; Pickkers, Peter; Joosten, Leo A B; van der Poll, Tom; Netea, Mihai G

    2016-04-01

    The acute phase of sepsis is characterized by a strong inflammatory reaction. At later stages in some patients, immunoparalysis may be encountered, which is associated with a poor outcome. By transcriptional and metabolic profiling of human patients with sepsis, we found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-γ, which suggested that metabolic processes might represent a therapeutic target in sepsis. PMID:26950237

  14. The interplay between microbiota and inflammation: lessons from peritonitis and sepsis.

    PubMed

    Lobo, Leandro A; Benjamim, Claudia F; Oliveira, Ana Carolina

    2016-07-01

    Mammals harbor a complex gut-associated microbiota, comprising bacteria that provide immunological, metabolic and neurological benefits to the host, and contribute to their well-being. However, dysregulation of the microbiota composition, known as dysbiosis, along with the associated mucosal immune response have a key role in the pathogenesis of many inflammatory diseases, including inflammatory bowel diseases (IBDs), type 1 and type 2 diabetes, asthma, multiple sclerosis, among others. In addition, outside the gut lumen, bacteria from microbiota are the causative agent of peritoneal inflammation, abdominal sepsis and systemic sepsis. Critical care interventions during sepsis by antibiotics induce dysbiosis and present acute and long-term poor prognosis. In this review, we discuss immunomodulatory effects of the microbial molecules and products, highlighting the role of Bacteroides fragilis, a human commensal with ambiguous interactions with the host. Moreover, we also address the impact of antibiotic treatment in sepsis outcome and discuss new insights for microbiota modulation. PMID:27525063

  15. Genetic variation in the TNF receptor-associated factor 6 gene is associated with susceptibility to sepsis-induced acute lung injury

    PubMed Central

    2012-01-01

    Background Recent studies showed that overwhelming inflammatory response mediated by the toll-like receptor (TLR)-related pathway was important in the development of acute lung injury (ALI). The aim of this study was to determine whether common genetic variation in four genes of the TLR signaling pathway were associated with sepsis-induced ALI susceptibility and risk of death in Chinese Han population. Methods Fourteen tag single nucleotide polymorphisms (tagSNPs) in MyD88, IRAK1, IRAK4 and TRAF6 were genotyped in samples of sepsis-induced ALI (n = 272) and sepsis alone patients (n = 276), and tested for association in this case-control collection. Then, we investigated correlation between the associated SNP and the mRNA expression level of the corresponding gene. And we also investigated correlation between the associated SNP and tumor necrosis factor alpha (TNF-α) as well as interleukin-6 (IL-6) concentrations in peripheral blood mononuclear cells (PBMCs) exposed to lipopolysaccharides (LPS) ex vivo. The mRNA expression level was determined using real-time quantitative Polymerase Chain Reaction (PCR) assays, and concentrations of TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Results The association analysis revealed that rs4755453, an intronic SNP of TRAF6, was significantly associated with susceptibility to sepsis-induced ALI. The C allele frequency of rs4755453 in the sepsis alone group was significantly higher than that in the sepsis-induced ALI group (P = 0.00026, odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.37–0.74). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons. TRAF6 mRNA expression levels in PBMCs from homozygotes of the rs4755453G allele were significantly higher than that in heterozygotes and homozygotes of the rs4755453C allele at baseline (P = 0.012 and P = 0.003, respectively) as well as after

  16. Relevant Outcomes in Pediatric Acute Respiratory Distress Syndrome Studies

    PubMed Central

    Yehya, Nadir; Thomas, Neal J.

    2016-01-01

    Despite distinct epidemiology and outcomes, pediatric acute respiratory distress syndrome (PARDS) is often managed based on evidence extrapolated from treatment of adults. The impact of non-pulmonary processes on mortality as well as the lower mortality rate compared to adults with acute respiratory distress syndrome (ARDS) renders the utilization of short-term mortality as a primary outcome measure for interventional studies problematic. However, data regarding alternatives to mortality are profoundly understudied, and proposed alternatives, such as ventilator-free days, may be themselves subject to hidden biases. Given the neuropsychiatric and functional impairment in adult survivors of ARDS, characterization of these morbidities in children with PARDS is of paramount importance. The purpose of this review is to frame these challenges in the context of the existing pediatric literature, and using adult ARDS as a guide, suggest potential clinically relevant outcomes that deserve further investigation. The goal is to identify important areas of study in order to better define clinical practice and facilitate future interventional trials in PARDS. PMID:27242980

  17. Acute Type A Aortic Dissection: for Further Improvement of Outcomes

    PubMed Central

    2012-01-01

    Despite improved outcomes of acute type A aortic dissection (AAAD), many patients die at the moment of onset, and hospital mortality is still high. This article reviews the latest literature to seek the best possible way to optimize outcomes. Delayed diagnosis is caused by variation in or absence of typical symptoms, especially in patients with neurological symptoms. Misdiagnosis as acute myocardial infarction is another problem. Improved awareness by physicians is needed. On arrival, quick admission to the OR is desirable, followed by assessment with transesophageal echocardiography, and malperfusion already exists or newly develops in the OR; thus, timely diagnosis without delay with multimodality assessment is important. Although endovascular therapy is promising, careful introduction is mandatory so as not to cause complications. While various routes are used for the systemic perfusion, not a single route is perfect, and careful monitoring is essential. Surgical treatment on octogenarians is increasingly performed and produces better outcomes than conservative therapy. Complications are not rare, and consent from the family is essential. Prevention of AAAD is another important issue because more patients die at its onset than in the following treatment. In addition to hereditary diseases, including bicuspid aortic valve disease, the management of blood pressure is important. PMID:23555530

  18. Associations between Single Nucleotide Polymorphisms of High Mobility Group Box 1 Protein and Clinical Outcomes in Korean Sepsis Patients

    PubMed Central

    Lee, Kwangha; Chang, Youjin; Song, Kyuyoung; Park, Yun Young; Huh, Jin Won; Hong, Sang-Bum; Lim, Chae-Man

    2016-01-01

    Purpose High mobility group box 1 (HMGB1) plays a central role in the pathogenesis of sepsis and multiple organ dysfunction syndromes. We investigated the associations of a single nucleotide polymorphism (SNP; rs1045411) in HMGB1 with various clinical parameters, severity, and prognosis in patients with sepsis, severe sepsis, or septic shock. Materials and Methods We enrolled 212 adult patients followed for 28 days. All patients were genotyped for rs1045411, and the serum levels of HMGB1 and several cytokines were measured. Results The proportions of patients according to genotype were GG (71.2%), GA (26.4%), and AA (2.4%). Among patients with chronic lung disease comorbidity, patients with a variant A allele had higher positive blood culture rates and higher levels of various cytokines [interleukin (IL)-1β, IL-6, IL-10, IL-17, and tumor necrosis factor-α] than those with the GG genotype. In the analysis of those with diabetes as a comorbidity, patients with a variant A allele had higher blood culture and Gram-negative culture rates than those with GG genotypes; these patients also had a higher levels of IL-17. In the analysis of those with sepsis caused by a respiratory tract infection, patients with a variant A allele had higher levels of IL-10 and IL-17 (all p<0.05). This polymorphism had no significant impact on patient survival. Conclusion The variant A allele of rs1045411 appears to be associated with a more severe inflammatory response than the GG genotype under specific conditions. PMID:26632390

  19. Sepsis and ARDS: The Dark Side of Histones

    PubMed Central

    Xu, Zhiheng; Huang, Yongbo; Mao, Pu; Zhang, Jianrong; Li, Yimin

    2015-01-01

    Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases. PMID:26609197

  20. Clinical Characteristics and 30-Day Outcomes of Intermittent Hemodialysis for Acute Kidney Injury in an African Intensive Care Unit

    PubMed Central

    Tumukunde, Janat; Ssemogerere, Lameck; Ayebale, Emmanuel; Agaba, Peter; Yakubu, Jamali; Lubikire, Aggrey; Nabukenya, Mary

    2016-01-01

    Introduction. Acute kidney injury (AKI) is a common occurrence in the intensive care unit (ICU). Studies have looked at outcomes of renal replacement therapy using intermittent haemodialysis (IHD) in ICUs with varying results. Little is known about the outcomes of using IHD in resource-limited settings where continuous renal replacement therapy (CRRT) is limited. We sought to determine outcomes of IHD among critically ill patients admitted to a low-income country ICU. Methods. A retrospective review of patient records was conducted. Patients admitted to the ICU who underwent IHD for AKI were included in the study. Patients' demographic and clinical characteristics, cause of AKI, laboratory parameters, haemodialysis characteristics, and survival were interpreted and analyzed. Primary outcome was mortality. Results. Of 62 patients, 40 had complete records. Median age of patients was 38.5 years. Etiologic diagnoses associated with AKI included sepsis, malaria, and ARDS. Mortality was 52.5%. APACHE II (OR 4.550; 95% CI 1.2–17.5, p = 0.028), mechanical ventilation (OR 13.063; 95% CI 2.3–72, p = 0.003), and need for vasopressors (OR 16.8; 95% CI 3.4–82.6, p = 0.001) had statistically significant association with mortality. Conclusion. IHD may be a feasible alternative for RRT in critically ill haemodynamically stable patients in low resource settings where CRRT may not be available. PMID:27042657

  1. Role of presepsin for the evaluation of sepsis in the emergency department.

    PubMed

    Pizzolato, Elisa; Ulla, Marco; Galluzzo, Claudia; Lucchiari, Manuela; Manetta, Tilde; Lupia, Enrico; Mengozzi, Giulio; Battista, Stefania

    2014-10-01

    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. PMID:24897403

  2. Examining acute health outcomes due to ozone exposure and their subsequent relationship to chronic disease outcomes

    SciTech Connect

    Ostro, B.D.

    1993-12-01

    Current evidence indicates that individuals exposed to short term elevations in ambient ozone may experience both upper and lower respiratory effects. Some respiratory symptoms and spirometric changes are mild and reversible in nature, while others involve more severe outcomes, including hospital admissions and emergency room visits. However, many questions remain about the effects of acute ozone exposure and the implications of this exposure for chronic disease outcomes. For example, the identification of sensitive subgroups, the delineation of the entire spectrum of health effects due to exposure to ozone, the potential synergy between viral infections and ozone exposure, and the nature of adaptation to ozone are not well characterized. In addition, studies that examine the association between acute responses to ozone and potential biological indicators of a chronic disease process would be desirable. This paper serves to provide an overview of the types of epidemiologic studies that may be appropriate and factors to consider in addressing these questions. 23 refs.

  3. Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis

    PubMed Central

    2013-01-01

    Introduction The pathophysiology of acute kidney injury (AKI) in sepsis is ill defined. We investigated parameters associated with low glomerular filtration, and their predictive value to discriminate transient from intrinsic septic AKI. Methods In 107 sepsis patients, AKI was defined by the Risk, Injury, Failure, Loss of Kidney Function, End-stage renal disease (RIFLE) urinary output or serum creatinine criterion, or both. Transient AKI (TAKI) versus intrinsic AKI was defined as RIFLE R, I, or F on the first day evolving to no AKI or not, respectively, over the following 5 days. Fractional excretion of sodium (FENa), urea (FEUrea), and NGAL (FENGAL) at admission (d0t0), 4 (d0t4), and 24 hours (d1) was determined. Results Including versus not including the urinary-output criterion of RIFLE increased AKI from 43% to 64.5%. Median uNGAL levels and FENGAL were lower in no AKI versus transient AKI when AKI was defined based on creatinine (P = 0.002 and P = 0.04, respectively), but not when based on urinary output (P = 0.9 and P = 0.49, respectively). FENa < 1% and FEUrea <35% was present in 77.3% and 63.2% of patients. Urinary NGAL was higher (P < 0.001) in those with high versus low fractional sodium excretion, but this was only in patients with transient or intrinsic AKI (P < 0.001 in subgroups), and not in patients without AKI. The negative predictive value for either intrinsic AKI or not restoring diuresis in patients with FENa > 0.36% and FEUrea > 31.5% was 92% and 94.5% respectively. Conclusions A low FENa and FEUrea is highly prevalent in the first hours of sepsis. In sepsis, oliguria is an earlier sign of impending AKI than increase in serum creatinine. A combination of a high FENa and a low FEUrea is associated with intrinsic AKI, whereas a combined high FENa and FEUrea is strongly predictive of transient AKI. PMID:24119730

  4. Risk Factors and Outcomes of Acute Kidney Injury in Patients With Acute Liver Failure

    PubMed Central

    Tujios, Shannan R.; Hynan, Linda S.; Vazquez, Miguel A.; Larson, Anne M.; Seremba, Emmanuel; Sanders, Corron M.; Lee, William M.

    2016-01-01

    BACKGROUND & AIMS Patients with acute liver failure (ALF) frequently develop renal dysfunction, yet its overall incidence and outcomes have not been fully assessed. We investigated the incidence of acute kidney injury (AKI) among patients with ALF, using defined criteria to identify risk factors and to evaluate its effect on overall outcomes. METHODS We performed a retrospective review of data from 1604 patients enrolled in the Acute Liver Failure Study Group, from 1998 through 2010. Patients were classified by the Acute Kidney Injury Network criteria, as well as for etiology of liver failure (acetaminophen-based, ischemic, and all others). RESULTS Seventy percent of patients with ALF developed AKI, and 30% received renal replacement therapy (RRT). Patients with severe AKI had higher international normalized ratio values than those without renal dysfunction (P < .001), and a higher proportion had advanced-grade coma (coma grades 3 or 4; P < .001) or presented with hypotension requiring vasopressor therapy (P < .001). A greater proportion of patients with acetaminophen-induced ALF had severe kidney injury than of patients with other etiologies of ALF; 34% required RRT, compared with 25% of patients with ALF not associated with acetaminophen or ischemia (P < .002). Of the patients with ALF who were alive at 3 weeks after study entry, significantly fewer with AKI survived for 1 year. Although AKI reduced the overall survival time, more than 50% of patients with acetaminophen-associated or ischemic ALF survived without liver transplantation (even with RRT), compared with 19% of patients with ALF attribute to other causes (P < .001). Only 4% of patients requiring RRT became dependent on dialysis. CONCLUSIONS Based on a retrospective analysis of data from more than 1600 patients, AKI is common in patients with ALF and affects short- and long-term outcomes, but rarely results in chronic kidney disease. Acetaminophen-induced kidney injury is frequent, but patients have

  5. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children

    PubMed Central

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-01-01

    Abstract Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness. A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression. HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05). Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern. PMID:27583886

  6. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

    PubMed

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-08-01

    Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05).Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern. PMID:27583886

  7. Mean platelet volume and cardiovascular outcomes in acute myocardial infarction

    PubMed Central

    Ranjith, Mangalachulli Pottammal; DivyaRaj, Rajendran; Mathew, Dolly; George, Biju; Krishnan, Mangalath Narayanan

    2016-01-01

    Objective High levels of mean platelet volume (MPV) may be associated with adverse outcomes in patients with myocardial infarction (MI). We examined the association between MPV and the risk of death and adverse cardiovascular outcomes in patients with MI. Methods We studied consecutive patients with MI admitted to a tertiary-care hospital during a period of 1 year. MPV was measured at admission and at third month. Patients were followed up for 1-year primary composite outcome of cardiovascular death, stroke, fatal or non-fatal MI and cardiac failure. Patients were classified according to tertile of baseline MPV. Results A total of 1206 patients with MI, including 934 men (77.4%) and 272 women (22.6%) were studied. The mean age of the study population was 56 years. At 1-year follow-up, 292 (28.57%) primary outcome occurred: cardiovascular mortality 78 (7.6%), fatal or non-fatal MI 153 (15.0%), stroke 30 (2.9%) and cardiac failure 128 (12.52%). Patients with the highest tertile MPV had higher primary outcome as compared with those with MPV in the lowest tertile (adjusted OR=2.31; 95% CI 1.60 to 3.35; p<0.001). Total mortality was also more in high-MPV group (adjusted OR 2.62; 95% CI 1.47 to 4.70; p<0.001). There were no significant changes in mean MPV values at admission from those at third month interval (9.15, (SD 0.99) vs 9.19 (SD 0.94); p=0.2). Conclusions Elevated MPV was associated with worse outcome in patients with acute MI. Elevated MPV in these patients may be due to inherently large platelets. Trial registration number http://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=5485&EncHid=98036.61144&modid=1&compid=19; CTRI/2012/12/003222.

  8. Severe sepsis during pregnancy.

    PubMed

    Pacheco, Luis D; Saade, George R; Hankins, Gary D V

    2014-12-01

    Severe sepsis is a major cause of mortality among critically ill patients. Early recognition accompanied by early initiation of broad-spectrum antibiotics with source control and fluid resuscitation improves outcomes. Hemodynamic resuscitation starts with fluid therapy followed by vasopressors if necessary. Cases refractory to first-line vasopressors (norepinephrine) will require second-line vasopressors (epinephrine or vasopressin) and low-dose steroid therapy. Resuscitation goals should include optimization of central venous oxygenation and serum lactate. PMID:25286297

  9. Early PREdiction of Severe Sepsis (ExPRES-Sepsis) study: protocol for an observational derivation study to discover potential leucocyte cell surface biomarkers

    PubMed Central

    Antonelli, Jean; Warner, Noel; Brown, Kenneth Alun; Wright, John; Simpson, A John; Rennie, Jillian; Hulme, Gillian; Lewis, Sion Marc; Mare, Tracey Anne; Cookson, Sharon; Weir, Christopher John; Dimmick, Ian; Keenan, Jim; Rossi, Adriano Giorgio; Shankar-Hari, Manu; Walsh, Timothy S

    2016-01-01

    Introduction Sepsis is an acute illness resulting from infection and the host immune response. Early identification of individuals at risk of developing life-threatening severe sepsis could enable early triage and treatment, and improve outcomes. Currently available biomarkers have poor predictive value for predicting subsequent clinical course in patients with suspected infection. Circulating leucocytes provide readily accessible tissues that reflect many aspects of the complex immune responses described in sepsis. We hypothesise that measuring cellular markers of immune responses by flow cytometry will enable early identification of infected patients at risk of adverse outcomes. We aim to characterise leucocyte surface markers (biomarkers) and their abnormalities in a population of patients presenting to the hospital emergency department with suspected sepsis, and explore their ability to predict subsequent clinical course. Methods and analysis We will conduct a prospective, multicentre, clinical, exploratory, cohort observational study. To answer our study question, 3 patient populations will be studied. First, patients with suspected sepsis from the emergency department (n=300). To assess performance characteristics of potential tests, critically ill patients with established sepsis, and age and gender matched patients without suspicion of infection requiring hospital admission (both n=100) will be recruited as comparator populations. In all 3 groups, we plan to assess circulating biomarker profiles using flow cytometry. We will select candidate biomarkers by cross-cohort comparison, and then explore their predictive value for clinical outcomes within the cohort with suspected sepsis. Ethics and dissemination The study will be carried out based on the principles in the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice. Ethics approval has been granted from the Scotland A Research Ethics Committee (REC) and Oxford C

  10. The role of the liver in sepsis

    PubMed Central

    Yan, Jun; Li, Song; Li, Shulin

    2014-01-01

    Despite the progress made in the clinical management of sepsis, sepsis morbidity and mortality rates remain high. The inflammatory pathogenesis and organ injury leading to death from sepsis are not fully understood for vital organs, especially the liver. Only recently has the role of the liver in sepsis begun to be revealed. Pre-existing liver dysfunction is a risk factor for the progression of infection to sepsis. Liver dysfunction after sepsis is an independent risk factor for multiple organ dysfunction and sepsis-induced death. The liver works as a lymphoid organ in response to sepsis. Acting as a double-edged sword in sepsis, the liver-mediated immune response is responsible for clearing bacteria and toxins but also causes inflammation, immunosuppression, and organ damage. Attenuating liver injury and restoring liver function lowers morbidity and mortality rates in patients with sepsis. This review summarizes the central role of liver in the host immune response to sepsis and in clinical outcomes. PMID:24611785

  11. Clinical profile and outcome of acute kidney injury related to pregnancy in developing countries: a single-center study from India.

    PubMed

    Godara, Suraj M; Kute, Vivek B; Trivedi, Hargovind L; Vanikar, Aruna V; Shah, Pankaj R; Gumber, Manoj R; Patel, Himanshu V; Gumber, Vandana M

    2014-07-01

    Acute kidney injury (AKI) is one of the most challenging and serious complications of pregnancy. We present our experience on the clinical profile and outcome of 57 patients with pregnancy-related AKI, of a total of 580 patients with AKI seen during the study period. This is a prospective single-center study in a civil hospital conducted from January to December 2010. The most common age group of the study patients was 20-25 years; 43.8% of the patients had received antenatal care. AKI was observed in the puerperium (n = 34), early pregnancy (n = 10) and late pregnancy (n = 13). The cause of AKI included puerperal sepsis (63.1%), pregnancy-induced hypertension (PIH) (33.33%), post-abortion (22.80%), ante-partum hemorrhage (APH) (14%) and post-partum hemorrhage (PPH) (8%). Complete, partial and no renal recovery was observed in 52.64%, 21.05% and 26.31% of the patients, respectively. Low platelet count and plasma fibrinogen and high bilirubin, D-dimer and activated partial thromboplast in time were observed more commonly in patients with partial recovery. Of the 57 patients, 50 received hemodialysis, three received peritoneal dialysis and seven patients were managed conservatively. A total of 13 patients developed cortical necrosis that was associated with sepsis in six, PPH and pre-eclampsia/eclampsia in three patients each and APH in one. Nine patients died, and the cause of death was septicemia in four, pre-eclampsia in three and APH and PPH in one patient each. In our study, puerperal sepsis was the most common etiological factor for pregnancy-related AKI. Prolonged oliguria or anuria were bad prognostic factors for renal recovery. Sepsis, thrombocytopenia, disseminated intra-vascular coagulation and liver involvement were associated with increased mortality. PMID:24969215

  12. Improving management of sepsis in the community.

    PubMed

    Culligan, Fiona

    2016-08-31

    Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Pathological changes in the circulation reduce the blood supply to major organs, causing them to fail. This may lead to death, therefore rapid recognition and treatment of sepsis is vital. Sepsis research has focused on patients in acute hospital settings. However, most cases of sepsis originate in the community, suggesting that the identification of sepsis and delivery of timely care is necessary before hospital admission. Therefore, it is essential that nurses practising in the community are provided with appropriate sepsis guidelines that can be implemented immediately. The UK Sepsis Trust has developed the General Practice Sepsis Decision Support Tool, which has been designed specifically for use in the community. This article provides an overview of how the tool is used in the community and how it works in conjunction with the 'Sepsis Six' care bundle and care bundles for hospital settings. Changes to the terminology used in relation to sepsis and recent guidelines are also explained. PMID:27577313

  13. Senegenin Ameliorate Acute Lung Injury Through Reduction of Oxidative Stress and Inhibition of Inflammation in Cecal Ligation and Puncture-Induced Sepsis Rats.

    PubMed

    Liu, Chun-Hong; Zhang, Wei-Dong; Wang, Jian-Jie; Feng, Shan-Dan

    2016-04-01

    The purpose of this study was to assess the protective effect of senegenin on acute lung injury (ALI) in rats induced by sepsis. Rat ALI model was reproduced by cecal ligation and puncture (CLP). All rats were randomly divided into five groups: group 1 (control), group 2 (CLP), group 3 (CLP + senegenin 15 mg/kg), group 4 (CLP + senegenin 30 mg/kg), and group 5 (CLP + senegenin 60 mg/kg). CLP + senegenin groups received senegenin by gavage daily for consecutive 5 days, respectively, while the mice in control and CLP groups were given an equivalent volume of saline. We detected the lung wet/dry weight ratios and the histopathology of the lung. The levels of lung tissue myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were determined. Meanwhile, the nuclear factor-kappa B (NF-κB) activation, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) levels were studied. The results demonstrated that senegenin treatment significantly attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, protein leak, infiltration of leukocytes, and MPO activity. In addition, senegenin markedly decreased MDA content and increased SOD activity and GSH level. Serum levels of TNF-α and IL-1β were also decreased by senegenin administration. Furthermore, senegenin administration inhibited the nuclear translocation of NF-κB in the lungs. These findings indicate that senegenin exerts protective effects on CLP-induced septic rats. Senegenin may be a potential therapeutic agent against sepsis. PMID:26945584

  14. Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression.

    PubMed

    Meng, L; Lv, Z; Yu, Z Z; Xu, D; Yan, X

    2016-01-01

    This study aimed to explore the protective effect of quercetin on acute lung injury (ALI) in rats with sepsis and the related mechanism. Rats were administered different doses of quercetin intraperitoneally, and blood samples and lung tissue were collected at 24 h after treatment. Arterial blood gases, lung water content, protein content, and cell counts in bronchoalveolar lavage fluid (BALF) were measured. Morphological changes in lung tissue pathology were observed under a light microscope. Serum intercellular adhesion molecule (ICAM)-1 and macrophage inflammatory protein 2 (MIP-2) levels were detected and ICAM-1 and MIP-2 mRNA expression in lung tissue was determined. Compared with that in the control model group, arterial blood gases, lung water content, protein content, and cell counts in BALF improved in the high- and low-dose quercetin groups (P < 0.05), with maximal improvement observed for the high-dose quercetin (P < 0.05). Lesions on the lungs improved in the high- and low-dose quercetin groups than those in the control model group, and the high-dose quercetin group showed better improvement than the low-dose group (P < 0.05). Compared with that in the sham-operated group, both serum and lung tissue ICAM-1 and MIP-2 expression increased significantly in the model group (P < 0.05). The quercetin groups presented lower ICAM-1 and MIP-2 expression than the control model group, with the lowest expression observed in the high-dose group (P < 0.05). Quercetin may protect against ALI in rats with sepsis by inhibiting ICAM-1 and MIP-2 expression. PMID:27525872

  15. Transplant Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia

    PubMed Central

    Mehta, Parinda A.; Zhang, Mei-Jie; Eapen, Mary; He, Wensheng; Seber, Adriana; Gibson, Brenda; Camitta, Bruce M.; Kitko, Carrie L.; Dvorak, Christopher C.; Nemecek, Eneida R.; Frangoul, Haydar A.; Abdel-Azim, Hisham; Kasow, Kimberly A.; Lehmann, Leslie; Vicent, Marta Gonzalez; Diaz Pérez, Miguel A.; Ayas, Mouhab; Qayed, Muna; Carpenter, Paul A.; Jodele, Sonata; Lund, Troy C.; Leung, Wing H.; Davies, Stella M.

    2015-01-01

    Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplant (HSCT) between 1990 and 2010. Thirty nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes and 27 (35%) had 45 chromosomes. Forty three (55%) patients were transplanted in first remission (CR1) while 35 (45%) were transplanted in ≥CR2. Twenty nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival (LFS), overall survival (OS), relapse, and treatment related mortality (TRM) for the entire cohort were 51%, 56%, 27% and 22% respectively. Multivariate analysis confirmed that mortality risks were higher for patients transplanted in CR2 (HR 2.16, p=0.05), with chromosome number ≤43 (HR 2.15, p=0.05) and for those transplanted in the first decade of the study period (HR 2.60, p=0.01). Similarly, treatment failure risks were higher with chromosome number ≤43 (HR 2.28, p=0.04) and the earlier transplant period (HR 2.51, p=0.01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes. PMID:25865650

  16. Biomarkers of acute kidney injury and associations with short- and long-term outcomes

    PubMed Central

    Schaub, Jennifer A.; Parikh, Chirag R.

    2016-01-01

    Acute kidney injury is strongly associated with increased mortality and other adverse outcomes. Medical researchers have intensively investigated novel biomarkers to predict short- and long-term outcomes of acute kidney injury in many patient care settings, such as cardiac surgery, intensive care units, heart failure, and transplant. Future research should focus on leveraging this relationship to improve enrollment for clinical trials of acute kidney injury. PMID:27239295

  17. Sepsis-induced Cardiomyopathy

    PubMed Central

    Romero-Bermejo, Francisco J; Ruiz-Bailen, Manuel; Gil-Cebrian, Julián; Huertos-Ranchal, María J

    2011-01-01

    Myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. During the sepsis-induced myocardial dysfunction, both ventricles can dilate and diminish its ejection fraction, having less response to fluid resuscitation and catecholamines, but typically is assumed to be reversible within 7-10 days. In the last 30 years, It´s being subject of substantial research; however no explanation of its etiopathogenesis or effective treatment have been proved yet. The aim of this manuscript is to review on the most relevant aspects of the sepsis-induced myocardial dysfunction, discuss its clinical presentation, pathophysiology, etiopathogenesis, diagnostic tools and therapeutic strategies proposed in recent years. PMID:22758615

  18. An Audit of Changes in Outcomes of Acute Pain Service

    PubMed Central

    Low, Sheng Jia; Wong, Stanley Sau Ching; Qiu, Qiu; Lee, Yvonne; Chan, Timmy Chi Wing; Irwin, Michael G.; Cheung, Chi Wai

    2015-01-01

    Abstract Acute pain services (APS) have evolved over time. Strategies nowadays emphasize multimodal analgesic regimes using a combination of nonopioid adjuvant analgesic drugs, peripheral nerve blocks, and local anaesthetic wound infiltration where appropriate. APS should be assessed over time to evaluate changes in outcomes which form the basis for future development. In this audit, data of patients under APS care in Queen Mary hospital, Hong Kong, between 2009 and 2012 were analyzed and compared with data from a previous audit between 1992 and 1995. The use of patient-controlled analgesia (PCA) was increased (from 69.3% to 86.5%, P < 0.001), while the use of epidural analgesia reduced (from 25.3% to 8.3%, P < 0.001) significantly. Although postoperative pain scores did not improve, PCA opioid consumption and the incidence of analgesia-related side effects were significantly less (all P < 0.001). More patients graded their postoperative analgesic techniques used as good when the results from these 2 audit periods were compared (P < 0.001 and P = 0.001 for PCA and epidural analgesia, respectively). In conclusion, there has been a change in analgesic management techniques, but there has been no improvement in overall pain relief. While changes over time have led to improvement in important parameters such as the incidence of side effects and patient satisfaction, further and continuous efforts and improvements are warrant to reduce acute pain relief and suffering of the patients after the surgery. PMID:26448012

  19. Extremes of Interferon-Stimulated Gene Expression Associate with Worse Outcomes in the Acute Respiratory Distress Syndrome.

    PubMed

    Nick, Jerry A; Caceres, Silvia M; Kret, Jennifer E; Poch, Katie R; Strand, Matthew; Faino, Anna V; Nichols, David P; Saavedra, Milene T; Taylor-Cousar, Jennifer L; Geraci, Mark W; Burnham, Ellen L; Fessler, Michael B; Suratt, Benjamin T; Abraham, Edward; Moss, Marc; Malcolm, Kenneth C

    2016-01-01

    Acute Respiratory Distress Syndrome (ARDS) severity may be influenced by heterogeneity of neutrophil activation. Interferon-stimulated genes (ISG) are a broad gene family induced by Type I interferons, often as a response to viral infections, which evokes extensive immunomodulation. We tested the hypothesis that over- or under-expression of immunomodulatory ISG by neutrophils is associated with worse clinical outcomes in patients with ARDS. Genome-wide transcriptional profiles of circulating neutrophils isolated from patients with sepsis-induced ARDS (n = 31) and healthy controls (n = 19) were used to characterize ISG expression. Hierarchical clustering of expression identified 3 distinct subject groups with Low, Mid and High ISG expression. ISG accounting for the greatest variability in expression were identified (MX1, IFIT1, and ISG15) and used to analyze a prospective cohort at the Colorado ARDS Network site. One hundred twenty ARDS patients from four urban hospitals were enrolled within 72 hours of initiation of mechanical ventilation. Circulating neutrophils were isolated from patients and expression of ISG determined by PCR. Samples were stratified by standard deviation from the mean into High (n = 21), Mid, (n = 82) or Low (n = 17) ISG expression. Clinical outcomes were compared between patients with High or Low ISG expression to those with Mid-range expression. At enrollment, there were no differences in age, gender, co-existing medical conditions, or type of physiologic injury between cohorts. After adjusting for age, race, gender and BMI, patients with either High or Low ISG expression had significantly worse clinical outcomes than those in the Mid for number of 28-day ventilator- and ICU-free days (P = 0.0006 and 0.0004), as well as 90-day mortality and 90-day home with unassisted breathing (P = 0.02 and 0.004). These findings suggest extremes of ISG expression by circulating neutrophils from ARDS patients recovered early in the syndrome are associated

  20. Acute Respiratory Distress Syndrome and Outcomes after Near-hanging

    PubMed Central

    Mansoor, Sahar; Afshar, Majid; Barrett, Matthew; Smith, Gordon S.; Barr, Erik A.; Lissauer, Matthew E.; McCurdy, Michael T.; Murthi, Sarah B.; Netzer, Giora

    2015-01-01

    Purpose Assess the case rate of Acute Respiratory Distress Syndrome (ARDS) after near-hanging, and the secondary outcomes of traumatic and/or anoxic brain injury, and death. Risk factors for the outcomes were assessed. Method Single-center, state-wide retrospective cohort study of consecutive patients admitted between August, 2002, and September, 2011, with a primary diagnosis of non-judicial "hanging injury". Results Of 56 patients, 73% were male. The median age was 31 (IQR: 16–56). Upon arrival, 9% (5/56) did not have a pulse, and 23% (13/56) patients were intubated. The median Glasgow Coma Scale (GCS) was 13 (IQR: 3–15); 14% (8/56) had a GCS=3. ARDS developed in 9% (5/56) of patients. Traumatic anoxic brain injury resulted in 9% (5/56) of patients. The in-hospital case fatality was 5% (3/56). Lower median GCS [3 (IQR: 3–7) vs. 14 (IQR: 3–15), p=0.0003] and intubation in field or in trauma resuscitation unit [100% (5/5) vs. 16% (8/51), p=0.0003] were associated with ARDS development. Risk factors of death were GCS=3 [100% (3/3) vs. 9% (5/53), p=0.002]; pulselessness upon arrival of emergency medical services [100% (3/3) vs. 4% (2/53), p<0.001]; and abnormal neurologic imaging [50% (1/2) vs. zero, p=0.04]. Conclusions The ARDS case rate after near-hanging is similar to the general trauma population. Low GCS and intubation are associated with increased risk of ARDS development. The rate of traumatic and/or anoxic brain injury in this population is low. PMID:25596627

  1. Acute promyelocytic leukemia during pregnancy: a systematic analysis of outcome.

    PubMed

    Verma, Vivek; Giri, Smith; Manandhar, Samyak; Pathak, Ranjan; Bhatt, Vijaya Raj

    2016-03-01

    The outcomes of acute promyelocytic leukemia (APL) in pregnancy are largely unknown. The MEDLINE database was systematically searched to obtain 43 articles with 71 patients with new-onset APL during pregnancy. Induction therapy included various regimens of all-trans retinoic acid (ATRA), cytarabine, and anthracycline and resulted in a complete remission rate of 93%. Obstetric and fetal complications included pre-term deliveries (46%), spontaneous/therapeutic abortion/intrauterine death (33.3%) and other neonatal complications (25.9%). Mothers diagnosed in the first trimester were more likely to experience obstetric (p < 0.01) and fetal (p < 0.01) complications. To our knowledge, this is the largest systematic review of APL in pregnancy. The vast majority of APL patients in pregnancy may achieve remission with initial induction therapy. APL or its therapy in pregnancy, however, is associated with a high risk of fetal and obstetrical complications. The results of our study may help in patient counseling and informed decision-making. PMID:26110880

  2. Differential Paradigms in Animal Models of Sepsis.

    PubMed

    Kingsley, S Manoj Kumar; Bhat, B Vishnu

    2016-09-01

    Sepsis is a serious clinical problem involving complex mechanisms which requires better understanding and insight. Animal models of sepsis have played a major role in providing insight into the complex pathophysiology of sepsis. There have been various animal models of sepsis with different paradigms. Endotoxin, bacterial infusion, cecal ligation and puncture, and colon ascendens stent peritonitis models are the commonly practiced methods at present. Each of these models has their own advantages and also confounding factors. We have discussed the underlying mechanisms regulating each of these models along with possible reasons why each model failed to translate into the clinic. In animal models, the timing of development of the hemodynamic phases and the varied cytokine patterns could not accurately resemble the progression of clinical sepsis. More often, the exuberant and transient pro-inflammatory cytokine response is only focused in most models. Immunosuppression and apoptosis in the later phase of sepsis have been found to cause more damage than the initial acute phase of sepsis. Likewise, better understanding of the existing models of sepsis could help us create a more relevant model which could provide solution to the currently failed clinical trials in sepsis. PMID:27432263

  3. Mitochondrial dysfunction during sepsis.

    PubMed

    Azevedo, Luciano Cesar Pontes

    2010-09-01

    Sepsis and multiple organ failure remain leading causes of death in intensive care patients. Recent advances in our understanding of the pathophysiology of these syndromes include a likely prominent role for mitochondria. Patient studies have shown that the degree of mitochondrial dysfunction is related to the eventual outcome. Associated mechanisms include damage to mitochondria or inhibition of the electron transport chain enzymes by nitric oxide and other reactive oxygen species (the effects of which are amplified by co-existing tissue hypoxia), hormonal influences that decrease mitochondrial activity, and downregulation of mitochondrial protein expression. Notably, despite these findings, there is minimal cell death seen in most affected organs, and these organs generally regain reasonably normal function should the patient survive. It is thus plausible that multiple organ failure following sepsis may actually represent an adaptive state whereby the organs temporarily 'shut down' their normal metabolic functions in order to protect themselves from an overwhelming and prolonged insult. A decrease in energy supply due to mitochondrial inhibition or injury may trigger this hibernation/estivation-like state. Likewise, organ recovery may depend on restoration of normal mitochondrial respiration. Data from animal studies show histological recovery of mitochondria after a septic insult that precedes clinical improvement. Stimulation of mitochondrial biogenesis could offer a new therapeutic approach for patients in multi-organ failure. This review will cover basic aspects of mitochondrial function, mechanisms of mitochondrial dysfunction in sepsis, and approaches to prevent, mitigate or speed recovery from mitochondrial injury. PMID:20509844

  4. Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials

    PubMed Central

    2013-01-01

    Background Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure. Methods Three investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria. Results Thirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality. Conclusions In this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures. PMID:23848435

  5. Acute megakaryoblastic leukemia, unlike acute erythroid leukemia, predicts an unfavorable outcome after allogeneic HSCT.

    PubMed

    Ishiyama, Ken; Yamaguchi, Takuhiro; Eto, Tetsuya; Ohashi, Kazuteru; Uchida, Naoyuki; Kanamori, Heiwa; Fukuda, Takahiro; Miyamura, Koichi; Inoue, Yoshiko; Taguchi, Jun; Mori, Takehiko; Iwato, Koji; Morishima, Yasuo; Nagamura-Inoue, Tokiko; Atsuta, Yoshiko; Sakamaki, Hisashi; Takami, Akiyoshi

    2016-08-01

    Acute erythroid leukemia (FAB-M6) and acute megakaryoblastic leukemia (FAB-M7) exhibit closely related properties in cells regarding morphology and the gene expression profile. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the mainstay of the treatment for both subtypes of leukemia due to their refractoriness to chemotherapy and high rates of relapse, it remains unclear whether allo-HSCT is curative in such cases due to their scarcity. We retrospectively examined the impact of allo-HSCT in 382 patients with M6 and 108 patients with M7 using nationwide HSCT data and found the overall survival (OS) and relapse rates of the M6 patients to be significantly better than those of the M7 patients after adjusting for confounding factors and statistically comparable with those of the patients with M0/M1/M2/M4/M5 disease. Consequently, the factors of age, gender, performance status, karyotype, disease status at HSCT and development of graft-vs.-host disease predicted the OS for the M6 patients, while the performance status and disease status at HSCT were predictive of the OS for the M7 patients. These findings substantiate the importance of distinguishing between M6 and M7 in the HSCT setting and suggest that unknown mechanisms influence the HSCT outcomes of these closely related subtypes of leukemia. PMID:27244257

  6. Predictive Value of IL-8 for Sepsis and Severe Infections after Burn Injury - A Clinical Study

    PubMed Central

    Kraft, Robert; Herndon, David N; Finnerty, Celeste C; Cox, Robert A; Song, Juquan; Jeschke, Marc G

    2014-01-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring post-burn inflammation is of paramount importance but so far there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As IL-8 is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict post-burn sepsis, infections, and mortality other outcomes post-burn. Plasma cytokines, acute phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days post injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure (MOF), and mortality were recorded. A cut-off level for IL-8 was determined using receiver operating characteristic (ROC) analysis. Statistical significance is set at (p<0.05). ROC analysis identified a cut-off level of 234 pg/ml for IL-8 for survival. Patients were grouped according to their average IL-8 levels relative to this cut off and stratified into high (H) (n=133) and low (L) (n=335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area (TBSA) burned and incidence of MOF (p<0.001). In the H group IL-8 levels were able to predict sepsis (p<0.002). In the H group, elevated IL-8 was associated with increased inflammatory and acute phase responses compared to the L group (p<0.05). High levels of IL-8 correlated with increased MOF, sepsis, and mortality. These data suggest that serum levels of IL-8 may be a valid biomarker for monitoring sepsis, infections, and mortality in burn patients. PMID:25514427

  7. The Severity of Cecal Ligature and Puncture-Induced Sepsis Correlates with the Degree of Encephalopathy, but the Sepsis Does Not Lead to Acute Activation of Spleen Lymphocytes in Mice.

    PubMed

    Jeremias, I C; Victorino, V J; Machado, J L; Barroso, W A; Ariga, S K; Lima, T M; Soriano, F G

    2016-07-01

    Septic encephalopathy represents the most frequently observed form of encephalopathy in intensive care units. Interactions between the immune and nervous systems have been observed in experimental sepsis. Therefore, the aim of the current study was to characterize the effect of different severities of sepsis on encephalopathy and the inflammatory profile of the spleen. We hypothesized that different grades of sepsis severity would lead to variations in encephalopathy and activation of spleen cells. We induced sepsis of different severities in Balb/c mice by cecal ligature and puncture (CLP). Six and 12 h after CLP induction, behavioral impairment was assessed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) test. The animals were then killed, and the plasma, spleen, and hippocampus were removed. Levels of the encephalopathy marker S100β were measured in plasma. Spleens were weighed and then a characterization of splenic lymphocytes was performed by flow cytometry (cytotoxic T lymphocyte, T helper lymphocytes, B lymphocytes, T regulatory cells, and Th17 cells). Cytokine levels in the spleen and hippocampus were determined by enzyme-linked immunosorbent assay (ELISA), and cytokine levels in plasma were performed with MilliPlex® technology. Our results showed that behavioral impairment as measured by the SHIRPA test and elevation in plasma S100β levels were significant in moderate and severe CLP groups compared to those in the sham control group. Regarding immunological alterations, we were unable to observe changes in the weights of the spleen and the profile of lymphocytes 6 h after CLP. However, several cytokines, including IL-6, IL-10, and IL-1β, were increased in spleen and plasma. In conclusion, we observed variations in encephalopathy as measured by plasma S100β, which were mediated by the severity of sepsis; however, we did not observe a different activation of spleen cells 6 h post-CLP, despite evidence of

  8. The role of platelets in sepsis.

    PubMed

    de Stoppelaar, Sacha F; van 't Veer, Cornelis; van der Poll, Tom

    2014-10-01

    Platelets are small circulating anucleate cells that are of crucial importance in haemostasis. Over the last decade, it has become increasingly clear that platelets play an important role in inflammation and can influence both innate and adaptive immunity. Sepsis is a potentially lethal condition caused by detrimental host response to an invading pathogen. Dysbalanced immune response and activation of the coagulation system during sepsis are fundamental events leading to sepsis complications and organ failure. Platelets, being major effector cells in both haemostasis and inflammation, are involved in sepsis pathogenesis and contribute to sepsis complications. Platelets catalyse the development of hyperinflammation, disseminated intravascular coagulation and microthrombosis, and subsequently contribute to multiple organ failure. Inappropriate accumulation and activity of platelets are key events in the development of sepsis-related complications such as acute lung injury and acute kidney injury. Platelet activation readouts could serve as biomarkers for early sepsis recognition; inhibition of platelets in septic patients seems like an important target for immune-modulating therapy and appears promising based on animal models and retrospective human studies. PMID:24966015

  9. Transfusion-associated bacterial sepsis.

    PubMed Central

    Wagner, S J; Friedman, L I; Dodd, R Y

    1994-01-01

    The incidence of sepsis caused by transfusion of bacterially contaminated blood components is similar to or less than that of transfusion-transmitted hepatitis C virus infection, yet significantly exceeds those currently estimated for transfusion-associated human immunodeficiency and hepatitis B viruses. Outcomes are serious and may be fatal. In addition, transfusion of sterile allogenic blood can have generalized immunosuppressive effects on recipients, resulting in increased susceptibility to postoperative infection. This review examines the frequency of occurrence of transfusion-associated sepsis, the organisms implicated, and potential sources of bacteria. Approaches to minimize the frequency of sepsis are discussed, including the benefits and disadvantages of altering the storage conditions for blood. In addition, the impact of high levels of bacteria on the gross characteristics of erythrocyte and platelet concentrates is described. The potentials and limitations of current tests for detecting bacteria in blood are also discussed. PMID:7923050

  10. Incidence and Outcomes of Acute Respiratory Distress Syndrome

    PubMed Central

    Chen, Wei; Chen, Yih-Yuan; Tsai, Ching-Fang; Chen, Solomon Chih-Cheng; Lin, Ming-Shian; Ware, Lorraine B.; Chen, Chuan-Mu

    2015-01-01

    Abstract Most epidemiological studies of acute respiratory distress syndrome (ARDS) have been conducted in western countries, and studies in Asia are limited. The aim of our study was to evaluate the incidence, in-hospital mortality, and 1-year mortality of ARDS in Taiwan. We conducted a nationwide inpatient cohort study based on the Taiwan National Health Insurance Research Database between 1997 and 2011. A total of 40,876 ARDS patients (68% male; mean age 66 years) were identified by International Classification of Diseases, 9th edition coding and further analyzed for clinical characteristics, medical costs, and mortality. The overall crude incidence of ARDS was 15.74 per 100,000 person-years, and increased from 2.53 to 19.26 per 100,000 person-years during the study period. The age-adjusted incidence of ARDS was 15.19 per 100,000 person-years. The overall in-hospital mortality was 57.8%. In-hospital mortality decreased from 59.7% in 1997 to 47.5% in 2011 (P < 0.001). The in-hospital mortality rate was lowest (33.5%) in the youngest patients (age 18–29 years) and highest (68.2%) in the oldest patients (>80 years, P < 0.001). The overall 1-year mortality rate was 72.1%, and decreased from 75.8% to 54.7% during the study period. Patients who died during hospitalization were older (69 ± 17 versus 62 ± 19, P < 0.001) and predominantly male (69.8% versus 65.3%, P < 0.001). In addition, patients who died during hospitalization had significantly higher medical costs (6421 versus 5825 US Dollars, P < 0.001) and shorter lengths of stay (13 versus 19 days, P < 0.001) than patients who survived. We provide the first large-scale epidemiological analysis of ARDS incidence and outcomes in Asia. Although the overall incidence was lower than has been reported in a prospective US study, this may reflect underdiagnosis by International Classification of Diseases, 9th edition code and identification of only patients with more severe ARDS in this

  11. Seeking Sepsis in the Emergency Department- Identifying Barriers to Delivery of the Sepsis 6.

    PubMed

    Bentley, James; Henderson, Susan; Thakore, Shobhan; Donald, Michael; Wang, Weijie

    2016-01-01

    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. PMID:27239303

  12. Seeking Sepsis in the Emergency Department- Identifying Barriers to Delivery of the Sepsis 6

    PubMed Central

    Bentley, James; Henderson, Susan; Thakore, Shobhan; Donald, Michael; Wang, Weijie

    2016-01-01

    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. PMID:27239303

  13. Sepsis in Buraidah Central Hospital, Qassim, Kingdom of Saudi Arabia

    PubMed Central

    Gasim, Gasim I.; Musa, Imad R; Yassin, Taha; Al Shobaili, Hani A.; Adam, Ishag

    2016-01-01

    Objectives Severe sepsis is a major public health concern and a frequent cause of intensive care unit (ICU) admission with a high fatality rate. Higher (Sequential Organ Failure Assessment score) SOFA score and co-morbidity of acute renal failure (ARF) are risk factors contributing to fatal outcome. This work was meant to study the epidemiology of sepsis in Buraidah central hospital. Methods This is a descriptive study conducted in the period from January 1, 2012, to June 29, 2012 to determine the epidemiology (incidence, clinical characteristics) and the outcome of sepsis in Buraidah hospital, Saudi Arabia. Results Out of 387 patients admitted to ICU, 62 (16%) patients had sepsis, their mean (SD) age was 62.7 (21.3) years. Three quarters of them 47 (75.8%) presented with septic shock. The median APACHE II score was 26.5 (8 to 48) and SOFA score 11 (5 to 21). The mean of duration of hospital stay was 11.95 days. The most frequent infection site was the pulmonary (69.5%). There were 37 isolated organism, gram-negative organisms (13; 35.13%) were the predominant isolates. There were 25 (40.3%) deaths; the majority of the deaths were due to septic shock 20(80%). There was a significant difference between deaths and the survivors, in the APACHI II score, SOFA score), and whether ventilated or not. Conclusions There was a high incidence of septic shock (and higher mortality) among the patients admitted to the ICU of Buraidah central hospital, especially among the elderly patients with respiratory infections. PMID:27103899

  14. Chinese Head Trauma Data Bank: Effect of Hyperthermia on the Outcome of Acute Head Trauma Patients

    PubMed Central

    Li, Jin

    2012-01-01

    Abstract Hyperthermia may accentuate the detrimental consequences of brain injury and worsen the outcome of patients with acute head trauma, especially severe traumatic brain injury (TBI). We explored the effect of different magnitudes and durations of hyperthermia in the first 3 days after injury on the outcome of 7145 patients with acute head trauma, including 1626 with severe TBI. The differences in mortality and unfavorable outcome between the normothermia group, mild fever group, moderate fever group, and high fever group were statistically significant (p<0.001). The mortality and unfavorable outcome of severe TBI patients in the groups also differed significantly (p<0.001). The mortality and unfavorable outcome of patients with 1 day, 2 days, and 3 days of high fever were significantly increased (p<0.01). Our data strongly indicate that both degree and duration of early post-trauma hyperthermia are closely correlated with the outcome of acute TBI patients, especially severely injured ones, which indicates that hyperthermia may play a detrimental role in the delayed mechanisms of damage after acute TBI. Prevention of early hyperthermia after acute head trauma is therefore essential to the management of TBI patients. PMID:22026424

  15. Estrogen sulfotransferase ablation sensitizes mice to sepsis

    PubMed Central

    Chai, Xiaojuan; Guo, Yan; Jiang, Mengxi; Hu, Bingfang; Li, Zhigang; Fan, Jie; Deng, Meihong; Billiar, Timothy R.; Kucera, Heidi; Gaikwad, Nilesh W.; Xu, Meishu; Lu, Peipei; Yan, Jiong; Fu, Haiyan; Liu, Youhua; Yu, Lushan; Huang, Min; Zeng, Su; Xie, Wen

    2015-01-01

    Sepsis is the host's deleterious systemic inflammatory response to microbial infections. Here we report an essential role for the estrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the cecal ligation and puncture (CLP) and lipopolysacharide (LPS) models of sepsis induce the expression of EST and compromise the activity of estrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised estrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes estrogen deactivation and sensitizes mice to CLP-induced inflammatory response. The induction of EST by sepsis is NF-κB dependent and EST is a NF-κB target gene. The reciprocal regulation of inflammation and EST may represent a yet to be explored mechanism of endocrine regulation of inflammation, which has an impact on the clinical outcome of sepsis. PMID:26259151

  16. Oestrogen sulfotransferase ablation sensitizes mice to sepsis.

    PubMed

    Chai, Xiaojuan; Guo, Yan; Jiang, Mengxi; Hu, Bingfang; Li, Zhigang; Fan, Jie; Deng, Meihong; Billiar, Timothy R; Kucera, Heidi R; Gaikwad, Nilesh W; Xu, Meishu; Lu, Peipei; Yan, Jiong; Fu, Haiyan; Liu, Youhua; Yu, Lushan; Huang, Min; Zeng, Su; Xie, Wen

    2015-01-01

    Sepsis is the host's deleterious systemic inflammatory response to microbial infections. Here we report an essential role for the oestrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the caecal ligation and puncture (CLP) and lipopolysaccharide models of sepsis induce the expression of EST and compromise the activity of oestrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised oestrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes oestrogen deactivation and sensitizes mice to CLP-induced inflammatory response. The induction of EST by sepsis is NF-κB dependent and EST is a NF-κB-target gene. The reciprocal regulation of inflammation and EST may represent a yet-to-be-explored mechanism of endocrine regulation of inflammation, which has an impact on the clinical outcome of sepsis. PMID:26259151

  17. [Biochemical diagnostics in acute pancreatitis recognition and outcome predicition].

    PubMed

    Olczyk, Paweł; Kozma, Ewa M; Olczyk, Krystyna; Komosińska-Vassev, Katarzyna

    2004-01-01

    Acute pancreatitis (AP) is a common disease associated with an improper activation of pancreatic zymogens leading to autodigestion of the gland and if excessive--to multiple organ dysfunction. Acute necrotizing pancreatitis manifested by 20% of patients with acute pancreatitis is a life threatening disorder requiring subsequent management in intensive care unit. Unfortunately, none of biochemical tests presently used for laboratory assessment of acute pancreatitis at the early stage of the disease is able to estimate accurately: diagnosis, etiology and severity. At present, diagnosis of acute pancreatitis is based on evaluation of serum amylase and lipase activity due to easy availability and simplicity of these enzymatic tests. Low specificity of the mentioned enzymes resulted in studies concerning pancreatic isoamylase, elastase-1, chymotrypsine, procarboxy-peptidase B, trypsinogen-2 and immunoreactive trypsinogen usefulness in the laboratory diagnosis of AP. The prediction of severity in acute pancreatitis using multifactorial scoring systems is cumbersome especially due to their complexity. On the other hand the biochemical method of choice, estimation of serum C reactive protein, is useless in the early phase of disease. Unfortunately, the computed tomography--the most accurate method in severity assessing--is not always available. Recent studies have brought some progress in severity predicting, such as phospholipase A2, cellular immunity markers, cytokines, activation peptides of trypsinogen and carboxypeptidase B, procalcitonine, pancreatitis associated protein and serum amyloid A. All these newly introduced biochemical methods allow to look optimistically into the future of laboratory diagnostics of the acute pancreatitis believing that the problem of diagnosing and predicting the AP severity will be solved. PMID:15850341

  18. Acute renal failure: outcomes and risk of chronic kidney disease.

    PubMed

    Block, C A; Schoolwerth, A C

    2007-09-01

    Acute renal failure (ARF) is a common condition, especially among the critically ill, and confers a high mortality. The incidence of ARF is increasing. Efforts such as the Acute Dialysis Quality Initiative (ADQI) are being undertaken to establish a consensus definition of ARF, and to distinguish between varying degrees of acute kidney injury that might confer a different prognosis. Data are emerging to allow comparison of the epidemiology of ARF across institutions internationally. There is ongoing recognition of the important interaction between ARF and chronic kidney disease and more information regarding recovery from ARF is available. Controversy exists regarding the optimal management of ARF. Recent publications emphasize the importance of timing and dose of renal replacement therapy rather than the modality of treatment (intermittent hemodialysis vs continuous therapies). These issues are explored in this review. PMID:17912228

  19. Hemostasis and endothelial damage during sepsis.

    PubMed

    Johansen, Maria Egede

    2015-08-01

    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

  20. Sepsis Questions and Answers

    MedlinePlus

    ... has kidney problems, sepsis can lead to kidney failure that requires lifelong dialysis. Top of Page How ... to prevent healthcare-associated infections. Recently, CDC has projects specifically focused on sepsis prevention so that we ...

  1. Acute Stress Disorder: Conceptual Issues and Treatment Outcomes

    ERIC Educational Resources Information Center

    Koucky, Ellen M.; Galovski, Tara E.; Nixon, Reginald D. V.

    2012-01-01

    Acute stress disorder (ASD) was included as a diagnosis to the 4th edition of the "Diagnostic and Statistical Manual" (American Psychiatric Association, 1994) as a way of describing pathological reactions in the first month following a trauma. Since that time, ASD has been the focus of some controversy, particularly regarding the theoretical basis…

  2. [Bacteraemia and sepsis].

    PubMed

    Kern, W V

    2011-02-01

    Recent news in the field of bloodstream infection and sepsis relevant for the practitioner include the recommendation in the newly revised German sepsis guideline to introduce selective intestinal decontamination with non-absorbable antimicrobial substances for the prevention of secondary infections in ventilated patients. This intervention, however, remains controversial because there are indications of unfavourable effects (increased development of resistance), and because the effect size has been rather low. Other news indicate not only that procalcitonin can be reasonably used as an aid to determine the duration of antibiotic treatment in community-acquired respiratory infection and pneumonia. A procalcitonin-based algorithm can also be used in critical care patients to shorten the duration of antibiotic administration without worsening outcomes. Recent data indicate that E. coli and S. aureus continue to be the most frequent pathogens isolated in bloodstream infection. The proportion of E. coli strains producing extended-spectrum beta lactamase (ESBL) is increasing. New epidemiologic evidence shows that infections with this pathogen, resistant to many standard antibiotics, are associated with an increased mortality rate, similar to infections due to methicillin-resistant Staphylococcus aureus (MSRA). The incidence of MRSA bacteraemia in Germany can now be estimated better as it has become a notifiable infection. PMID:21271477

  3. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

    PubMed Central

    Spearman, Paul W.; Stoll, Barbara J.

    2015-01-01

    Synopsis Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation and early initiation of therapy are required to prevent adverse outcomes. The following chapter reviews recent trends in epidemiology, and provides an update on risk factors, diagnostic methods and management of neonatal sepsis. PMID:23481106

  4. Prospective Study on the Clinical Course and Outcomes in Transfusion-Related Acute Lung Injury

    PubMed Central

    Looney, Mark R.; Roubinian, Nareg; Gajic, Ognjen; Gropper, Michael A.; Hubmayr, Rolf D.; Lowell, Clifford A.; Bacchetti, Peter; Wilson, Gregory; Koenigsberg, Monique; Lee, Deanna C.; Wu, Ping; Grimes, Barbara; Norris, Philip J.; Murphy, Edward L.; Gandhi, Manish J.; Winters, Jeffrey L.; Mair, David C.; Schuller, Randy M.; Hirschler, Nora V.; Rosen, Rosa Sanchez; Matthay, Michael A.; Toy, Pearl

    2014-01-01

    Objective Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases. Design Prospective case study with controls. Setting University of California, San Francisco and Mayo Clinic, Rochester. Patients We prospectively enrolled 89 patients with transfusion-related acute lung injury, 164 transfused controls, and 145 patients with possible transfusion-related acute lung injury. Interventions None. Measurements and Main Results Patients with transfusion-related acute lung injury had fever, tachycardia, tachypnea, hypotension, and prolonged hypoxemia compared with controls. Of the patients with transfusion-related acute lung injury, 29 of 37 patients (78%) required initiation of mechanical ventilation and 13 of 53 (25%) required initiation of vasopressors. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury had an increased duration of mechanical ventilation and increased days in the ICU and hospital compared with controls. There were 15 of 89 patients with transfusion-related acute lung injury (17%) who died, whereas 61 of 145 patients with possible transfusion-related acute lung injury (42%) died and 7 of 164 of controls (4%) died. Patients with transfusion-related acute lung injury had evidence of more systemic inflammation with increases in circulating neutrophils and a decrease in platelets compared with controls. Patients with transfusion-related acute lung injury and possible transfusion-related acute lung injury also had a statistically significant increase in plasma interleukin-8, interleukin-10, and interleukin-1 receptor antagonist posttransfusion compared with controls. Conclusions In conclusion, transfusion-related acute lung injury produced a condition

  5. Acute intermittent porphyria: A critical diagnosis for favorable outcome

    PubMed Central

    Divecha, Chhaya; Tullu, Milind S.; Gandhi, Akanksha; Deshmukh, Chandrahas T.

    2016-01-01

    Acute intermittent porphyria (AIP) is an inherited metabolic disorder characterized by the accumulation of toxic metabolites of the heme pathway. It rarely presents in the prepubertal age group. AIP often presents with nonspecific and nonlocalizing symptoms. Moreover, several commonly used medications and stress states are known to precipitate an attack. We present the case of a previously healthy 5 years female who was diagnosed as acute central nervous system infection/inflammation at admission. It was the presence of red flags that led to a correct diagnosis. Besides supportive management, a dedicated search for intravenous hemin (chemically heme arginate, aminolevulinic acid synthase inhibitor, and drug of choice) was attempted. Unexpected help was rendered by doctors from a medical college in Gujarat, and two ampoules could be obtained. The patient received three doses of intravenous hemin; however, she succumbed later. This case is presented for the diagnostic and therapeutic challenges faced in developing countries. PMID:27555700

  6. High Homocysteine and Blood Pressure Related to Poor Outcome of Acute Ischemia Stroke in Chinese Population

    PubMed Central

    Liu, Changjiang; Zhao, Liang; Zhou, Mo; Sun, Wenjie; Xu, Tan; Tong, Weijun

    2014-01-01

    Objectives To assess the association between plasma homocysteine (Hcy), blood pressure (BP) and poor outcome at hospital discharge among acute ischemic stroke patients, and if high Hcy increases the risk of poor outcome based on high BP status in a northern Chinese population. Methods Between June 1, 2009 and May 31, 2013, a total of 3695 acute ischemic stroke patients were recruited from three hospitals in northern Chinese cities. Demographic characteristics, lifestyle risk factors, medical history, and other clinical characteristics were recorded for all subjects. Poor outcome was defined as a discharge modified Rankin Scale (mRS) score ≥3 or death. The association between homocysteine concentration, admission blood pressure, and risk of poor outcome following acute ischemic stroke was analyzed by using multivariate non-conditional logistic regression models. Results Compared with those in the lowest quartile of Hcy concentration in a multivariate-adjusted model, those in the highest quartile of Hcy concentration had increased risk of poor outcome after acute ischemic stroke, (OR = 1.33, P<0.05). The dose-response relationship between Hcy concentration and risk of poor outcome was statistically significant (p-value for trend  = 0.027). High BP was significantly associated with poor outcome following acute ischemic stroke (adjusted OR = 1.44, 95%CI, 1.19–1.74). Compared with non-high BP with nhHcy, in a multivariate-adjusted model, the ORs (95% CI) of non-high BP with hHcy, high BP with nhHcy, and high BP with hHcy to poor outcome were 1.14 (0.85–1.53), 1.37 (1.03–1.84) and 1.70 (1.29–2.34), respectively. Conclusion The present study suggested that high plasma Hcy and blood pressure were independent risk factors for prognosis of acute ischemic stroke, and hHcy may further increase the risk of poor outcome among patients with high blood pressure. Additionally, the results indicate that high Hcy with high BP may cause increased susceptibility

  7. Long-term physiologic outcome after acute farmer's lung

    SciTech Connect

    Cormier, Y.; Belanger, J.

    1985-06-01

    We performed a follow-up study of 61 patients who had an acute episode of farmer's lung (54 men and seven women). Twenty-four subjects had ceased all contact with the barn, while 37 had continued farming. Pulmonary function tests for all subjects showed an initial improvement after the acute episode: 92.4 percent of predicted for carbon monoxide diffusing capacity (Dco) after one year, compared to 61.5 percent at diagnosis; and 6.01 L for total lung capacity (TLC) after three years, compared to 5.35 L. Subsequently, pulmonary function decreased over time. Five years or more after the acute episode, pulmonary function tests in subjects who had continued farm work were not worse than those of subjects who had ceased contact for Dco (68.1 of predicted vs 80.6 percent, respectively and for TLC (5.55 L vs 5.90 L. This study shows that during a long-term follow-up, subjects with farmer's lung who stayed on the farm have subnormal values for pulmonary function but comparable values to those who left their farm.

  8. Identification of adults with sepsis in the prehospital environment: a systematic review

    PubMed Central

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

    2016-01-01

    Objective Early identification of sepsis could enable prompt delivery of key interventions such as fluid resuscitation and antibiotic administration which, in turn, may lead to improved patient outcomes. Limited data indicate that recognition of sepsis by paramedics is often poor. We systematically reviewed the literature on prehospital sepsis screening tools to determine whether they improved sepsis recognition. Design Systematic review. The electronic databases MEDLINE, EMBASE, CINAHL, the Cochrane Library and PubMed were systematically searched up to June 2015. In addition, subject experts were contacted. Setting Prehospital/emergency medical services (EMS). Study selection All studies addressing identification of sepsis (including severe sepsis and septic shock) among adult patients managed by EMS. Outcome measures Recognition of sepsis by EMS clinicians. Results Owing to considerable variation in the methodological approach adopted and outcome measures reported, a narrative approach to data synthesis was adopted. Three studies addressed development of prehospital sepsis screening tools. Six studies addressed paramedic diagnosis of sepsis with or without use of a prehospital sepsis screening tool. Conclusions Recognition of sepsis by ambulance clinicians is poor. The use of screening tools, based on the Surviving Sepsis Campaign diagnostic criteria, improves prehospital sepsis recognition. Screening tools derived from EMS data have been developed, but they have not yet been validated in clinical practice. There is a need to undertake validation studies to determine whether prehospital sepsis screening tools confer any clinical benefit. PMID:27496231

  9. Dysphagia May Be an Independent Marker of Poor Outcome in Acute Lateral Medullary Infarction

    PubMed Central

    Kim, Tae Jung; Nam, Hyunwoo; Hong, Jeong-Ho; Yeo, Min-Ju; Chang, Jun-Young; Jeong, Jin-Heon; Kim, Beom Joon; Bae, Hee-Joon; Ahn, Jin Young; Kim, Jong Sung

    2015-01-01

    Background and Purpose The functional recovery after the lateral medullary infarction (LMI) is usually good. Little is known about the prognostic factors associated with poor outcome following acute LMI. The aim of this study was to identify the factors associated with poor long-term outcome after acute LMI, based on experiences at a single center over 11 years. Methods A consecutive series of 157 patients with acute LMI who were admitted within 7 days after symptom onset was evaluated retrospectively. Clinical symptoms were assessed within 1 day after admission, and outcomes were evaluated over a 1-year period after the initial event. The lesions were classified into three vertical types (rostral, middle, and caudal), and the patients were divided into two groups according to the outcome at 1 year: favorable [modified Rankin Scale (mRS) score ≤1] and unfavorable (mRS score ≥2). Results Of the 157 patients, 93 (59.2%) had a favorable outcome. Older age, hypertension, dysphagia, requirement for intensive care, and pneumonia were significantly more prevalent in the unfavorable outcome group. The frequencies of intensive care (13%) and mortality (16.7%) were significantly higher in the rostral lesion (p=0.002 and p=0.002). Conditional logistic regression analysis revealed that older age and initial dysphagia were independently related to an unfavorable outcome at 1 year [odds ratio (OR)=1.04, 95% confidence interval (95% CI)=1.001-1.087, p=0.049; OR=2.46, 95% CI=1.04-5.84, p=0.041]. Conclusions These results suggest that older age and initial dysphagia in the acute phase are independent risk factors for poor long-term prognosis after acute LMI. PMID:26256660

  10. Plasma C-Reactive Protein and Clinical Outcomes after Acute Ischemic Stroke: A Prospective Observational Study

    PubMed Central

    Matsuo, Ryu; Ago, Tetsuro; Hata, Jun; Wakisaka, Yoshinobu; Kuroda, Junya; Kuwashiro, Takahiro; Kitazono, Takanari; Kamouchi, Masahiro

    2016-01-01

    Background and Purpose Although plasma C-reactive protein (CRP) is elevated in response to inflammation caused by brain infarction, the association of CRP with clinical outcomes after acute ischemic stroke remains uncertain. This study examined whether plasma high-sensitivity CRP (hsCRP) levels at onset were associated with clinical outcomes after acute ischemic stroke independent of conventional risk factors and acute infections after stroke. Methods We prospectively included 3653 patients with first-ever ischemic stroke who had been functionally independent and were hospitalized within 24 h of onset. Plasma hsCRP levels were measured on admission and categorized into quartiles. The association between hsCRP levels and clinical outcomes, including neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin scale ≥3 at 3 months), were investigated using a logistic regression analysis. Results Higher hsCRP levels were significantly associated with unfavorable outcomes after adjusting for age, sex, baseline National Institutes of Health Stroke Scale score, stroke subtype, conventional risk factors, intravenous thrombolysis and endovascular therapy, and acute infections during hospitalization (multivariate-adjusted odds ratios [95% confidence interval] in the highest quartile versus the lowest quartile as a reference: 0.80 [0.65–0.97] for neurological improvement, 1.72 [1.26–2.34] for neurological deterioration, and 2.03 [1.55–2.67] for a poor functional outcome). These associations were unchanged after excluding patients with infectious diseases occurring during hospitalization, or those with stroke recurrence or death. These trends were similar irrespective of stroke subtypes or baseline stroke severity, but more marked in patients aged <70 years (Pheterogeneity = 0.001). Conclusions High plasma hsCRP is independently associated with unfavorable clinical outcomes after acute ischemic stroke. PMID:27258004

  11. Predicting long-term outcomes of acute aortic dissection: a focus on gender.

    PubMed

    Divchev, Dimitar; Najjar, Tarek; Tillwich, Falko; Rehders, Tim; Palisch, Holger; Nienaber, Christoph A

    2015-03-01

    Acute aortic disease ranks as the 19th leading cause of death with steadily increasing incidence. The prevalence of aneurysms varies depending on the localization along the aorta with a mortality of aortic rupture of around 80%. Traditionally, aortic disease affects men more frequently than women, however, with a varying gender ratio. Nevertheless, in the setting of acute aortic dissection, the International Registry of Acute Aortic Dissections identified significant gender-related differences in the management of both sexes with acute aortic conditions. Current data suggest that women are at an increased risk of both dying from aortic dissection and having aorta-related complications than men. This review aims to report on current evidence of gender impact on natural history, treatment and outcomes in patients with acute aortic dissection. PMID:25608580

  12. Nurse Value-Added and Patient Outcomes in Acute Care

    PubMed Central

    Yakusheva, Olga; Lindrooth, Richard; Weiss, Marianne

    2014-01-01

    Objective The aims of the study were to (1) estimate the relative nurse effectiveness, or individual nurse value-added (NVA), to patients’ clinical condition change during hospitalization; (2) examine nurse characteristics contributing to NVA; and (3) estimate the contribution of value-added nursing care to patient outcomes. Data Sources/Study Setting Electronic data on 1,203 staff nurses matched with 7,318 adult medical–surgical patients discharged between July 1, 2011 and December 31, 2011 from an urban Magnet-designated, 854-bed teaching hospital. Study Design Retrospective observational longitudinal analysis using a covariate-adjustment value-added model with nurse fixed effects. Data Collection/Extraction Methods Data were extracted from the study hospital's electronic patient records and human resources databases. Principal Findings Nurse effects were jointly significant and explained 7.9 percent of variance in patient clinical condition change during hospitalization. NVA was positively associated with having a baccalaureate degree or higher (0.55, p = .04) and expertise level (0.66, p = .03). NVA contributed to patient outcomes of shorter length of stay and lower costs. Conclusions Nurses differ in their value-added to patient outcomes. The ability to measure individual nurse relative value-added opens the possibility for development of performance metrics, performance-based rankings, and merit-based salary schemes to improve patient outcomes and reduce costs. PMID:25256089

  13. Elevated Cardiac Troponin in Acute Stroke without Acute Coronary Syndrome Predicts Long-Term Adverse Cardiovascular Outcomes

    PubMed Central

    Bhatt, Reema; Bove, Alfred A.

    2014-01-01

    Background. Elevated cardiac troponin in acute stroke in absence of acute coronary syndrome (ACS) has unclear long-term outcomes. Methods. Retrospective analysis of 566 patients admitted to Temple University Hospital from 2008 to 2010 for acute stroke was performed. Patients were included if cardiac troponin I was measured and had no evidence of ACS and an echocardiogram was performed. Of 200 patients who met the criteria, baseline characteristics, electrocardiograms, and major adverse cardiovascular events (MACE) were reviewed. Patients were characterized into two groups with normal and elevated troponins. Primary end point was nonfatal myocardial infarction during follow-up period after discharge. The secondary end points were MACE and death from any cause. Results. For 200 patients, 17 patients had positive troponins. Baseline characteristics were as follows: age 63.1 ± 13.8, 64% African Americans, 78% with hypertension, and 22% with previous CVA. During mean follow-up of 20.1 months, 7 patients (41.2%) in elevated troponin and 6 (3.3%) patients in normal troponin group had nonfatal myocardial infarction (P = 0.0001). MACE (41.2% versus 14.2%, P = 0.01) and death from any cause (41.2% versus 14.5%, P = 0.017) were significant in the positive troponin group. Conclusions. Elevated cardiac troponin in patients with acute stroke and no evidence of ACS is strong predictor of long-term cardiac outcomes. PMID:25530906

  14. Discovery of the gene signature for acute lung injury in patients with sepsis Address for reprint requests and other correspondence: J. A. Howrylak, UPMC Montefiore NW 628, 3459 5th Ave., Pittsburgh, PA 15213 (e-mail: howrylakj@upmc.edu).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    PubMed Central

    Howrylak, Judie A.; Dolinay, Tamas; Lucht, Lorrie; Wang, Zhaoxi; Christiani, David C.; Sethi, Jigme M.; Xing, Eric P.; Donahoe, Michael P.; Choi, Augustine M. K.

    2009-01-01

    The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) was described 30 yr ago, yet making a definitive diagnosis remains difficult. The identification of biomarkers obtained from peripheral blood could provide additional noninvasive means for diagnosis. To identify gene expression profiles that may be used to classify patients with ALI, 13 patients with ALI + sepsis and 20 patients with sepsis alone were recruited from the Medical Intensive Care Unit of the University of Pittsburgh Medical Center, and microarrays were performed on peripheral blood samples. Several classification algorithms were used to develop a gene signature for ALI from gene expression profiles. This signature was validated in an independently obtained set of patients with ALI + sepsis (n = 8) and sepsis alone (n = 1). An eight-gene expression profile was found to be associated with ALI. Internal validation found that the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 100% accuracy, corresponding to a sensitivity of 100%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 100%. In the independently obtained external validation set, the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 88.9% accuracy. The use of classification models to develop a gene signature from gene expression profiles provides a novel and accurate approach for classifying patients with ALI. PMID:19174476

  15. Response of lung γδ T cells to experimental sepsis in mice

    PubMed Central

    Hirsh, Mark; Dyugovskaya, Larissa; Kaplan, Viktoria; Krausz, Michael M

    2004-01-01

    γδ T cells link innate and adaptive immune systems and may regulate host defence. Their role in systemic inflammation induced by trauma or infection (sepsis) is still obscured. The present study was aimed to investigate functions of lung γδ T cells and their response to experimental sepsis. Mice were subjected to caecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI), or to the sham operation. Animals were killed 1, 4, and 7 days postoperatively; lungs were examined by histology, and isolated cells were studied by flow cytometry. Absolute number of γδ T cells progressively increased in lungs during sepsis, and reached a seven-fold increase at day 7 after CLP (3·84 ± 0·41 × 105/lung; P = 0·0002 versus sham). A cellular dysfunction was revealed one day after CLP, as manifested by low cytolytic activity (22·3 ± 7·1%; P < 0·05 versus sham), low interferon-γ (IFN-γ; 8·5 ± 2·5%; P < 0·05 versus control) and interleukin-10 (IL-10) expression, and high tumour necrosis factor-α expression (19·5 ± 1·7%; P < 0·05 versus control). The restoration of cytotoxicity, and increase in IFN-γ and IL-10 expression was observed at day 7 of CLP-induced sepsis. In summary, our results demonstrate significant progressive accumulation of γδ T cells in lungs during CLP-induced ALI. The temporary functional suppression of lung γδ T cells found early after CLP may influence the outcome of sepsis, possibly being associated with uncontrolled inflammatory lung damage. PMID:15096194

  16. Transfusion-related risk of secondary bacterial infections in sepsis patients: a retrospective cohort study.

    PubMed

    Juffermans, Nicole P; Prins, David J; Vlaar, Alexander P J; Nieuwland, Rienk; Binnekade, Jan M

    2011-04-01

    There is a need for insight into factors that contribute to late mortality of sepsis patients. Immunomodulatory effects have been ascribed to blood transfusion. This retrospective cohort study investigates the association between the development of nosocomial bacterial infection and transfusion of leukodepleted red blood cells (RBCs) or platelets (PLTs) in survivors of the initial phase of sepsis. Patients diagnosed with sepsis after admission to the intensive care unit of a tertiary referral hospital were included. Of 134 patients with sepsis, 67 received a blood transfusion (50%). A secondary infection developed in 19 patients (14%). A multiple logistic regression model revealed that the use of immunosuppressive medication with an odds ratio (OR) of 1.17 (95% confidence interval [CI], 1.04-1.31), but not Acute Physiology and Chronic Health Evaluation II score, malignancy, HIV infection, alcohol abuse, or diabetes mellitus, was a risk factor for nosocomial infection. In an adjusted model, the amount of transfused RBCs was associated with secondary infection with an OR of 1.18 (95% CI, 1.01-1.37). Storage time of RBCs was a relevant confounder of the effect of the amount of RBCs on infection, with an adjusted OR of 1.25 (95% CI, 1.04-1.51), P = 0.02. Also, the amount of transfused PLTs was associated with secondary infection, with an OR of 1.36 (95% CI, 1.05-1.78). In conclusion, transfusion of RBCs and PLTs is associated with the onset of secondary bacterial infection in sepsis patients. Storage time of RBCs influences this increased risk. These findings suggest that immunomodulatory effects of blood transfusion contribute to adverse outcome in the convalescent phase of sepsis. PMID:21192282

  17. Clinical, Electroencephalographic, and Neuroradiological Outcome Predictors in Acute Nonhypoxic Encephalopathy: A Nine-Year Cohort Study.

    PubMed

    Sutter, Raoul; Kaplan, Peter W

    2016-01-01

    Marked impairment of consciousness, brain lesion on neuroimaging, and nonreactive electroencephalographic (EEG) background activity are established outcome predictors in patients with hypoxic encephalopathy. In this observational cohort study, we aimed to assess the predictive value of clinical, neuroimaging and EEG characteristics for outcome in different types of acute nonhypoxic encephalopathic patients. All adult intensive care unit patients from a tertiary academic medical care center with clinical and EEG evidence of acute nonhypoxic encephalopathy were included from 2004 to 2012. Clinical data, neuroimaging studies, EEG characteristics, and outcome were assessed. In-hospital death was the main outcome. Median age of 262 patients was 65 years (range 18-98 years). Mortality was 12.6%. In Poisson regression analyses, older age (P=.02), intracranial hemorrhage (P=.008), coma (P=.012), and nonreactive EEG background activity (P<.0001) were independently associated with death with nonreactive EEG being the strongest predictor (relative risk 3.74; 95% confidence interval 2.02-6.91). Subgroup analysis revealed no significant effect modification for the predictive value of nonreactive EEG by the presence or absence of coma and different types of acute brain lesions. In conclusion, this study identifies and quantifies the independent predictive value of older age, intracranial hemorrhage, coma, and nonreactive EEG for death, in patients with different types of acute nonhypoxic encephalopathy. These results add further credence to the limited body of evidence that EEG provides important prognostic information in different types of acute encephalopathy not related to hypoxic brain injury. Further studies are warranted to analyze the robustness of this predictor in larger subpopulations with specific etiologies of acute nonhypoxic encephalopathies. PMID:25828484

  18. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children

    PubMed Central

    Gilchrist, James J.; Heath, Jennifer N.; Msefula, Chisomo L.; Gondwe, Esther N.; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M.; Molyneux, Elizabeth M.; Graham, Stephen M.; Drayson, Mark T.; Molyneux, Malcolm E.

    2016-01-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. PMID:27170644

  19. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children.

    PubMed

    Gilchrist, James J; Heath, Jennifer N; Msefula, Chisomo L; Gondwe, Esther N; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M; Molyneux, Elizabeth M; Graham, Stephen M; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

    2016-07-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. PMID:27170644

  20. Hospital readmission and healthcare utilization following sepsis in community settings

    PubMed Central

    Liu, Vincent; Lei, Xingye; Prescott, Hallie C; Kipnis, Patricia; Iwashyna, Theodore J; Escobar, Gabriel J

    2014-01-01

    Background Sepsis, the most expensive cause of hospitalization in the US, is associated with high morbidity and mortality. However, healthcare utilization patterns following sepsis are poorly understood. Objective To identify patient-level factors which contribute to post-sepsis mortality and healthcare utilization. Design, Setting, Patients A retrospective study of sepsis patients drawn from 21 community-based hospitals in Kaiser Permanente Northern California in 2010. Measurements We determined one-year survival and use of outpatient and facility-based healthcare before and after sepsis and used logistic regression to identify the factors that contributed to early readmission (within 30 days) and high utilization (≥15% of living days spent in facility-based care). Results Among 6,344 sepsis patients, 5,479 (86.4%) survived to hospital discharge. Mean age was 72 years with 28.9% of patients aged <65 years. Post-sepsis survival was strongly modified by age; one-year survival was 94.1% for <45 year olds and 54.4% for ≥85 year olds. A total of 978 (17.9%) patients were readmitted within 30 days; only a minority of all rehospitalizations were for infection. After sepsis, adjusted healthcare utilization increased nearly threefold compared with pre-sepsis levels and was strongly modified by age. Patient factors including acute severity of illness, hospital length of stay, and the need for intensive care were associated with early readmission and high healthcare utilization, however, the dominant factors explaining variability—comorbid disease burden and high pre-sepsis utilization—were present prior to sepsis admission. Conclusion Post-sepsis survival and healthcare utilization were most strongly influenced by patient factors already present prior to sepsis hospitalization. PMID:24700730

  1. Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

    SciTech Connect

    Chessells, J.; Leiper, A.; Rogers, D.

    1984-10-01

    Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients.

  2. Longitudinal language outcomes following intrathecal chemotherapy for acute lymphoblastic leukaemia.

    PubMed

    Lewis, Fiona M; Perry, Meghan L; Murdoch, Bruce E

    2013-04-01

    Intrathecal chemotherapy (ITC) is the treatment option for acute lymphoblastic leukaemia (ALL). Neurocognitive deficits have been described following ITC, but language status post-treatment is yet to be clarified. This study examined the language skills of nine children following ITC for ALL (mean age 7;8 years and 3;2 years post-diagnosis at baseline measurement) and nine age- and sex-matched controls, at baseline then 2 years later, using a battery of tests assessing general language skills. An assessment of cognitively-demanding high level language skills was undertaken on a sub-group of the children (n =12). Statistical analysis revealed no significant difference between children treated with ITC and controls when comparing change in performance scores from baseline measurement to 2 years post-baseline measurement. Descriptive analysis of three of the ALL participants in the Intermediate Stage survivorship at language re-assessment indicated no clinically-significant change in performance over 2 years for all measures except receptive language skills, which improved over the time for two of the children. As language skills continue to develop into late adolescence, the need for the monitoring of language abilities of children treated at a young age with ITC as they enter the Intermediate and Late Stages of survivorship is discussed. PMID:22663017

  3. Contrast-Induced Acute Kidney Injury: Definition, Epidemiology, and Outcome

    PubMed Central

    Meinel, Felix G.; De Cecco, Carlo N.; Schoepf, U. Joseph

    2014-01-01

    Contrast-induced acute kidney injury (CI-AKI) is commonly defined as a decline in kidney function occurring in a narrow time window after administration of iodinated contrast material. The incidence of AKI after contrast material administration greatly depends on the specific definition and cutoff values used. Although self-limiting in most cases, postcontrast AKI carries a risk of more permanent renal insufficiency, dialysis, and death. The risk of AKI from contrast material, in particular when administered intravenously for contrast-enhanced CT, has been exaggerated by older, noncontrolled studies due to background fluctuations in renal function. More recent evidence from controlled studies suggests that the risk is likely nonexistent in patients with normal renal function, but there may be a risk in patients with renal insufficiency. However, even in this patient population, the risk of CI-AKI is probably much smaller than traditionally assumed. Since volume expansion is the only preventive strategy with a convincing evidence base, liberal hydration should be encouraged to further minimize the risk. The benefits of the diagnostic information gained from contrast-enhanced examinations will still need to be balanced with the potential risk of CI-AKI for the individual patient and clinical scenario. PMID:24734250

  4. Clinical Outcomes of Silk Patch in Acute Tympanic Membrane Perforation

    PubMed Central

    Lee, Jun Ho; Lee, Joong Seob; Kim, Dong-Kyu

    2015-01-01

    Objectives The silk patch is a thin transparent patch that is produced from silk fibroin. In this study, we investigated the treatment effects of the silk patch in patients with traumatic tympanic membrane perforation (TTMP). Methods The closure rate, otorrhea rate, and closure time in all patients and the closure time in successful patients were compared between the paper patch and silk patch groups. Results Demographic data (gender, site, age, traumatic duration, preoperative air-bone gap, and perforation size and location) were not significantly different between the two groups. The closure rate and otorrhea rate were not significantly different between the two groups. However, the closure time was different between the two groups (closure time of all patients, P=0.031; closure time of successful patients, P=0.037). Conclusion The silk patch which has transparent, elastic, adhesive, and hyper-keratinizing properties results in a more efficient closure time than the paper patch in the treatment of TTMP patients. We therefore believe that the silk patch should be recommended for the treatment of acute tympanic membrane perforation. PMID:26045909

  5. Outcomes and humanistic issues related to treatment of acute bronchospasm.

    PubMed

    Okamoto, Lynn J

    2006-09-01

    Because of emergency department visits and hospitalizations, the economic costs associated with asthma, chronic obstructive pulmonary disease (COPD), and bronchospasm are a significant portion of total overall treatment costs. A small proportion of patients account for most of the costs, due to disease severity and acute exacerbations. Disease management programs, sponsored by insurance groups and employers, are lowering health and disability costs and reducing days missed from work and school because of exacerbations. Quality-of-life patient assessments are available to assist practitioners in evaluating disease status. Evidenced-based medicine analysis can show that less expensive therapies are not necessarily cost-effective. A study of the rate of hospital admissions from the emergency department showed that although levalbuterol therapy in the emergency department was more costly than racemic albuterol therapy, total overall treatment costs were reduced because of decreased hospitalizations in the levalbuterol-treated patients. Thus, providers, payers, and patients should examine all the scientific evidence (safety, efficacy or effectiveness, economics, and humanistic benefits) to make the most informed health care decision. PMID:16945064

  6. Mechanical thrombectomy in pediatric acute ischemic stroke: Clinical outcomes and literature review.

    PubMed

    Madaelil, Thomas P; Kansagra, Akash P; Cross, DeWitte T; Moran, Christopher J; Derdeyn, Colin P

    2016-08-01

    There are limited data on outcomes of mechanical thrombectomy for pediatric stroke using modern devices. In this study, we report two cases of pediatric acute ischemic stroke treated with mechanical thrombectomy, both with good angiographic result (TICI 3) and clinical outcome (no neurological deficits at 90 days). In addition, we conducted a literature review of all previously reported cases describing the use of modern thrombectomy devices. Including our two cases, the aggregate rate of partial or complete vessel recanalization was 100% (22/22), and the aggregate rate of favorable clinical outcome was 91% (20/22). This preliminary evidence suggests that mechanical thrombectomy with modern devices may be a safe and effective treatment option in pediatric patients with acute ischemic stroke. PMID:26945589

  7. Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE.

    PubMed

    Nguyen, H Bryant; Jaehne, Anja Kathrin; Jayaprakash, Namita; Semler, Matthew W; Hegab, Sara; Yataco, Angel Coz; Tatem, Geneva; Salem, Dhafer; Moore, Steven; Boka, Kamran; Gill, Jasreen Kaur; Gardner-Gray, Jayna; Pflaum, Jacqueline; Domecq, Juan Pablo; Hurst, Gina; Belsky, Justin B; Fowkes, Raymond; Elkin, Ronald B; Simpson, Steven Q; Falk, Jay L; Singer, Daniel J; Rivers, Emanuel P

    2016-01-01

    Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions. PMID:27364620

  8. Implications of the new international sepsis guidelines for nursing care.

    PubMed

    Kleinpell, Ruth; Aitken, Leanne; Schorr, Christa A

    2013-05-01

    Sepsis is a serious worldwide health care condition that is associated with high mortality rates, despite improvements in the ability to manage infection. New guidelines for the management of sepsis were recently released that advocate for implementation of care based on evidence-based practice for both adult and pediatric patients. Critical care nurses are directly involved in the assessment of patients at risk for developing sepsis and in the treatment of patients with sepsis and can, therefore, affect outcomes for critically ill patients. Nurses' knowledge of the recommendations in the new guidelines can help to ensure that patients with sepsis receive therapies that are based on the latest scientific evidence. This article presents an overview of new evidence-based recommendations for the treatment of adult patients with sepsis, highlighting the role of critical care nurses. PMID:23635930

  9. Early seizures in patients with acute stroke: Frequency, predictive factors, and effect on clinical outcome

    PubMed Central

    Alberti, Andrea; Paciaroni, Maurizio; Caso, Valeria; Venti, Michele; Palmerini, Francesco; Agnelli, Giancarlo

    2008-01-01

    Background Early seizure (ES) may complicate the clinical course of patients with acute stroke. The aim of this study was to assess the rate of and the predictive factors for ES as well the effects of ES on the clinical outcome at hospital discharge in patients with first-ever stroke. Patients and methods A total of 638 consecutive patients with first-ever stroke (543 ischemic, 95 hemorrhagic), admitted to our Stroke Unit, were included in this prospective study. ES were defined as seizures occurring within 7 days from acute stroke. Patients with history of epilepsy were excluded. Results Thirty-one patients (4.8%) had ES. Seizures were significantly more common in patients with cortical involvement, severe and large stroke, and in patient with cortical hemorrhagic transformation of ischemic stroke. ES was not associated with an increase in adverse outcome (mortality and disability). After multivariate analysis, hemorrhagic transformation resulted as an independent predictive factor for ES (OR = 6.5; 95% CI: 1.95–22.61; p = 0.003). Conclusion ES occur in about 5% of patients with acute stroke. In these patients hemorrhagic transformation is a predictive factor for ES. ES does not seem to be associated with an adverse outcome at hospital discharge after acute stroke. PMID:18827922

  10. Outcome Prediction of Consciousness Disorders in the Acute Stage Based on a Complementary Motor Behavioural Tool

    PubMed Central

    Jöhr, Jane; Gilart de Keranflec'h, Charlotte; Van De Ville, Dimitri; Preti, Maria Giulia; Meskaldji, Djalel E.; Hömberg, Volker; Laureys, Steven; Draganski, Bogdan; Frackowiak, Richard; Diserens, Karin

    2016-01-01

    Introduction Attaining an accurate diagnosis in the acute phase for severely brain-damaged patients presenting Disorders of Consciousness (DOC) is crucial for prognostic validity; such a diagnosis determines further medical management, in terms of therapeutic choices and end-of-life decisions. However, DOC evaluation based on validated scales, such as the Revised Coma Recovery Scale (CRS-R), can lead to an underestimation of consciousness and to frequent misdiagnoses particularly in cases of cognitive motor dissociation due to other aetiologies. The purpose of this study is to determine the clinical signs that lead to a more accurate consciousness assessment allowing more reliable outcome prediction. Methods From the Unit of Acute Neurorehabilitation (University Hospital, Lausanne, Switzerland) between 2011 and 2014, we enrolled 33 DOC patients with a DOC diagnosis according to the CRS-R that had been established within 28 days of brain damage. The first CRS-R assessment established the initial diagnosis of Unresponsive Wakefulness Syndrome (UWS) in 20 patients and a Minimally Consciousness State (MCS) in the remaining13 patients. We clinically evaluated the patients over time using the CRS-R scale and concurrently from the beginning with complementary clinical items of a new observational Motor Behaviour Tool (MBT). Primary endpoint was outcome at unit discharge distinguishing two main classes of patients (DOC patients having emerged from DOC and those remaining in DOC) and 6 subclasses detailing the outcome of UWS and MCS patients, respectively. Based on CRS-R and MBT scores assessed separately and jointly, statistical testing was performed in the acute phase using a non-parametric Mann-Whitney U test; longitudinal CRS-R data were modelled with a Generalized Linear Model. Results Fifty-five per cent of the UWS patients and 77% of the MCS patients had emerged from DOC. First, statistical prediction of the first CRS-R scores did not permit outcome differentiation

  11. Sepsis: From Pathophysiology to Individualized Patient Care

    PubMed Central

    László, Ildikó; Trásy, Domonkos; Molnár, Zsolt; Fazakas, János

    2015-01-01

    Sepsis has become a major health economic issue, with more patients dying in hospitals due to sepsis related complications compared to breast and colorectal cancer together. Despite extensive research in order to improve outcome in sepsis over the last few decades, results of large multicenter studies were by-and-large very disappointing. This fiasco can be explained by several factors, but one of the most important reasons is the uncertain definition of sepsis resulting in very heterogeneous patient populations, and the lack of understanding of pathophysiology, which is mainly based on the imbalance in the host-immune response. However, this heroic research work has not been in vain. Putting the results of positive and negative studies into context, we can now approach sepsis in a different concept, which may lead us to new perspectives in diagnostics and treatment. While decision making based on conventional sepsis definitions can inevitably lead to false judgment due to the heterogeneity of patients, new concepts based on currently gained knowledge in immunology may help to tailor assessment and treatment of these patients to their actual needs. Summarizing where we stand at present and what the future may hold are the purpose of this review. PMID:26258150

  12. Acute kidney injury-incidence, prognostic factors, and outcome of patients in an Intensive Care Unit in a tertiary center: A prospective observational study

    PubMed Central

    Korula, Sara; Balakrishnan, Sindhu; Sundar, Shyam; Paul, Vergis; Balagopal, Anuroop

    2016-01-01

    Background and Aims: The information regarding the incidence of acute kidney injury (AKI) in medical Intensive Care Units (ICUs) in South India is limited. The aim of the study was to find the incidence, prognostic factors, and outcome of patients with AKI. We also assessed whether only urine output criteria of risk, injury, failure, loss, end (RIFLE) classification can be used to look at the outcome of AKI. Patients and Methods: This was a prospective, cross-sectional study of 6 months duration in a 28 bedded medical ICU of a tertiary center. AKI was defined as an absolute creatinine value of>1.6 mg/dl or a 25% increase from baseline creatinine values. Results: The incidence of AKI was 16.1%, and mortality was 7.8% in our study population. Among patients with AKI 87 (75.7%) patients had sepsis. 71.3% patients had metabolic acidosis on admission, and 47.8% patients were in shock. 57.4% of patient's required mechanical ventilation (MV). 39.1% of AKI patients required renal replacement therapy (RRT). Requirement of RRT was significantly affected by increasing age, Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores on admission, serum creatinine, and use of vasopressors. 49.5% of patients with AKI died within 28 days. Increasing age, MV, hemodialysis (HD), hypertension, chronic kidney disease, and requirement of noradrenaline support were associated with increasing 28 days mortality. The maximum RIFLE score with urine output criteria showed association to the requirement of HD in univariate analysis but did not show relation to mortality. Conclusion: The incidence of AKI was 16.1% in critically ill patients. In patients with AKI, 39.1% patients required HD and 28 days mortality was 49.5%. The study also showed good univariate association of urine output criteria of RIFLE classification to the requirement of HD in AKI patients. PMID:27390456

  13. Trends in One-Year Outcomes of Dialysis-Requiring Acute Kidney Injury in Denmark 2005-2012: A Population-Based Nationwide Study

    PubMed Central

    Carlson, Nicholas; Hommel, Kristine; Olesen, Jonas Bjerring; Soja, Anne-Merete; Vilsbøll, Tina; Kamper, Anne-Lise; Torp-Pedersen, Christian; Gislason, Gunnar

    2016-01-01

    Background Dialysis-requiring acute kidney injury (AKI) is associated with substantial mortality and risk of end-stage renal disease (ESRD). Despite considerable growth in incidence of severe AKI, information pertaining to trends in outcomes remains limited. We evaluated time trends in one year risks of ESRD and death in patients with dialysis-requiring AKI over an eight year period in Denmark. Methods In a retrospective nationwide study based on national registers, all adults requiring acute renal replacement therapy between 2005 and 2012 were identified. Patients with preceding ESRD were excluded. Through individual-level cross-referencing of administrative registries, information pertaining to comorbidity, preceding surgical interventions, and concurrent other organ failure and sepsis was ascertained. Comparisons of period-specific one year odds ratios for ESRD and death were calculated in a multiple logistic regression model. Results A total of 13,819 patients with dialysis-requiring AKI were included in the study. Within one year, 1,017 (7.4%) patients were registered with ESRD, and 7,908 (57.2%) patients died. The one-year rate of ESRD decreased from 9.0% between 2005 and 2006 to 6.1% between 2011 and 2012. Simultaneously, the one-year mortality rate decreased from 58.2% between 2005 and 2006 to 57.5% between 2011 and 2012. Consequently, the adjusted odds ratios for the period 2011–2012 (with the period 2005–2006 as reference) were 0.75 (0.60–0.95, p = 0.015) and 0.87 (95% CI 0.78–0.97, p = 0.010) for ESRD and death, respectively. Conclusions In a nationwide retrospective study on time trends in one year outcomes following dialysis-requiring AKI, risk of all-cause mortality and ESRD decreased over a period of 8 years. PMID:27459297

  14. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  15. A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study

    PubMed Central

    Lyons, Jason J; Greene, Tracy L; Haley, James M

    2015-01-01

    Objective To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Design Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients’ designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Setting Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Participants Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. Main outcome measure ‘Suspected infection’ was the established gold standard to assess clinical decision support clinimetric performance. Results A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying ‘suspected infection’ as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. Conclusion A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis. PMID:26688744

  16. Method for Assigning Priority Levels in Acute Care (MAPLe-AC) predicts outcomes of acute hospital care of older persons - a cross-national validation

    PubMed Central

    2011-01-01

    Background Although numerous risk factors for adverse outcomes for older persons after an acute hospital stay have been identified, a decision making tool combining all available information in a clinically meaningful way would be helpful for daily hospital practice. The purpose of this study was to evaluate the ability of the Method for Assigning Priority Levels for Acute Care (MAPLe-AC) to predict adverse outcomes in acute care for older people and to assess its usability as a decision making tool for discharge planning. Methods Data from a prospective multicenter study in five Nordic acute care hospitals with information from admission to a one year follow-up of older acute care patients were compared with a prospective study of acute care patients from admission to discharge in eight hospitals in Canada. The interRAI Acute Care assessment instrument (v1.1) was used for data collection. Data were collected during the first 24 hours in hospital, including pre-morbid and admission information, and at day 7 or at discharge, whichever came first. Based on this information a crosswalk was developed from the original MAPLe algorithm for home care settings to acute care (MAPLe-AC). The sample included persons 75 years or older who were admitted to acute internal medical services in one hospital in each of the five Nordic countries (n = 763) or to acute hospital care either internal medical or combined medical-surgical services in eight hospitals in Ontario, Canada (n = 393). The outcome measures considered were discharge to home, discharge to institution or death. Outcomes in a 1-year follow-up in the Nordic hospitals were: living at home, living in an institution or death, and survival. Logistic regression with ROC curves and Cox regression analyses were used in the analyses. Results Low and mild priority levels of MAPLe-AC predicted discharge home and high and very high priority levels predicted adverse outcome at discharge both in the Nordic and Canadian data sets

  17. Use of antiplatelet agents in sepsis: a glimpse into the future.

    PubMed

    Akinosoglou, Karolina; Alexopoulos, Dimitrios

    2014-02-01

    As mechanisms of sepsis pathophysiology have been elucidated with time, sepsis may be considered nowadays, as an uncontrolled inflammatory and pro-coagulant response to a pathogen. In this cascade of events, platelets play a key role, via interaction with endothelial cells and modulation of both innate and adaptive immune system. In that manner, inhibition of platelet function could represent a useful tool for attenuating inflammatory response and improving outcomes. Data on current antiplatelet agents, including acetylsalicylic acid, P2Y12 inhibitors and GPIIb/IIIa antagonists, in animal models are promising. Clinical data in patients hospitalized for pneumonia, at risk for acute lung injury, and/or critically ill revealed an association between antiplatelet therapy and reduction in both short-term mortality and prevalence of acute lung injury, as well as, the need for intensive care unit admission, without a concomitant increased bleeding risk. In need of innovative approach in the treatment of sepsis, further prospective, interventional, randomized trials are pivotal to establish potential use of antiplatelet agents in this context. PMID:24103487

  18. Sepsis: a roadmap for future research.

    PubMed

    Cohen, Jonathan; Vincent, Jean-Louis; Adhikari, Neill K J; Machado, Flavia R; Angus, Derek C; Calandra, Thierry; Jaton, Katia; Giulieri, Stefano; Delaloye, Julie; Opal, Steven; Tracey, Kevin; van der Poll, Tom; Pelfrene, Eric

    2015-05-01

    Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments. Existing models of clinical research seem increasingly unlikely to produce new therapies that will result in a step change in clinical outcomes. In this Commission, we set out our understanding of the clinical epidemiology and management of sepsis and then ask how the present approaches might be challenged to develop a new roadmap for future research. PMID:25932591

  19. Acute CSF interleukin-6 trajectories after TBI: associations with neuroinflammation, polytrauma, and outcome.

    PubMed

    Kumar, R G; Diamond, M L; Boles, J A; Berger, R P; Tisherman, S A; Kochanek, P M; Wagner, A K

    2015-03-01

    Traumatic brain injury (TBI) results in a significant inflammatory burden that perpetuates the production of inflammatory mediators and biomarkers. Interleukin-6 (IL-6) is a pro-inflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. We hypothesized that cohort heterogeneity, temporal inflammatory profiles, and concurrent inflammatory marker associations are critical to characterize when targeting subpopulations for anti-inflammatory therapies. Toward this objective, we used serial cerebrospinal fluid (CSF) samples to generate temporal acute IL-6 trajectory (TRAJ) profiles in a prospective cohort of adults with severe TBI (n=114). We examined the impact of injury type on IL-6 profiles, and how IL-6 profiles impact sub-acute (2weeks-3months) serum inflammatory marker load and long-term global outcome 6-12months post-injury. There were two distinct acute CSF IL-6 profiles, a high and low TRAJ group. Individuals in the high TRAJ had increased odds of unfavorable Glasgow Outcome Scale (GOS) scores at 6months (adjusted OR=3.436, 95% CI: 1.259, 9.380). Individuals in the high TRAJ also had higher mean acute CSF inflammatory load compared to individuals in the low TRAJ (p⩽0.05). The two groups did not differ with respect acute serum profiles; however, individuals in the high CSF IL-6 TRAJ also had higher mean sub-acute serum IL-1β and IL-6 levels compared with the low TRAJ group (p⩽0.05). Lastly, injury type (isolated TBI vs. TBI+polytrauma) was associated with IL-6 TRAJ group (χ(2)=5.31, p=0.02). Specifically, there was 70% concordance between those with TBI+polytrauma and the low TRAJ; in contrast, isolated TBI was similarly distributed between TRAJ groups. These data provide evidence that sustained, elevated levels of CSF IL-6 are associated

  20. Long-Term Outcomes of Acute Low-Tone Hearing Loss

    PubMed Central

    Roh, Kyung Jin; Lee, Eun Jung; Park, Ah Young; Choi, Byeong Il

    2015-01-01

    Background and Objectives Although acute low-tone hearing loss has been associated with cochlear hydrops or early stage Meniere's disease, its prognosis in the short-term has been reported to be better than sudden hearing loss. However, recurrence of hearing loss and possible progression to Meniere's disease remain important concerns in the clinical setting. This study aims to investigate the long-term audiological outcomes of acute low-tone hearing loss. Subjects and Methods A retrospective review of patients presenting with a first attack of acute low-tone hearing loss was performed. Of the 77 patients, 33 were followed up for more than 3 months. Progression, recovery of hearing loss and recurrence of hearing loss were examined. Also, correlation between long-term outcomes and associated clinical factors were analyzed. Results Twenty-five patients (75.7%) had complete hearing recovery, five patients (15.1%) had partial recovery, two patients (6.0%) had no recovery, and one patient (3.0%) had progression of hearing loss 1 month after initial treatment. Thirty-three patients were followed up for more than 3 months (mean 22 months, range 3-79 months). Recurrences of acute low-tone hearing loss were observed in five patients (15.2%). All of the recurrences occurred during the first 12 months of follow-up. Long-term prognosis correlated with the initial therapy results (R2=0.693). Conclusions Recurrences of hearing loss were documented in five patients (15.2%), and all of these cases occurred within one year of the first attack. Audiological outcomes after initial therapy may predict the recurrence of acute low-tone hearing loss. PMID:26413572

  1. Sepsis-Induced Osteoblast Ablation Causes Immunodeficiency.

    PubMed

    Terashima, Asuka; Okamoto, Kazuo; Nakashima, Tomoki; Akira, Shizuo; Ikuta, Koichi; Takayanagi, Hiroshi

    2016-06-21

    Sepsis is a host inflammatory response to severe infection associated with high mortality that is caused by lymphopenia-associated immunodeficiency. However, it is unknown how lymphopenia persists after the accelerated lymphocyte apoptosis subsides. Here we show that sepsis rapidly ablated osteoblasts, which reduced the number of common lymphoid progenitors (CLPs). Osteoblast ablation or inducible deletion of interleukin-7 (IL-7) in osteoblasts recapitulated the lymphopenic phenotype together with a lower CLP number without affecting hematopoietic stem cells (HSCs). Pharmacological activation of osteoblasts improved sepsis-induced lymphopenia. This study demonstrates a reciprocal interaction between the immune and bone systems, in which acute inflammation induces a defect in bone cells resulting in lymphopenia-associated immunodeficiency, indicating that bone cells comprise a therapeutic target in certain life-threatening immune reactions. PMID:27317262

  2. Good visual outcome in an immunocompromised patient with bilateral acute retinal necrosis syndrome: A case report

    PubMed Central

    Marrocos de Aragão, Ricardo E.; Barreira, Ieda M.A.; Arrais, Barbara L.A.; Pereira, Leidiane A.; Ramos, Carine S.

    2013-01-01

    Acute retinal necrosis (ARN) is an uncommon necrotizing, fulminant retinopathy caused by the herpes simplex virus types 1 or 2 or by the varicella zoster vírus with visually devastating consequences. Generally it occurs in patients who are systemically healthy, but occasionally occurs in immunocompromised host. We report a case of bilateral ARN in a patient with AIDS with a good final visual outcome. PMID:25278806

  3. Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury

    PubMed Central

    2011-01-01

    Introduction Sepsis is the leading cause of acute kidney injury (AKI) in critical patients. The optimal timing of initiating renal replacement therapy (RRT) in septic AKI patients remains controversial. The objective of this study is to determine the impact of early or late initiation of RRT, as defined using the simplified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification (sRIFLE), on hospital mortality among septic AKI patients. Methods Patient with sepsis and AKI requiring RRT in surgical intensive care units were enrolled between January 2002 and October 2009. The patients were divided into early (sRIFLE-0 or -Risk) or late (sRIFLE-Injury or -Failure) initiation of RRT by sRIFLE criteria. Cox proportional hazard ratios for in hospital mortality were determined to assess the impact of timing of RRT. Results Among the 370 patients, 192 (51.9%) underwent early RRT and 259 (70.0%) died during hospitalization. The mortality rate in early and late RRT groups were 70.8% and 69.7% respectively (P > 0.05). Early dialysis did not relate to hospital mortality by Cox proportional hazard model (P > 0.05). Patients with heart failure, male gender, higher admission creatinine, and operation were more likely to be in the late RRT group. Cox proportional hazard model, after adjustment with propensity score including all patients based on the probability of late RRT, showed early dialysis was not related to hospital mortality. Further model matched patients by 1:1 fashion according to each patient's propensity to late RRT showed no differences in hospital mortality according to head-to-head comparison of demographic data (P > 0.05). Conclusions Use of sRIFLE classification as a marker poorly predicted the benefits of early or late RRT in the context of septic AKI. In the future, more physiologically meaningful markers with which to determine the optimal timing of RRT initiation should be identified. PMID:21645350

  4. Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome

    PubMed Central

    2013-01-01

    Background Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. Methods Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient’s condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. Results Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. Discussion In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. Conclusion Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission. PMID:24180319

  5. Public Awareness of Sepsis Is Low in Sweden

    PubMed Central

    Mellhammar, Lisa; Christensson, Bertil; Linder, Adam

    2015-01-01

    Background. Sepsis is a serious and common condition with high mortality and morbidity. The public awareness, knowledge, and perception of sepsis in Sweden are unknown. Methods. A survey was performed using an online interview distributed to adults, aged 18–74, between March 6 and 9, 2015. Results. A total of 1001 people responded to the survey. Twenty-one percent of participants had heard of sepsis, whereas more than 86% had heard of each of the other conditions listed; for example, stroke (95%), chronic obstructive pulmonary disease (COPD) (95%), and leukemia (92%). Of those who had heard of sepsis, 93% responded that it is an infection or blood poisoning in an open question. The respondents who had heard of each disease estimated its mortality. For sepsis, the mortality was estimated at an average of 30%, which was at the same level as estimated mortalities for prostate and breast cancer but lower than for stroke, COPD, and leukemia. Conclusions. The awareness and knowledge of sepsis is low. The mortality for sepsis is not as overestimated as for many other diseases. The lack of awareness of sepsis might be a target to improve the outcome for sepsis patients by reducing the prehospital delay and hence enable early interventions. An increased general awareness might also raise interest for funding for research in this area and for its priority in healthcare support. PMID:26634220

  6. Serum Triglyceride Level: A Predictor of Complications and Outcomes in Acute Pancreatitis?

    PubMed Central

    Tariq, Hassan; Gaduputi, Vinaya; Peralta, Richard; Abbas, Naeem; Nayudu, Suresh Kumar; Thet, Phyo; Zaw, Tin; Hui, Shirley; Chilimuri, Sridhar

    2016-01-01

    Aim. To study serum triglyceride level as a predictor of complications and outcomes in acute pancreatitis. Methods. In this retrospective observational study, 582 patients admitted with acute pancreatitis, who had serum triglyceride levels measured within the first 24 hours, were divided into two groups. The study group consisted of patients with a triglyceride level ≥2.26 mmol/L (group 2) and the control group consisted of triglyceride level of <2.26 mmol/L (group 1). We collected data for baseline demographics, laboratory values, incidence of complications (local and systemic), admission to the intensive care unit (ICU), ICU length of stay, length of total hospital stay, and death in the two groups. Results. A triglyceride level of ≥2.26 mmol/L was found to be an independent predictor of developing altered mental status (p: 0.004), pancreatic necrosis (p: 0.001), acute respiratory distress syndrome (p: 0001), systemic Inflammatory response syndrome (p: 0.001), acute kidney injury (p: 0.001), hospital length of stay (LOS) (p: 0.002), admission to intensive care unit (ICU) (p: 0.002), and ICU LOS (p: 0.003). Conclusion. A triglyceride level of ≥2.26 mmol/L on admission in acute pancreatitis is an independent predictor of developing local and systemic complications, hospital LOS, admission to ICU, and ICU LOS.

  7. Predictors of Longitudinal Outcomes after Unstable Response to Acute Phase Cognitive Therapy for Major Depressive Disorder

    PubMed Central

    Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.; Jarrett, Robin B.

    2015-01-01

    After patients with major depressive disorder (MDD) respond to acute-phase cognitive therapy (CT), continuation-phase treatments may be applied to improve long-term outcomes. We clarified which CT responders experience remission, recovery, relapse, and recurrence by testing baseline demographic, clinical, and personality variables. The sample of CT responders at higher risk of relapse (N = 241) was randomized to 8 months of continuation-phase CT (C-CT), double-blinded fluoxetine or pill placebo, and followed 24 months (Jarrett & Thase, 2010). Patients with lower positive emotionality and behavioral activation at the end of acute-phase CT showed increased risk for relapse/recurrence of MDD. In addition, patients with lower positive emotionality and behavioral activation, as well as higher residual depression (including emotional, cognitive, and social facets), showed decreased probability of remission (≥6 continuous weeks of minimal or absent symptoms) after acute-phase CT. Finally, patients with greater residual depression, as well as younger age and earlier MDD onset, showed decreased probability of recovery (≥35 continuous weeks of minimal or absent symptoms) after acute-phase CT. Moderator analyses did not reveal differential prediction across the continuation phase treatment arms. These results may help clinicians gauge the prognoses and need for continuation treatment among MDD patients who respond to acute-phase CT. PMID:25985046

  8. Impact of Oxandrolone Treatment on Acute Outcomes After Severe Burn Injury

    PubMed Central

    Pham, Tam N.; Klein, Matthew B.; Gibran, Nicole S.; Arnoldo, Brett D.; Gamelli, Richard L.; Silver, Geoffrey M.; Jeschke, Marc G.; Finnerty, Celeste C.; Tompkins, Ronald G.; Herndon, David N.

    2013-01-01

    Pharmacologic modulation of hypermetabolism clearly benefits children with major burns, however, its role in adult burns remains to be defined. Oxandrolone appears to be a promising anabolic agent although few outcome data are as yet available. We examined whether early oxandrolone treatment in severely burned adults was associated with improved outcomes during acute hospitalization. We evaluated for potential associations between oxandrolone treatment and outcomes in a large cohort of severely burned adults in the context of a multicenter observational study. Patients were dichotomized with respect to oxandrolone treatment, defined as administration within 7 days after admission, with duration of at least 7 days. Acute hospitalization outcomes were compared with univariate and multivariate analyses. One hundred seventeen patients were included in this analysis. Mean patient age was 42.6 years (range, 18–86); 77% were male, with an average TBSA of 44.1%. Baseline and injury characteristics were similar among treatment and nontreatment cohorts. Oxandrolone treatment (N =59) did not impact length of stay but was associated with a lower mortality rate (P = .01) by univariate analysis. Oxandrolone treatment was independently associated with higher survival by adjusted analyses (P = .02). Examination of early oxandrolone treatment in this cohort of severely burned adults suggests that this therapy is safe and may be associated with improved survival. Further studies are necessary to define the exact mechanisms by which oxandrolone is beneficial during inpatient treatment. PMID:18849836

  9. Pharmacological management of sepsis

    SciTech Connect

    Fletcher, J.R.

    1985-01-01

    Systemic sepsis continues to be the most-difficult management problem in caring for the combat casualty. The complications of sepsis pervade all areas of injury to soldiers in the field, whether it is mechanical (missiles), thermal (burns), chemical, biological, or radiation injury. With the advent of tactical nuclear weapons, the problem of sepsis will be much higher in future wars than has previously been experienced through the world. The purpose of this chapter is a) to review the data suggesting pharmacological agents that may benefit the septic patient, and b) to emphasize the adjunctive therapies that should be explored in clinical trials. The pharmacological management of sepsis remains controversial. Most of the drugs utilized clinically treat the symptoms of the disease and are not necessarily directed at fundamental mechanisms that are known to be present in sepsis. A broad data base is emerging, indicating that NSAID should be used in human clinical trials. Prostaglandins are sensitive indicators of cellular injury and may be mediators for a number of vasoactive chemicals. Opiate antagonists and calcium channel blockers require more in-depth data; however, recent studies generate excitement for their potential use in the critically ill patient. Pharmacological effects of antibiotics, in concert with other drugs, suggest an entirely new approach to pharmacological treatment in sepsis. There is no doubt that new treatment modalities or adjunctive therapies must be utilized to alter the poor prognosis of severe sepsis that we have observed in the past 4 decades.

  10. Discharge hemoglobin and outcome in patients with acute nonvariceal upper gastrointestinal bleeding

    PubMed Central

    Lee, Jae Min; Kim, Eun Sun; Chun, Hoon Jai; Hwang, Young-Jae; Lee, Jae Hyung; Kang, Seung Hun; Yoo, In Kyung; Kim, Seung Han; Choi, Hyuk Soon; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck

    2016-01-01

    Background and study aims: Many patients with acute gastrointestinal bleeding present with anemia and frequently require red blood cell (RBC) transfusion. A restrictive transfusion strategy and a low hemoglobin (Hb) threshold for transfusion had been shown to produce acceptable outcomes in patients with acute upper gastrointestinal bleeding. However, most patients are discharged with mild anemia owing to the restricted volume of packed RBCs (pRBCs). We investigated whether discharge Hb influences the outcome in patients with acute nonvariceal upper gastrointestinal bleeding. Patients and methods: We retrospectively analyzed patients with upper gastrointestinal bleeding who had received pRBCs during hospitalization between January 2012 and January 2014. Patients with variceal bleeding, malignant lesion, stroke, or cardiovascular disease were excluded. We divided the patients into 2 groups, low (8 g/dL ≤ Hb < 10 g/dL) and high (Hb ≥ 10 [g/dL]) discharge Hb, and compared the clinical course and Hb changes between these groups. Results: A total of 102 patients met the inclusion criteria. Fifty patients were discharged with Hb levels < 10 g/dL, whereas 52 were discharged with Hb levels > 10 g/dL. Patients in the low Hb group had a lower consumption of pRBCs and shorter hospital stay than did those in the high Hb group. The Hb levels were not fully recovered at outpatient follow-up until 7 days after discharge; however, most patients showed Hb recovery at 45 days after discharge. The rate of rebleeding after discharge was not significantly different between the 2 groups. Conclusions: In patients with acute upper gastrointestinal bleeding, a discharge Hb between 8 and 10 g/dL was linked to favorable outcomes on outpatient follow-up. Most patients recovered from anemia without any critical complication within 45 days after discharge. PMID:27540574

  11. Demographics, Clinical Characteristics, Management, and Outcomes of Acute Heart Failure Patients: Observations from the Oman Acute Heart Failure Registry

    PubMed Central

    Panduranga, Prashanth; Sulaiman, Kadhim; Al-Zakwani, Ibrahim; Alazzawi, Aouf AbdlRahman; Abraham, Abraham; Singh, Prit Pal; Narayan, Narayan Anantha; Rajarao, Mamatha Punjee; Khdir, Mohammed Ahmed; Abdlraheem, Mohamad; Siddiqui, Aftab Ahmed; Soliman, Hisham; Elkadi, Osama Abdellatif; Bichu, Ruchir Kumar; Al Lawati, Kumayl Hasan

    2016-01-01

    Objectives We sought to describe the demographics, clinical characteristics, management and outcomes of patients in Oman with acute heart failure (AHF) as part of the Gulf aCute heArt failuRe rEgistry (CARE) project. Methods Data were analyzed from 988 consecutive patients admitted with AHF to 12 hospitals in Oman between 14 February and 14 November 2012. Results The mean age of our patients was 63±12 years. Over half (57%) were male and 95% were Omani citizens. Fifty-seven percent of patients presented with acute decompensated chronic heart failure (ADCHF) while 43% had new-onset AHF. The primary comorbid conditions were hypertension (72%), coronary artery disease (55%), and diabetes mellitus (53%). Ischemic heart disease (IHD), hypertensive heart disease, and idiopathic cardiomyopathy were the most common etiologies of AHF in Oman. The median left ventricular ejection fraction of the cohort was 36% (27–45%) with 56% of the patients having heart failure with reduced ejection fraction (< 40%). Atrial fibrillation was seen in 15% of patients. Acute coronary syndrome (ACS) and non-compliance with medications were the most common precipitating factors. At discharge, angiotensin converting enzyme inhibitors and beta-blockers were prescribed adequately, but aldosterone antagonists were under prescribed. Within 12-months follow-up, one in two patients were rehospitalized for AHF. In-hospital mortality was 7.1%, which doubled to 15.7% at three months and reached 26.4% at one-year post discharge. Conclusions Oman CARE was the first prospective multicenter registry of AHF in Oman and showed that heart failure (HF) patients present at a younger age with recurrent ADCHF and HF with reduced ejection fraction. IHD was the most common etiology of HF with a low prevalence of AHF, but a high prevalence of acute coronary syndrome and non-compliance with medications precipitating HF. A quarter of patients died at one-year follow-up even though at discharge medical therapy was

  12. Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis.

    PubMed

    Zheng, Yijun; Zhu, Duming

    2016-01-01

    Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis. PMID:27413421

  13. Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis

    PubMed Central

    Zheng, Yijun; Zhu, Duming

    2016-01-01

    Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis. PMID:27413421

  14. Effect of upper airway obstruction in acute stroke on functional outcome at 6 months

    PubMed Central

    Turkington, P; Allgar, V; Bamford, J; Wanklyn, P; Elliott, M

    2004-01-01

    Background: The aim of this study was to determine whether upper airway obstruction occurring within the first 24 hours of stroke onset has an effect on outcome following stroke at 6 months. Traditional definitions used for obstructive sleep apnoea (OSA) are arbitrary and may not apply in the acute stroke setting, so a further aim of the study was to redefine respiratory events and to assess their impact on outcome. Methods: 120 patients with acute stroke underwent a sleep study within 24 hours of onset to determine the severity of upper airway obstruction (respiratory disturbance index, RDI-total study). Stroke severity (Scandinavian Stroke Scale, SSS) and disability (Barthel score) were also recorded. Each patient was subsequently followed up at 6 months to determine morbidity and mortality. Results: Death was independently associated with SSS (OR (95% CI) 0.92 (0.88 to 0.95), p<0.00001) and RDI-total study (OR (95% CI) 1.07 (1.03 to 1.12), p<0.01). The Barthel index was independently predicted by SSS (p = 0.0001; r = 0.259; 95% CI 0.191 to 0.327) and minimum oxygen saturation during the night (p = 0.037; r = 0.16; 95% CI 0.006 to 0.184). The mean length of the respiratory event most significantly associated with death at 6 months was 15 seconds (sensitivity 0.625, specificity 0.525) using ROC curve analysis. Conclusion: The severity of upper airway obstruction appears to be associated with a worse functional outcome following stroke, increasing the likelihood of death and dependency. Longer respiratory events appear to have a greater effect. These data suggest that long term outcome might be improved by reducing upper airway obstruction in acute stroke. PMID:15115859

  15. Is there a relationship between admission blood glucose level following acute poisoning and clinical outcome?

    PubMed Central

    Sabzghabaee, Ali Mohammad; Eizadi-Mood, Nastaran; Gheshlaghi, Farzad; Adib, Nooshin; Safaeian, Leila

    2011-01-01

    Introduction The aim of this study was to investigate the relationship between the admission blood glucose level following acute poisoning, severity of acute poisoning and clinical outcome. Material and methods This prospective study was conducted on 345 deliberate self-poisoning patients. Standard demographic and clinical information; admission blood glucose level; poisoning severity score and outcome were recorded. Patients with a history of diabetes mellitus, receipt of pre-sampling intravenous dextrose solution or glucocorticoids, and poisoning with toxic agents which produce hyper- or hypoglycaemia were excluded. Results Mean age of the patients was 27.5 ±8.6 years. Females outnumbered males (57.9%). Oral ingestion of more than one drug (46.7%) and opiates (14.2%) were the main causes of poisoning. Blood glucose values ranged from 50 mg/dl to 396 mg/dl. Hyper- and hypoglycaemia were observed in 23.8% and 13.91% respectively. A total of 24.41% and 22.92% of the patients in hyper- and hypoglycaemic groups had grade 3 and 4 severity score in comparison with 4.18% in the normoglycaemic group. Development of complications and death were 14.64% and 10.42% in patients with hyper- and hypoglycaemia versus 3.73% in patients with normoglycaemia. A significant difference between normoglycaemic and hyperglycaemic patients in the severity of poisoning and clinical outcome was observed (P < 0.001). Conclusions Admission blood glucose levels may have a relationship with the severity of poisoning and clinical outcome following acute poisoning. PMID:22291737

  16. Waterlow score as a surrogate marker for predicting adverse outcome in acute pancreatitis.

    PubMed

    Gillick, K; Elbeltagi, H; Bhattacharya, S

    2016-01-01

    Introduction Introduced originally to stratify risk for developing decubitus ulcers, the Waterlow scoring system is recorded routinely for surgical admissions. It is a composite score, reflecting patients' general condition and co-morbidities. The aim of this study was to investigate whether the Waterlow score can be used as an independent surrogate marker to predict severity and adverse outcome in acute pancreatitis. Methods In this retrospective analysis, a consecutive cohort was studied of 250 patients presenting with acute pancreatitis, all of whom had their Waterlow score calculated on admission. Primary outcome measures were length of hospital stay and mortality. Secondary outcome measures included rate of intensive care unit (ICU) admission and development of complications such as peripancreatic free fluid, pancreatic necrosis and pseudocyst formation. Correlation of the Waterlow score with some known markers of disease severity and outcomes was also analysed. Results The Waterlow score correlated strongly with the most commonly used marker of disease severity, the Glasgow score (analysis of variance, p=0.0012). Inpatient mortality, rate of ICU admission and length of hospital stay increased with a higher Waterlow score (Mann-Whitney U test, p=0.0007, p=0.049 and p=0.0002 respectively). There was, however, no significant association between the Waterlow score and the incidence of three known complications of pancreatitis: presence of peripancreatic fluid, pancreatic pseudocyst formation and pancreatic necrosis. Receiver operating characteristic curve analysis demonstrated good predictive power of the Waterlow score for mortality (area under the curve [AUC]: 0.73), ICU admission (AUC: 0.65) and length of stay >7 days (AUC: 0.64). This is comparable with the predictive power of the Glasgow score and C-reactive protein. Conclusions The Waterlow score for patients admitted with acute pancreatitis could provide a useful tool in prospective assessment of disease

  17. Anticoagulant modulation of inflammation in severe sepsis

    PubMed Central

    Allen, Karen S; Sawheny, Eva; Kinasewitz, Gary T

    2015-01-01

    Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severely ill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis. PMID:25938026

  18. Outcomes of allogeneic hematopoietic cell transplantation in patients with biphenotypic acute leukemia.

    PubMed

    Mori, Jinichi; Ishiyama, Ken; Yamaguchi, Takuhiro; Tanaka, Junji; Uchida, Naoyuki; Kobayashi, Takeshi; Fukuda, Takahiro; Kanamori, Heiwa; Miyamura, Koichi; Takahashi, Satoshi; Eto, Tetsuya; Hirokawa, Makoto; Mori, Shinichiro; Nagamura, Tokiko; Atsuta, Yoshiko; Takami, Akiyoshi

    2016-01-01

    The outcomes of allogeneic hematopoietic cell transplantation (HSCT) in patients with biphenotypic acute leukemia (BAL) remain unclear. We retrospectively analyzed the outcomes of HSCT in BAL patients in Japan in comparison to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) using the registration data from a nationwide database. The data of 90, 5371, and 3301 patients with BAL, AML, and ALL, respectively, were included in the analysis. The median follow-up period was 1481.5 days (range: 0–5556). The 5-year overall survival (OS) of the BAL, AML, and ALL patients were 39.6, 41.8, and 42.0 %, respectively (BAL vs. AML, P = 0.98 BAL vs. ALL, P = 0.77). A multivariate analysis revealed that, in comparison to BAL, AML with a better-risk karyotype was associated with superior OS. An analysis of the prognostic factors of BAL patients showed that OS was significantly longer in patients who were in their first complete remission in comparison to patients who were not in remission. Our data suggest that HSCT is an effective treatment for BAL patients, regardless of the presence of any known poor prognostic factors other than a non-remission status. PMID:26499506

  19. Outcome of Acute Graft Rejection Associated with Hemodynamic Compromise in Pediatric Heart Transplant Recipients

    PubMed Central

    Tissot, Cecile; Buckvold, Shannon; Gralla, Jane; Ivy, D. Dunbar; Pietra, Biagio A.; Miyamoto, Shelley D.

    2011-01-01

    We sought to analyze the outcome of hemodynamically significant acute graft rejection in pediatric heart transplant recipients from a single-center experience. Acute graft rejection remains a major cause of morbidity and mortality for patients who undergo orthotopic heart transplantation and has been associated with the severity of the rejection episode. A retrospective review of all children experiencing a hemodynamically significant rejection episode after orthotopic heart transplantation was performed. Fifty-three patients with 54 grafts had 70 rejection episodes requiring intravenous inotropic support. Forty-one percent of these patients required high-dose inotropic support, with the remaining 59% of patients requiring less inotropic support. Overall graft survival to hospital discharge was 41% for patients in the high-dose group compared to 94% in the low-dose group. Six-month graft survival in patients who required high-dose inotropes remained at 41% compared to 44% in the low-dose group. Hemodynamically significant acute graft rejection in pediatric heart transplant recipients is a devastating problem with poor short- and long-term outcomes. Survival to hospital discharge is dismal in patients who require high-dose inotropic support. In contrast, survival to discharge is quite good in patients who require only low-dose inotropic support; however, six-month graft survival in this group is low secondary to a high incidence of graft failure related to worsening or aggressive transplant coronary artery disease. PMID:20963408

  20. Outcomes before and after the Implementation of a Critical Pathway for Patients with Acute Aortic Disease

    PubMed Central

    Shin, Kyu Chul; Lee, Hye Sun; Park, Joon Min; Joo, Hyun-Chel; Ko, Young-Guk; Park, Incheol

    2016-01-01

    Purpose Acute aortic diseases, such as aortic dissection and aortic aneurysm, can be life-threatening vascular conditions. In this study, we compared outcomes before and after the implementation of a critical pathway (CP) for patients with acute aortic disease at the emergency department (ED). Materials and Methods This was a retrospective observational cohort study. The CP was composed of two phases: PRE-AORTA for early diagnosis and AORTA for prompt treatment. We compared patients who were diagnosed with acute aortic disease between pre-period (January 2010 to December 2011) and post-period (July 2012 to June 2014). Results Ninety-four and 104 patients were diagnosed with acute aortic disease in the pre- and post-periods, respectively. After the implementation of the CP, 38.7% of acute aortic disease cases were diagnosed via PRE-AORTA. The door-to-CT time was reduced more in PRE-AORTA-activated patients [71.0 (61.0, 115.0) min vs. 113.0 (56.0, 170.5) min; p=0.026]. During the post-period, more patients received emergency intervention than during the pre-period (22.3% vs. 36.5%; p=0.029). Time until emergency intervention was reduced in patients, who visited the ED directly, from 378.0 (302.0, 489.0) min in the pre-period to 200.0 (170.0, 299.0) min in the post-period (p=0.001). The number of patients who died in the ED declined from 11 to 4 from the pre-period to the post-period. Hospital mortality decreased from 26.6% to 14.4% in the post-period (p=0.033). Conclusion After the implementation of a CP for patients with acute aortic disease, more patients received emergency intervention within a shorter time, resulting in improved hospital mortality. PMID:26996561

  1. A qualitative exploration of discharge destination as an outcome or a driver of acute stroke care

    PubMed Central

    2014-01-01

    of discharge destination made early in an acute admission by allied health professionals, has a powerful influence over the care and rehabilitation provided, and the ultimate outcomes for stroke patients. PMID:24774583

  2. How Can the Microbiologist Help in Diagnosing Neonatal Sepsis?

    PubMed Central

    Paolucci, Michela; Landini, Maria Paola; Sambri, Vittorio

    2012-01-01

    Neonatal sepsis can be classified into two subtypes depending upon whether the onset of symptoms is before 72 hours of life (early-onset neonatal sepsis—EONS) or later (late-onset neonatal sepsis—LONS). These definitions have contributed greatly to diagnosis and treatment by identifying which microorganisms are likely to be responsible for sepsis during these periods and the expected outcomes of infection. This paper focuses on the tools that microbiologist can offer to diagnose and eventually prevent neonatal sepsis. Here, we discuss the advantages and limitation of the blood culture, the actual gold standard for sepsis diagnosis. In addition, we examine the utility of molecular techniques in the diagnosis and management of neonatal sepsis. PMID:22319539

  3. Predictors of poor hospital discharge outcome in acute stroke due to atrial fibrillation.

    PubMed

    Tian, Melissa J; Tayal, Ashis H; Schlenk, Elizabeth A

    2015-02-01

    Atrial fibrillation (AF) is a frequent cause of acute ischemic stroke that results in severe neurological disability and death despite treatment with intravenous thrombolysis (intravenous recombinant tissue plasminogen activator [rtPA]). We performed a retrospective review of a single-center registry of patients treated with intravenous rtPA for stroke. The purposes of this study were to compare intravenous rtPA treated patients with stroke with and without AF to examine independent predictors of poor hospital discharge outcome (in-hospital death or hospital discharge to a skilled nursing facility, long-term acute care facility, or hospice care). A univariate analysis was performed on 144 patients receiving intravenous rtPA for stroke secondary to AF and 190 patients without AF. Characteristics that were significantly different between the two groups were age, initial National Institutes of Health Stroke Scale score, length of hospital stay, gender, hypertension, hyperlipidemia, smoking status, presence of large cerebral infarct, and hospital discharge outcome. Bivariate logistic regression analysis indicated that patients with stroke secondary to AF with a poor hospital discharge outcome had a greater likelihood of older age, higher initial National Institutes of Health Stroke Scale scores, longer length of hospital stay, intubation, and presence of large cerebral infarct compared with those with good hospital discharge outcome (discharged to home or inpatient rehabilitation or signed oneself out against medical advice). A multivariate logistic regression analysis showed that older age, longer length of hospital stay, and presence of large cerebral infarct were independent predictors of poor hospital discharge outcome. These predictors can guide nursing interventions, aid the multidisciplinary treating team with treatment decisions, and suggest future directions for research. PMID:25503541

  4. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients.

    PubMed

    Claushuis, Theodora A M; van Vught, Lonneke A; Scicluna, Brendon P; Wiewel, Maryse A; Klein Klouwenberg, Peter M C; Hoogendijk, Arie J; Ong, David S Y; Cremer, Olaf L; Horn, Janneke; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Zwinderman, Aeilko H; Bonten, Marc J; Schultz, Marcus J; van der Poll, Tom

    2016-06-16

    Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratified according to platelet counts (very low <50 × 10(9)/L, intermediate-low 50 × 10(9) to 99 × 10(9)/L, low 100 × 10(9) to 149 × 10(9)/L, or normal 150 × 10(9) to 399 × 10(9)/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 10(9)/L and 50 × 10(9) to 99 × 10(9)/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts < 50 × 10(9)/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 × 10(9)/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal

  5. A Systematic Review of Music Therapy Practice and Outcomes with Acute Adult Psychiatric In-Patients

    PubMed Central

    Carr, Catherine; Odell-Miller, Helen; Priebe, Stefan

    2013-01-01

    Background and Objectives There is an emerging evidence base for the use of music therapy in the treatment of severe mental illness. Whilst different models of music therapy have been developed in mental health care, none have specifically accounted for the features and context of acute in-patient settings. This review aimed to identify how music therapy is provided for acute adult psychiatric in-patients and what outcomes have been reported. Review Methods A systematic review using medical, psychological and music therapy databases. Papers describing music therapy with acute adult psychiatric in-patients were included. Analysis utilised narrative synthesis. Results 98 papers were identified, of which 35 reported research findings. Open group work and active music making for nonverbal expression alongside verbal reflection was emphasised. Aims were engagement, communication and interpersonal relationships focusing upon immediate areas of need rather than longer term insight. The short stay, patient diversity and institutional structure influenced delivery and resulted in a focus on single sessions, high session frequency, more therapist direction, flexible use of musical activities, predictable musical structures, and clear realistic goals. Outcome studies suggested effectiveness in addressing a range of symptoms, but were limited by methodological shortcomings and small sample sizes. Studies with significant positive effects all used active musical participation with a degree of structure and were delivered in four or more sessions. Conclusions No single clearly defined model exists for music therapy with adults in acute psychiatric in-patient settings, and described models are not conclusive. Greater frequency of therapy, active structured music making with verbal discussion, consistency of contact and boundaries, an emphasis on building a therapeutic relationship and building patient resources may be of particular importance. Further research is required to

  6. Acute outcome of treating patients admitted with electrical storm in a tertiary care centre

    PubMed Central

    Prabhu, Mukund A.; Namboodiri, Narayanan; Prasad BV, Srinivas; Abhilash, S.P.; Thajudeen, Anees; Ajith, Kumar V.K.

    2016-01-01

    Background Electrical storm (ES) is a life threatening emergency. There is little data available regarding acute outcome of ES. Aims The study aimed to analyze the acute outcome of ES, various treatment modalities used, and the factors associated with mortality. Methods This is a retrospective observational study involving patients admitted with ES at our centre between 1/1/2007 and 31/12/2013. Results 41 patients (mean age 54.61 ± 12.41 years; 86.7% males; mean ejection fraction (EF) 44.51 ± 16.48%) underwent treatment for ES. Hypokalemia (14.63%) and acute coronary syndrome (ACS) (14.63%) were the commonest identifiable triggers. Only 9 (21.95%) patients already had an ICD implanted. Apart from antiarrhythmic drugs (100%), deep sedation (87.8%), mechanical ventilation (24.39%) and neuraxial modulation using left sympathetic cardiac denervation (21.95%) were the common treatment modalities used. Thirty-three (80.49%) patients could be discharged after a mean duration of 14.2 ± 2.31 days. Eight (19.5%) patients died in hospital. The mortality was significantly higher in those with EF < 35% compared to those with a higher EF (8 (42.11% vs 0 (0%), p = 0.03)). There was no significant difference in mortality between those with versus without a structural heart disease (8 (21.1% vs 0 (0%), p = 0.32)). Comparison of mortality an ACS with ES versus ES of other aetiologies (3 (50%) vs 5 (14.29) %, p = 0.076)) showed a trend towards significance. Conclusion With comprehensive treatment, there is reasonable acute survival rate of ES. Hypokalemia and ACS are the commonest triggers of ES. Patients with low EF and ACS have higher mortality.

  7. Association of acute myeloid leukemia's most immature phenotype with risk groups and outcomes.

    PubMed

    Gerber, Jonathan M; Zeidner, Joshua F; Morse, Sarah; Blackford, Amanda L; Perkins, Brandy; Yanagisawa, Breann; Zhang, Hao; Morsberger, Laura; Karp, Judith; Ning, Yi; Gocke, Christopher D; Rosner, Gary L; Smith, B Douglas; Jones, Richard J

    2016-05-01

    The precise phenotype and biology of acute myeloid leukemia stem cells remain controversial, in part because the "gold standard" immunodeficient mouse engraftment assay fails in a significant fraction of patients and identifies multiple cell-types in others. We sought to analyze the clinical utility of a novel assay for putative leukemia stem cells in a large prospective cohort. The leukemic clone's most primitive hematopoietic cellular phenotype was prospectively identified in 109 newly-diagnosed acute myeloid leukemia patients, and analyzed against clinical risk groups and outcomes. Most (80/109) patients harbored CD34(+)CD38(-) leukemia cells. The CD34(+)CD38(-) leukemia cells in 47 of the 80 patients displayed intermediate aldehyde dehydrogenase expression, while normal CD34(+)CD38(-) hematopoietic stem cells expressed high levels of aldehyde dehydrogenase. In the other 33/80 patients, the CD34(+)CD38(-) leukemia cells exhibited high aldehyde dehydrogenase activity, and most (28/33, 85%) harbored poor-risk cytogenetics or FMS-like tyrosine kinase 3 internal tandem translocations. No CD34(+) leukemia cells could be detected in 28/109 patients, including 14/21 patients with nucleophosmin-1 mutations and 6/7 acute promyelocytic leukemia patients. The patients with CD34(+)CD38(-) leukemia cells with high aldehyde dehydrogenase activity manifested a significantly lower complete remission rate, as well as poorer event-free and overall survivals. The leukemic clone's most immature phenotype was heterogeneous with respect to CD34, CD38, and ALDH expression, but correlated with acute myeloid leukemia risk groups and outcomes. The strong clinical correlations suggest that the most immature phenotype detectable in the leukemia might serve as a biomarker for "clinically-relevant" leukemia stem cells. ClinicalTrials.gov: NCT01349972. PMID:26819054

  8. Leukocytosis in Patients with Neurologic Deterioration after Acute Ischemic Stroke is Associated with Poor Outcomes

    PubMed Central

    Kumar, Andre D.; Boehme, Amelia K.; Siegler, James E.; Gillette, Michael; Albright, Karen C.; Martin-Schild, Sheryl

    2016-01-01

    Background Neurologic deterioration (ND) after acute ischemic stroke (AIS) has been shown to result in poor outcomes. ND is thought to arise from penumbral excitotoxic cell death caused in part by leukocytic infiltration. Elevated admission peripheral leukocyte levels are associated with poor outcomes in stroke patients who suffer ND, but little is known about the dynamic changes that occur in leukocyte counts around the time of ND. We sought to determine if peripheral leukocyte levels in the days surrounding ND are correlated with poor outcomes. Methods Patients with AIS who presented to our center within 48 hours of symptom onset between July 2008 and June 2010 were retrospectively identified by chart review and screened for ND (defined as an increase in National Institutes of Health Stroke Scale score ≥2 within a 24-hour period). Patients were excluded for steroid use during hospitalization or in the month before admission and infection within the 48 hours before or after ND. Demographics, daily leukocyte counts, and poor functional outcome (modified Rankin Scale score 3–6) were investigated. Results Ninety-six of the 292 (33%) patients screened had ND. The mean age was 69.5 years; 62.5% were male and 65.6% were black. Patients with a poor functional outcome had significantly higher leukocyte and neutrophil levels 1 day before ND (P =.048 and P =.026, respectively), and on the day of ND (P =.013 and P =.007, respectively), compared to patients with good functional outcome. Conclusions Leukocytosis at the time of ND correlates with poor functional outcomes and may represent a marker of greater cerebral damage through increased parenchymal inflammation. PMID:23031742

  9. Indications, algorithms, and outcomes for coronary artery bypass surgery in patients with acute coronary syndromes.

    PubMed

    Yerokun, Babatunde A; Williams, Judson B; Gaca, Jeffrey; Smith, Peter K; Roe, Matthew T

    2016-06-01

    For patients with a non-ST-segment elevation acute coronary syndrome (NSTE-ACS), guideline recommendations and treatment pathways focus on revascularization for definitive treatment if the patient is an appropriate candidate. Despite the widespread use of revascularization for NSTE-ACS, most patients undergo a percutaneous coronary intervention, whereas a minority of patients undergo coronary artery bypass grafting. Focusing specifically on the USA, the contemporary utilization, preoperative and perioperative considerations, and outcomes of NSTE-ACS patients undergoing coronary artery bypass grafting have not been comprehensively reviewed. PMID:26945187

  10. Acute care of older patients in the emergency department: strategies to improve patient outcomes

    PubMed Central

    McCabe, John J; Kennelly, Sean P

    2015-01-01

    Older patients in the emergency department (ED) are a vulnerable population who are at a higher risk of functional decline and hospital reattendance subsequent to an ED visit, and have a high mortality rate in the months following an ED attendance. The delivery of acute care in a busy environment to this population presents its own unique challenge. The purpose of this review is to detail the common geriatric syndromes encountered in the ED as well as the appropriate strategies and instruments, which can be utilized to support the clinical decision matrix and improve outcomes. PMID:27147890